<%BANNER%>

Emotional Reactivity in Parkinson's Disease

Permanent Link: http://ufdc.ufl.edu/UFE0021090/00001

Material Information

Title: Emotional Reactivity in Parkinson's Disease Psychophysiological and Psychosocial Correlates
Physical Description: 1 online resource (108 p.)
Language: english
Creator: Miller, Kimberly
Publisher: University of Florida
Place of Publication: Gainesville, Fla.
Publication Date: 2008

Subjects

Subjects / Keywords: depression, emotion, mood, parkinson, psychophysiology, startle
Clinical and Health Psychology -- Dissertations, Academic -- UF
Genre: Psychology thesis, Ph.D.
bibliography   ( marcgt )
theses   ( marcgt )
government publication (state, provincial, terriorial, dependent)   ( marcgt )
born-digital   ( sobekcm )
Electronic Thesis or Dissertation

Notes

Abstract: Preliminary work in our laboratory suggests that patients with Parkinson's disease (PD) may demonstrate diminished physiological reactivity to threatening pictures. This may be due to the fact that the amygdala is known to exhibit pathology in PD, and is a neural structure that plays a key role in processing threat signals in the environment. Our primary aim was to further explore the possibility of reduced emotional reactivity to threatening stimuli in PD, as indexed by emotional modulation of the startle eyeblink reflex. Our secondary aim was to examine the psychosocial impact of any reactivity deficits by determining whether they are associated with depression and with the misattribution of depression by patients spouses. Twenty-four non-demented PD patients in the 'off' medication state and 24 age- and education-matched controls viewed neutral, pleasant, disgusting (mutilations and contaminations), and threatening (human and animal attack) pictures. During this time, white noise bursts were binaurally presented to elicit startle eyeblinks. Participants also completed the Beck Depression Inventory, 2nd edition (BDI-II) and spouses completed a surrogate-report version of this measure. Contrary to predictions, PD patients did not display reduced startle potentiation to threatening pictures depicting attack. Instead, diminished reactivity to pictures of mutilations was found. Neither self- nor surrogate-report ratings of depression were associated with eyeblink magnitude. Additionally, spousal and PD patient depression ratings were significantly correlated, indicating that spouses do not appear to misattribute PD symptoms to depression. We hypothesized that PD patients may have a general deficit in physiological responsivity to highly arousing negative stimuli, as opposed to an emotion-specific deficit. Mutilation pictures are particularly arousing because they represent a threat to bodily integrity; as such, it may be that mutilation pictures were the only category of pictures sufficiently arousing to detect a between-groups difference in physiological reactivity. A secondary finding suggests that spouses may serve as accurate surrogate reporters of mood when PD patients are unable to report upon their own mood. In sum, results suggest that PD patients have aberrant physiological emotional reactivity, but this does not appear to be related to spousal perceptions of mood.
General Note: In the series University of Florida Digital Collections.
General Note: Includes vita.
Bibliography: Includes bibliographical references.
Source of Description: Description based on online resource; title from PDF title page.
Source of Description: This bibliographic record is available under the Creative Commons CC0 public domain dedication. The University of Florida Libraries, as creator of this bibliographic record, has waived all rights to it worldwide under copyright law, including all related and neighboring rights, to the extent allowed by law.
Statement of Responsibility: by Kimberly Miller.
Thesis: Thesis (Ph.D.)--University of Florida, 2008.
Local: Adviser: Bowers, Dawn.

Record Information

Source Institution: UFRGP
Rights Management: Applicable rights reserved.
Classification: lcc - LD1780 2008
System ID: UFE0021090:00001

Permanent Link: http://ufdc.ufl.edu/UFE0021090/00001

Material Information

Title: Emotional Reactivity in Parkinson's Disease Psychophysiological and Psychosocial Correlates
Physical Description: 1 online resource (108 p.)
Language: english
Creator: Miller, Kimberly
Publisher: University of Florida
Place of Publication: Gainesville, Fla.
Publication Date: 2008

Subjects

Subjects / Keywords: depression, emotion, mood, parkinson, psychophysiology, startle
Clinical and Health Psychology -- Dissertations, Academic -- UF
Genre: Psychology thesis, Ph.D.
bibliography   ( marcgt )
theses   ( marcgt )
government publication (state, provincial, terriorial, dependent)   ( marcgt )
born-digital   ( sobekcm )
Electronic Thesis or Dissertation

Notes

Abstract: Preliminary work in our laboratory suggests that patients with Parkinson's disease (PD) may demonstrate diminished physiological reactivity to threatening pictures. This may be due to the fact that the amygdala is known to exhibit pathology in PD, and is a neural structure that plays a key role in processing threat signals in the environment. Our primary aim was to further explore the possibility of reduced emotional reactivity to threatening stimuli in PD, as indexed by emotional modulation of the startle eyeblink reflex. Our secondary aim was to examine the psychosocial impact of any reactivity deficits by determining whether they are associated with depression and with the misattribution of depression by patients spouses. Twenty-four non-demented PD patients in the 'off' medication state and 24 age- and education-matched controls viewed neutral, pleasant, disgusting (mutilations and contaminations), and threatening (human and animal attack) pictures. During this time, white noise bursts were binaurally presented to elicit startle eyeblinks. Participants also completed the Beck Depression Inventory, 2nd edition (BDI-II) and spouses completed a surrogate-report version of this measure. Contrary to predictions, PD patients did not display reduced startle potentiation to threatening pictures depicting attack. Instead, diminished reactivity to pictures of mutilations was found. Neither self- nor surrogate-report ratings of depression were associated with eyeblink magnitude. Additionally, spousal and PD patient depression ratings were significantly correlated, indicating that spouses do not appear to misattribute PD symptoms to depression. We hypothesized that PD patients may have a general deficit in physiological responsivity to highly arousing negative stimuli, as opposed to an emotion-specific deficit. Mutilation pictures are particularly arousing because they represent a threat to bodily integrity; as such, it may be that mutilation pictures were the only category of pictures sufficiently arousing to detect a between-groups difference in physiological reactivity. A secondary finding suggests that spouses may serve as accurate surrogate reporters of mood when PD patients are unable to report upon their own mood. In sum, results suggest that PD patients have aberrant physiological emotional reactivity, but this does not appear to be related to spousal perceptions of mood.
General Note: In the series University of Florida Digital Collections.
General Note: Includes vita.
Bibliography: Includes bibliographical references.
Source of Description: Description based on online resource; title from PDF title page.
Source of Description: This bibliographic record is available under the Creative Commons CC0 public domain dedication. The University of Florida Libraries, as creator of this bibliographic record, has waived all rights to it worldwide under copyright law, including all related and neighboring rights, to the extent allowed by law.
Statement of Responsibility: by Kimberly Miller.
Thesis: Thesis (Ph.D.)--University of Florida, 2008.
Local: Adviser: Bowers, Dawn.

Record Information

Source Institution: UFRGP
Rights Management: Applicable rights reserved.
Classification: lcc - LD1780 2008
System ID: UFE0021090:00001


This item has the following downloads:


Full Text
xml version 1.0 encoding UTF-8
REPORT xmlns http:www.fcla.edudlsmddaitss xmlns:xsi http:www.w3.org2001XMLSchema-instance xsi:schemaLocation http:www.fcla.edudlsmddaitssdaitssReport.xsd
INGEST IEID E20101113_AAAAMS INGEST_TIME 2010-11-13T16:14:30Z PACKAGE UFE0021090_00001
AGREEMENT_INFO ACCOUNT UF PROJECT UFDC
FILES
FILE SIZE 1053954 DFID F20101113_AACMWX ORIGIN DEPOSITOR PATH miller_k_Page_089.tif GLOBAL false PRESERVATION BIT MESSAGE_DIGEST ALGORITHM MD5
81e3d5fe653000b1f7f3ca16e5f181d5
SHA-1
6ab0807b86d3c1a9d4d5dc8c315a70a439cf0a64
2286 F20101113_AACNDG miller_k_Page_052.txt
45012676b16af5e98af0ed9ac4c5c52a
a029c3341d595eb0cbbb14a4b397184ab089aab1
55966 F20101113_AACMYA miller_k_Page_014.pro
8cc5182bf5cf94365015ae3b627c030e
b42b337821a32f58e6641eed70bb48269f319e0c
2023 F20101113_AACNCS miller_k_Page_037.txt
86128b0320df2f8478e97d81e2ac4076
0eeeb050c53a068142e2148a667af2be9912cf7b
F20101113_AACMXM miller_k_Page_105.tif
0c921aaa7aaa7c691a4c34aaa82919bc
005c4d523f20edcc124578283cafbbf6a6b9e86b
F20101113_AACMWY miller_k_Page_090.tif
4d8f7b6cb4902ee15b6cf1478de75362
c73745067ca5d3b1da6780e1d397d93a7a76440d
2273 F20101113_AACNDH miller_k_Page_053.txt
1b56a5d2fdeafdf46fc6247f15cceb13
21b62991d21f64fa0f3f544444a52b32f3303e72
55331 F20101113_AACMYB miller_k_Page_015.pro
28c717f76662123e28ae37ffd2db01cb
08afb48ceddb5dc36afc27d54c5597d42b7d6816
2090 F20101113_AACNCT miller_k_Page_038.txt
842ca94a62e7dd072ab4ff2bb79fb582
f82428f99861f2871fa6a167d07c0a3dd954a65e
F20101113_AACMXN miller_k_Page_106.tif
2810a23b6f121642a18cc963ce3c3c4b
c0765f5fc19b76980eeb1bf6b1134e64ea788203
F20101113_AACMWZ miller_k_Page_091.tif
bfcc9a0806d7d42c1ab53e4bd0d6b192
f95cc78973326fdf5fefe32b15bb9f5ed6b07c6d
2148 F20101113_AACNDI miller_k_Page_054.txt
5d06685928dafd2f6cd24a7977394640
e58d5120edf271dcddecae75d8ad96d159d63c22
52308 F20101113_AACMYC miller_k_Page_016.pro
64ea3a547a4f7128251e2c8d2aab96ab
ecc4336e2c228b3e4489ce8e1da55e6928d93d6a
2080 F20101113_AACNCU miller_k_Page_039.txt
3f5052a8afeeb9dba48ea8f38c642960
1610e430dc8214b527f5cc2dea69af51224c4a2b
F20101113_AACMXO miller_k_Page_107.tif
81d79c02d7ce4adaf928090141dfcef1
250eba485dfd400703d8e047d0bc0d95d1a13f67
2178 F20101113_AACNDJ miller_k_Page_055.txt
50c648c83c933d77aa4d79b289c0eed9
972f2479f312848f752a49c928730128182aa45f
55160 F20101113_AACMYD miller_k_Page_017.pro
2e1afcfc8f641daa61dc31d7e7e53a6b
401d48fee5f4695a14e17c54cbcc62cd4a7513ea
2111 F20101113_AACNCV miller_k_Page_040.txt
8ce4da3bdf9be4b8e94b5f0c90b46535
3741d9dcfae3f73f8e83c345b2545bb14d525a63
F20101113_AACMXP miller_k_Page_108.tif
c8991f89d155abdd3d8bfda3ab1bb1d6
23f8ec61a579584f6ef34fe41623b09ea2071fdf
2237 F20101113_AACNDK miller_k_Page_056.txt
edada0ba7fbae57be1c6d1adcfc1ed98
203ccace3835a869f175c524c2d007151588fd9e
53469 F20101113_AACMYE miller_k_Page_018.pro
b605c164ce521d35e4d5cbf918b568f4
446d2eead22216b1677e12edad3c29045f2ede09
2095 F20101113_AACNCW miller_k_Page_041.txt
c9d891103d0d097a430ff5bbb8802cbf
1f7b566d05756e42545cb8998f4b4683ac065708
8421 F20101113_AACMXQ miller_k_Page_001.pro
1bfd735304afa8c0a10d887b904168b5
a0095bf9d9241241871b57a9a05d2826904aa5e3
2171 F20101113_AACNDL miller_k_Page_057.txt
bac901f2c054a7d7018bd698899bd262
f9c34d7f9db0a5de41c5c565745d501465ed6215
54798 F20101113_AACMYF miller_k_Page_019.pro
00aab91df02d55bd90cc6ecd4d891348
e0031c8bcd71e6f7d7f69d8c2fb0098e6cafb36b
2062 F20101113_AACNCX miller_k_Page_043.txt
bd9a5d50da0daa7d5c62e69609b6a63c
340afac0b827748032d9742070c04b288a592922
939 F20101113_AACMXR miller_k_Page_002.pro
6f53635c72370621bee7964ed7aa788f
bd935f9279d01a7a9ca427935f0d7d0a6ae00f27
2156 F20101113_AACNDM miller_k_Page_058.txt
d81120434b168e2b5afb52d21fbfa67c
40141d8d6b319944fabe111a5187e559ec19dc13
51341 F20101113_AACMYG miller_k_Page_020.pro
89615c89e3fcca6d86e34bb9ee362ebb
86e1dadd8f13d227fae3b29dc2247f695e22c097
F20101113_AACNCY miller_k_Page_044.txt
4f35db8c64efd343eb91602d3e522ae6
abca1b8b776a54d6f5b07c6871d7816ecf9220d0
2757 F20101113_AACMXS miller_k_Page_003.pro
50e493aca1419581aabdec2cb7d17b53
1a8125aba1e06b62d39df9bb1809c53794e4325f
713 F20101113_AACNEA miller_k_Page_073.txt
f7c6f2e652242713ec9006125bf16183
5b8f6ef8181dd310d39e394f6b92b7149fb6efa6
2176 F20101113_AACNDN miller_k_Page_059.txt
ac76a8654f48e2084c26f438641cb939
768562f972c7ebe48c53247a0175a7c7dcb9ea66
54300 F20101113_AACMYH miller_k_Page_021.pro
6c856901eea035d76e5a8297e02e5e66
dfa85fb07eb8d427b36365efd7cee4c0801ff593
2193 F20101113_AACNCZ miller_k_Page_045.txt
d00451f4e014f85fe3911a86d6f06195
745180dd15901f6e31a9aff777ccf72f65722393
779 F20101113_AACNEB miller_k_Page_074.txt
69c88244e612083f4e64c271a33a0058
6f2aa2ff7e170608ae5535d2a0a82a218e28653d
2271 F20101113_AACNDO miller_k_Page_060.txt
cd66c459878fec91c93e8db8c4e939a6
e24d56fbc067e7cd1645947494353c8f7bb625a6
56393 F20101113_AACMYI miller_k_Page_023.pro
f3766aea0b65140f42e67945b2c06e0b
f8848e0f852b9e4661af40fea83252a39c8df11f
11984 F20101113_AACMXT miller_k_Page_004.pro
db66546c2b2891e4f9ca95ea2334da07
158062f082e835f9308054843066388e1cec4412
2105 F20101113_AACNEC miller_k_Page_075.txt
f5c261553c943ac1792e74e175bdc483
43dec5df6de86f3e7a36a72e434f09153de137fa
2260 F20101113_AACNDP miller_k_Page_061.txt
d23d0d527f696cc3b8d0370ec47ba5c1
c4b7a7c3bd24ad4bd468f7b8d729d04d8ce09376
57076 F20101113_AACMYJ miller_k_Page_024.pro
e52a704c008d52c0aefe40fbd5971201
e43b2644e70307490005169265baa4fa3bf8eefc
104956 F20101113_AACMXU miller_k_Page_005.pro
8f84f52b30f74354e4dbf682f35d38e9
fd57963fe1f6a5e527441ff9de9bb1b1893d0c3f
2151 F20101113_AACNED miller_k_Page_076.txt
6e604d3f358c2b3354d8eafc250ded44
ac33f134d2119d68c89f7c5e4ccc18769c8620c7
2138 F20101113_AACNDQ miller_k_Page_062.txt
1372628fdc04fb8c7a1f0512f8788fb8
26a845fc20b61e013318fa5f7c06b14b25b7db84
56356 F20101113_AACMYK miller_k_Page_025.pro
0a8479824a183c27933a1faebfe87fc6
f71ec87e7876ec2fd9542760ad68cea56698fa47
112123 F20101113_AACMXV miller_k_Page_006.pro
3da449000a59f8eb67fc0555bd3c9820
91dc8d9d634e6579cca18034d8e153459dee308e
2100 F20101113_AACNEE miller_k_Page_078.txt
51e839d57400aba16d13bd5bf4f01bee
bfcaa2b1dcb39ce431829f52f3c4025dc164ae09
2033 F20101113_AACNDR miller_k_Page_063.txt
0b8ce0de2e69dffbeed7c5e47f294b5c
375521cd26d1dbdf4d2ef212de08b5b77a148c18
56328 F20101113_AACMYL miller_k_Page_026.pro
a1b1f5a1df8f0c0db5620c80f4e476e2
73c9a3a560514412f394a14ffdc5a75fd173f411
46215 F20101113_AACMXW miller_k_Page_010.pro
164d4506f29167f2bb31ab20f647c588
cb3a902755ee35db69d1bfda5df65efff7b5eaa1
2227 F20101113_AACNEF miller_k_Page_079.txt
9e41e6058141e691006e813425926bd6
99f4607e76f8b63ac8b97ae7fb8be3d4f3a45e9b
52044 F20101113_AACMZA miller_k_Page_043.pro
770b85acf04db13ca45c325b663f7bf7
eeb6f266a11190ffdd79fab0e062388ba1fa5727
1773 F20101113_AACNDS miller_k_Page_064.txt
45778040c0b8acec8f23f549d4fee296
4943c6b4351c866aa8a5a6bdb87e46e736c66b75
55704 F20101113_AACMYM miller_k_Page_028.pro
82ddfb24795e5b74f388f38f2d498868
4a41e8670d06ece67f4605b506a918131b901819
27010 F20101113_AACMXX miller_k_Page_011.pro
5b01d9cca3f99f441670065be7177d7e
49914df096d6e37143638300942dd83948e77dc1
2324 F20101113_AACNEG miller_k_Page_080.txt
158d78c1caa6dff3f866f6593fd4c4ed
eafcee06325c4666c3cfdfccfefb31c9ab30a70b
55997 F20101113_AACMZB miller_k_Page_045.pro
723eb29b3f8377b52e9a488d924c307f
a4d292a88cd82da106dcd646ee74d418bc912280
841 F20101113_AACNDT miller_k_Page_065.txt
8a1e65d5ea5840db0aa7b607e5c7a0b6
4bac82f661d552489075cba8c50a418248550d1d
55586 F20101113_AACMYN miller_k_Page_029.pro
a6d1ece93a8f614903eaf769add610f6
b1e0390371932b83a97567ef49e62e47421d773e
47837 F20101113_AACMXY miller_k_Page_012.pro
c5d3414466e20c1c748f2edcb98057bc
91df909f533a2a9346864c5622301e0c42dbf1b8
2284 F20101113_AACNEH miller_k_Page_081.txt
8f78039feaf888ee4c56840be492a11f
0e16b9518ac09ebeba5b88bb879f54d9556c2ab8
27898 F20101113_AACMZC miller_k_Page_046.pro
42f7ddefd279235a6989bcdc4eb05d1c
54222a056e1e61426da9d1cf733fb54b6a1df53e
2313 F20101113_AACNDU miller_k_Page_066.txt
eb3f6f37088a5eaf4026c36ed7236372
61bccc53ecb64c0cf87bd5f0096d7d6691d894d9
13518 F20101113_AACMYO miller_k_Page_030.pro
ae96010e2640fbd381de14fd2ef50b09
7df5a3dc153b1193173d8e22527db9f3b867ac35
56276 F20101113_AACMXZ miller_k_Page_013.pro
d7e42cecd18f7c306b60bbc8026fbdbd
3bc1f1bc52f758528dba286047f99380e8a444c6
2303 F20101113_AACNEI miller_k_Page_082.txt
e13cf8d28af4386c0f574d2c846dbaf4
28eaab0fd0e5f2ee29e522cd5861e3c1f979fe07
43280 F20101113_AACMZD miller_k_Page_047.pro
b7d34208de387551ff87d346a3891eea
9bd52c0eec2c1d032b60d32ed6f21469c5a4c0d0
2427 F20101113_AACNDV miller_k_Page_067.txt
e4d065d6cfa4cdfbd676748e048f6598
1c9288e72f620615cde55d11508800ae95cef686
22079 F20101113_AACMYP miller_k_Page_031.pro
49b609e0d6c75b1cd8bca2098e80d055
28bec4564dd4ed8b511a5ad1d15d6d770ab5f07e
2376 F20101113_AACNEJ miller_k_Page_083.txt
ac53edc1634062d2c5833d569a7ffc10
d9927dedd0a7146c6bf0661d23ddf6d30963e636
48819 F20101113_AACMZE miller_k_Page_048.pro
6cec2cc4dcaea9e52d191bfd52b2dde3
4fddffadc0766b8c14320bc5916e824246d88f98
1418 F20101113_AACNDW miller_k_Page_069.txt
513dd77d74811c1c86a8e37c70d6a208
fbf4887d638bea8bc3abda9ee4df03674ba80bf7
7144 F20101113_AACMYQ miller_k_Page_032.pro
5e1ec0f7326a149354b489b9d656cb24
66bf8a68518abe15c83ef235e1b574395f9d2904
2220 F20101113_AACNEK miller_k_Page_084.txt
36b1c7a8b49e9036135807c3d583481c
c3df1ee08bf8f6cb5fc565e1c50f3a36a704454a
52299 F20101113_AACMZF miller_k_Page_049.pro
e2cb1109ae5e7ecfe07bea2b08fe80a4
e2a254f37986ce1f6f7e7033a66e71585490a9f2
620 F20101113_AACNDX miller_k_Page_070.txt
4bb6aa90aa0c90821a2ca1142e2e4583
bf6f16c8f7e37d6e53b302091e0341b733a8fbde
11459 F20101113_AACMYR miller_k_Page_033.pro
6d3c2c800e0447210a8ea7488686d6c1
c5d7966efd549e5a36b5865afcb3e23c48cf83e4
2224 F20101113_AACNEL miller_k_Page_085.txt
14ef3d6ce54ddfb53fc1513a39ad8f37
622cc2c35bcdd4d430a045187052567ea0b1e05e
53906 F20101113_AACMZG miller_k_Page_050.pro
ce25bb6de178a0409167efe76397bc55
ad7a5517471b8f1584cf417b5f3f6f99c5151957
990 F20101113_AACNDY miller_k_Page_071.txt
32ce027f625645c5afd1580a3f87d409
5a90b96ae5679d0ba89bebccd3402c7b39ef0a7c
47676 F20101113_AACMYS miller_k_Page_034.pro
69b64f419603afd7daf24f2a44092427
e5a0334b768c6076c97b3a8bf92aa85bd81da7a0
2681 F20101113_AACNFA miller_k_Page_100.txt
ea22790070edfd65b6e2ce113b5b268b
7a49778d006f965bb6077bf39cb4e0f9ec8c8e0a
2231 F20101113_AACNEM miller_k_Page_086.txt
2c7390ca7f636f340e10bb2ec85cf92b
a734ab6ce2007c6575ab49ca932d31f7795fd2d2
52686 F20101113_AACMZH miller_k_Page_051.pro
fcba8db7efb562d84b371142c97ef908
9e7511a1441584f04e17a9562416c9241b82af3a
439 F20101113_AACNDZ miller_k_Page_072.txt
f5ac2f450d1d0d688c37af9cdd52ee17
cebc1e0fb813d0ede700757aaa685e4cf952a5b2
55644 F20101113_AACMYT miller_k_Page_035.pro
074a412f72c33be5178a3fa7ff2cfab6
98d59a0de0de035d2ad5785ee5ae7cf89e930a45
2634 F20101113_AACNFB miller_k_Page_101.txt
de3b2cec5c4af0cc347e144a8b95fe4d
8942331d1b1ecebcb83e1bd858c7cdf27c10ba89
2074 F20101113_AACNEN miller_k_Page_087.txt
36f9f72a7161559bba2c90405f393609
fe466d0072762573f242b11a0a98959f5ad17b1f
57135 F20101113_AACMZI miller_k_Page_053.pro
53e727cea8640632181bec99fb691a43
d4c7dd0f28c83bc5920fda2b989fb99679f6e3c1
2806 F20101113_AACNFC miller_k_Page_103.txt
092cf3016e9d04fe154caeb8c7095fb9
ed8659c793ca85ea74cdfb6e3c4f1b4608bbaa4a
2052 F20101113_AACNEO miller_k_Page_088.txt
fbcaca6c65a2e8cc131db9bc9d467f00
26952c81a2e9ba58d84ac58e56c8e4f83fb76250
54799 F20101113_AACMYU miller_k_Page_036.pro
bc036ef8eafeb349f926197bc7b3e30f
116cf9a52ae312dccfecd768e6313040ab42071f
2658 F20101113_AACNFD miller_k_Page_104.txt
501d813c3489b639bf4471a4346239a8
3d6a286e423b1f4913e3d64067065b9315a9ae1a
2258 F20101113_AACNEP miller_k_Page_089.txt
e8d4a5ea656d9588a8045f52a4ff199a
5cc104be884278cdc59e1becf27d25bbd32d43c2
54544 F20101113_AACMZJ miller_k_Page_054.pro
16298b6d39ce612588c72dd17bb7c594
2ef122f0821b63bbb3ae435c0808b027dfef6746
50962 F20101113_AACMYV miller_k_Page_037.pro
7c1b6c62e4a22d33c5529e187fc5785b
697357612f357927804ce165965ce942e27d5df1
2792 F20101113_AACNFE miller_k_Page_105.txt
213ce41a51fe1af72a67d72ae37b8153
fa21b953b8cbd0feaa9d7528d07495fa775a2444
2346 F20101113_AACNEQ miller_k_Page_090.txt
706528993be748ea4c027faf5682809d
bb295a36620e76e7c9229af10b33699ce5e752af
54879 F20101113_AACMZK miller_k_Page_055.pro
e0a731d75db80775ad796added9e8b2a
dc4c45892afc27f79f8c1bb73aa1f4e2d1c54fd0
52784 F20101113_AACMYW miller_k_Page_038.pro
c78affc9a86cd7c30c08a1ba3a20c1aa
14681fecc00c94f09cb2efa1025b0c0248b89c71
2914 F20101113_AACNFF miller_k_Page_106.txt
57da7ddb922f324a04ea9f5f4bb6f93e
9437a904d8b3e63761587abfdd198b53b35edae5
2266 F20101113_AACNER miller_k_Page_091.txt
2cc33529827c28f7867ad0d01482cd18
feb8237eba7b58d58e3f42a66cef0cf55fe3acb7
57056 F20101113_AACMZL miller_k_Page_056.pro
23a152400e962aa7b5915dbaa39ebed2
43184e0773d0999bfb6f730a2d741a604608e588
52901 F20101113_AACMYX miller_k_Page_039.pro
99b31412cb318ffcb1179e93048eed0d
50618312ce4a411447bb6f4e5ea75c457ad454ea
2435 F20101113_AACNFG miller_k_Page_107.txt
a05a72271db2a54d36c28ed41291e471
2f8d4e6194e1054b8865f0a98139cff06f733980
2272 F20101113_AACNES miller_k_Page_092.txt
3ea25377a3386a226bcdc9025ab48074
3f9eb52633b77c519479e0059726fef46e353a58
54947 F20101113_AACMZM miller_k_Page_057.pro
f865a2672f152fefc35b1acfb18df66e
ebd30f0a04af62d158f5ad63b3532a387f37d566
53415 F20101113_AACMYY miller_k_Page_040.pro
c7b3ceb81419e68ca67a5c0f56d1ef3a
4253401ce86f6d7833482a11c4b63805f1d11bd7
525669 F20101113_AACNFH miller_k.pdf
e3399a4863e71a443956ab53256152a1
e769f945386cb29a05c28f16ef79566f87ef9dfa
2119 F20101113_AACNET miller_k_Page_093.txt
0fb02d5f48ea0624b8b1c29ad9d24ba2
dfd57af67d1b73c36d9c4ce0c4c284a1eb538f25
54898 F20101113_AACMZN miller_k_Page_058.pro
2730c9baf03efde2fece96c2c6efffc6
70b64fa26c9cb1df2f4bd8e7fe839fcf92888e82
50136 F20101113_AACMYZ miller_k_Page_042.pro
b2d7749266e2a65cfc49968dc1e0ea42
f3ad48d94273d38e27a5c40496a299731bd0e790
9117 F20101113_AACNFI miller_k_Page_023thm.jpg
c543ea7d4d0d8141aac83858472bda9b
bd50c61ff78a0fc627c3c5cb53d5f2911d030762
492 F20101113_AACNEU miller_k_Page_094.txt
33a55d4a749b9c2d0915f456cb15ea62
47af1cb31d143b0d90472f29b7e32a394f92d10d
55455 F20101113_AACMZO miller_k_Page_059.pro
dcd7b57c01a3835c87cedbc264c03cb1
e52ece16759307aa853b96456d293cc20f95e680
17401 F20101113_AACNFJ miller_k_Page_008.QC.jpg
e3aacc66f31f7c9c479ff071c0533d1c
ddf493bc247e5b5fa0b5998a32cc40ddde2fab3c
1389 F20101113_AACNEV miller_k_Page_095.txt
ff796b48932861444b99971b22b8b6fb
a8de2f7557466136b05ceb066a8e3767b04ca53b
56916 F20101113_AACMZP miller_k_Page_060.pro
9946e4ac6c034691e661af14e25b3d51
6d345dfae5c943b337697e4c29e3017fc7f4eb24
16057 F20101113_AACNFK miller_k_Page_007.QC.jpg
a1d5e038791b13fd119e744f552e1db6
8f7d4b903ff15d128c87ba18196e63c26eb2bd66
1740 F20101113_AACNEW miller_k_Page_096.txt
1256da62bdf9fe3bf38badd436282b01
7294251a913e7fb5af91fe8c6b478ba7d231d810
57329 F20101113_AACMZQ miller_k_Page_061.pro
1c217b817c9aedef6162fcc621592b2a
d19e763d27cce34c42690f9b454dd952ecabb3f2
8906 F20101113_AACNGA miller_k_Page_104thm.jpg
6cc690226b2430f82213e6e05cfa70da
f8c7511144d7eac5fd2d5cb1539b34a784f81cc1
31864 F20101113_AACNFL miller_k_Page_066.QC.jpg
3fe17df42accbc15f08b5a5112ef7a1d
5e667eabc07678d35ff353b7726e4f8aa2baf512
1517 F20101113_AACNEX miller_k_Page_097.txt
c6fff5360e1baa0b6a4af12d3978d125
4d9b0a85c0ab86e3048645fc2a0f97e8b30f4b10
52766 F20101113_AACMZR miller_k_Page_062.pro
e4586bebcade44890946710a7b11b6ea
3472dd4b61b4d0fc803b6b555cd342e530545eaa
36642 F20101113_AACNFM miller_k_Page_102.QC.jpg
32329af4dd776e34a1f2ad8a1bcd919a
2da2c3ba9ecd5151e5b23547c469d2e979863d50
2360 F20101113_AACNEY miller_k_Page_098.txt
33f2ffc9e3ab39dfdd331aafc76a4f0b
7de5a61abd0be6a9db9df33664f09d09bc56f29b
51666 F20101113_AACMZS miller_k_Page_063.pro
a58134c0da5bee2e52f9620dc8fc7679
5043fce6fd782b575640bda1fee9965b516e9d62
8878 F20101113_AACNGB miller_k_Page_036thm.jpg
07297159729c49aec843250b88854f28
8b2f796d51c878f59d25130ec2da3cf94c561c32
30657 F20101113_AACNFN miller_k_Page_064.QC.jpg
846c4af582e83aa00c0c98102730912c
16de1a4659552b1c2fbba4e32996d4fb93e84d8a
2573 F20101113_AACNEZ miller_k_Page_099.txt
d7aec1b77e84a4b7d4010e2f7def1d16
881215dcc9334c4c17b2f8277e61de001f384140
44246 F20101113_AACMZT miller_k_Page_064.pro
d4e2115d3d28cd31b0652e04c84aab70
b9d6a6c6607fb57de4bb1c63df74682f10293938
8379 F20101113_AACNGC miller_k_Page_035thm.jpg
c938d5923557d89aef64c46d1c787a58
0282364cef3dceaa816ee08662e2482818db6e99
5840 F20101113_AACNFO miller_k_Page_069thm.jpg
cc74fbe79968f47e562d9e479ac00c6a
72d9c4e26059d49d287adc0a257dde52a906f4b3
18550 F20101113_AACMZU miller_k_Page_065.pro
1c9d4abd485d98116bdf086805e80df5
6374ca01f3e91efc987a78cdb05db14bfbaa292b
8884 F20101113_AACNGD miller_k_Page_022thm.jpg
dd80279b2bcf2838c52c173845da2cc4
b59366536a89c3295b0a89d8e1231a4c5f925622
9167 F20101113_AACNFP miller_k_Page_056thm.jpg
fb11b2d4f0667601e5e12f49a9c59e72
d66de41987307d1606742c9f921cf585348f8e0e
8327 F20101113_AACNGE miller_k_Page_049thm.jpg
d9111c5efb0baec2c029fa77478814a2
18dced4d48ad9fcb7a21755ad169b27c88f16fad
34989 F20101113_AACNFQ miller_k_Page_058.QC.jpg
b22ef1ae9688bacdd43a2d39bae65140
5eeddae9108f5614bf029f2da4be5e27675f00d5
50381 F20101113_AACMZV miller_k_Page_066.pro
17e7aa0052bbeefc453b97f2ef2d6dac
0f66852a1821ef31774400b64a6749357ca0062d
32421 F20101113_AACNGF miller_k_Page_042.QC.jpg
b83735eeff499e05608aa5bb6b146b03
44723705839e3f955213aeeedf385c23921e2642
13221 F20101113_AACNFR miller_k_Page_073.QC.jpg
6a856001e917e40d9e66a02a79800ada
09f8137b55d14e4f723cdb86a1e7f9698677de64
53306 F20101113_AACMZW miller_k_Page_067.pro
baf5fa5b7982659412e3d5719353289e
f9831bd0fb8218980e69af33c532b25f12cc3151
8540 F20101113_AACNFS miller_k_Page_043thm.jpg
4c67d77352c34f6ef2f6d46fa418cc32
acafeaad7dba55e01a4ea1dec968b3f91ad1519e
32473 F20101113_AACMZX miller_k_Page_068.pro
5d49cc500f0fb158dc8516f99f945c28
f4d158b9cbe5ffb3b45bef82021d565a7a5b8967
8652 F20101113_AACNGG miller_k_Page_055thm.jpg
cf8b3b4daba03631e0948307c756af54
463612a74cf03f70f01fb6a5839155f31146aff6
1056 F20101113_AACNFT miller_k_Page_003thm.jpg
cffd3e08a02995d3534343940fb89be1
d389464238c88cd4f26985c16aa8d515dacd3178
32662 F20101113_AACMZY miller_k_Page_069.pro
b4c4ec4af174572e432c9e3eab5d9290
04ca1208e73f9b209588365045e6325fe8518289
36209 F20101113_AACNGH miller_k_Page_076.QC.jpg
3ed01c54b9d800e9d36899da5624fc8b
bf0d6564f4476c46499c38ed0df1102214199c01
5806 F20101113_AACNFU miller_k_Page_068thm.jpg
9822644ddb8321b7e23714ab204a1f77
6305483d557f55903667a181035d26b1ecefeca0
11481 F20101113_AACMZZ miller_k_Page_070.pro
82e65245dcbf43c59538d4d9a387c225
a164ba6a65f3be84907a4fcc5a555baeac38040d
F20101113_AACNGI miller_k_Page_062thm.jpg
b7691ced683f575ded46a86430023912
bbe9ee19aedeed291bcdb9e929608ceedf73214a
5854 F20101113_AACNFV miller_k_Page_096thm.jpg
c047343b6807fbfad1167b68bc88586f
e3e0f2b90c1d1968d7cc9ec58f941d71a18ecab4
35436 F20101113_AACNGJ miller_k_Page_006.QC.jpg
160dc3f1e8bb1f335dd2e75f80fcea4f
a4532af5e4337e9f0278f619e27bbf59543a1cc1
36884 F20101113_AACNFW miller_k_Page_092.QC.jpg
c8177b28729f18a92ec49bf38a903015
8d9a19a5e58844cb9f08f5cadfd622475a692706
2735 F20101113_AACNGK miller_k_Page_108thm.jpg
e09a1ac69b084fa7662dff341fd9960f
736d877f00b2ba3b675cf49d20ca4cd7c5d1a2d4
8806 F20101113_AACNFX miller_k_Page_027thm.jpg
996703fb91a83b9fb89f37f0485a5240
07560b080d3fc06b79e67c2bf28c496a29e762e8
9355 F20101113_AACNHA miller_k_Page_090thm.jpg
156b2f25eacdbf89aa878afeebf7c5e9
03d5f5e34e2ac571b7d76a29f411c1d51f700a07
8324 F20101113_AACNGL miller_k_Page_020thm.jpg
6a10fcba268d3b03bd58011618e79933
51884c90eaeb735b2ddef98152388445069243d6
8666 F20101113_AACNFY miller_k_Page_087thm.jpg
b76fdcab3a399cca29a2ffa43f2573ca
8508bf446210d71c035abbb7e294f9d5c309b557
10355 F20101113_AACNHB miller_k_Page_030.QC.jpg
99c694a90d62c6a7056540d63a8d1233
3bd54024daf9d4f2eaa0e311ce7227bba46253c5
8082 F20101113_AACNGM miller_k_Page_075thm.jpg
6e426f54c0aa30b9a26e03125598e03e
165e31185ec4cf5bb6b2920f0e7c75bbd8cfe826
21413 F20101113_AACNFZ miller_k_Page_068.QC.jpg
2d61637b5ec22563bd663fbc49157215
4c4e4c0d66a29912dcdf49636f464355f23140b8
8549 F20101113_AACNGN miller_k_Page_039thm.jpg
8aa75365f7cd3323df9a70a8a162aa65
ff6facf9a0dd07b832e31d845ca19b80d6aa2ead
23040 F20101113_AACNHC miller_k_Page_095.QC.jpg
32e3e4f1be6db41a7054887c7e8e1e3d
80ab61475efba47ece12632a76ff7a2937f30a6b
28872 F20101113_AACNGO miller_k_Page_067.QC.jpg
9219d6582113ab60d89243ba268add86
133dd7ba2e72f1d6ab7f514addd8e3b8148798c7
8951 F20101113_AACNHD miller_k_Page_092thm.jpg
d2689b095f413f39b39f272fb7473516
d14212364df0eea32628a8fcf177d6c5db569566
37557 F20101113_AACNGP miller_k_Page_036.QC.jpg
ecc4a8ac7590ee577ac50bf099b38f4e
27b186d49446e313beb8143da4509b69e8d1d6eb
37898 F20101113_AACNHE miller_k_Page_024.QC.jpg
1136cae4c377e6112d43d7f98144220e
22d401dad757e11d1e3aca5f6fa2e6ac17d810c5
38237 F20101113_AACNGQ miller_k_Page_081.QC.jpg
b4481e2bf7c6ff06d523d2bde6c7901d
d0105f2e50161d7dcab544fdbe63d26ad89c8f00
36165 F20101113_AACNHF miller_k_Page_013.QC.jpg
c9502506e8f82d995f1b377d77aa5db0
99e699f9b05fbd2741c4f600a804f2e4ac85cfe8
32156 F20101113_AACNGR miller_k_Page_048.QC.jpg
7ab215b141f09a90a9ea987fbb6d2d3d
076e6748fc05559a913701256850d67e5c23198f
37639 F20101113_AACNHG miller_k_Page_014.QC.jpg
06ecc0a5ab61938b9722ff33a0bbcc94
938f27fbf250dbc22db3f19adb327d0be327700e
2485 F20101113_AACNGS miller_k_Page_030thm.jpg
0ae8861322cae7ee34681ece7e8707ca
09262627f8ff7ca7c43652d9badb55ef1b28ff3e
37125 F20101113_AACNHH miller_k_Page_045.QC.jpg
f4cb6a1498b4d045635b0407fe0cd555
76095630482310aa43896480250e01585d791515
36620 F20101113_AACNGT miller_k_Page_085.QC.jpg
b115ef91d98086d9c8ec7074fdd5fb6d
a7a38058de9c013aa5525030ef1bc5cc1ae9952c
6614 F20101113_AACNHI miller_k_Page_005thm.jpg
9ac27b38da0de1a1807463acbd530579
03fc56516da1d0fa7ee5aee438670b3dcc7ef0bc
5563 F20101113_AACNGU miller_k_Page_095thm.jpg
1bcdd4cbb0dc273f1273e1df924c7fef
fe8377aba2f32ca157878be713a401dc8e576630
34030 F20101113_AACNHJ miller_k_Page_087.QC.jpg
21743c28126747b43305fd13d9f4c1a9
a8a9d9ac45cab5ef79b4071e01a5a4d85b1c0483
38677 F20101113_AACNGV miller_k_Page_104.QC.jpg
b4a0fb65b6dc24ce999453fde21a8c3a
b7adf4e45f63b0271f3ca2abc5a3ed3f004e7a1c
37003 F20101113_AACNHK miller_k_Page_101.QC.jpg
604994966efcf1039fce2e01b81f6afe
f33984090c3557fda942b2e71736c76e46228df5
14729 F20101113_AACNGW miller_k_Page_074.QC.jpg
cf38606d94eef9bff83ec43639c7bcd5
0beda04809dc0476fc115880171b159b49e10f3b
9000 F20101113_AACNIA miller_k_Page_083thm.jpg
9abe4cb68cec5e52f2e72ec9b6b44a6b
bd746084678bdcbf6c6747a8090c0d95102667e0
4017 F20101113_AACNHL miller_k_Page_072thm.jpg
2c1cccf2a2d65a49c2bfadab3853a9be
f1b6b0e30ef468dbe1fa4e8f31d620802f364cc5
8656 F20101113_AACNGX miller_k_Page_001.QC.jpg
e1efe8418beff83cfdaa9a27c3020092
893c41e96aaeb19ca38f4ecf07a3451b966ce7ef
22304 F20101113_AACNIB miller_k_Page_096.QC.jpg
b17f91e44b9284b6cf33a65c709766b2
53f90ed640f1175c6672ebcc2065fac56cc2e323
6842 F20101113_AACNHM miller_k_Page_067thm.jpg
4557df0d9358b353bc1a9447732faca7
ff44832ec838af4c3a6986dfbe851b1ab20e3162
8746 F20101113_AACNGY miller_k_Page_045thm.jpg
57346003b1bc786e3f7e43578c2b4fa7
69e401b3dc067e6425ae6ebee54009ff8a798c14
8904 F20101113_AACNIC miller_k_Page_057thm.jpg
84bf7f5d9a842ac219b69bf6873bf50d
5984ac8b0814a10192a132e686a847d0fe07f61e
8837 F20101113_AACNHN miller_k_Page_015thm.jpg
1fca7acd381fb4d0e3fcc1fdbff8657f
87fc06a22688768862fb7e891bb39da01412f5c1
33722 F20101113_AACNGZ miller_k_Page_098.QC.jpg
624772c33c8132a06dba08b5201ff253
18c8553adb76084aa0aae8e454c6bd17db8e22c0
9244 F20101113_AACNHO miller_k_Page_089thm.jpg
409106dac277bd0407e7586b64d5b854
606e5af235678345a4fe5ddcaea1034cbc483b74
38287 F20101113_AACNID miller_k_Page_053.QC.jpg
17bc7a1c7c5bb4eb7ed89123bb5617bc
9bbd6d2252a0cef46decee5b3190c3d214affb51
9055 F20101113_AACNHP miller_k_Page_052thm.jpg
581f6f0912433e6c8893b682fdc09f81
a9f9decdb674a6dbe85c33c2bb3a2b994c8c7ef3
9083 F20101113_AACNIE miller_k_Page_025thm.jpg
e74459887bde8604837b4e172a615c0f
daaa79534599928d07558d2c33c8134f315fb438
11813 F20101113_AACNHQ miller_k_Page_072.QC.jpg
cfc63fa6a49b5536898951a9d5ef7856
50e436e4581b61f9c91242c5700aed30c1cccdba
4074 F20101113_AACNIF miller_k_Page_033thm.jpg
f549e3c60b1eb4e78a820ec22b671283
469adb0be3fe0306766e105fc87beaf77e8ec555
8392 F20101113_AACNHR miller_k_Page_051thm.jpg
c5e27a236951aa03e4b12bcf7c0aa99d
6d7774bec77aa1d94ad3fc44c0d9836e6e7061a9
27577 F20101113_AACNIG miller_k_Page_005.QC.jpg
ab19b4072e2084acf723eec30973ee7f
bc4c155982e70221549dff2f0f3f10c542e19a1e
8764 F20101113_AACNHS miller_k_Page_098thm.jpg
63c39522b894e0ce37486cd9926377cf
696d58f0869a2e92a898f731d6645069ed806884
8787 F20101113_AACNIH miller_k_Page_050thm.jpg
634429576a7bfedd29e858c91f7a38f6
538e1c08a9815fdd842172d8a67b537e4a891f4b
8683 F20101113_AACNHT miller_k_Page_038thm.jpg
5175a1229cd2a21fd793f40f8a96c749
5a26aa5b824e71b88167caf86002c4ac2d4b6649
F20101113_AACNII miller_k_Page_062.QC.jpg
0a414b6596770737ec24855594e4fc30
1c82352c696eea361be247a5c3e21c66962277d7
8102 F20101113_AACNHU miller_k_Page_066thm.jpg
441bdee2d4a5cee850d2237ad61f1e47
f9a931d0411142de3057a271bcce5290fe7db688
34800 F20101113_AACNIJ miller_k_Page_021.QC.jpg
a7698988ea3dc49923de966798bd0dc1
5cca35b9e3e82d8a01861cbbacc4eb592f46de21
34247 F20101113_AACNHV miller_k_Page_041.QC.jpg
e9f1fa05f48ce035720197362b9a9845
8157e67128f2a6175b1b4b4bb035ea3499debe45
33759 F20101113_AACNIK miller_k_Page_107.QC.jpg
1b28843a8d28d83b76578029ea619f9f
6b720c8df3bae2a58527fe77cae880fba8705ff5
8670 F20101113_AACNHW miller_k_Page_093thm.jpg
895021f3a9e4cfee1e137de4afbc355e
a4b003fb8b09d269d9891c20ae0c33a150c250b6
2086 F20101113_AACNIL miller_k_Page_001thm.jpg
5c2e48dbae4676e84c7c9565f2ffc516
408ad90954077fd69cae3c4b6055471c6cc57c77
8744 F20101113_AACNHX miller_k_Page_021thm.jpg
3f94c10884008b78fe1954d4fe1901c6
ec7cb434f71815140b8ec0d73904ebe904667747
36305 F20101113_AACNJA miller_k_Page_015.QC.jpg
920b40d796b33f2eeeea7efdb2fbe6db
b87ea7559484d3f58b4621454b2874c23fcc4778
3824 F20101113_AACNIM miller_k_Page_031thm.jpg
64c1b7d92a79a3b38b1f3bf50f36d6a4
28103ee731c5b7a5f66a16d496e21478eadb44ac
12238 F20101113_AACNHY miller_k_Page_033.QC.jpg
ad31765ed47815a06f8995a55ce0b4e0
4635652d8ebf3a1039ca7e12f6e3bfa041c7a22c
4584 F20101113_AACNJB miller_k_Page_074thm.jpg
de5253f5b4e18ee3aabfb87f6e49bc6a
4fbeb68ec0a48666c80fe26edcae788428146a9c
38679 F20101113_AACNIN miller_k_Page_105.QC.jpg
250f2de79e4bc7d71c5e711e823da291
0ad489d8685cc013fd95e453a16a36c079f9b05a
4118 F20101113_AACNHZ miller_k_Page_007thm.jpg
d316df0c2702c724a8412149be3d4b39
f75a3695499bb3bca9ed3debfc07e2e3dac7973e
36576 F20101113_AACNJC miller_k_Page_025.QC.jpg
1f31672fd0f6077f0e31551fa2cf77c7
eeb5e8bb4ca99116d8485dafd29a9bf884365e23
6072 F20101113_AACNIO miller_k_Page_097thm.jpg
53901785be1d80af2b3c5fcff110cbec
86f54002a0a018f31eef004bdbf4451e2ac2d811
8922 F20101113_AACNJD miller_k_Page_058thm.jpg
04919b516f895a2e2a3a61251b7f6bbb
4447063c1a3d97c8ecea759f7a27d703c92e6ea0
37443 F20101113_AACNIP miller_k_Page_089.QC.jpg
e97bb639d1f933182db7d930e214730c
d437cfc25463016301219a0c458f76381c453ea9
38467 F20101113_AACNIQ miller_k_Page_082.QC.jpg
610c7de3071087cd81eaa1005f7e727e
bc8686f949141b585b82788cc1bf518386c01b46
35685 F20101113_AACNJE miller_k_Page_050.QC.jpg
134db0c24d7a51772c8a2228125636d0
b2bed464a00f399c3087e495e178d8a0e7ddec9e
4966 F20101113_AACNIR miller_k_Page_046thm.jpg
258afeff99dbf71be6364470d5d86fac
03cc3b250f7a5f29e9a91fc5d458773e3c878e0e
37331 F20101113_AACNJF miller_k_Page_060.QC.jpg
2b8589cb9f40bbc27144b3c12a343148
fe6bb1cd9e3d885a659d78d1197126ab80676ee5
36842 F20101113_AACNIS miller_k_Page_027.QC.jpg
066e4e85bd861197ecb1278a46921408
b3a31f934778b44f1da0ed4229efa973b7a7a432
34697 F20101113_AACNJG miller_k_Page_063.QC.jpg
33d878ddd31beee8e6ef27b0d61cfa2f
77fbecd34967dd9b59e15a24479738ebf1e099ab
F20101113_AACNIT miller_k_Page_102thm.jpg
ffa88728483e07a221d8f4212cc3f07b
987f9ce0b83c50336e27186d32cabff614908e55
37080 F20101113_AACNJH miller_k_Page_084.QC.jpg
4e885adf3b3e86fd859e9c7c0c064cba
a68134398371afae9b4dd483ac7aa4d673e79546
9136 F20101113_AACNIU miller_k_Page_100thm.jpg
53938a00fe176ecc84696cff2dbd0261
f701b84eb0eb759bc5617d0439a5e6d0fd7488f8
37033 F20101113_AACNJI miller_k_Page_091.QC.jpg
999fd6f37cfee9deabee3cae5ed676f4
3dd74beed43d8bbea149fdc1a0b9c1b3091cdc7b
8548 F20101113_AACNIV miller_k_Page_107thm.jpg
7079488b4671f5ec3a827c1c640bfebe
c227651cda5ef12099085403146dd6bcb14257ad
35171 F20101113_AACNJJ miller_k_Page_093.QC.jpg
88084eef676018540b50980f9c9a7768
495b0ca146c5f52cd509fb6096d1c453c8dd58b1
3065 F20101113_AACNIW miller_k_Page_065thm.jpg
2aecc7d74a782334f8daf1f40bf93db2
d108e923c51713edaa67ffe8709b4b2af9772186
15840 F20101113_AACNJK miller_k_Page_009.QC.jpg
803cc417dc7b78091ab731a6cd038e78
cdc037775948a2d60250084694ad0f949ee969b5
37822 F20101113_AACNIX miller_k_Page_083.QC.jpg
779d10132b9f2294562c3e6f1a08cd89
2173435032307d03fdc018422ad1b74b94c105ea
36127 F20101113_AACNKA miller_k_Page_028.QC.jpg
41e0b43eb2cd5454b584557e84d88d8d
1321bf43f493f2b3fc73911c4567cb1fcf9ac62f
13852 F20101113_AACNJL miller_k_Page_070.QC.jpg
81c14b7af8751870c39b914a6f0ce3fc
543fe36e244a2c57d7f51fd19d722042d7c4e37a
9444 F20101113_AACNIY miller_k_Page_106thm.jpg
86907de551071a2393f594598519cc35
a691dfbad6fc7bba3132bfe8dec78a52ae74e2f6
9031 F20101113_AACNKB miller_k_Page_094.QC.jpg
3928a5a90d67fcb838b8335555b97d2c
ce5a80847a917a4702aa439ab7a75ef60b527a5a
36653 F20101113_AACNJM miller_k_Page_077.QC.jpg
28f277ac1ca6a550621d5b0d5a2217e0
83a97a9e8e92563012150975cde3d7058293999d
11529 F20101113_AACNIZ miller_k_Page_065.QC.jpg
e4eabfd3332b1a2e6f31566f476c8223
506643cbcd904408240b39a01d7079a6fdfd99df
34846 F20101113_AACNKC miller_k_Page_078.QC.jpg
db16873d4a126394f180f869b193bc30
bfa5f0599ea5546d0f5d3ee2bbf2aa35651e3079
9115 F20101113_AACNJN miller_k_Page_080thm.jpg
7874b7c5aa93e2b091fa1ad74302b3a5
512b599a4c9473760787861e1920f83d377d6858
30365 F20101113_AACNKD miller_k_Page_010.QC.jpg
14e98ae862532fd84a2bca0260ecc2c5
9c09a3b6e673bee90a6ae09a5b833b81d18b035d
35526 F20101113_AACNJO miller_k_Page_043.QC.jpg
b88e8b1ee2ae70c72f19ae3adbb64224
a581aebf4c581860ab589923e5fe5249ea62b9ff
8376 F20101113_AACNKE miller_k_Page_078thm.jpg
c9ad0fb2c0578aaba7fd13e0bdfc453c
5ecea0560b4f31f875080fcde9efd6fd4f5f211d
24079 F20101113_AACNJP miller_k_Page_097.QC.jpg
c453ae0263d8a6f2918c9b883d1da941
57dd88cb4eae20f938a05a1b71ad1a1a983b37d0
1208 F20101113_AACNJQ miller_k_Page_002.QC.jpg
d1ea1e23d6e50ebaef5c7434ba75039f
50a88ec248718cf1b7d07ccc21de3031afc9587e
4245 F20101113_AACNKF miller_k_Page_009thm.jpg
f780dfd793b5b8ca0b35dd1f025f6ee3
e56d5c4479ab11744a710b3101f024f8e8cfc961
19158 F20101113_AACNJR miller_k_Page_011.QC.jpg
c9c902a43b23d3aff30605d02f564ca7
3da79d93d419ddef03f715c050b6e0895336852d
2281 F20101113_AACNKG miller_k_Page_094thm.jpg
8578e284329a55bf122757a9b595821a
84c98b4612e7598bbb0671f2b230f90de4e1a2c0
36010 F20101113_AACNJS miller_k_Page_019.QC.jpg
59752828048fe5124e141deb90634312
da4f717919bb5de467ac1e52418fd80d56a3e4d2
4961 F20101113_AACNKH miller_k_Page_071thm.jpg
0c870fc6dc4cbaad75078b12ce4a2500
8ccfc2a15f5d71d530fbf15eec4bfcdca0521cdb
9477 F20101113_AACNJT miller_k_Page_004.QC.jpg
6ddf94b71388624999bfa4fa05e7f695
6391dde79b4436f27d2ad686cfd2c1cce7f95866
8713 F20101113_AACNKI miller_k_Page_054thm.jpg
e0081e242afd595ec5bc41098c451446
944e9e65855c67d69b4f94482a0b85368f16336d
34273 F20101113_AACNJU miller_k_Page_020.QC.jpg
178da606574c52ed71bd6f59758a4d1a
a54a327e8c43d04fb9736f108bb20964c2de21ee
33559 F20101113_AACNKJ miller_k_Page_088.QC.jpg
4bfc1f0a43ae8cf4975af8c47f1b8807
47f49301cb30ebca298646ea38d62e480c38993a
9137 F20101113_AACNJV miller_k_Page_084thm.jpg
17dc0fe0476a187b653c9b1137591182
65e76d51bd22da74f1b35bb5797a8e89cb44a165
38061 F20101113_AACNKK miller_k_Page_052.QC.jpg
ba435df1f8cd931b5e1e793ce330b15f
2bffe13fd721444456b7a283c62e225335dd8260
9135 F20101113_AACNJW miller_k_Page_091thm.jpg
984d2c5908739547d7b626900c35c2fc
3e5b4f64c7b2fffa5f30bf80964de7b13f1333b9
9142 F20101113_AACNLA miller_k_Page_082thm.jpg
c08d565cb80116b97d02e9934b0daf38
8571ab217ac05c3cb22219d18345f22fdeea9617
8854 F20101113_AACNKL miller_k_Page_099thm.jpg
a0dc69513a69445ce31fce09f3746851
3f4cfc31a8574cfc0dfea7d5a6b43c34b439365d
36894 F20101113_AACNJX miller_k_Page_079.QC.jpg
f31519772b94e7ff641207248f6ace38
4a7a8fc62c0de9a5105aa8968d1c6ecd0d4386fd
2172 F20101113_AACNLB miller_k_Page_003.QC.jpg
06e133ecab9e8333c9aaac12e0878405
ec3deff7dda77c6a1c40d4b3a4e2910389c7ae03
35377 F20101113_AACNKM miller_k_Page_054.QC.jpg
22c655ab290e65b4ddc59d519eb95f77
486fb92d52cd08779fffdf12987b643296a34002
8862 F20101113_AACNJY miller_k_Page_029thm.jpg
5b070daa82599b54da1dcc76dbc3be2e
2b7076da7b9e1c0da9938530dc64953843af095c
8332 F20101113_AACNLC miller_k_Page_063thm.jpg
cc1bb1f2c3928734e56aacf92e57a456
e4ea17234bc0c5e0be391f38faa4f4ba4a5bc7a5
35037 F20101113_AACNKN miller_k_Page_051.QC.jpg
e2d52cf9603d9193fe972ceec8d38dde
40827b25d132f1fda4ef5490b07979a07ec38d81
20848 F20101113_AACNJZ miller_k_Page_069.QC.jpg
d7a1d1c5814b433f771b7ff68bac857b
f216d14d38c6638afb812d6389f6a1e86090a0ab
9026 F20101113_AACNLD miller_k_Page_026thm.jpg
e43f758b8231e98bd1b039602a45e774
8a36fa34634cf6a20bb51d21488075e85d341877
F20101113_AACNKO miller_k_Page_099.QC.jpg
19551491ec254736e6cb67131a896646
ac0a99b4c3b9ac3716f7184e84c458f89b842425
32136 F20101113_AACNKP miller_k_Page_012.QC.jpg
0da72f7b6c4d409c201b60806f3ef0e1
cf9cdc80e9d7e709f0a3defce9f82c96e48f0831
35678 F20101113_AACNLE miller_k_Page_039.QC.jpg
03bf2f33912a9fba33d10b0ddb9bf686
c5758cd24bc42b067eb13d2b065110b1543db9b9
8334 F20101113_AACNKQ miller_k_Page_037thm.jpg
977fbb49479bded100f056a848495a56
3955f1b7a1c571f72e71c90b4a16afb3198c5c2a
8586 F20101113_AACNLF miller_k_Page_044thm.jpg
e169fa8d89a3fffdc60e3f65706c7fcd
0421f8ad460990f83b2a2e338468b66c3a784267
8529 F20101113_AACNKR miller_k_Page_040thm.jpg
f86cd2cd00292ba0d8f5c2bcf260e1fd
3ed6f679057788395b3dddf8c5ec94dfb743a4b0
7908 F20101113_AACNKS miller_k_Page_012thm.jpg
487b6733a9dd3afd0590467be52d962e
c3f8a9c464e44f8df674159591400ef04f709081
29383 F20101113_AACNLG miller_k_Page_034.QC.jpg
fd921b968ef76758399636d4cb154774
c10c320712e43a2d13ac729a7452a9c5d2081ba8
20131 F20101113_AACNKT miller_k_Page_046.QC.jpg
cd8277afc42c4a74ce32c59d6c4fa5cf
6fcd8a3677bbfb61488d415bd01bdf6a872e1eee
9047 F20101113_AACNLH miller_k_Page_059thm.jpg
9e6f3fe4422df95294de2a2161c56bec
a5e4237130de4e5bc23332602e7757ccf5ae1bfd
8705 F20101113_AACNKU miller_k_Page_014thm.jpg
92da42e53d973cb80516b1eb720daeeb
9cb7f5c73c30455493ed5274cd590dcc8e7fdd62
8174 F20101113_AACNLI miller_k_Page_048thm.jpg
2de34896b2a2f9ecdcc9d85daebe7480
fae0594459bd2d8244f74c57a5a71ec71e57a02a
36640 F20101113_AACNKV miller_k_Page_055.QC.jpg
9cfb64531b10c0f3d3b60e3adbc6a98f
7cced5293406e784a09e00c704781a7d4f133b8b
37246 F20101113_AACNLJ miller_k_Page_022.QC.jpg
681e2a1ca4c386d0570fb6ef97b268d8
5d0193a8ab42e3fdbe4e4b0201dda90f3b15ba39
8857 F20101113_AACNKW miller_k_Page_017thm.jpg
4cdae7a04f864f5689ece863850b8002
385751d485f9495cbaa06e6061c6e8161d5f1388
8589 F20101113_AACNLK miller_k_Page_006thm.jpg
20b7a91b137904e6277a6f8339f555b5
1428f184f1498312678ff38ae665a695f583a9f9
39033 F20101113_AACNKX miller_k_Page_106.QC.jpg
d49453ea129d206e344a6ee85c370a7a
7c10e776605cb1306d66ef15f43db22960d05b1d
35351 F20101113_AACNMA miller_k_Page_049.QC.jpg
cdf19f11ec184cc67ce92fe8e88b1c19
2662d24fb94ad1e739b1c1750cc87efae39a0135
7335 F20101113_AACNLL miller_k_Page_047thm.jpg
17cdc13221c9ac9a698c90928d100ea2
de9c22ab43bef3beafa9570e697627d8277e6c2b
37375 F20101113_AACNKY miller_k_Page_059.QC.jpg
c390e9710a1a30f67c114f7d354f3a2c
cf8fb3c27df70d4fbbec2f2fd7755007c82a278d
39354 F20101113_AACNMB miller_k_Page_090.QC.jpg
fdffdd0d8055bfbe9d4da22c8095bdb8
9050e1cacd1b0ecbabee035e1d27a71348f1239a
9134 F20101113_AACNLM miller_k_Page_053thm.jpg
909f709e455694f4e8a635d3542f7dba
d8dd548c64ba536f424a0ab398328634cd039a93
4605 F20101113_AACNKZ miller_k_Page_011thm.jpg
cd328bc6ab176a2d1fa1f44505297028
0f6814e46e34cec0b2b4830d0260d5251f79dd6b
4461 F20101113_AACNMC miller_k_Page_008thm.jpg
4167a1291887a6718e7ee4dae4ff4690
2881107c87b4de50f4bcd7c59fe4c14f4c1867d2
8925 F20101113_AACNLN miller_k_Page_085thm.jpg
840d9aa253041b2dc975e837ff4f28a1
95be441dc5bbcab5c9a3646d2f410271924d5779
7284 F20101113_AACNMD miller_k_Page_064thm.jpg
5e638813ea02393b9049dc20f3a14b65
982826275a1487ccf41736fed74176166f7dfdea
29581 F20101113_AACNLO miller_k_Page_047.QC.jpg
8095710e88132ffbad6dca7242239d6b
bead7d545e0a64264fb1ce13a129fa5cc1ce3378
9448 F20101113_AACNME miller_k_Page_103thm.jpg
c14d0bad6b39aa0f43f3193dc23939a7
1c2d9b449cd965905b180e98105ecbef86cb937b
9018 F20101113_AACNLP miller_k_Page_105thm.jpg
1a2a80df50e841aab7e1c3c787e8e875
624e17a3794eca2f5d7525b34e667c7aefa00c01
37683 F20101113_AACNMF miller_k_Page_061.QC.jpg
be3f52ec2d75757be2ae155c2b140f79
8f65280c17300442965aa53e4d716e71969edfe2
39773 F20101113_AACNLQ miller_k_Page_103.QC.jpg
eb1e7959d949a86f2a224ab26a0bbac6
4603cc9b65451784c9e3ca2a0544140e1dde62d2
8871 F20101113_AACNMG miller_k_Page_013thm.jpg
48643f77b46a4f2fed40daff252bce4a
966bfc0db2690575d6dd526771c49156797fc34f
4379 F20101113_AACNLR miller_k_Page_073thm.jpg
8e7ae3549627bed48ebcad71249c1afb
336bc4598b28ad08115060a37a8b5f883f40f4bf
35555 F20101113_AACNLS miller_k_Page_018.QC.jpg
71b511f12d9888b576df9955ea874970
7c114fa9f144967b9404fbe726fde19bf2e4d1c0
8347 F20101113_AACNMH miller_k_Page_088thm.jpg
3a59b3021280793c5bec5fa85e8b2571
287729c3e93e7522b2a4ed3cacb1a4b128dccab7
13625 F20101113_AACNLT miller_k_Page_031.QC.jpg
f8161a55c149891eb4610c9f769fb247
685336c896076da52a3d3879c848a391b9fb6954
8457 F20101113_AACNMI miller_k_Page_041thm.jpg
36014d80f1bc3443507ca56903fef536
213d9d28fdbf83d87e339657137d1cec6ebdb54b
2304 F20101113_AACNLU miller_k_Page_004thm.jpg
98a7bac32d84c5e75075feb612386c60
c4a47546bf7523fadb8687fccf885b386956ed21
34231 F20101113_AACNMJ miller_k_Page_037.QC.jpg
0b00f8d87f3b1d42fff40c9ec7ed15b9
e143317a2c04cf8eed1a7bb7291fef4640f06648
8999 F20101113_AACNLV miller_k_Page_086thm.jpg
d6b31332fd607e4ab1fcadcb0c787f24
c74267720bfb5335ed7f52a99858072caef3fffa
33688 F20101113_AACNMK miller_k_Page_035.QC.jpg
fb2adf8d39f30978e9681c2d489d9273
2ba16986c1310925a99b09ce858d218c4692d85e
8835 F20101113_AACNLW miller_k_Page_018thm.jpg
a75c7bed24cd388c37d62f4b1dae1b39
bf6d8670fdc875592a9afb3607e206f123c1e033
8813 F20101113_AACNNA miller_k_Page_076thm.jpg
cd4fcda82781f34b8faebf6ddd6f9559
bda2ece840ae79dbdd17d313fa848e2f85e91153
8396 F20101113_AACNML miller_k_Page_042thm.jpg
af989a0a9e138095e0e4b1eb0586b2f0
86149bdcc4fb556bf8f7fc880f7a9afc266fc451
8963 F20101113_AACNLX miller_k_Page_081thm.jpg
471cc4e6c6ff6de73b9b56c89f1ded7a
b67d724388fa58c355ce9c5028812129bc896bee
F20101113_AACNNB miller_k_Page_077thm.jpg
8677f8520f3f1a2c999d30db2cd866ad
38e0f927a48c60dbb18534d7a94a366153f27fa3
4489 F20101113_AACNMM miller_k_Page_070thm.jpg
ff405abc1f145d45d63facc5fa569e7c
42eab49ac794c5a032313adc6920d14adb27f801
3531 F20101113_AACNLY miller_k_Page_032thm.jpg
aacdc598599bb6e961a4421cf67c85c6
bd062e18a6d2a751435ed310f91b71c05b0a02e7
54353 F20101113_AACMKA miller_k_Page_027.pro
15f0fff7aa829680e7dacd6b9571ab6b
61a0bfc83d1b33a03679931cb5a0548b6a7b63fe
38476 F20101113_AACNNC miller_k_Page_080.QC.jpg
a5335b73d5bd3cbffec1ccccb0a6e0b3
bded060d48c7a90a31859c0c5633f773669aa8de
8945 F20101113_AACNMN miller_k_Page_101thm.jpg
9629a5df7659913e8bf74a9885fa2c00
dcfb6da4caa8429b003f1878028b12a066a5e33a
9162 F20101113_AACNLZ miller_k_Page_060thm.jpg
e2262ade738878ff7b2df5adf2e2869b
36eaaebd72604414a5fa1e9be7d69bf370c17595
F20101113_AACMKB miller_k_Page_086.tif
453a08feef43e7d2a0298a0369342564
9edced80bcc0980e7535146b8e21847643b49252
36591 F20101113_AACNND miller_k_Page_086.QC.jpg
96f4dd8a53dde4e53c3c66ab7561e38e
29037479c812ced30728e759344d27893bc9916a
162552 F20101113_AACNMO UFE0021090_00001.xml FULL
d33e3efbd85964fc21a7f781234b713e
68fee280b0dcc88b44534520b19f48752c345feb
1979 F20101113_AACMKC miller_k_Page_042.txt
8f2f2ac92ef72a3e8c53ecb862c4fd6e
a588fd1194959d19d808579f641ea6e356d7add2
37432 F20101113_AACNNE miller_k_Page_100.QC.jpg
eac02e77434bb1811163a7a6c8c37eae
384b2faa0739ac8243902154033dd524ca3df5e9
7838 F20101113_AACNMP miller_k_Page_010thm.jpg
46c91bfcf02730c94c74e7c4f46ace33
b1aad27aa5782875320a6011492371b997056b71
35859 F20101113_AACMKD miller_k_Page_038.QC.jpg
116bd09d35f203f670983b2307130cf2
7ef905d4c8ad56d2aa7dc628593d2ebdb943f97e
8810 F20101113_AACNMQ miller_k_Page_016thm.jpg
894e9cd554110cc3444780483687f3d5
8fb5b3d77c5f93501af139af8cc2406d207c6d60
26407 F20101113_AACMKE miller_k_Page_009.pro
0f2f7a05dcaf21aac13df87bc5db289b
27dab9ddbc92a1d173bc0a060a652c24849b22e9
8749 F20101113_AACNMR miller_k_Page_019thm.jpg
55c65f8c799a09b87b4e9ac36de1b9c8
70e6aeb292289ac64064d4769e68eeecb8322ba8
53371 F20101113_AACMKF miller_k_Page_041.pro
0f74aff4558f1cdda9f8ecb02e3a553a
1eca77f941e5e0bb3c1203e40293f10d8eaff19e
37608 F20101113_AACNMS miller_k_Page_026.QC.jpg
a40377f576b0d3b14d1c65d42fc88ecb
6b45536d2b6eb0582dba66e5b3465747adbcda21
9028 F20101113_AACNMT miller_k_Page_028thm.jpg
ddbba289592e1223a77d387ee1c36b2d
2e4565742ef729fd97a978fd6519a7171980e422
7599 F20101113_AACMKG miller_k_Page_034thm.jpg
fad31c01976b22f929524daffb6ddbdc
2c85bc0fd4a722a8561dbcdd7ea164c801bf199e
36613 F20101113_AACNMU miller_k_Page_029.QC.jpg
647b8df96a7263b34957d8a49f886c5b
34085218276e62a8f482708b424c10b266dc4984
36311 F20101113_AACMKH miller_k_Page_108.jp2
bec2327eb2df74d05122c8fdadfcc200
782f720e5bdd292c2a8110bf4be6bab4297298c3
36149 F20101113_AACNMV miller_k_Page_044.QC.jpg
10072979c9bc0ace7c59757772fb1633
5522b1e4c24bbfa8e0a687f291fe992d405bd45c
1696 F20101113_AACMKI miller_k_Page_068.txt
f1e9d77571b7e7b3d9f04b76ac31a655
fc7a03e54b66cf9d11df69ca9c95375f7babeb06
36897 F20101113_AACNMW miller_k_Page_056.QC.jpg
970898915695a7cb395cbbeb728fb3da
d5ab451bbd2bec12fc7a0043d8c441af86cb4b1a
32709 F20101113_AACMKJ miller_k_Page_030.jp2
cb95e69442b2bbf09709bb6cb783d249
14cda4295808b27cc231178c7a386e75665139fa
36253 F20101113_AACNMX miller_k_Page_057.QC.jpg
c233548bfe47e8acb31fb26194e27b65
e62cf30a7c7032b1c8a8ef6ff02715bce0709f91
65208 F20101113_AACMKK miller_k_Page_101.pro
42acbf0ac10e943e1d03eb507b5747b0
9a58fe96a7b07765b251c51174f275970a7eea6d
9085 F20101113_AACNMY miller_k_Page_061thm.jpg
c4d2d69469784c7a5db0042b2d0cad7d
7cb1c72c2b8351715b948882f206aa4e0f5dd04e
1992 F20101113_AACMKL miller_k_Page_012.txt
f64454005269d1864ffb2ed5765655cf
8a6828189ee37a527ea07bafb3a81f6daba2b7ad
16034 F20101113_AACNMZ miller_k_Page_071.QC.jpg
904b47bfe3847ffaf7f79b9e90448a4b
c191f6b8c035bef7711f3221552ce01bc8867c6e
122238 F20101113_AACMLA miller_k_Page_084.jp2
d9f599f2ddce5b2fec26f7f199a0436a
8650774a3291bd0600b05cd3f2682a08b0e4092f
310611 F20101113_AACMKM miller_k_Page_032.jp2
4b7cf05b83aef952d45204103a5c78e8
db8da1ad207d8d8842fa0711addebe0ff284b652
103928 F20101113_AACMJY miller_k_Page_088.jpg
1c3ac62446beadb60847a0e668988cfa
610ab98f079955fa36313aef5f1251f2735ed791
534 F20101113_AACMLB miller_k_Page_002thm.jpg
98c4f234b3d221d056686077cb7ebb65
5fbe692769e8d5af56c7acd98d9467ac35a5a0a0
2212 F20101113_AACMKN miller_k_Page_025.txt
fd5252edb40f53df4210667df9472293
37b535383373cad460da679fde3d9f8e777fd932
64993 F20101113_AACMJZ miller_k_Page_102.pro
8f8142f49fb2a77790865e9cd73500ce
997cdcc21a9fb0c7f8a02eb85e9b9bc2da879bd8
33723 F20101113_AACMLC miller_k_Page_075.QC.jpg
479ec4f3ce49186a5088529d573e903a
89a37ae3e08728122a26a139afeafbf8c7e10591
113665 F20101113_AACMKO miller_k_Page_038.jp2
990fdde27941e1414238d6ac5f244d22
65b82ac7abfe2da1d850c2702c1a43ad2a7b715b
8948 F20101113_AACMLD miller_k_Page_079thm.jpg
5b5e7a0f00b65653b5928e757bc49e9c
e995459d1d5f74ae2887a23ea061e9d9b7ce9dd3
36545 F20101113_AACMKP miller_k_Page_017.QC.jpg
23742bc0f5f63a967a6f71ef9370fbda
2ad2f5d411af8263e0a2c6c718daa44d2dba9cf2
34586 F20101113_AACMLE miller_k_Page_040.QC.jpg
e5344c0801031ed108247d012cc4fd65
936c58dda25451e2595178ff043592a75a37926d
F20101113_AACMKQ miller_k_Page_046.tif
653d760c9bddb532cfce640a62a8a104
49b299c33c28a09ae1ed7f5c1e4841d624a6ce58
101602 F20101113_AACMLF miller_k_Page_010.jp2
7aa55aea9c3bd7268d6996b6d14b4149
d76a7924b51d8c5d66770f40899c2b3d38573839
36760 F20101113_AACMLG miller_k_Page_023.QC.jpg
70a0722f922f29757f4fdfefecd8c54c
6f10ddcc26dd7c13de615c849a8c3badedacefe1
619 F20101113_AACMKR miller_k_Page_108.txt
2ea3b0d6320299ba6df8bac274bc3370
1fdc88797a99c936044492f22269fe6c1caaa5f1
27358 F20101113_AACMKS miller_k_Page_094.jpg
86adeef948495bf7b5b01e355393ebb9
d6063e0c31189098ac47c9491f57e01f9a111fc6
103356 F20101113_AACMLH miller_k_Page_067.jpg
ac68c98e71859ea86023d47afbb9f2d2
aa32a67843f4bdcce7cc0d62d09761792303c832
106578 F20101113_AACMKT miller_k_Page_066.jp2
fefec2633dc679e3dd9530b18462149a
27f7ca978d2510ec3691b59e95b091e9b9e73b28
27612 F20101113_AACMLI miller_k_Page_001.jpg
e686658ab589f39a3c89c443a4db9804
c806f60be7f362ffec93bfc6a610612998e9278f
33228 F20101113_AACMKU miller_k_Page_008.pro
6c08bb46d27e1bfdc71360d4a94ba3a3
15ffc1e6eeb7759764bdf154d623933ce2e64e47
53728 F20101113_AACMLJ miller_k_Page_044.pro
d51fafd32852ea2fa9ba53c408471ed4
3ead1d33b3b13f7057f5065f85f6fabd249dc1d1
F20101113_AACMKV miller_k_Page_093.tif
74f8c93a53a31b151b22bdce4d61558e
a97e833e2b44c961f8e52d1b82fbdf2589885ac4
11304 F20101113_AACMLK miller_k_Page_108.QC.jpg
b8a3e9d8c6d3799d93f5b8a432aba586
140744b63ec7e88d9e7f772dd73b39fa0fcf639b
108383 F20101113_AACMKW miller_k_Page_076.jpg
9c5b6187c79c9ce7cbc926bb715afbac
9b4239cda5bcaee97cf7f2253645ab46ac1f524c
63447 F20101113_AACMMA miller_k_Page_007.jpg
029d982fb3b6644b326a4ede09e1dc7e
2321524101e9c71ed275a833164d73e354a94505
136195 F20101113_AACMLL miller_k_Page_104.jpg
272854998882a2be78165c575b747c49
51d4fdbda8fcbf5d8976fbf36746b8fa73e35e62
54658 F20101113_AACMKX miller_k_Page_022.pro
bf0e41be2229a5d14753c8e8d0d79a4c
98800fdeb90e3858418292dea55af886f73f89f1
60054 F20101113_AACMMB miller_k_Page_008.jpg
f626a7f1b2cfbc3f16d74435a2415f71
dc8c03695568a443a439a2cb4d708b8a1741b6ff
107576 F20101113_AACMLM miller_k_Page_058.jpg
512e02968a95358791e2ff429cca5355
e4c2bb7e34921640abc176c87ab881513bd3c2c1
35740 F20101113_AACMKY miller_k_Page_007.pro
fa6d8b27e4d99112e8804c9c26b129ae
b41a584a69dbcaa75dcc0018a553e6e2bc423956
53450 F20101113_AACMMC miller_k_Page_009.jpg
15a3cd7d750c8179fac5cce23940eaa6
ca7b6e036f1df2126c29d72c3873af672a8ef4ba
35140 F20101113_AACMLN miller_k_Page_016.QC.jpg
8197da5224973638bb6dfa13dac95bff
ca0e149dbaac044e364af045a7fd85a38846690c
9039 F20101113_AACMKZ miller_k_Page_024thm.jpg
d3de549d7211b63e6f0acc3b287b0f60
da99e8b150a3498db804d11dcd2c4c4f272acf02
97644 F20101113_AACMMD miller_k_Page_010.jpg
5c1094f7b1d2ead2c7e5dba91910296c
1c3f4b65e3e4e290fe45ce7463d16eb66d16c9e9
2203 F20101113_AACMLO miller_k_Page_077.txt
39ba2d6717b5c62662c4b67764180f1e
beceb2236cd9180d2a35ba146eede26af8ce488b
57673 F20101113_AACMME miller_k_Page_011.jpg
8e89624f8c9141a2fd699c77ef001085
adc289297adcc312a084144ee1c3bb0d34363bb1
2624 F20101113_AACMLP miller_k_Page_102.txt
2f5f66cb29c463d620d5cd36e731e869
79436dc296b99e2712a2a79509e7ac3816918352
99007 F20101113_AACMMF miller_k_Page_012.jpg
59cca9de04f214ff5c9dafda3230be83
eca3dd64907e8bd882e8d9bdd1ec212b8e44f619
57610 F20101113_AACMLQ miller_k_Page_052.pro
62efd6a13835e55872ce0b056e2a9d29
320e6ec126b561f1173569859e07249b4c952681
111007 F20101113_AACMMG miller_k_Page_013.jpg
fafcac22d93d939dc995b3ac481ae134
cb4833e2c159175760f5adba0495d8eb75ac3b90
11441 F20101113_AACMLR miller_k_Page_032.QC.jpg
8747f30de1a2e454edb2f214432a8dec
6f07991bb15cad4c3cbeacaf2b3720441e158473
113438 F20101113_AACMMH miller_k_Page_014.jpg
b4fd18297631ca60ca02e77f7a1ee679
bf26631319bb54c49aea322bc5137585adf5637e
125461 F20101113_AACMLS UFE0021090_00001.mets
483f136c9b52f19506b9dbdf5f81e8a5
91c162406cb7382a514fef1da13514930067f219
112426 F20101113_AACMMI miller_k_Page_015.jpg
7d2600c869a67fa38297f2b36beb292a
5aab2e6179478c0266be27318a03095ae50c7797
108243 F20101113_AACMMJ miller_k_Page_016.jpg
e810858a355267c5a9fcde3bc9fea173
0d3b01b0c26ea26b90dc7306ff8722144bc38652
4163 F20101113_AACMLV miller_k_Page_002.jpg
4a361869e77067516ef7878672e75de7
e02f2cf17989e83573bf7fe4572a1f6f023d76d2
111819 F20101113_AACMMK miller_k_Page_017.jpg
260274b91bafdaa3eb6aa255d379adfe
6f0ef0df05ac80968097920a6639345601bff9c0
8313 F20101113_AACMLW miller_k_Page_003.jpg
50248894c815f6544d78bef2094f6ed1
3fdfe67ab952b019a77cea7c325ed7f64409a221
107972 F20101113_AACMML miller_k_Page_018.jpg
ad0dcca30105cd50d60ab64d53e72a00
6a222e3f42775d00a2629b5d47ea92c873dc5af0
28985 F20101113_AACMLX miller_k_Page_004.jpg
94b852bd1055b8f995b053ace5540f27
172daa0a17dd501888f962f2b02efc4542a7d289
33843 F20101113_AACMNA miller_k_Page_033.jpg
532395537a531f13b06c7245cd806879
4f5ae581406b34c17be07d68fd29a6d6e6f9a103
111380 F20101113_AACMMM miller_k_Page_019.jpg
fb4abb90c585020ad6f0f5b40fb2b2e0
391533bd61f1dd90122f5dcb19006141abe78f0a
127734 F20101113_AACMLY miller_k_Page_005.jpg
0f5b3531bac7159d8c6390f9a7179e6c
1cb43c43078fd3c507001d5bd56c004606ecbfff
94297 F20101113_AACMNB miller_k_Page_034.jpg
68e320548fa365094b537ce538d5689f
df77401c5b6250c5c9100a22f72b12e2dbd24d76
103965 F20101113_AACMMN miller_k_Page_020.jpg
a1808cd5ae1692c278645b7b1e022d2a
a05bcec4d107ea66c31e23d57d956eeaeb8f902b
159986 F20101113_AACMLZ miller_k_Page_006.jpg
60df54a5d4db923144b53bf73dfb7776
2207ee012a0263480537a3f37843c0b24ef2a54e
107792 F20101113_AACMNC miller_k_Page_035.jpg
0829017b4d8a3d148368044c6eedf5e5
b9dea72a30cbe7c0160f6f0a37d665198861e857
108550 F20101113_AACMMO miller_k_Page_021.jpg
849958751d81d1831faa81c1ff9e04ac
630eb0fc732572a619b7c02ad60f64c270cee996
112099 F20101113_AACMND miller_k_Page_036.jpg
1bb932db0b07fb77ef8bbf7588a314d4
98c2b0ca5401482cf4f13d9df5f27d92250723c0
112115 F20101113_AACMMP miller_k_Page_022.jpg
87bd569a72cab71e936fbe77cf74d9e1
3a998f48f4724725d1e6661bf67cb3e7850821ec
102869 F20101113_AACMNE miller_k_Page_037.jpg
d38e92c789d4f98b89b49d7a559a0716
91af9782316a9cb902ccc0cfa028d7721d3f7088
114390 F20101113_AACMMQ miller_k_Page_023.jpg
127677e25b7585ebb95e755a202008ac
db59f0bbb8ebe0eec7148a2da01ab1df8c4940e0
106400 F20101113_AACMNF miller_k_Page_038.jpg
0819a1e030428c698d88675d5593f0c9
af9ac4976ff9d95d1767a388a04a6eeadebe0417
117118 F20101113_AACMMR miller_k_Page_024.jpg
3d6968db1a03ff81c92c8f8fa7f6f27c
f6b881d6f8db77155c1762bbae176a8c111877ee
106795 F20101113_AACMNG miller_k_Page_039.jpg
205958df0e3b9d99bc66580fdb436ee1
16eeab9476dcd0f4053f7debeb9b5ad6a5d92921
113117 F20101113_AACMMS miller_k_Page_025.jpg
98d520e55b0186ddce21a7ba313cfc7f
376fc3e744a79e09f962461beea8553137cae760
106338 F20101113_AACMNH miller_k_Page_040.jpg
1b3ef26a3a4a8721757179923ae0bd24
f9579baa6762f517c8c28a476ad26059fb2d57f4
112373 F20101113_AACMMT miller_k_Page_026.jpg
761fa0543078fa00081433b2d679a64e
95a542f45f697b1a956915d141ba08ccb17faa5d
107442 F20101113_AACMNI miller_k_Page_041.jpg
99b3e0beb8a8effcd97dd1c4844f349a
e06c4d569b5673394a88d753ed6f7b338c2de8b1
110827 F20101113_AACMMU miller_k_Page_027.jpg
27df786bd163805edc35b2101c1bbefa
62bfcd15b33136cdecc5579cb92675b2c906d4b2
110459 F20101113_AACMMV miller_k_Page_028.jpg
a82737f314dfe1e529d282ed508edccd
f67d02ed595e7576730c8c01832778a23f478d15
101710 F20101113_AACMNJ miller_k_Page_042.jpg
98eb9dec245915451887e73a4bc3fc79
61ebfaa03ebcc1c3a57f769f588957c95b58defc
112052 F20101113_AACMMW miller_k_Page_029.jpg
b2032c01d7e503aed9913c3cc2e23cbd
ccabb6acfa7141537a137317688d7c587234cb7a
105191 F20101113_AACMNK miller_k_Page_043.jpg
4754f4c8bce7feb68226c602504463bd
84a86ef9e6ebfc4ab4b6624ccc709c6ff7c005d1
30036 F20101113_AACMMX miller_k_Page_030.jpg
1fb394e1b67469215699241a1faa37a2
6d5eed0f9b1ad3d73506a228a994a8d50b6eaf75
115101 F20101113_AACMOA miller_k_Page_060.jpg
89a2ffd52ef77dfb3385d27f69c23cd8
6191a59e8479e61da9f3f45a80b20a78bd53905d
107631 F20101113_AACMNL miller_k_Page_044.jpg
c42ebf19bebd235452df9b76194037f2
a6dc93a8b1ecb251ee642b337290cd566f7e22bc
51007 F20101113_AACMMY miller_k_Page_031.jpg
8bdc71a638148b99b7b62ea938557bfe
888abbdb765ee7970651c55cf0234c912e7389a9
115462 F20101113_AACMOB miller_k_Page_061.jpg
5777e09ba81a50aac9b8a2f4a793b566
9a7dcedb3e72cd1ce9bccf215da1a1c40f4844bb
112285 F20101113_AACMNM miller_k_Page_045.jpg
6126492517377d562fab4b4dd7afcb86
0ba3af5b2ed159d2c79c5b1b5fcd9146d57c64ea
33923 F20101113_AACMMZ miller_k_Page_032.jpg
a5444b7485e2342229fef2cbf4f61d71
258e3a2b1324dd5f1b0bf51ff761013af7ba6e56
108068 F20101113_AACMOC miller_k_Page_062.jpg
5dee31938136a062d95469ad8d1ca04b
66f9532ab533d5d430bfeb0b5ab05010919d30c5
59482 F20101113_AACMNN miller_k_Page_046.jpg
f29128a7364891ec517b7e57dda9e764
63eb3b612a9c2ee0dfe04953d05657736b977976
104425 F20101113_AACMOD miller_k_Page_063.jpg
11c4f241acc12c508b6562f3cde98456
78047933d8e1a55b218330cee11354d66ab9a28f
91172 F20101113_AACMNO miller_k_Page_047.jpg
bb14075b823be62a68fb8e530cdb7280
6f005f1b61e0bbeda580770f36ef927980d6e230
91662 F20101113_AACMOE miller_k_Page_064.jpg
f155cf0a8cb6440ebcd2dad9ec0a81fc
3f83a9524ea31da19e32ea6c1c5780a6b23cf357
99885 F20101113_AACMNP miller_k_Page_048.jpg
a272119a695a57ad32178513df51b4b0
1c338243d3af3da05073828397335d8219a2762f
38547 F20101113_AACMOF miller_k_Page_065.jpg
92235db3699314e9ecf9db318357e1dd
b4ac68c5ca32139eb29cfb0956d79d15821efd7a
105098 F20101113_AACMNQ miller_k_Page_049.jpg
7ccbe5eeedf45cc17f1ea93ae2d7aea5
aeae1d75ba2f42c596384029f1e7725aa4931923
101334 F20101113_AACMOG miller_k_Page_066.jpg
f3fbe05717d3b9ddc6f2e346fec80074
df4f7bb75ea13c437fff0cafe78b7d99194421fe
108362 F20101113_AACMNR miller_k_Page_050.jpg
7e6ecab3d7d8b0f352676a49e7141d0d
1ea0f4f55aeee543d670d3cb3a5fa7fed58e6710
64950 F20101113_AACMOH miller_k_Page_068.jpg
58e84663f43f10902cbcd4de590b5113
4db06809beefb58b340ff59aa9ea49f0acb934d1
107166 F20101113_AACMNS miller_k_Page_051.jpg
491af90cb9159a9f11df71c1aa6bf9a5
ea42e71aabd123955d232b18f577be920adcfa80
66143 F20101113_AACMOI miller_k_Page_069.jpg
ff428d4a9fb9443ca04385e2f9ab71c9
92592fcf860a41f63986cfc3c854846e43b3339d
114676 F20101113_AACMNT miller_k_Page_052.jpg
48c6633e60ca06ab84610e58ab537d2e
19dfb862e00b34b5da8d61aff8061e83548acb6b
38060 F20101113_AACMOJ miller_k_Page_070.jpg
9d7cbe735d86adecf7c06256b9cdf058
ff356172b38ef89d48e7e5f09e6462dcc0db782a
114500 F20101113_AACMNU miller_k_Page_053.jpg
d10957a74c06c79f268274e4e52dc18f
c6721980678a23ffaaf8432ddf2055601b7bbf5a
108132 F20101113_AACMNV miller_k_Page_054.jpg
4b364eae41d76b4005a5ba61a1d1ce47
7f69751ee1c4b7f0304f19eff012058696c2b3c1
49324 F20101113_AACMOK miller_k_Page_071.jpg
909e6cc7b58cdf41d4d66817894c965f
8f5f3e1ac0a796d6eda18a951a692fa63f8310db
107828 F20101113_AACMNW miller_k_Page_055.jpg
73b0f20d6d92adab6f02cccb824d67b2
60d896bac091128b3ba9cd20b7c5975c68a7e9d7
115058 F20101113_AACMPA miller_k_Page_089.jpg
915c3faa1b99637e62e8ceffeffc71f0
b103f87442aa77a6614dea69b334a1efc70c967e
30143 F20101113_AACMOL miller_k_Page_072.jpg
8c97eab35dc9eefaaf58bf3b6e583331
2935e5687a52715515eae281f84e486f8f6cfd9c
113474 F20101113_AACMNX miller_k_Page_056.jpg
e1c715d84f3c1816bcd79fa420af09ff
95559978147d3330f357f44a79b54213c52718ce
117975 F20101113_AACMPB miller_k_Page_090.jpg
27808ec7dff2c083bb713e5286837d49
104992166c0fd3a1040a4ae4e8d96864f1ac5b95
36610 F20101113_AACMOM miller_k_Page_073.jpg
682d7cd1b23d5dbfe4164c9d41cb4301
358a2c48f635711c542d4b925cc3a228ae9c156d
110010 F20101113_AACMNY miller_k_Page_057.jpg
c9c3690b4ad0f389859abe93afb4ff6f
df49ef4e1e02a7d9121fab9c30a024f5d155696a
114543 F20101113_AACMPC miller_k_Page_091.jpg
71189167cf64bbe0b561d40ca05e7db2
84c7dc994f2527c61e03b3959694e349a907122d
42103 F20101113_AACMON miller_k_Page_074.jpg
81e08d7cf670f67a7c6c8222b285ca20
e214eee192817a0a9692780df117de0733542220
113038 F20101113_AACMNZ miller_k_Page_059.jpg
2375ece9ee4ed17dcf1482f92c680d83
0fa2de5dc60dde1a34b59e4509050d35345d6149
113368 F20101113_AACMPD miller_k_Page_092.jpg
5259c08a65cbc054fafd1b41e5ebde75
80e59751434c08155e01eb6c780f6f8b471cad6c
102561 F20101113_AACMOO miller_k_Page_075.jpg
56778202bdf3a4741570d2ae2a21730b
91ff593611b501fbcff576803f234c4a5ce2aee3
108905 F20101113_AACMPE miller_k_Page_093.jpg
317be31f3af207ec1dfb2fd46dda7f2a
0a49948dbcb69b211abdf8d6e942ec5b48492323
111850 F20101113_AACMOP miller_k_Page_077.jpg
e51a2aa934174ffa5c2f7643fd73cd2a
7b7e33b0eca1f215ec1206c0b8c156380077a629
73166 F20101113_AACMPF miller_k_Page_095.jpg
6bb7149fd822e9da456ef71851068905
7e0fffa2e83965f2a96377fe76b3924413a747d9
106281 F20101113_AACMOQ miller_k_Page_078.jpg
5981d9a0887e6faf11a29205355750a0
95528e6d89f6c1217285064c7149d87f47551555
83362 F20101113_AACMPG miller_k_Page_096.jpg
d08a3f9d030804c9e042b04f5ae04358
b413e8f8c8aaeb4c3c41cb33f53c207f49eeddba
113664 F20101113_AACMOR miller_k_Page_079.jpg
70b4c7aac5165b82b192980b4b017015
97ccaede9f15f88912ab2e8e3a2eb1ac6a874ff9
73969 F20101113_AACMPH miller_k_Page_097.jpg
3dea127e205e184581bd20f443c1bc47
425f326b3c2479d935c47f4e15aaec6387758969
118189 F20101113_AACMOS miller_k_Page_080.jpg
bdda30c7a0ac0743f3db127766bd0ec4
ee4ade20ed77795898a902927c10a598ca950ef2
112925 F20101113_AACMPI miller_k_Page_098.jpg
a75c4c31b12bbe21e1fcc39735f50ca8
01033aca01572703188b2678259d6dce1c47cb83
116450 F20101113_AACMOT miller_k_Page_081.jpg
9963548006a0bedece2945daab2cffe2
f73e3aec4ebd6645dd89e54e056945c675a0008b
130681 F20101113_AACMPJ miller_k_Page_099.jpg
fc47b9bc1348a092fe0bb010167d1ebc
3c2fa2bf515e2670a385a344b436737e9aedea41
117184 F20101113_AACMOU miller_k_Page_082.jpg
e6e44365d7465968f698db7579d65251
60f990d730c8ac9d93920b6b7bd78437ef31ed6c
133945 F20101113_AACMPK miller_k_Page_100.jpg
79a4cb6b58662fcb8a995517ceb45a3d
fe948c3f7c276c438b92b5fb5c1804c93d1209d2
116565 F20101113_AACMOV miller_k_Page_083.jpg
b72318151bd192c5d0e57d9a304d7ad0
b1af23da4706969d0b4bee00bcaec3efe23d010b
114817 F20101113_AACMOW miller_k_Page_084.jpg
7b2ebf5831f9a57e1b6986f17a7a8809
edc8635f9d31101e80dde61f7e871227a589c531
129026 F20101113_AACMPL miller_k_Page_101.jpg
09f8f2a9b6cdc7a0c0f8d67a17f449f7
71183ab84f89fe755170fa5c6d78375dbd3de98d
112180 F20101113_AACMOX miller_k_Page_085.jpg
8832238e734a345ac9c0d8c55b6ac45e
be1a899b8a4c5dba655b6ec592d87130bcca1a65
981116 F20101113_AACMQA miller_k_Page_009.jp2
76a46cc3a685db970836b88afd4ecd63
3475367c9e07ed5dabf2cf315c88d7a6ed32361a
128054 F20101113_AACMPM miller_k_Page_102.jpg
6bb944d737e913052e31aaf5401f3b02
2e4e4f4060e113a3f230ce2cbbdf09d276ba24f8
113241 F20101113_AACMOY miller_k_Page_086.jpg
9195b1e3d9e2c7517e61e22e4f683635
3410ceb91cdc41a17426dd58289580a1779e635c
60989 F20101113_AACMQB miller_k_Page_011.jp2
699eb276400ed9248c74446ffe5f9830
a764465de562efd915c26ce329784c6d3ad173ea
142176 F20101113_AACMPN miller_k_Page_103.jpg
e8aad9cd369ac9ee553f1e8d1c287b87
79c4aadc68384be2b49c1355cdf7ca7f1d83435e
106524 F20101113_AACMOZ miller_k_Page_087.jpg
511f5c843d3978dcbd7eaf998a871d10
d39b7932d10f51b92556c7ee558fbb7e38f46dc1
106247 F20101113_AACMQC miller_k_Page_012.jp2
d6235214132f6d7d24170dd72e60e73c
f15fd75717350b57188291e0926938747c22bc93
119243 F20101113_AACMQD miller_k_Page_013.jp2
549ce8695ed7e84b85a3a32ff1da1543
52bb9b53819889c471e9b2e73d8ae6200a8ad9f0
135361 F20101113_AACMPO miller_k_Page_105.jpg
67fdff5750a993864d33fb4206cc0f9a
044a2fdc812f0754564c6bd3e86e276a6a1b4735
120599 F20101113_AACMQE miller_k_Page_014.jp2
128237dee2633fed78ce08d8799fa2eb
1995f3045458b693fcfe07045eb39cf6646edb8d
141246 F20101113_AACMPP miller_k_Page_106.jpg
0c636ce73f9f3ca36dbb9dadd6feaa92
1448c89e849e917269353e42cfc635bc09808744
120163 F20101113_AACMQF miller_k_Page_015.jp2
ef522b23c74f84ccf3154457026f9d43
5943481d60ab2bb81900774edb8e96efbe59af25
119191 F20101113_AACMPQ miller_k_Page_107.jpg
ae5bb4bb8fa410f52234b5f01d708dc3
1c7ea8c7dab9c5d04cb1ca6751eacbeb76b73c22
115848 F20101113_AACMQG miller_k_Page_016.jp2
a2ae1e0bdefd2a05e92b74500bd42d47
91600fab70a0fbad11c80a46ce265f91eb6c2694
34168 F20101113_AACMPR miller_k_Page_108.jpg
52b21da0a11e63aaafa3b746fd4d277b
b93a0361e2e409a9b4cb32cd145d0f8c8820eb2b
120343 F20101113_AACMQH miller_k_Page_017.jp2
ca7e31fec06f8c20e2452e49fb5675b1
185086bcf83fff73d7a63b230ca7751632a698db
26076 F20101113_AACMPS miller_k_Page_001.jp2
015a5fa8f04911e54422cab695c6501c
b86bd4b0f6c2e4e640282c1070cc41fdb091eb3f
117899 F20101113_AACMQI miller_k_Page_018.jp2
76f8b691ae0c7d27806d89380549eb4c
3726369ad12a3aef9f43a4ba43cca7e94f57e2b4
5526 F20101113_AACMPT miller_k_Page_002.jp2
113cca666dcb0b562c5cf3a262cf23a4
e20a9f835c02075f7212a9896f34055ca57981bb
118637 F20101113_AACMQJ miller_k_Page_019.jp2
bbb45f8652d7ed0a98a9fbb84432c933
2899a789727ceef6dd7106299db2e76f6f75390c
9545 F20101113_AACMPU miller_k_Page_003.jp2
4f218c065312c6c684db98f07c2a6cc9
d91a31a17c78c4148cdba26f54b1bce0c4baa7a9
111421 F20101113_AACMQK miller_k_Page_020.jp2
f053d97562f496ce6fc16e1a696841d5
a8d48e8651797032f0a67a011e66c38de6737d63
29731 F20101113_AACMPV miller_k_Page_004.jp2
a74ef6cbfb088b733907bf4b82ebb619
0443aee44585d43e7ae78976914aa929e297de99
116799 F20101113_AACMQL miller_k_Page_021.jp2
29a8eae99722bc9027ffe40d35068ee6
40bd250e6ef6065abcc937246f9438c9ba93a1a8
1051964 F20101113_AACMPW miller_k_Page_005.jp2
fcadf43046ee3551c8f721d06916abdc
a67ec10059d484e49a1404d25bed06d17c7b10c3
113356 F20101113_AACMRA miller_k_Page_039.jp2
586044a16688fe3f2913bead579bcd97
f25977e60a688c9e8229f09117b8e74b1b6783c3
1051965 F20101113_AACMPX miller_k_Page_006.jp2
589dbe1afb8478a5f7e632981a5b458e
6b7444ba071024e58dc595adf29668ef484d66c3
113004 F20101113_AACMRB miller_k_Page_040.jp2
9fb84517551119930939f5c0547d7504
6060951a075b2451c37e9778b3a5a9829cef3b1b
118905 F20101113_AACMQM miller_k_Page_022.jp2
2e09f5d14c6679338f2bb56a79608572
17c0cb672b821af1a89804c998c79e5aeb01df37
1051954 F20101113_AACMPY miller_k_Page_007.jp2
ffd2869f04c8de09d8b4d5a6e167d2b5
06ba5d2c8a878c8d3b1a856781635581d729705d
114691 F20101113_AACMRC miller_k_Page_041.jp2
4361e8f17ac9d51bd15bea970b13c87f
8d9e2398437aedaded83261056f82bbaa9d1bc63
121512 F20101113_AACMQN miller_k_Page_023.jp2
19b99dbbe56ac196a0c48cd4e1789d4f
e58c427c8c5d34b6ae751c51c71b72085f810fb5
1051981 F20101113_AACMPZ miller_k_Page_008.jp2
65e10e3d743d13ab01b42451aeefae8e
6c55bd80c0653a50753c1943ee2095601d4e0996
109049 F20101113_AACMRD miller_k_Page_042.jp2
dcc12040f738b5f90a523ad1a40919c3
b14b86e1002bb9834e44671e4d152be4ac1c9ad2
122115 F20101113_AACMQO miller_k_Page_024.jp2
09ea0197b9e5b54e19434a1d8f13044d
ff71f1935b791ab10f2367d423fad768d5b57ad3
113300 F20101113_AACMRE miller_k_Page_043.jp2
251459e118ec8a74301aa319590e6989
4a71dd610a054f57b4c23b2322a3da288a3e67fa
121539 F20101113_AACMQP miller_k_Page_025.jp2
ef905b7eee20291eb602ac50267a9140
2ed440b922d46885da48bf4dd63f640e527115b3
116872 F20101113_AACMRF miller_k_Page_044.jp2
fff8f15b586755f554e34447223b181e
5938e278f46957337bdc15b3d61b5f9393c8e3ce
119508 F20101113_AACMQQ miller_k_Page_026.jp2
93de75e9cfdce9b46a7709e6c940fe02
ed6751057f2aa8515a8b298aaacca199d45da691
121102 F20101113_AACMRG miller_k_Page_045.jp2
bf0c8a1ab98d4d96f43b3befd07e2bae
ab8cb9962833bf734d3ca489c3d7c9c13f5e654f
117199 F20101113_AACMQR miller_k_Page_027.jp2
e3fd2cb99cb9764229f72aec127c5c44
8e51f35c1e0f862398b835f6ebaaacf93eeda796
63511 F20101113_AACMRH miller_k_Page_046.jp2
71884c44c3ef0d222f621973297f3c9d
393b65a3f031aa2c7dc6a083b13fb734e91dfb4d
118321 F20101113_AACMQS miller_k_Page_028.jp2
e15a15e8c7cc0d7f9287aeaf6d1e9624
f8df227f21c44df6480a405343b82d0812c97726
95737 F20101113_AACMRI miller_k_Page_047.jp2
e0cbd827450a71d89b0a32711471ec65
b831de3a8915af7953e1e2eea49c710858888fca
120062 F20101113_AACMQT miller_k_Page_029.jp2
29a4dc9046ab78575988f344e6734a48
c70f6d0fdf651c007314f86d7f296a6ab31791b7
104790 F20101113_AACMRJ miller_k_Page_048.jp2
f59b521291e9ab3ac2bfd28ad2759f49
454aa2ae63390a6325c610e8e8a390bd6f73f631
519148 F20101113_AACMQU miller_k_Page_031.jp2
6a3552d37f179d0e02336c8f1cee23ed
ba08e5c229beafda4201c460c5fb76d8c1a7253a
113355 F20101113_AACMRK miller_k_Page_049.jp2
60e1c368586dc601217c02e1a332bf2d
111ce231142e1e576efb72da16b6256c843c6e63
306818 F20101113_AACMQV miller_k_Page_033.jp2
54c16e4cc4535870ea05df079b00a71d
4dbb62171c167ad7470d9efff2b950f57261d557
115991 F20101113_AACMRL miller_k_Page_050.jp2
a809b8d2ddf92d6131a060beb3512369
62eaaf4652a831564765263689af88f0d28030de
102217 F20101113_AACMQW miller_k_Page_034.jp2
573c4e14b2328c07c5812f47f0124f35
9ffe8e9036bcb75157f05509535e9f68f5cf03b4
112007 F20101113_AACMRM miller_k_Page_051.jp2
82249ce77edaf0b6e9de9adb68c8d611
ec53e70952fcc7005dae3390f1962b2392e7a451
118465 F20101113_AACMQX miller_k_Page_035.jp2
fd7e180bf4f43a398e35d0fe404b3bd9
529ef20885470e1b671af55e0bd5f6bc09c84856
40078 F20101113_AACMSA miller_k_Page_065.jp2
8929e42131afa00f639e642bdefef8a9
d78c9e5d1b9aeae307ae576e4ad214af6d67a770
118361 F20101113_AACMQY miller_k_Page_036.jp2
797cca5e113caf36f719b633ebf3a799
9931c3fd2d5152a88f97e031bb867fb53e5dd31a
105931 F20101113_AACMSB miller_k_Page_067.jp2
f6f7bd2fe009272fdaf228f40276fb82
2fd1a7ffd22318c10541b300cd7a38e8d0bc82fc
121950 F20101113_AACMRN miller_k_Page_052.jp2
f5bf3b4b095dc24746dfebbd2675fb5d
9c7d4fc65f0f7ca2db26b0a32af3ccb655ae2b28
109921 F20101113_AACMQZ miller_k_Page_037.jp2
765300863567f43e72cd8ea14a3dd36a
99c77576bd139828e8eea3b468936e53acc94072
62655 F20101113_AACMSC miller_k_Page_068.jp2
0a62b1961108f9ba2eacd6414434aa77
a74b9716078324add8fce04758ef7aec2569a7ae
122725 F20101113_AACMRO miller_k_Page_053.jp2
34de99e763a73e31d5fd9c359eeff506
4feb7e94d4ebb55a3944f150e2b6349e5b756f9e
64997 F20101113_AACMSD miller_k_Page_069.jp2
8998f9fadb00136209bf04436a6065a5
7f2b500f2f1321b0621837cd006a04e083129bbf
115842 F20101113_AACMRP miller_k_Page_054.jp2
a46262b3374b87fec0884ba92aab2b83
880e9031fb45493186bf2fd27dd38e18885abef9
328653 F20101113_AACMSE miller_k_Page_070.jp2
9605a6118055bfd72aef8c474fd22ebb
34f09e91ceb8ab3fbb54589a54d1947ed6c6ae00
117201 F20101113_AACMRQ miller_k_Page_055.jp2
ad5127ed683ac45f5dd56abe53841e2b
7b7b29d627e50aca228b5e0df6acde2c89c0096c
444620 F20101113_AACMSF miller_k_Page_071.jp2
d1c77c64040a5d33d3466b44fbf0f3d8
efa7f44a9f0c72f9b2883d35a48f5669ed41edb6
121256 F20101113_AACMRR miller_k_Page_056.jp2
2b24666096f5daa0c6df691cf07a72fe
274fa78cc7d1e0f571140b47df693b2ff58afae2
234881 F20101113_AACMSG miller_k_Page_072.jp2
d8380316f7f5744409fbbcb97ab846e2
12eabf8b15d3d2e45b027ffc41bcdc65cb0e9042
118643 F20101113_AACMRS miller_k_Page_057.jp2
dce84fb04550dbc27254f6468bb35f75
8bb5b232aa164c4cf9ced4ef81dedf74bbd5c979
298471 F20101113_AACMSH miller_k_Page_073.jp2
05adf903a978155bddf3e0d07e9db49f
397596df23232542ca550b4c4973d740da96f4b0
117486 F20101113_AACMRT miller_k_Page_058.jp2
5aee77ed1df6987ea7acb7ad047d488e
7756ab1e9227c1d4b536c4585b43d5f30a8b8d40
373302 F20101113_AACMSI miller_k_Page_074.jp2
388874851cbfdec8c406f913d279d7e2
977179f6195160deb6c4233fff76ddaac67ba395
121141 F20101113_AACMRU miller_k_Page_059.jp2
3e3c9fbb264db50d346117c21e14626f
a3565b686885fed9d2a21c0a848d2913e24a2115
108658 F20101113_AACMSJ miller_k_Page_075.jp2
e04994d4de7ef17bce51c85c86aaeab8
ba657beb77d21b5e2836b09bd3357ebc232202ba
122634 F20101113_AACMRV miller_k_Page_060.jp2
99e26ec3d5a74196e815039510d68126
77eacbb66987f30703db00b2b658aedfa8840143
115012 F20101113_AACMSK miller_k_Page_076.jp2
c401b606682b76f747ac7c01cbf83b19
ba521743db473fc27ec89b4dc7de43eabfd95f86
121499 F20101113_AACMRW miller_k_Page_061.jp2
b0fff7156e7d9902eac9f47c0aa9fce2
b565bc3fc694bb37cc13c5795069626595c2dc96
118044 F20101113_AACMSL miller_k_Page_077.jp2
bff2267cd1fb19d9c0d114b97246e050
a697805438b5ef90447427892372a9401799378d
114939 F20101113_AACMRX miller_k_Page_062.jp2
43424918bbd543a271ab02eafb85ed5c
4a682d0b468ab2ee44923b8c2e32dbb013b74010
115227 F20101113_AACMTA miller_k_Page_093.jp2
656f8ee4aa1c4531239de4095cbbe646
22484cd30a73bc193a8224f797fd6fcd0ea37f63
113372 F20101113_AACMSM miller_k_Page_078.jp2
b101add22207f072db81b3c3eb9ea59d
e8cd07ec6254c3f2d0748ef4aca5bcb978fa2e3a
111190 F20101113_AACMRY miller_k_Page_063.jp2
72db1a05be5f694d5d402d0dff72211a
4af728b18c91b084ed914bcd38185f39a13b9d8a
29807 F20101113_AACMTB miller_k_Page_094.jp2
6545840faa24a307cdfd3fdd5af706a4
3b37c6c945e628b21f7a97364991035ae76515b3
121229 F20101113_AACMSN miller_k_Page_079.jp2
0b672640c5af6510e5b3b9dfc3c9d4d4
71825e1fc423b08bfb492f7fa9112ab2abe84bbd
97413 F20101113_AACMRZ miller_k_Page_064.jp2
f1414dabe2c91f8feec55a80ce31d374
5a45e6d7a865ab47fe43729058c0d4ee8263897a
75547 F20101113_AACMTC miller_k_Page_095.jp2
fdca919496c2707abad8f79240e862dd
fce61fb6526ee10b9b235c99252b0a5171138293
84407 F20101113_AACMTD miller_k_Page_096.jp2
d6f9bee27af746d9ebbcbe99f687be4d
2964472aede1f0bdcc4a89687ff207d18c36421e
126376 F20101113_AACMSO miller_k_Page_080.jp2
e46ec4d0aa7696da03d1989dc55265b7
817f65020b479f5c0dd3721e61fcf979de3d8e03
77965 F20101113_AACMTE miller_k_Page_097.jp2
5c0cc86849e8abb86cbadd43a56534ee
5af0e3d2d034b1fcee890c0f5982ced386bad4fc
123459 F20101113_AACMSP miller_k_Page_081.jp2
edc7dbb65b92c04727358e7845d5c936
c54f08a3ac0347e904a1f322d395a734e8315909
125504 F20101113_AACMTF miller_k_Page_098.jp2
69b5a3fea726feaafb1a01f42f4f1398
062610e9b703ee30974a771e7f9f5edd1313ff89
125662 F20101113_AACMSQ miller_k_Page_082.jp2
608e6c86bb1c9563e63273fbc4dc5211
ca3c3061765486feaf61bb26e5308d4be79cf415
136643 F20101113_AACMTG miller_k_Page_099.jp2
38c04181a16e619d43112ccd2defb0ab
cbff18519fdfcf43897dd26cf2e262f5314dece6
124733 F20101113_AACMSR miller_k_Page_083.jp2
c00b19539d5cc1d06f6cc89b76de9639
9803d9c080584aeb9ca66752d890dd626b9624bc
139772 F20101113_AACMTH miller_k_Page_100.jp2
7cb7127ae0e29240a8bd466f215484af
240837191237a2984297dcedb94b73ce6b512ba1
119304 F20101113_AACMSS miller_k_Page_085.jp2
473254fbb957c071a1fcc3a2bb711e2f
0aac8b1a6092a2b717a647c7a6d1147451778b83
135842 F20101113_AACMTI miller_k_Page_101.jp2
f05a69a5ce2759fc9ede232b43674a60
17e51c8d6d4d0e77b17a210d8bac9d264dbe5d09
121612 F20101113_AACMST miller_k_Page_086.jp2
2d3db8d886fd636139aec14255b56c7b
5f78dee74af8207b1cc065f3adef6d4a90ee1299
138982 F20101113_AACMTJ miller_k_Page_102.jp2
8e0116f7122d208fba5d88ab44ab395d
166e6567e1c4cb9e41506a12c8a114931620c4fa
111809 F20101113_AACMSU miller_k_Page_087.jp2
8ec0f8a1ef20532736fdb4ec7454568f
18dcd64a38aa2afec35b444dd313e1d52049dcc2
146451 F20101113_AACMTK miller_k_Page_103.jp2
8d099c5725b9681cba6911aa13a7ad65
8bb9cdfb4a56edb9e33fab2e81bdf4dc5bf0794a
110971 F20101113_AACMSV miller_k_Page_088.jp2
18e69a8c2f4966928fd9fe7cc4c8f866
95d5c03200cef0884a4493fbffecab5254dcffcd
141758 F20101113_AACMTL miller_k_Page_104.jp2
72192eeb38386f53974b5ecce3098af6
35cf493a01c8ecef3a32a950952a8c0b7fcc22dd
122949 F20101113_AACMSW miller_k_Page_089.jp2
6c0d6c84bc11811165b3cbea9f655f17
210c4e6eaad6510b2594bca3ca011907edf750df
F20101113_AACMUA miller_k_Page_012.tif
fe118a9a1024b77160fd68eca6077ab7
ba3664b791c654c3680964dad807d663ca00c23c
145093 F20101113_AACMTM miller_k_Page_105.jp2
9a8c68d21fe72861121171b096ceb1e9
1f91d38fb464cb4915536c0a1420c8f98801eaf4
127140 F20101113_AACMSX miller_k_Page_090.jp2
fc25560e29eceac11c08df08ac892821
2bd89d78b201471c35723464aee88b60d388052d
F20101113_AACMUB miller_k_Page_013.tif
1f9a4cc4a25b400365ac481b9665727a
c771b8046cd09c1ee5fd3832d9bd8fdd00cb2881
152832 F20101113_AACMTN miller_k_Page_106.jp2
bfb5d3f8d7fcf8a773665badce0716d2
06f2a73e0eea1bcc26438ef8c299c23026300767
123308 F20101113_AACMSY miller_k_Page_091.jp2
029bc6897e7f48fc9da60ccf477fb334
ada72aad2bbb936074849a077ce203a10f9adca2
F20101113_AACMUC miller_k_Page_014.tif
fe85de07e3f1ba44b8addf4d02be2f34
bdc61d9a75ae4eeb3583430cbfbb6e16450ba315
129064 F20101113_AACMTO miller_k_Page_107.jp2
3623c1964349176514ff7c2a1ef7cd60
0a116397ca92389511a3f2fe8b2d2d5e8b9440a6
120869 F20101113_AACMSZ miller_k_Page_092.jp2
22026017467660b55e826b92e2f18f16
02097fa31e5d69ed369cdcdf1387fca104175b9e
F20101113_AACMUD miller_k_Page_015.tif
6a795901dfe18b423b8cea0f86d25ad5
f8e596058d4da1aa039dc9e882527b87a9424240
F20101113_AACMUE miller_k_Page_016.tif
766e460291958327fed69feb69860421
784df2b2d4b76e223909588a1a7ff1cd0cb48465
F20101113_AACMTP miller_k_Page_001.tif
9a729fab8d1d97b9c0ca73532ed35271
4b2beac7c612c6e8be623fe6dd31b7ce1556a96d
F20101113_AACMUF miller_k_Page_017.tif
dc57c84d6a163b1e09da0cd75dfff1ee
507e9832a6f44ba0c475e01a24ab46ee3f5abcfe
F20101113_AACMTQ miller_k_Page_002.tif
9c6a7ecb969733c2806cdeb52cf98219
310607cefcca2c1f511d369c84f0a8e6111491cf
F20101113_AACMUG miller_k_Page_018.tif
7674ccc7e4db5c0693f70994659d74b0
58915a52415cefa582fac7cfaa43a9e8f4e9edc9
F20101113_AACMTR miller_k_Page_003.tif
2c3e0ffb500078c2dc9f91a3d8a3ed7f
4e538f97534bd885c22496feb26fae9275488612
16226 F20101113_AACNAA miller_k_Page_071.pro
4d4cfd1e774510428d03190e88550252
0f65c125a47c258bf8e41351ec053abb8ff834e0
F20101113_AACMUH miller_k_Page_019.tif
59f8ad752cc72deb473191df2b161527
3f3f741512bd872789c1932535c8309e40ed3534
F20101113_AACMTS miller_k_Page_004.tif
8e2bcc55e2de430f82c7e7c845675450
39837cfb6d2649449ec93f368748c0ad1c9ff99b
5293 F20101113_AACNAB miller_k_Page_072.pro
3fd7e42dcde4d8b7784fb71f6b6b9d61
3b31ed47309197ddb3099d54dd7c94bf496b3846
F20101113_AACMUI miller_k_Page_020.tif
a0fb4e4867f2fd92e9ce3326cc42993b
90077cac8a4c7f94f025170fc795dea7e292986d
25271604 F20101113_AACMTT miller_k_Page_005.tif
90e78e88ede27002cc9957bb63fc023d
269bc1d0d5348ffd728b7cf4579bfde37468872f
10206 F20101113_AACNAC miller_k_Page_073.pro
70c82ed3da13eed2ec5fb840891e0683
1cf103e0461e3020349899fe805b1e5c9e1155ab
F20101113_AACMUJ miller_k_Page_021.tif
db83f714d45e065705c9a07cf02f175d
45959841e4f04db3f56f329c3ef0738e41a178d6
F20101113_AACMTU miller_k_Page_006.tif
dfabf590bbdc6244d25cc21f14537b0e
63aad59a8020429d74c28886c13e3668ad07cf3a
11354 F20101113_AACNAD miller_k_Page_074.pro
b884983f9d4f68614d366050defe894a
dcf4ec22650a32cc552f27afcd0f889bc4cb1765
F20101113_AACMUK miller_k_Page_022.tif
4fda79f2989fdc947e08bd5bfaac0521
01e38a6a95eadb809218deb86c64d95cf7840466
F20101113_AACMTV miller_k_Page_007.tif
3b6b0e510184ed3f1b81067d9554e407
6e04cf198061084471a5abacc2312695c94a1856
50592 F20101113_AACNAE miller_k_Page_075.pro
633e2fa637b32b9218573234bf310bf7
aa57e2040b3b134689aa33c46a7a87c8ec696072
F20101113_AACMUL miller_k_Page_023.tif
085fcebf75d27962dbb8ff3a97d2837f
59bb751f82d56fac8839054b56ab18dc5601373d
F20101113_AACMTW miller_k_Page_008.tif
d0c614347f3d35adee421440085038fb
e87b4eb9ec9cc7fcd93caff802d44374eb5e733c
53664 F20101113_AACNAF miller_k_Page_076.pro
f7c61faaf3262b5755094b2aa008599f
a09f5c9d50daaa6f1bd28e43a8ad580021a680d7
F20101113_AACMTX miller_k_Page_009.tif
2f20fc9c890b80f00f5d1c78a725657c
2c8a2576d05b1af56cd8b6a87d06e938a9dc7c61
55987 F20101113_AACNAG miller_k_Page_077.pro
7e9ac8d7ed536e351d9572edac2977ef
7c9d7f717058d6d53810e11f872f7b97c5692ccf
F20101113_AACMVA miller_k_Page_038.tif
00228e2ee34035f91a4b100056917f4c
3fe6452e043d5d6c6881d02f3649e531de091fc2
F20101113_AACMUM miller_k_Page_024.tif
8e2090e8ca28871a075523559a84484b
86e0c6cf3cff1b74b7d655d7dc1e2e3adff3d6d9
F20101113_AACMTY miller_k_Page_010.tif
7970d4b2d0e9f12f684e8a41cdba767b
d0b65f91d8c65cc55911216038b0a6e3900792b7
53297 F20101113_AACNAH miller_k_Page_078.pro
401c3c5e7cabdc1caf2d7a7c0603c571
a677264cd1186ef460826f01711bb023f999fca1
F20101113_AACMVB miller_k_Page_039.tif
eae31cb839d383f29c96ae8dd7dd7fc9
36528bdc0a985370d2e755787f14c3541332d7e5
F20101113_AACMUN miller_k_Page_025.tif
3ffd6b78a3e9e79136c8f9a24664c0d1
9cc7d49cf90c5678499a51b142202c7d41184112
F20101113_AACMTZ miller_k_Page_011.tif
68bcb29df4fb1478306a2a46de32bd6b
8c065d09efe414a6eef43ab38f997e1b0772e98f
56856 F20101113_AACNAI miller_k_Page_079.pro
f34a1464ba5206ffcea459d2b2a99911
c18d89de1002799fdec0439c9629e9a33f324c91
F20101113_AACMVC miller_k_Page_040.tif
2f4bf2b537a62133e00ddde38c8bc16c
ce9a59ddb252ec19489041ecb77ce6bcdd164835
F20101113_AACMUO miller_k_Page_026.tif
de40740858b3d340681bbdf98e8b962b
e083b6d811e8eec60599bc322b5a6485a0fc541b
59400 F20101113_AACNAJ miller_k_Page_080.pro
050bc1f07e1b5c3093ace75db309b907
e25acaccbfd0e8bbc2aa3a61af2feb5d866558d0
F20101113_AACMVD miller_k_Page_041.tif
e5fec93bc0960e9d5f3b102837acf8c3
8156946ee92f571d27ed8652dcf01819855734aa
F20101113_AACMUP miller_k_Page_027.tif
3a8cca2724cfc08788367e988435c4d5
c93ab2ebd991528395d58d89afbd828edac8546f
58545 F20101113_AACNAK miller_k_Page_081.pro
46f38898e358fda5b8ed9dde90451ddc
1a5e1128099f40bc1e6dd4da367290aeac3013b9
F20101113_AACMVE miller_k_Page_042.tif
0b16b654fcf793085e399dc156cb64e2
dedbdecc1e06c501fef4f012f90bbfac74448ff2
59038 F20101113_AACNAL miller_k_Page_082.pro
a7af263f006f7eeab522221c12beaae7
07cc9cb00c6a1223186c1c4bd520d8f7d36e6285
F20101113_AACMVF miller_k_Page_043.tif
2b1dfdbe018caf81467234bd29f1156f
203047c5df63279f519711f4a64cb458ed861dda
F20101113_AACMUQ miller_k_Page_028.tif
a8c3a49e2960f348fb53507b9e4d8b4c
a32abf7f7fa484ebff1a642a0e1217f147ad3c34
34109 F20101113_AACNBA miller_k_Page_097.pro
a8e26d5ce734f6dd67c6edfbe08cc50b
d12e3cc0f31b0577405c1ed2171cd30984da2533
61119 F20101113_AACNAM miller_k_Page_083.pro
e0a7af6937e3a56dbae23d1821c13b50
c07b82c4064ddbb164c0c747b90afe4cea8c60e3
F20101113_AACMVG miller_k_Page_044.tif
7f95d740b8dc211ef83194db5f4fa483
155b63887cd1d9e13c54a22a111c4e97b36f6d44
F20101113_AACMUR miller_k_Page_029.tif
699327db5920d0cd21646581292d010e
1a695677d4dad4eb6a54904d146bde499a8267c9
57561 F20101113_AACNBB miller_k_Page_098.pro
0d307081c9b4808b69c64a8cd47cae3b
05abb04eb8685c0ef5a3c98e58b3c7b93be7e386
56739 F20101113_AACNAN miller_k_Page_084.pro
7e34c48d334bf29f9e67bdbe9ceaaacd
f8a16adefacd758a3de8dba1f308af899c606d92
F20101113_AACMVH miller_k_Page_045.tif
0e4250c11509ed3e4c17d5e2942bbe1e
b4237b45671c913e97aae773bde9454378a8c89e
F20101113_AACMUS miller_k_Page_030.tif
7c0761bc674d603bfcc60046aa27d1bb
bd185fbd62ff07a7dadb2962fc70e930686efeb2
63825 F20101113_AACNBC miller_k_Page_099.pro
9c22fbd7a33e4c7beb3fb95632b33df6
01fba961f7988b4aaa99a3db9d3c3c6418efdb9f
55658 F20101113_AACNAO miller_k_Page_085.pro
3ce001706cffc4cbe38640d091b7d6bf
04ddfb2366dfc5aa446ffdf5d976fea9a175ba89
F20101113_AACMVI miller_k_Page_047.tif
23dfe89011632e499c567188d78d1438
ffe8b5888061e7d0aa3032bda4f2594b20a98afa
F20101113_AACMUT miller_k_Page_031.tif
e721ecdcc84938bdbb481892a72bbd35
20b5ad64db72d283d453904ec4aac1911ad48f3b
66173 F20101113_AACNBD miller_k_Page_100.pro
8a8ffd1e62f48e16d73ef79df020e8e7
25d975c4332b1a7ada983d538649329227a9387a
57044 F20101113_AACNAP miller_k_Page_086.pro
3ee9b114c5963ff62d1fb2b38f1aaf4d
f6954b81ef06cd7eeba09af4e67d7ff1e7f04820
F20101113_AACMVJ miller_k_Page_048.tif
026e66e3fac7a08d3d80b26b2848db9b
8faf7232eab6bb8ecc98996c6ef72ffe2260fac8
8423998 F20101113_AACMUU miller_k_Page_032.tif
9800ca9dd54aab5cfc17e86260aca828
7eb24f04652e26d035840791987eacabea0b1bc1
70036 F20101113_AACNBE miller_k_Page_103.pro
1af17b232cdc759d1e837841c472a358
737e770dcdd757fdb62f2997a8e1364cd9f24da2
51650 F20101113_AACNAQ miller_k_Page_087.pro
ebac3c75fd075fe1532fd657cf2f8377
2c02b8fe7c464331c9df627f1184ec36108cd1dc
F20101113_AACMVK miller_k_Page_049.tif
6f8f353713c7254d98cbb7b7b7e74efd
0d88cbd4614a8ce1355d05f4ba54fc3a25cb3f39
F20101113_AACMUV miller_k_Page_033.tif
1ecb451169b044bf15582613f837ea2b
5d67d705bf504ae279b3639471598b3999f7725e
65773 F20101113_AACNBF miller_k_Page_104.pro
2dacf15def757dd56e0d271ccd4fcb69
5f1336e36b17c417d4452124dfb6f026d780324c
52023 F20101113_AACNAR miller_k_Page_088.pro
61921e1e9c8c6dc3587dece1b36475e5
6864308b75c8fc09ca86b3459bb2b3c78753cf25
F20101113_AACMVL miller_k_Page_050.tif
6647d33e7825246a2c464a5b8e2096b4
f171c09b97d34a1b939d559ada1422f68a4c2f55
F20101113_AACMUW miller_k_Page_034.tif
89483e419cdbae1515c05353b2876b49
dd7f2d3c40b144001f5642b03e22aa53e26c2698
69032 F20101113_AACNBG miller_k_Page_105.pro
fb38166739d054a8bdb495880328880c
32e8b84eee0f97dafe616ff98697a05e869559de
F20101113_AACMWA miller_k_Page_065.tif
7c877c88f41e7e29ac2fc14aa57c1b3d
8fa5fe224eab98a788269fef5a78c8038cdcdd37
57743 F20101113_AACNAS miller_k_Page_089.pro
8a74023da8c1b94479a206ba38764e9e
e118d4cc30b3e643e10d2443d3eefeac3b21a454
F20101113_AACMVM miller_k_Page_051.tif
2b7b82062694020a8a349fe559be8c07
89a5bc849596e07f2413ae4f5fd6ffdf903842aa
F20101113_AACMUX miller_k_Page_035.tif
4af49b0ca39ee0cfa71a289e75850804
d7ef8c310d5363006e4b47feebd98353e1309dad
72568 F20101113_AACNBH miller_k_Page_106.pro
2f02be2d1e16f803757d3efb51921003
2ded16ab867e2e17a937a3cf784d8d0c0a64b19f
F20101113_AACMWB miller_k_Page_066.tif
cc49fc4c3cf18c6787f56132969c5bda
f4c3ac196e2279fdd50cd890848c6ff17b1cafd4
59749 F20101113_AACNAT miller_k_Page_090.pro
5cbe17b0f32bbed3843bf4619f097502
9671fea5c02c10587123e775fd61101639c055dd
F20101113_AACMVN miller_k_Page_052.tif
a242095ece936892d5ac364af46d510b
edd942b57063a4f2729cf08ecd80f2d453900a27
F20101113_AACMUY miller_k_Page_036.tif
177d1aecf252c41d00d04aee2a8ea7a4
1a21e4851817c1e0c38e4d7544d365b4cdf7d6f9
60053 F20101113_AACNBI miller_k_Page_107.pro
d4d654e0774f5a8d6467bc4da9811395
b5d4c1a4fce13e196f05eff30dfb97aefe8f03cf
F20101113_AACMWC miller_k_Page_067.tif
d65e4500861e371063c335101111c3fa
e4c458c45abd15c90eb6e45d2d92b5129bce8bdb
57942 F20101113_AACNAU miller_k_Page_091.pro
d28e895adb90abd1a6f2be57e6f84fdf
f66c7a7a6a5365f965a943f8ad0ee1459e3ee884
F20101113_AACMVO miller_k_Page_053.tif
3bceb4498e57d2a97e7794662235cdc6
ada750be1725e4f9bba5cc6b39e7b187181f83a1
F20101113_AACMUZ miller_k_Page_037.tif
168be44197f8daade496a5c48ec25264
1b6123abbf1757f5a72243fa5e40b19a4e198e78
F20101113_AACMWD miller_k_Page_068.tif
de28530598396195b509bb250b298333
6eb276cb8f75e7f150c76c33ec90e69c90b0228f
57309 F20101113_AACNAV miller_k_Page_092.pro
aa6cfc8aeb1dd29109fe65b0b0e14144
24971af7f042830e01edc3bf79b78110818f1fb6
F20101113_AACMVP miller_k_Page_054.tif
e9ee4c6ddfc61d69ffbbccda419d2e2c
2f6acdaf1d4d1ead5853702e6fbe42be9fbc0c67
14625 F20101113_AACNBJ miller_k_Page_108.pro
fd8684d88c19b0966bbab7355817eea4
1c3231decd36980e5d90a95c34d527f20b509ad1
F20101113_AACMWE miller_k_Page_069.tif
733433daa1d3fe2bbc669ed93d2a3aaa
e099557fbd3ec81657470bd554de089164af178f
53960 F20101113_AACNAW miller_k_Page_093.pro
032315faeb1d7ea9ccad37c96d1d5e88
fd431cf8cbb004782abfb1336ed35319a363cffb
F20101113_AACMVQ miller_k_Page_055.tif
26e24de92e238efa014a9f4c6f4ccbce
785829a1601dd0e3c3d91b1e574b44881973881d
496 F20101113_AACNBK miller_k_Page_001.txt
a9333ab3851b44a1cf40d76bbb69f6b3
4a2653d6610857b0e53f4f9cac19e469b0518c0b
F20101113_AACMWF miller_k_Page_070.tif
f275e260f65ed82750b379fd1bf5205c
f76635cd82f759e1009c49628a256b149180d6d0
12229 F20101113_AACNAX miller_k_Page_094.pro
01f3cf62ec9c6f4489c9113ad24cac79
fd6f39ee4a6eb5ecae783ceb8356b41895620123
92 F20101113_AACNBL miller_k_Page_002.txt
104c8f6c980fde73f72e1325905f41e9
7fa69bc0d724102f91d5aad73e2c3ed968566246
F20101113_AACMWG miller_k_Page_071.tif
691050af727d72795a38d3bb6503097e
2816b3f237c9105a27da67a89e74002c75b40a1e
32889 F20101113_AACNAY miller_k_Page_095.pro
6bad40f7d091b383dd426b1893911f5a
f5f88c82249f3d034126252b223fd9e091148920
F20101113_AACMVR miller_k_Page_056.tif
2e0144eb7e0baf8bd2e88482d5ffa6b1
ea3c45d070461ebfa2c4857da9916b260c6dd0ac
2098 F20101113_AACNCA miller_k_Page_018.txt
0502b573c8dc55cca368c26a18a0e879
9a6b597665e6debd2a010b21cfeb4ae977a4465f
164 F20101113_AACNBM miller_k_Page_003.txt
d6442b95a8bf54e73f4ac9fa56e4ebcd
e2290ce3be427a0a9dff6d37a6389529c1aafcfd
F20101113_AACMWH miller_k_Page_072.tif
8429420078092816d53869cc241b4f77
73716a1208bfdd0324393f771902d1e5d2c5ca58
39178 F20101113_AACNAZ miller_k_Page_096.pro
c6b3bbf294ca0bedfa94cc86e89b48a9
901402b50cd0ac1b7ac7d5a10678dbf7fffbb89f
F20101113_AACMVS miller_k_Page_057.tif
cb707e048a0117bc429f295689a95ffa
02bb3725a26cb5f27432db4b38dc773d3f9d6ba0
F20101113_AACNCB miller_k_Page_019.txt
107dfb65c337af3ba6ae39e23f4020a2
c47703d85fff89c471563258f447d46d019048a1
516 F20101113_AACNBN miller_k_Page_004.txt
9b33f660099ecf2a31eb0f66875b5444
08b93d232ff44f5669101361740a9f6dcc4ab386
F20101113_AACMWI miller_k_Page_073.tif
01dacdfe923ed82a6bf401ebe28c027a
4f0cad9f29ea9fbda8cfc6d6374f4650bafb1191
F20101113_AACMVT miller_k_Page_058.tif
fe8013f9c05409ee20ce9d016006e569
0b3d7f7242a2588fe724520854b72c17fb9e4698
2047 F20101113_AACNCC miller_k_Page_020.txt
b21d465a1fc7a548a871d84a011b7a74
541099b217417981e8eebfb1fe0ed4ceb42f36ef
4303 F20101113_AACNBO miller_k_Page_005.txt
bfbfa8dd9131bc8b015d942e251c92ee
07b93015484987b4c4d6c32f6c6d1a80ab73edb0
F20101113_AACMWJ miller_k_Page_074.tif
c4b8adbb81c6b8bffa77afb6bc4062ac
ba8727c89c2b892bab59860e04595ec5fcc9582d
F20101113_AACMVU miller_k_Page_059.tif
9544663b2cfdddc4b9f3a1e4e7d147cf
c204ba68332c23f786e406bc7f4e7fe5aca9fbc7
F20101113_AACNCD miller_k_Page_021.txt
65e70ae171a4c708d41741494a1696e2
024d3644b21fe561d598b012e3c8ec2790733a82
4561 F20101113_AACNBP miller_k_Page_006.txt
39a7c5134d78c9c10d0437cf2b42d23e
601d356dd94b5a04fcf2a94db1fc727eb081489d
F20101113_AACMWK miller_k_Page_075.tif
1ee7e421c2a7c05e2303860a87893001
78c0e35835a024edd27cc9c971b0593962381fb0
F20101113_AACMVV miller_k_Page_060.tif
18dc89ce523b070cdae0224268e4248a
e3376ad6c18522d49e8761e44eb80797861f5378
F20101113_AACNCE miller_k_Page_022.txt
76772547203eab785f62d63ab5bcf293
f593d353d7d1016a7036a7216978a90edb8c3141
1463 F20101113_AACNBQ miller_k_Page_007.txt
9541a05bd98953b1683178b08cbe05c3
4b246ca213829c0a169b96e11ffd670d419fe514
F20101113_AACMWL miller_k_Page_076.tif
7ad3933ce6e84be41957da55b9f4946d
418d1e6d90070dc0ebc0e7c12bf14b5ba7884383
F20101113_AACMVW miller_k_Page_061.tif
ea12aa5e7182795b518a9437a3a0e135
dd00720d84fde477d68af8aad028f515e41de371
2206 F20101113_AACNCF miller_k_Page_023.txt
53d297e18d518c2b54d2b130b9ad9f09
efab72b40503b69e3f8ea763ccbf5a99790f5797
1382 F20101113_AACNBR miller_k_Page_008.txt
ab698d59d19cf419a306561dd44208fe
8190c7d04305f2000ef8e3e1a810df837c805e96
F20101113_AACMWM miller_k_Page_077.tif
9f817d7a5e50950d2940d36a0d6d3665
da566523607833c1737529c6958503e7ffba8855
F20101113_AACMVX miller_k_Page_062.tif
56521868fe92133d21312a2fe33a7f90
6454d208c21b38622cb4646646ea3f8f69a85b92
2256 F20101113_AACNCG miller_k_Page_024.txt
c1ae206a46b623a31a50c177ba790dbd
ceea3d5a4a2fddb379b974ffbe95ccc18e32ec70
F20101113_AACMXA miller_k_Page_092.tif
ee069580c7a5562f2b1586a028b9b67c
2066bbbc80381c48b13834d33e8d4be00e6882d9
1095 F20101113_AACNBS miller_k_Page_009.txt
d18358c650a4e8fe063ae037f5ef0f7e
b21c3c9bfd04f0aa1b75e4345ebd86d50ee8bdab
F20101113_AACMWN miller_k_Page_078.tif
8bef5ac9ec711f4d996f6c34885fbb1b
2c035093421f2f0a9a10765cca3d9b86d8763366
F20101113_AACMVY miller_k_Page_063.tif
7ce62749151123ae199d6907f67aced1
da0b167c6dd3a3cffeaab4597391880d6769171e
2251 F20101113_AACNCH miller_k_Page_026.txt
11c93bd9431a24c57d7b687b231c8899
5a046342fa7e61d2cbb0e6bb1e0e95af434344eb
F20101113_AACMXB miller_k_Page_094.tif
676a6ae6baeeead3423f6d1b3a2220f2
0049d9f9311e407a894933900c8cee390b2c44a4
2029 F20101113_AACNBT miller_k_Page_010.txt
d2a57056a054873f7cdeaf92c98ce1e3
5a7cd7c5a5aedc16c437543f08c4073d7e055c4e
F20101113_AACMWO miller_k_Page_079.tif
4a2fca671d1b198238d1e6f7f45c0f59
ab5907b720f4d7a34e142940f5a564e88cfb3cd7
F20101113_AACMVZ miller_k_Page_064.tif
aeca6b9aba6e55c474faaf50ec3e46d9
4797ea82617860114e67a4dca9b634312428d382
2182 F20101113_AACNCI miller_k_Page_027.txt
8f5b2d82ae71af128529abea4e117906
e4477b5a44bf32ba61f613d64c01b89a18aa8155
F20101113_AACMXC miller_k_Page_095.tif
a2769e2aa9a0bb1d164cab14db7e82e9
5adfb65259508bd42c70b3d6ca1ef4b539051c1a
1075 F20101113_AACNBU miller_k_Page_011.txt
9b876b7a8f99db2825b2bc73b2c651a6
efca8a6511af7f3f40f8475973d8def7247933e3
F20101113_AACMWP miller_k_Page_080.tif
cd526614af5e8fd93e8b07a635880d71
3940610767bb329bf97e5f70311b9b173fc3f340
F20101113_AACNCJ miller_k_Page_028.txt
1e5bc97f1cc437a8c0cf43a3d5667202
fd325a53a2510657234b4057c05695bd6d849e9a
F20101113_AACMXD miller_k_Page_096.tif
b7f83fa34c4b9539e9271072f9efd4e3
bfc596ad71435a1136458d0f2db51b90c5fbf690
2214 F20101113_AACNBV miller_k_Page_013.txt
634e3d1484f487c401567266acee9bea
600a99b8bcbd7258985881b4d8f6e9c75a2dd56f
F20101113_AACMWQ miller_k_Page_081.tif
155f4fdd35c7bc12e13c55ca9be7c554
808342bb97c754168bb1f582464c402b8643f8c7
F20101113_AACNCK miller_k_Page_029.txt
fefb8bb949f6851b808cf8ffb76fc4d7
b4ddd9b20a3eae0496dab43058914c667148c1d7
F20101113_AACMXE miller_k_Page_097.tif
808b86036c2c1a03573ee861f022ff58
8b445c5a9ce1740b6048f322cb1da08f86555837
2223 F20101113_AACNBW miller_k_Page_014.txt
89ff9c8074e13ce15a901ffb2bf22b29
9a5eaa50b964a9fcfa63f5e231ecef0e24effda2
F20101113_AACMWR miller_k_Page_082.tif
c78974397cc1c219233c766b8c41056e
180d97f1188e69c1245ff1df5893ffb3ec48d7a8
538 F20101113_AACNCL miller_k_Page_030.txt
bc9ecbb4e0990de5c347cddb01560767
d3e71987b839972d7ce961477957e39859c8214f
F20101113_AACMXF miller_k_Page_098.tif
f09184a7dfc4dbd9a5911aba32ef7022
d38c76530829ab2d37d3b8a023c1c291be70a736
2167 F20101113_AACNBX miller_k_Page_015.txt
cdd5a94427528e725dd63a69f6bb942d
b1b4f4bef4fa88950165cf99d05d0549822233af
1114 F20101113_AACNDA miller_k_Page_046.txt
6b6fbd39ef2b0f530fa06090121f293d
4a5871b3cec7e206f73b0a330d764dce208ee592
1259 F20101113_AACNCM miller_k_Page_031.txt
6a925eb4ec60dca96f387900ae0f503a
b6b9dc2f9a1b58311ed8c16207341ebd0361f939
F20101113_AACMXG miller_k_Page_099.tif
fa096241226c83cf9ae7a22b98345fba
ef5d4641a2e6934fa0b18da44fe997cea37425e5
2083 F20101113_AACNBY miller_k_Page_016.txt
2762a8155d05e933b47328a1c7e64335
4e999d4e416dc365012399abfe4c2936371c6e2c
F20101113_AACMWS miller_k_Page_083.tif
20ad6de898fa2c6ea69ae23756052d5b
296e47b8a806a4f468a2735644e9e88e92b8ea95
1858 F20101113_AACNDB miller_k_Page_047.txt
632eeec058a9c15c70876c26dea1ebcc
ed499ce0094f2f72845dc53f5cd724ca1d56bbca
352 F20101113_AACNCN miller_k_Page_032.txt
d2130ba8eb40a6ae1e69e987df4b8946
295d1f78be31b7acafcfbfef1852cd8abdd826dc
F20101113_AACMXH miller_k_Page_100.tif
0f1d751ef6593a7dede8cf5b28499021
951a86dbc24d20341bc73181f8ba925d44d99621
2161 F20101113_AACNBZ miller_k_Page_017.txt
aeb5de7ca51169d18b4f2cc79808ba6d
5a0bc9a495df255eff46487a93c91208790acdd6
F20101113_AACMWT miller_k_Page_084.tif
10c49247b077fb606b84f6c234ea5a17
37e3dec70c408dd1cdca6fdf99d60936c7f8f61b
1987 F20101113_AACNDC miller_k_Page_048.txt
c6028dce6230a3273945df90c87b7140
05a84034536bae85396eace775f8586bd23c3442
644 F20101113_AACNCO miller_k_Page_033.txt
3090af528119741b0d93c5643d6066bd
413da49ae0b74ab7d6ab0106eeee2047db166656
F20101113_AACMXI miller_k_Page_101.tif
a5a9b41ff8abb428dccf06888456aee6
6a100f1163adc7d3b508820c027cdf5e00f34f46
F20101113_AACMWU miller_k_Page_085.tif
6b90b3c9c6eee02274d15446e24f9d83
0d51d3d509a7345296f41bfe6908b0891ec10177
2058 F20101113_AACNDD miller_k_Page_049.txt
ba67ec2f259e788f2cf298dddfdf5025
5e9041b48898cfac2db72dde580c775d6ec4ebb1
2053 F20101113_AACNCP miller_k_Page_034.txt
a3a5cdcb285bbad33ea414fb875cc301
190356c7d3af174c40bc1242e9c21d8e955e32ad
F20101113_AACMXJ miller_k_Page_102.tif
56556964bc00564b5f7a7fb89ea9fcc1
abd3b3fc9346cb7a136fc0edd7524566c598214e
F20101113_AACMWV miller_k_Page_087.tif
a1f76bfc5a26b8bf6c5db417eb147df2
1359f2d289bc2f6db014c6aa758e1e3b106a90ee
F20101113_AACNDE miller_k_Page_050.txt
35305ae0533c748a710f485ff390fd6e
35984d71cc97b26835855669d4ab1b1f1b8cc4cb
F20101113_AACNCQ miller_k_Page_035.txt
5e7e6dabf594dacfed31c74babb6fd1c
d8926d7defad58bf07b608f0433d3eaabe9922b3
F20101113_AACMXK miller_k_Page_103.tif
2fc8c497ad62ba54401653ee71504d27
3e607a592f72cb965b734171836cbfbf78eaf837
F20101113_AACMWW miller_k_Page_088.tif
00c888af5f14e1623d15bd484fb1129d
ad0cd905b0fb42d74179a2afa1fcedcd963d35fa
F20101113_AACNDF miller_k_Page_051.txt
f912a0705c9ccccc467ef6a62ce1a3d6
900fed6f40a7871a4c4748eed08af47b03caf1ca
F20101113_AACNCR miller_k_Page_036.txt
3233f59cc87fd8b2778d66939af21a5b
5698a26b03cc903ef90b0688b07c034cb4705643
F20101113_AACMXL miller_k_Page_104.tif
07b77b1354c51496e3c4c1773caf7c02
1d1169cfc185bddb9ddd18aa7729af5b253dce0f







EMOTIONAL REACTIVITY IN PARKINSON'S DISEASE: PSYCHOPHYSIOLOGICAL
AND PSYCHOSOCIAL CORRELATES




















By

KIMBERLY M. MILLER


A DISSERTATION PRESENTED TO THE GRADUATE SCHOOL
OF THE UNIVERSITY OF FLORIDA IN PARTIAL FULFILLMENT
OF THE REQUIREMENTS FOR THE DEGREE OF
DOCTOR OF PHILOSOPHY

UNIVERSITY OF FLORIDA

2008

































2008 Kimberly M. Miller



































To my parents for teaching me the value of perseverance, self-confidence, and a sense of humor.









ACKNOWLEDGMENTS

I would like to thank Dawn Bowers for her mentorship, Michael Okun and all those

affiliated with the UF Movement Disorders Center for help in participant recruitment, and

Michael Marsiske for statistical guidance. I would like to specially thank the many people who

made my dissertation possible by participating in this study. I gratefully acknowledge NIH/

National Institute of Neurological Disorders and Stroke for grant support









TABLE OF CONTENTS

page

A C K N O W L E D G M E N T S ..............................................................................................................4

L IST O F T A B L E S ................................................................................................... . 8

L IST O F FIG U RE S ............................................................................... 9

ABSTRACT ............................................ .. ......... ........... 10

CHAPTER

1 IN T R O D U C T IO N ....................................................................................... .................... 12

Statem ent and Overview of the Problem .................................................................... ...... 12
Motor and Cognitive Symptoms in Parkinson's Disease .................................................14
Em otional Processing in Parkinson's D isease.............................................. .................. 16
M ood D disturbance .......................................................... ............ ....... .... 16
E m otional E expression ......... .............................................................. ... ....... ....... 17
Perception of Em option .................. ...................................... ................. 18
Physiological Reactivity ............................................. .. ..... ................. 19
Mechanisms of Emotional Changes .....................................20
Changes to Neurotransmitters Implicated in Emotion .......................................... 20
Lim bic System N europathology.......... ......... ................ ...................... ............... 22
Emotional Modulation of the Startle Eyeblink Response..................................................24
Basic Startle in Parkinson's D isease............................................... ............................ 26
Psychosocial Effects of Emotional Changes in Parkinson's Disease................................26
Prelim inary Findings .................................... ... ........... .......... .... 27
S p ecific A im s........................................................................... 2 8
S p ecific A im 1 ......................................................................... 2 9
S p e c ific A im 2 ........................................................................................................... 2 9

2 M A TER IA L S A N D M ETH O D S ........................................ .............................................34

O v erv iew ........................ ..........................34..........
P a rtic ip a n ts .............................................................................................................................3 4
Session 1 (Screening): M materials and Procedures........................................ ............... 36
Session 2 (Psychophysiology): Materials and Procedures ............................................. 38
Medication Wash-Out for Parkinson Patients...................................... ............... 38
P ictu re S tim u li ........................................................................................................... 3 9
Psychophysiology Procedure................................................. .............................. 41
Valence and Arousal Ratings of Pictures ......... ................... ............................42
Post Hoc Ratings of Basic Emotions....... ........................................ ... ...... ......... 43
Psychophysiology D ata R eduction........... ......... .................................. .... ........... 43
P rim ary Statistical A naly ses ...................... .. .. ......... .. ............................ ........................ 44
S p ecific A im 1 ......................................................................... 4 4









S p e c ific A im 2 ........................................................................................................... 4 5

3 R E S U L T S ..........................................................................4 7

P participant C characteristics ............................................................................ ....................47
Cognitive and M ood M easures............................................ ................... ...............47
B aselin e Startle E y eb link ................................................................................ ..................4 8
Em otion-M odulated Startle Eyeblink......................................................... ............. 48
D discarded Trials................................................... 48
L ate n cy .........................................................................4 8
M magnitude ................................................... ........................ 49
Verification of typical pattern of startle modulation ........... ...........49
P rim ary an aly sis ................................................................................................. 5 0
Habituation Pattern ............................ ....................................... 51
Valence and Arousal Ratings................................................. 52
P ost H oc B asic Em option R atings............................................ ................... ................ ..53
Arousal Level as Measured by Skin Conductance Response ..........................................55
Re-Examination of Eyeblink Magnitude via Idiographic Analysis ...............................57
Individual Categorization of Pictures ....................................... ........... 58
Emotion-Modulated Startle Eyeblink Magnitude ..................................................59
Influence of Trait Positive and Negative Affectivity and Trait Anxiety on Startle
E yeblink M magnitude ...........................................................................................60
Influence of Depression on Eyeblink M magnitude ....................... ....................................... 61
Influence of Psychotropic M medications ............................. ...............................62
Spousal Perception of Depression: Relationship to Self-Reported Depression and Startle
E yeblink M magnitude ............... ...... .............. .. ........... ............... ......62
Surrogate BDI-II: Comparison with Self-Report BDI-II ........................................... 63
Relationship between Surrogate BDI-II and Startle Eyeblink Magnitude ....................64
Influence of Disease Severity and Duration on Startle Eyeblink Magnitude..................64

4 DISCUSSION ............... ............. ................ .........75

Sum m ary of Findings ...................................................................... 75
A im 1 ..................................... .......................... ..................................... 7 6
Emotion-Modulated Startle Eyeblink Magnitude: Comparison of Present and Prior
Study Findings ........................................ .. ........ ...................76
Reduced Startle Eyeblink Magnitude to Mutilation Pictures in Parkinson's Disease:
Proposed M mechanism s .............. ......... ... ... .................................. ...... 77
Influence of individual personality differences on emotion-modulated startle
eyeblink m agnitude............................. .................... ...... ...78
Reduced emotional reactivity in PD: Specific to "horror"? ..................................80
Subjective ratings of valence, arousal, and basic discrete emotions ........................81
Arousal as measured by skin conductance response ................. ........................82
Reduced physiological arousal: A translational deficit? ........................................83
A im 2 ........... ..... .. ... .... .. .. ............. ............ .. .. ......... .... .... ............... .. 8 5
Influence of Depression on Emotion-Modulated Startle Eyeblink Magnitude ...............85









Accurately Assessing Depression: Comparison of Self- and Surrogate Report
M measures ................ ...................... ......... ....... ........ ........................... 85
Relationship between Surrogate-Report Depression and Emotion-modulated Startle
Eyeblink M magnitude ......... .... ........ .. .. .. ........... ......... .. ... .... 87
Study Limitations...................... ..... ... ..... .......... ............ 87
Conceptual and Methodological Issues in Emotion Research....................................90
Significance of the Study ........... .................. .... ......... ... ..... .......... 92

APPENDIX

A NORMATIVE VALENCE AND AROUSAL RATINGS FOR PICTURE STIMULI.........95

B SKIN CONDUCTANCE RESPONSE DATA ACQUISITION AND REDUCTION
PROCEDURES ................................ .. ... .... .... ............ 97

D ata A cqu isitio n ................................. ....................... ................................... 9 7
D ata R e d u c tio n ................................................................................................................. 9 7

LIST OF REFERENCES ............ ....... ........................... ..................... 98

B IO G R A PH IC A L SK E T C H ........................................... ......... ................... .......................... 108









LIST OF TABLES


Table page

3-1 Demographic and clinical characteristics by group............... ............ ...............65

3-2 Scores on cognitive and mood measures scores by group..................... .............. 66

3-3 Valence and arousal ratings of affective pictures by apriori picture category and
g ro u p ............................................................................................. 6 7

3-4 P ost hoc basic em otion ratings by group ................................................ .....................67

3-5 Regression analysis of contributions of group membership and BDI-II scores upon
eyeblink m agnitudes ..................................... ...... ....... ... ...... ......68

3-6 BDI-II self- and surrogate- report scores by group.............................................. 68

3-7 Regression analysis of contributions of group membership, self-report BDI-II scores,
and Surrogate BDI-II scores upon startle eyeblink magnitudes .....................................69

A-i International Affective Picture System (IAPS) Normative Valence and Arousal
R atin g s ......................................................... .................................. 9 5









LIST OF FIGURES


Figure p e

1-1 Simplified direct loop in the PD patient's dysfunctional motor system........................31

1-2 Two hypothesized striato-thalamo-cortical loops involved in emotion.............................32

1-3 Preliminary findings of emotion-modulated startle eyeblink magnitude in PD patients
a n d c o n tro ls .......................................................... ................. 3

3-1 Pattern of emotion- modulated startle eyeblink magnitudes by valence and group ..........70

3-2 Startle eyeblink magnitudes by a priori picture category and group ..............................71

3-3 Skin conductance response by valence and group.................................. ..................... 72

3-4 Skin conductance response by a priori picture category and group...............................73

3-5 Startle eyeblink magnitudes by post hoc emotion category and group .............................74









Abstract of Dissertation Presented to the Graduate School
of the University of Florida in Partial Fulfillment of the
Requirements for the Degree of Doctor of Philosophy

EMOTIONAL REACTIVITY IN PARKINSON'S DISEASE: PSYCHOPHYSIOLOGICAL
AND PSYCHOSOCIAL CORRELATES

By

Kimberly M. Miller

August 2008

Chair: Dawn Bowers
Major: Psychology

Preliminary work in our laboratory suggests that patients with Parkinson's disease (PD)

may demonstrate diminished physiological reactivity to threatening pictures. This may be due to

the fact that the amygdala is known to exhibit pathology in PD, and is a neural structure that

plays a key role in processing threat signals in the environment. Our primary aim was to further

explore the possibility of reduced emotional reactivity to threatening stimuli in PD, as indexed

by emotional modulation of the startle eyeblink reflex. Our secondary aim was to examine the

psychosocial impact of any reactivity deficits by determining whether they are associated with

depression and with the misattribution of depression by patients' spouses.

Twenty-four non-demented PD patients in the "off' medication state and 24 age- and

education-matched controls viewed neutral, pleasant, disgusting (mutilations and

contaminations), and threatening (human and animal attack) pictures. During this time, white

noise bursts were binaurally presented to elicit startle eyeblinks. Participants also completed the

Beck Depression Inventory, 2nd edition (BDI-II) and spouses completed a surrogate-report

version of this measure.

Contrary to predictions, PD patients did not display reduced startle potentiation to

threatening pictures depicting attack. Instead, diminished reactivity to pictures of mutilations was









found. Neither self- nor surrogate-report ratings of depression were associated with eyeblink

magnitude. Additionally, spousal and PD patient depression ratings were significantly correlated,

indicating that spouses do not appear to misattribute PD symptoms to depression.

We hypothesized that PD patients may have a general deficit in physiological responsivity

to highly arousing negative stimuli, as opposed to an emotion-specific deficit. Mutilation pictures

are particularly arousing because they represent a threat to bodily integrity; as such, it may be

that mutilation pictures were the only category of pictures sufficiently arousing to detect a

between-groups difference in physiological reactivity. A secondary finding suggests that spouses

may serve as accurate surrogate reporters of mood when PD patients are unable to report upon

their own mood. In sum, results suggest that PD patients have aberrant physiological emotional

reactivity, but this does not appear to be related to spousal perceptions of mood.









CHAPTER 1
INTRODUCTION

Statement and Overview of the Problem

Parkinson's disease (PD) is a neurodegenerative disease that affects approximately half a

million to one million people in the United States (McDonald, Richard, & DeLong, 2003), with

50,000 new cases diagnosed each year (National Institute of Neurological Disorders and Stroke,

2001). PD involves progressive depletion of dopaminergic neurons within the substantial nigra

and is characterized by bradykinesia (slowed movements), rigidity, tremor, and postural

instability. While these motor symptoms are the defining feature of Parkinson's disease,

neuropsychiatric symptoms are prevalent and can be the most disturbing, disabling, and

misunderstood aspects of the disease. Disturbances of mood and motivation are common and

include depression, anxiety, and apathy.

In addition to neuropsychiatric symptoms, patients with Parkinson's disease have difficulty

communicating emotion using nonverbal signals such as facial expression and emotional tone of

voice (Blonder, Gur, & Gur, 1989; Borod et al., 1990; Buck & Duffy, 1980; Jacobs, Shuren,

Bowers, & Heilman, 1995; Smith, Smith, & Ellgring, 1996). One of the prototypical clinical

features of Parkinson's disease is "masked facies," a term that refers to the expressionless facial

demeanor of PD patients. Diminished facial expressivity occurs relatively early on in the disease

course and appears to be unrelated to depression (Katiskitis & Pilowsky, 1991; Smith et al.,

1996). Findings of reduced facial expressivity in PD raise the possibility of impairments in

emotional reactivity (how an individual responds physiologically, subjectively, or overtly). To

date few studies have investigated the topic of emotional reactivity in Parkinson disease from a

multicomponential framework.









Although Parkinson patients are not as facially or prosodically expressive as their healthy

counterparts, they typically report subjective feelings that are comparable in intensity during

tasks such as viewing emotional pictures (Bowers, Miller, Bosch, et al., 2006; Simons,

Pasqualini, Reddy, & Wood, 2004; Smith et al., 1996). However, self-report ratings are

potentially unreliable because they are subject to demand characteristics, meaning that the

participant may simply respond in the fashion that is expected of him or her.

Our study measured emotional reactivity in Parkinson patients with a method that does not

rely on facial expression, prosody (both of which are known to be affected in PD), or self-report.

Instead, emotional modulation of the startle eyeblink reflex was used as an index of emotional

reactivity. This paradigm rests on the well-documented principle that the size of the startle

eyeblink is directly modulated by an individual's emotional state. Additionally, because the

response that is being measured is near impossible to voluntarily control, it does not rely on the

participant's explicit attention, training, or cooperation (Bradley, 2000).

The overall aims of our study were twofold. The primary aim was to examine whether

emotional reactivity deficits in Parkinson's disease differentially affect specific emotions. A

recent study in our laboratory found that PD patients demonstrated significantly reduced

reactivity in response to viewing unpleasant pictures, but not pleasant or neutral pictures

(Bowers, Miller, Mikos, et al., 2006). In apost hoc analysis, this finding was parsed apart by

comparing PD patients' emotional reactivity to threat-inducing pictures (i.e., pictures suggesting

imminent attack, such as a snake preparing or bite or a gun pointed at the viewer) versus other

types of unpleasant pictures (i.e., mutilated bodies, a plane crash, a starving person; Miller,

2004). The threat-inducing pictures appeared to account for the diminished startle reactivity in

the PD patients. The current study aimed to replicate this finding while addressing several









methodological limitations of the initial study. Namely, the present study used a larger number of

pictures, an apriori design, and specifically compared threat -inducing pictures to another

discrete emotional category of unpleasant stimuli that are similarly high in arousal level: disgust-

inducing pictures. Additionally, PD patients were tested while off their dopaminergic medication

(unlike in the previous study) so that any potentially restorative effect dopaminergic medication

may have on emotional reactivity would not confound the interpretation of results.

The second aim of the present study was to examine the relationship between emotional

reactivity deficits in PD patients and family members' perceptions of depressive

symptomatology in the patient. This aim is fuelled by findings from previous research that

diminished use of nonverbal communication signals by Parkinson patients poses significant

psychosocial problems, particularly in terms of incorrect attributions of negative mood state or

depression by family members and health care providers (Pentland, Pitcaim, Gray, & Riddle,

1987, 1988; Pitcairn, Clemie, Gray, & Pentland, 1990a, 1990b).

The distinct contribution of this study is its focus on measuring emotional reactivity in

Parkinson's disease via a method that is not confounded by deficits in facial/vocal expression or

self-report reliability issues. Furthermore, increased understanding of emotional reactivity

deficits accompanying PD may prove to be clinically useful in reducing healthcare providers'

and family members' attributions that the patient is apathetic, depressed, or uninterested due to

lack of overt emotional reaction. Before describing the hypotheses in further detail, a brief

overview of Parkinson's disease will be presented, followed by a discussion of changes in

emotional functioning associated with the disease.

Motor and Cognitive Symptoms in Parkinson's Disease

Behaviorally, Parkinson's disease is characterized by motor symptoms including resting

tremor, bradykinesia (slowed movement), rigidity (increased muscle tone), and akinesia









(difficulty initiating or maintaining a body movement [Hughes, Ben-Shlomo, Daniel, & Lees,

1992; Hughes, Daniel, Kilford, & Lees, 1992]). Additionally, Parkinson's patients may

experience diminished facial expressivity ("masked facies"), loss of postural reflexes, and/or

motoric "freezing" when attempting to walk (Fahn, 2003). These motoric symptoms are thought

to be caused primarily by a depletion of dopaminergic neurons in the substantial nigra, which

then affects a cascade of structures involved in the production of voluntary movement,

particularly the basal ganglia. The neural circuitry involved in Parkinson's disease is shown in

Figure 1-1. It has been estimated that patients with PD have a 60-85% cell loss of dopaminergic

neurons in the substantial nigra (Pogarell & Oertel, 1999). As such, dopamine replacement

therapy (using levodopa, a dopamine precursor that is able to cross the blood-brain barrier) is the

major medical approach to treating the motor symptoms of Parkinson's (Fahn, 2003). Initially,

the motor symptoms of Parkinson's disease are dramatically improved by dopaminergic therapy.

Over time, however, medications become less effective and are associated with dramatic "on"

and "off" medication fluctuations in symptoms. This has led to recent surgical treatments for

Parkinson's disease, including the implantation of small stimulating micro-electrodes into

specific brain regions within the basal ganglia (i.e., internal segment of the globus pallidus,

subthalamic nucleus). The conceptual idea behind deep brain stimulation and other surgical

treatments for Parkinson's disease is to change the imbalance of activation and inhibition that

results from dopaminergic depletion (Benabid, 2003).

Although the motor symptoms of Parkinson's disease are the primary focus of

pharmacotherapy and surgical treatments, various nonmotor symptoms (e.g., cognitive problems,

dementia, psychosis, anxiety, insomnia, autonomic dysfunction, and mood disturbances) also

occur and can be particularly disturbing and disabling. Common cognitive sequalae include









slowed thinking (bradyphrenia), impaired "set-shifting," reduced working memory, and

forgetfulness (Cools, Barker, Sahakian, & Robbins, 2001; Dimitrov, Grafman, Soares, & Clark,

1999; Fahn, 2003; Gauntlett-Gilbert, Roberts, & Brown, 1999; van Spaendonck, Berger,

Horstink, Borm, & Cools, 1995). Moreover, about is it estimated that 30-50% of Parkinson's

patients eventually develop frank dementia (Jacobs, Stern, & Mayeux, 2000).

Myriad studies have investigated the pattern of motoric and cognitive deficits found in

Parkinson's disease. Fewer have delved into the domain of emotional changes that accompany

Parkinson's disease, the focus of the current study. In the following section, the literature

concerning emotional changes in PD is reviewed.

Emotional Processing in Parkinson's Disease

Emotional processing can be broadly conceptualized as encompassing four domains: mood

(subjective emotional experience), perception, expression, and physiology. Research to date

suggests that PD patients may exhibit difficulties in at least three of these domains, each of

which are considered in turn below.

Mood Disturbance

Depression is a significant problem in Parkinson's disease, with one- third to one- half of

all patients suffering from a depression syndrome (Cummings, 1992; Dooneief et al., 1992;

McDonald et al., 2003; Slaughter, Slaughter, Nichols, Holmes, & Martens, 2001). In addition to

decreasing quality of life, depression and other psychiatric disturbance in Parkinson patients

appear to exacerbate motoric symptoms (Cummings, 1992). Accumulating evidence over the

years suggests that depression in PD may be secondary to the underlying neuroanatomical

degeneration, rather than simply a reaction to psychosocial stress and disability, although the

latter may clearly play a role as well. The incidence of depression is correlated with changes in

central serotonergic function and neurodegeneration of specific dopaminergic-, serotonergic-,









and noradrenergic- mediated cortical and subcortical pathways (Bur, 2002; German et al., 1992;

Mayberg et al., 1990; Remy, Doder, Lees, Turjanski, & Brooks, 2005).

Other common psychiatric disturbances in Parkinson's disease are anxiety and apathy

(Fahn, 2003). Apathy refers to diminished emotional reactivity to both positive and negative

events, lack of motivation to engage in goal-directed behavior or cognition, and a subjective

sense of indifference (Marin, 1991). Approximately 40 to 50% of Parkinson's patients have been

described as meeting criteria for apathy, based on assessment through various apathy rating

scales (Isella et al., 2002; Kirsch-Darrow, Fernandez, Marsiske, Okun, & Bowers, 2006;

Starkstein et al., 1992), with higher levels of apathy in Parkinson's patients relative to equally

disabled patients with severe osteoarthritis (Pluck & Brown, 2002). Those patients with high

levels of apathy are not more likely to be depressed or anxious than those with the lowest levels

of apathy (Kirsch-Darrow et al., 2006; Pluck & Brown, 2002). Like depression, it has been

argued that apathy is more likely a direct consequence of disease-related physiological changes

than a psychological reaction or adaptation to disability (Brown & Pluck, 2000; Pluck & Brown,

2002).

Emotional Expression

In addition to mood disturbances, patients with Parkinson's disease also have impaired

ability to communicate emotion using various nonverbal signals such as facial expression (the

"masked facies" of Parkinson's disease) and prosody (Blonder et al., 1989; Borod et al., 1990;

Buck & Duffy, 1980; Jacobs et al.; Smith et al., 1996). Diminished facial expressivity occurs

relatively early in the disease course and has been found to be unrelated to depression (Katiskitis

& Pilowsky, 1991; Smith et al., 1996). Recent studies from our laboratory using sophisticated

computer imaging techniques have found that the facial movements in Parkinson's disease are

actually smaller in amplitude, slower to initiate, occur less frequently, and correlate with other









motor symptoms of Parkinson's disease such as bradykinesia (Bowers, Miller, Bosch, et al.,

2006). Diminished use of nonverbal communication signals by Parkinson patients can create a

host of psychosocial problems, ranging from misdiagnosis of depression to the misattribution of

negative emotion states by family members and health care providers. These problems will be

discussed in greater detail in subsequent sections.

Perception of Emotion

Research literature regarding the perception of emotional information (faces, scenes,

prosody) in PD is inconsistent at best. Some investigators have found that individuals with

Parkinson's disease are impaired when asked to identify emotional faces, emotional prosody, or

emotional scenes (Blonder et al., 1989; Jacobs et al., 1995; Scott, Caird & Williams, 1984;

Sprengelmeyer et al., 2003). Others, however, have not documented differences between

Parkinson's disease patients and healthy controls (Adolphs, Schul, & Tranel, 1998; Madeley,

Ellis, & Mindham, 1995). Some possibilities that may account for these discrepancies are

methodological inconsistencies regarding the severity of Parkinson's disease, whether patients

are tested on versus off medications, and the extent of co-existing cognitive impairment or mood

disturbance.

Recently, a particular interest has emerged with respect to the possibility that Parkinson's

patients may have specific difficulties with processing of negatively-valenced emotions such as

fear and/or disgust relative to other emotions. Some researchers have found that PD patients

appear to be more impaired at recognizing aversive facial expressions (i.e., anger, disgust, fear)

than other expressions. For example, Kan, Kawamura, Hasegawa, Mochizuki, & Nakamura

(2002) found that PD patients were selectively impaired at recognizing fear and disgust facial

expressions. However, not all researchers have found impairments in recognition of emotional

facial expressions (Adolphs, et al., 1998; Madeley et al., 1995).









Physiological Reactivity

A fourth domain within the multicomponential framework of emotion processing is

physiological reactivity, which can be studied in the laboratory via measuring subjects'

physiological reactivity to emotional materials. There are several methods commonly used in the

measurement of psychophysiologic reactivity. One method is skin conductance response (SCR)

to emotional stimuli. This is accomplished by applying electrodes that essentially measure

"palm sweat" on the inside of the hands. In general, the larger the SCR, the greater the

physiological arousal the subject has experienced in response to the emotional stimulus.

Although measurement of SCR can be useful, it has limitations. First, individuals vary

considerably in how their SCR to emotional stimuli habituates over time. Some individuals

habituate after a few trials, whereas others do not appear to habituate much at all. Secondly, 15-

20% of healthy people are "nonresponders;" that is, they to do not exhibit a discernable

difference in SCR to varying types of emotional stimuli (Bradley, 2000; O'Gorman, 1990).

Finally, excess motor activity (such as tremor in the hands) can dramatically interfere with skin

conductance recordings (Bradley, 2000). For these reasons, SCR data do not always produce

consistent results, may not detect subtle between-groups differences in physiological responding,

and may not be the most appropriate physiologic measure for patients with a movement disorder.

Another widely used index of emotional reactivity is emotional modulation of the startle

eyeblink response (Lang, Bradley, & Cuthbert, 1990; Vrana, Spence, & Lang, 1988). This index

takes advantage of the reflexive eyeblink that naturally occurs in response to an abrupt, jarring

stimulus. In essence, a priming effect occurs whereby negatively-valenced stimuli augment the

size of the eyeblink and positively-valenced stimuli decrease the size of the eyeblink. It is this

measure that served as the index of emotional reactivity in the present study and is described in









detail in a later section. However, first the potential mechanisms for the emotional processing

deficits just reviewed will be discussed.

Mechanisms of Emotional Changes

There are at least two mechanisms that may affect emotional processing in Parkinson's

disease. First, research suggests that PD patients experience changes (decreased

neurotransmitter production or reduced binding) to several neurotransmitters involved in

emotion. It has been proposed that the emotional changes observed in PD patients may be a

consequence of the loss of nigro-striatal dopamine and/or the loss of mesolimbic and

mesocortical dopamine, which in turn may affect serotonin and norepinephrine-producing

regions of the brain (the dorsal raphe nuclei and the locus coeruleus, respectively). Secondly,

evidence of pathological changes to the structural integrity of key limbic structures has been

found in the brains of individuals with Parkinson's disease. Both of these mechanisms are

discussed in turn below.

Changes to Neurotransmitters Implicated in Emotion

It is thought that some of the emotional changes found in PD may be in part linked to

limbic circuitry subserved by the neurotransmitter dopamine. There are three main systems

through which dopamine depletion may affect emotional processing in PD by disrupting

modulation of these systems: the striato-thalamo-cortico loops, the mesolimbic circuit, and the

mesocortical circuit. Beginning with the first of these, Alexander, DeLong, & Strick (1986)

proposed a network of five parallel striato-thalamo-cortical circuits that allow frontal cortical

activity to be modulated by ascending input from the basal ganglia/thalamus through direct and

indirect pathways. Two of these circuits involve key limbic areas such as the orbitofrontal cortex

(OFC), the anterior cingulate cortex (ACC), and the nucleus accumbens. General schematas of

these two circuits are shown in Figure 1-2.









Outside of these striato-thalamo-cortical circuits, the dopamine-mediated mesolimbic

pathway is implicated in emotional processing as well. The ventral tegmental area has

dopaminergic connections to the ventral striatum (which consists of the nucleus accumbens and

olfactory tubercle) of the basal ganglia. Changes in dopaminergic input to the ventral striatum

can then affect the associated striato-thalamo-cortical circuits, and thus depletion of dopamine

may affect the ability of limbic structures to influence frontal cortical activity. Finally, the

mesocortical circuit connects the ventral tegmental area to the cortex, and provides yet another

way in which dopamine depletion may affect emotional functioning. Cortical dopamine release

modulates the descending cortico-striatal fibers, potentially influencing the activity of the striato-

thalamo-cortico circuits (Brown & Pluck, 2000).

With respect to mood changes in PD, Mayberg et al. (1990) found reduced metabolic

activity in the inferior-orbitofrontal cortex and caudate of depressed PD patients, with severity of

depression having an inverse relationship with orbitofrontal metabolism. This suggests that

depression in PD is associated with dysfunction of these areas. Mayberg and colleagues have

proposed the following explanation of how serotonin is affected by loss of dopamine:

dopaminergic efferents from the ventral tegmental area project to the OFC (mesocortical) which

then project to limbic structures such as the dorsal raphe nuclei, where serotonin is produced. In

this way, disruption to the meso-cortico-limbic dopamine circuitry may affect the serotonergic

cell bodies in the dorsal raphe.

Dysfunction of dopaminergic pathways may potentially disrupt noradrenergic cells in a

similar way. In a recent PET study, Remy et al. (2005) used a tracer that binds with strong

affinity to epinephrine and dopamine transporters, but with much weaker affinity to serotonin

transporters. They found that non-depressed PD patients had significantly higher binding of this









tracer in the locus coeruleus, mediodorsal thalamus, ventral striatum, ACC, and right amygdala.

These authors pointed out the locus coeruleus sends noradreneric projections to the ventral

striatum. Thus, a loss of dopamine to the ACC/MOFC "limbic loop" may indirectly affect

norephinephrine cells in the same way that serotonin is proposed to be affected.

In sum, depletion of dopamine in PD (in both the Alexander loops and the mesolimbic and

mesocortical loops) may in turn affect norepinephrine and serotonin through connected circuitry.

Changes in the dopaminergic, noradrenergic, and serotonergic systems may then lead to changes

in mood and emotional processing.

Limbic System Neuropathology

Recently, several investigators have found evidence of neuropathological changes to

limbic structures in Parkinson patients. In a post-mortem study, Harding and colleagues

(Harding, Stimson, Henderson, & Halliday, 2002) found a 20% reduction in amygdalar volume

of PD patients compared to normal controls, in addition to the presence of Lewy bodies in many

subjects' amygdali. Ouchi and colleagues (1999) found a 30-45% reduction of dopamine agonist

binding in the amygdali of PD patients, as well as a 48% reduction in dopamine agonist binding

in the orbitofrontal cortex, another key limbic region. They speculated this might be due to a loss

of pre-synaptic dopamine terminals in these regions. A histological study of brains of deceased

PD patients (Braak & Braak, 2000) found cytoskeletal damage to neurons in the amygdala,

anterior cingulate cortex, raphe nucleus and locus coeruleus.

Evidence of pathology of the amygdala is particularly relevant to the current study. The

amygdala is a small, almond-shaped structure located in the anterior temporal lobe. It has

consistently been implicated in the recognition of fearful stimuli and the response to fearful or

threatening situations. Monkeys with lesions of the amygdala do not display normal fear

reactions to threatening stimuli, such as snakes (Amaral, 2003; Kluiver & Bucy, 1939). In









humans, lesions of the amygdala have been associated with behavioral placidity, diminished

physiologic reactivity, and impairments in recognizing fearful faces (Calder et al., 1996; Young

et al., 1995). Electrical stimulation of the amygdala elicits many of the behaviors used to define

the state of "fear," such as tachycardia, increased galvanic skin response, corticosteroid release,

and increased startle (Davis, 1992).

The fact that the amygdala has been shown to exhibit neuropathology in PD brings up the

issue as to whether Parkinson's patients might have a diminished emotional reactivity to

threatening stimuli, or difficulty interpreting expressions of fear in others. Although researchers

have investigated the ability of PD patients to recognize fearful faces, no published study to date

has examined physiologic reactions to fear-evoking stimuli. However, preliminary work

suggests that PD patients may show diminished emotional reactivity specific to threat-inducing

materials (Miller, 2004). With regards to the facial recognition literature, Kan et al. (2002) found

that PD patients were selectively impaired at recognizing fear and disgust facial expressions;

however, neither Adolphs et al. (1998), Madeley et al. (1995), nor Pell and Leonard (2005) found

consistent impairments in PD patients' ability to recognize emotional facial expressions.

Importantly, these studies involved recognition of faces as opposed to viewing emotion-eliciting

pictures, as will be the case in the current study. In an fMRI experiment using threat-inducing

pictures from the International Affective Picture System (which will be used in the current

study), Hariri, Mattay, Tessitore, Fera, & Weinberger (2003) found a significant bilateral

amygdala BOLD response when healthy subjects were asked to simply match a threatening

picture to a picture identical to it. This suggests that amygdala is involved in processing of

threat-inducing pictures, although it is unknown whether pathology to its structure would result

in deficits in emotional processing and emotional reactivity specifically. Tessitore et al. (2002)









reported that viewing of facial expressions of fear was associated with robust bilateral amygdala

response in healthy subjects, but absent in PD patients who had been withdrawn from levodopa.

Administration of levodopa partially restored amygdala BOLD response, but not to the degree

present in healthy subjects. This raises the possibility that the loss of dopamine characterizing

PD may affect processing of emotional materials by neural circuitry that includes the amygdala,

and bolsters the argument for the withdrawal of all dopaminergic medications from PD

participants in the current study. Recently, Yoshimura, Kawamura, Masaoka, & Homma (2005)

reported an absence of event-related potentials from the amygdali of PD patients while viewing

fearful faces. Thus, the literature clearly suggests abnormal amygdala responsivity in PD patients

during the processing of fear- or threat- inducing stimuli.

Emotional Modulation of the Startle Eyeblink Response

The current study employs emotional modulation of the startle eyeblink response as a

means through which to measure emotional reactivity. In order to understand the mechanism of

the phenomenon of emotional modulation of the startle eyeblink response, it is first necessary to

describe the basic startle reflex and how it is neurally mediated. In mammals, an automatic

startle response occurs at the abrupt onset of a stimulus, such as a jarring noise or flash of light.

This response is protective for the organism and is characterized by limb and trunk movements

of the body, as well as a reflexive eyeblink (Bradley & Vrana, 1993). In humans, the eyeblink

has been used to measure the startle reflex response because it is the most reliable, easily

recorded, and quickest component of the startle response.

A variety of studies over the past decade have documented that the size of the startle

eyeblink is directly modulated by an individual's emotional state. In humans, startle response

magnitude (as indexed by reflexive eyeblink) is augmented when an individual is involved in an

emotionally aversive task. Conversely, startle responses are attenuated during more pleasant









tasks. This valence modulation of startle is observed across a variety of tasks involving picture

viewing, imagining emotional situations, and anticipation of shock (Bradley, 2000; Bradley,

Codispoti, Cuthbert, & Lang, 2001; Lang et al., 1990). The enhancement of startle has been

viewed as a "priming" effect, whereby the protective withdrawal reflex is primed during

unpleasant emotional states and inhibited during pleasant emotional states.

The neural circuitry of startle and its modulation has been exquisitely detailed in studies by

Davis and colleagues using a rodent model (Davis, 1992; Davis, Gendelman, Tischler, &

Gendelman, 1982). In brief, the basic startle circuitry is mediated entirely at the level of

brainstem. However, startle responses can be directly modulated (i.e., potentiated or inhibited)

by input from the central nucleus of the amygdala via its projection to the brainstem. Electrical

stimulation of the amygdala in rats facilitates startle (Rosen & Davis, 1988), while lesions of the

amygdala diminish fear-potentiated and shock-sensitized startle responses but leave basic startle

intact (Hitchcock & Davis, 1991; Hitchcock, Sananes, & Davis, 1989). Thus, dysfunction of the

amygdala does not eliminate the basic startle responseper se. Rather, it eliminates potentiation

of startle reactivity during aversive emotional states. In humans, for example, temporal lobe

ablations involving the amygdala are associated with reduced startle modulation during viewing

of aversive pictures or while listening to negative sentences (Bowers et al., 2001).

The use of the startle response as an index of emotional reactivity in a Parkinson's sample

has several advantages. First, because it does not require a voluntary motor response (as

measurements of facial expressivity or vocal prosody do), it eliminates the confounding problem

that the movements being used as an index of expressivity may be affected by the motor

symptoms of PD. Secondly, measurement of physiological reaction does not depend on self-

report (as many paper-and-pencil measures of mood and emotion do), and thus the demand









characteristics associated with it are minimal since the eyeblink response is difficult to

voluntarily control (Bradley, 2000).

Basic Startle in Parkinson's Disease

Relevant to the present study is the question of whether PD patients might have a basic

defect in startle eyeblink reactivity per se. Conceivably, Parkinson's patients could have motor

abnormalities that reduce or minimize the size of the eyeblink response. This, in turn, would

result in reduced startle eyeblink magnitudes in response to negative emotional pictures, giving

rise to the impression of diminished emotional reactivity to unpleasant stimuli. However, two

studies have reported that while the latency of startle is slightly delayed in PD, the magnitude or

size of the basic startle eyeblink response to acoustic stimuli does not differ significantly

between PD patients and controls (Kofler et al., 2001; Vidailhet, Rothwell, Thompson, Lees, &

Marsden, 1992). Similarly, we recently found no significant difference in startle magnitude

between PD patients and age-matched controls tested in our laboratory (Bowers, Miller, Mikos,

et al., 2006). Taken together, these findings suggest that Parkinson patients do NOT have a basic

defect in basic startle reactivity, as indexed by size of the eyeblink response.

Psychosocial Effects of Emotional Changes in Parkinson's Disease

As described, Parkinson's disease is characterized by overt affective changes including

a reduction in facial and vocal expressivity. These changes have the potential to effect the

perception and treatment of PD patients by those closest to them, and are the focus of the second

aim of the current study. In an investigation directed at testing the observation that PD patients

tend to be interpreted as "cold" or "unfeeling," Pentland et al. (1987, 1988) found that when

silent video footage of PD patients was shown to health professionals, the patients were rated as

being significantly more hostile, anxious, suspicious, unhappy, and bored than controls with

heart disease. In a follow-up study, tape recordings of interviews with PD patients and heart









disease controls were presented to naive listeners and produced similar findings (Pitcairn et al.,

1990b). In both these studies there was no measurable difference between the two subject

groups with regard to affect or personality measures, and none of the patients were suffering

from depression. These authors suggested that the non-verbal behavior of PD patients,

characterized by upper body rigidity and a lack of hand movement, contributes greatly to the

misattribution of depression. To date, no study has examined the effect of emotional changes on

family members' perceptions of the PD patient. Thus, the second specific aim of the current

study is to obtain spousal ratings of perception of depression symptoms in their relative with PD

and compare these to the PD patients' self-report ratings of depression. This will allow for

investigation of whether emotional reactivity deficits are associated with greater misperception

of depression in PD patients by family members.

Preliminary Findings

Bowers, Miller, Mikos, et al. (2006) recently completed a study of emotional modulation

of startle in 23 PD patients while on dopaminergic medication and 17 age-matched controls. All

participants were presented with 44 pictures from the International Affective Picture System

(Lang, Bradley, & Cuthbert, 2001 a), with one-third of the pictures being unpleasant in valence,

one-third being pleasant, and one-third neutral. Data analysis revealed a significant Emotion

Category x Group interaction (F(1,33)= 4.60, p<.05), with PD patients exhibiting significantly

smaller eyeblink magnitudes than controls while viewing unpleasant pictures. In contrast,

eyeblink magnitudes during viewing of pleasant pictures were comparable to that of controls.

These data suggest that PD patients may have a selective deficit in emotional reactivity to

unpleasant stimuli.

To determine whether certain types of unpleasant pictures were more contributory to

diminished startle reactivity than others, apost hoc exploratory analysis was conducting by









categorizing the unpleasant pictures into "threatening" versus "other" types of unpleasant

pictures (Miller, 2004). This post hoc division was partially determined by the fact that the

stimulus set contained several pictures designed to induce feelings of fear or threat (i.e., a gun

pointed at the subject, a dog with fangs open ready to bite), but fewer pictures representative of

other negative emotions (i.e., disgust, sadness, etc.). Again, the Emotion Category x Group

interaction was significant (F(1, 28)= 5.31, p<.05), with Parkinson's patients displaying smaller

eyeblinks than controls in response to the threat-inducing slides (Figure 1-3). However, this

exploratory analysis had several limitations, including the fact that the analyses werepost hoc in

nature and the total number of "threat" pictures was small. Thus, the current study was designed

to better control for these limitations. This was done by using a larger number of unpleasant

pictures, an apriori design, and by specifically comparing threat-inducing pictures to another

discrete emotional category of unpleasant stimuli that are similarly high in arousal level: disgust-

inducing pictures. This allowed for an examination of whether the deficits previously observed

in PD patients were due to aversive stimuli in general, stimuli that are extremely arousing or

upsetting, or stimuli that are threatening in nature. Additionally, PD patients underwent an

overnight (12-hour) anti-parkinsonian medication wash-out so that presence of symptom-

alleviating medication would not confound the interpretation of emotional reactivity results.

Specific Aims

Although much research has pointed to emotional expressivity deficits in Parkinson's

disease, few studies have examined possible emotional reactivity deficits in PD. Preliminary

work suggests that Parkinson patients may demonstrate a significantly diminished reactivity to

threatening or fear-inducing emotional materials, compared to their healthy counterparts. This

may be due to the fact that the amygdala has been known to exhibit pathology in PD, and is a









neural structure that plays a key role in processing and interpreting threat signals in the

environment. As such, the present study has the following specific aims:

Specific Aim 1

The first aim tested the hypothesis that Parkinson patients would demonstrate reduced

emotional reactivity, as indexed by emotional modulation of startle, to threatening pictures. This

aim was based on the view that the amygdala appears to play a specific role in the processing of

threat-inducing stimuli coupled with prior findings of amygdala atrophy in Parkinson's disease.

Therefore, startle eyeblink magnitudes while viewing threat-inducing pictures were directly

compared against eyeblink magnitudes while viewing another category of similarly arousing and

unpleasant stimuli (i.e., disgust pictures). It was predicted that PD patients would demonstrate

reduced startle potentiation in response to threat-inducing stimuli compared to healthy age-

matched controls, whereas they would not differ from controls in eyeblink magnitudes to disgust

pictures. This aim examined the possibility of an emotion-specific reactivity deficit in PD.

Specific Aim 2

The second aim was to explore the relationship between emotional reactivity deficits in

Parkinson's disease and spousal- and self-report measures of mood. This aim consisted of two

key aspects. The first involved determining whether emotional reactivity deficits are correlated

with depressive symptomatology. Based on prior work, it was predicted that depression and

startle eyeblink magnitudes would not be significantly associated (Bowers, Miller, Mikos, et al.,

2006). This prediction was further supported by Allen, Trinder, & Brennan's (1999) study,

which found that severe depression affected emotional modulation of startle eyeblink, whereas

mild to moderate depression did not. The second aspect involved examination of spousal ratings

of perception of depression for both PD patients and controls. A greater discrepancy between self

and spousal ratings of depression for PD patients than for controls was predicted. Specifically, it









was predicted that spouses of PD patients would perceive their significant other as being more

depressed than they truly are. Ostensibly, this would be due to their misattributing symptoms of

PD (e.g., masked facies) to depression. Finally, the relationship between discrepancy in self-

versus spousal- depression ratings and emotion-modulated startle eyeblink magnitude was

examined to determine whether misattribution of mood state by others is associated with reduced

physiological emotional reactivity.













Striatum

.4.-
S Thalamus
SN(VA, VL)




MGP

SNr


Figure 1-1. Simplified direct loop in the PD patient's dysfunctional motor system. The striatum
receives excitatory projections from the cortex, but input from the SNc is impaired
due to a reduction of dopamine. This results in the striatum not receiving enough
excitatory input to exert its inhibitory influence over the MGP and SNr. The MGP
and SNr, free of inhibition from the striatum, provide inhibitory influence over the
thalamus, thus preventing the thalamus from providing excitatory output to the
cortex. The inhibition of the thalamus and lack of cortical activation results in poverty
of movement. (SNc = substantial nigra pars compact, MGP = medial globus pallidus,
SNr = substantial nigra pars reticularis, VA= ventral anterior nucleus, VL= ventral
lateral nucleus).





























Figure 1-2. Two hypothesized striato-thalamo-cortical loops involved in emotion. A) ACC
loop. B) OFC loop. (G.P.= globus pallidus, SNr = substantial nigra pars reticularis,
mdm = medial dorsomedial nucleus, DM= dorsomedial nucleus, VA= ventral anterior
nucleus).



















OControls
50
S50 Parkinson
48

446

$ 44

42
Threat Other unpleasant pictures

Emotion Category

Figure 1-3. Preliminary findings of emotion-modulated startle eyeblink magnitude in PD
patients and controls. PD patients showed significantly smaller eyeblink magnitudes
in response to "threat" pictures. Error bars indicate standard errors of means.









CHAPTER 2
MATERIALS AND METHODS

Overview

All participants came to the laboratory on two separate occasions, spaced no more than

two weeks apart. The first session was a screening session, during which cognitive and mood

measures were administered and a medical and psychiatric history was taken. The second session

consisted of the psychophysiology experiment and emotion ratings. Additionally, participants

with significant others were given the Surrogate BDI-II to take home for their partner to

complete.

Participants

All study participants were between 50 and 85 years old. Parkinson patients were recruited

from the Movement Disorders Center at the University of Florida as well as from ongoing

studies within the Cognitive Neuroscience laboratory. Controls were recruited via flyers posted

in the community and in newspapers, as well as from a list of participants from prior experiments

who had indicated an interest in being contacted for future studies. Informed consent to

participate in this research was obtained following University of Florida IRB guidelines.

Exclusion criteria for the control group included

* History of head injury, neurological disease, learning disability, substance abuse, or major
psychiatric disorder

* Current use of psychotropic medications

* Current medical illness that could potentially affect cognition (e.g., cancer or HIV)

* Less than nine years of formal education

* Possible dementia or disturbance in cognition. This was determined by a score greater than
1.5 standard deviations below age- and education-appropriate norms (i.e., below 7th
percentile) on either the Dementia Rating Scale, 2nd Edition (DRS-II) total score or on the
delayed recall portions of California Verbal Learning Test, 2nd Edition (CVLT-II) and









Logical Memory II total recall score from the Wechsler Memory Scales, 3rd Edition
(WMS-III)

* Significant depression symptomatology. This was determined by a score > 19 (the cut
score for moderate depression recommended by Beck, Steer, and Brown, 1996) on the
Beck Depression Inventory, 2nd Edition. Previous research has found that individuals with
severe levels of depression symptoms have a different pattern of startle modulation relative
to healthy controls (Allen et al., 1999; Kaviani et al., 2004). As such, high levels of
depression symptoms may affect startle modulation.

All Parkinson patients included in the study were diagnosed by a fellowship-trained

movement disorders neurologist. Parkinson patients were subject to the same exclusion criteria

as controls. The only exception was that PD patients were not excluded if they were currently

taking antidepressants or anti-anxiety medications. Additional exclusion criteria specific to the

PD group included

* Evidence of secondary or atypical parkinsonism (as suggested by history of stroke,
exposure to toxins or neuroleptics, history of encephalitis, neurological signs or upper
motor neuron disease, cerebellar involvement, or lack of response to levodopa therapy)

* Presence of a co-morbid movement disorder

* Unstable medication regime resulting in severe dyskinesias or freezing

* Hoehn and Yahr stage greater than three (due to safety concerns in the off-medication
condition

* Prior neurosurgical treatments including deep brain stimulation or lesion surgery.

The initial sample of participants consisted of 28 Parkinson patients and 27 healthy

controls. Three PD patients were excluded after the screening session due to BDI-II scores over

19, indicating moderate-to-severe depression. One was excluded for double vision due to its

potential influence on perception of affective pictures. One control was excluded due to

diagnosis of ADHD and learning disorder revealed during the screening session, and one due to

substance abuse and apparent intoxication during the screening session. Another control decided









against participating in the experimental session due to sensitivity to seeing blood. Thus, a total

of 24 PD patients and 24 controls completed all study procedures.

Session 1 (Screening): Materials and Procedures

During the screening session, all participants were administered the Dementia Rating

Scale, 2nd Edition (DRS-II; Mattis, 2001), the California Verbal Learning Test, 2nd Edition

(CVLT-II; Delis, Kramer, Kaplan, & Ober, 2000), the Wechsler Memory Scales, 3rd Edition

(WMS-III) Logical Memory I and II subtests (Wechsler, 1997), the Boston Naming Test (BNT;

Kaplan, Goodglass, and Weintraub, 2001), and the Beck Depression Inventory, 2nd Edition (BDI-

II; Beck, 1996). The PD patients were tested while on their normal dopaminergic medications so

that test performance would estimate their typical level of cognitive and motoric functioning.

Measures administered are described briefly below. At the completion of Session 1, participants

with a spouse were asked to bring home a copy of the Surrogate BDI-II for their spouse to

complete and bring or mail back to the laboratory.

The Dementia Rating Scale, 2nd Edition is a screening measure for dementia that yields a

total score, as well as subscale scores in the domains of attention, initiation/ perseveration,

construction, conceptualization, and memory. The authors report a test-retest reliability of .97

and a split-half reliability of .90 (Jurica, Leitten, & Mattis, 2001). The DRS-II has been

validated for use on various neurological populations, including patients with Parkinson's

disease. For screening purposes, total raw scores were converted to age- and education-corrected

MOANS (Mayo Older American Normative Studies; Lucas et al., 1998) scaled scores, then

percentiles, to determine study eligibility.

The California Verbal Learning Test, 2nd Edition is a verbal memory task that involves

repeated presentations of a list of sixteen words. The words can be grouped into semantic

categories, allowing for assessment of voluntary and cued use of strategy in learning. The test









includes both immediate and delayed recall of list material. Test-retest and split-half reliabilities

for subscores of the various CVLT-II indices are generally above .80 (Delis et al., 2000).

The Wechsler Memory Scales, 3rd Edition (WMS-III) Logical Memory I and II subtests

assess ability to recall information presented in narrative format. Two stories are read by an

examiner, and immediate and delayed recall for story details are tested. The second story is

presented twice, allowing for analysis of learning slope. Test-retest and split-half reliabilities for

Logical Memory I total recall and Logical Memory II total recall subscores are above .80

(Wechsler, 1997).

The Boston Naming Test, 2nd Edition (BNT) is a confrontation naming task consisting of

60 ink drawings varying in degree of familiarity (Kaplan et al., 2001). The test has been shown

to effectively elicit naming impairments in aphasic patients, and has been found to be

significantly correlated with tests of verbal knowledge and reading ability (Lezak, Howieson,

and Loring, 2004).

The Beck Depression Inventory, 2nd Edition (BDI-II) is a self-report questionnaire

presented in multiple choice format designed to measure presence and degree of symptoms of

depression. It consists of twenty-one items, each scored from 0 to 3. This widely used measure of

depression symptomatology has internal consistency and test-retest reliability both above .9

(Beck, Steer, and Brown, 1996). The BDI-II manual recommends the following cut score

guidelines: 0-13 minimal depression, 14-19 mild depression, 20-28 moderate depression, and 29

and above severe depression (Beck et al., 1996).

The Surrogate BDI- II is a measure created explicitly for use in the current study. It is

identical to the BDI-II, with the exception that the word "I" was replaced by "my family

member." Both control and PD participants with spouses were asked to bring home this









questionnaire to give to their spouse. The questionnaire was accompanied by a letter that

included instructions and a description of the purpose of the questionnaire. This letter, as well as

the Surrogate BDI-II, was approved by the University of Florida IRB. The Surrogate BDI-II

included the following instructions for spouses: "This questionnaire consists of 21 groups of

statements. Please read each group of statements carefully and choose the one statement from

each group that best describes your evaluation of how your family member has been thinking,

feeling, or acting over the past TWO WEEKS, including today. For some statements, you may

not know how s/he has been feeling or thinking; this is okay, just make your best guess. If

several statements in the group seem to apply equally well, circle the highest number for the

group." The spouse was asked to complete the questionnaire on the same day that their partner

participated in the experiment so that self- and surrogate BDI-II scores would refer to the same

time period.

Although the concept of a Surrogate BDI-II has not been previously used with a PD

population, Logsdon and Teri (1995) have used a surrogate version of the BDI (first edition) in

which caregivers reported depressive symptoms in patients with Alzheimer's disease. They

reported that coefficient alpha levels were comparable to levels reported for the traditional self-

report format and concluded that the BDI was appropriate for surrogate reporting of depression

symptoms.

Session 2 (Psychophysiology): Materials and Procedures

Medication Wash-Out for Parkinson Patients

Parkinson participants were asked to withhold all anti-Parkinson medications for at least

twelve hours prior to participating in Session 2. This is because it is unknown how anti-

Parkinson medications may affect emotional reactivity at the physiological level. Because one

aim of the study was to characterize any emotional reactivity deficits found in Parkinson's









disease, it was essential that any medication that might alleviate or mask potential deficits be

withheld during study participation. The half-life of the most potent PD medication, levodopa, is

about 60-90 minutes, whereas the most commonly used dopamine agonists, pramipexole and

ropinirole, have a half-life between 3-8 hours. Thus, participants with PD were asked to

withhold all dopa medications overnight for a period of at least 12 hours. Based on these half-

lives, it is reasonable to expect that a 12-hour time span would normally place the PD participant

in the "off' medication state.

Picture Stimuli

The picture stimuli used in the psychophysiology portion of the study consisted of

48 primary pictures (24 unpleasant (further subdivided into 12 disgust and 12 threat), 12 neutral,

and 12 pleasant). Unpleasant pictures were limited to pictures intended to elicit feelings of

disgust and threat/fear because other negative emotions, such as anger and sadness, have been

shown to be difficult to elicit reliably (Smith et al., 1996) and because disgust and fear are

emotions associated with similarly high physiological arousal. Pictures were drawn from the

International Affective Picture System (IAPS; Lang et al., 2001a) and were chosen based on the

normative study data published for the IAPS (Lang, Bradley, & Cuthbert, 2001b) and a study in

which 135 subjects were asked to rate IAPS pictures in terms of the discrete emotions the

pictures elicited (Bradley, Codispotti, Sabatinelli, & Lang, 2001). The latter study found that

both men and women rated pictures of contamination (e.g., dirty toilets, vomit, feces),

accidents/injuries, and mutilated bodies as primarily very high in disgust, whereas pictures of

animal attacks and humans attacking one another were rated as primarily very high in fear

(Bradley, Codispotti, Sabatinelli, et al., 2001). Thus, these types of pictures were selected when

creating the disgust and threat picture sets for the current study.









The disgust pictures were further subdivided into 6 mutilation pictures and 6

contamination pictures. This subdivision was based on neuroimaging (fMRI) findings in normal

adults indicating that distinct neural responses occurred to mutilation pictures versus

contamination pictures (Wright, He, Shapira, Goodman, and Liu, 2004). In brief, both types of

pictures (mutilation, contamination) resulted in insula activation; however, the mutilation

pictures also caused greater activation of the occipital temporal cortex and unique activation of

the right superior parietal cortex relative to the contamination pictures. Subdividing the disgust

pictures into mutilation and contamination pictures allowed for the examination of potential

differences in emotion ratings and startle eyeblink reactivity for these two types of stimuli.

The pleasant and unpleasant (i.e., threat and disgust) pictures were equivalent with regards

to average arousal ratings reported by participants in Lang et al.'s (2001b) IAPS normative

study. With regards to valence ratings, normative ratings placed the pleasant pictures as

equidistant from the "most pleasant" anchor point as the threat and disgust pictures were from

the "most unpleasant" anchor point on the 1-9 rating scale. The neutral pictures had an average

valence rating that fell in the middle of the rating scale and an average arousal rating that was

lower than the pleasant, threat, and disgust pictures. A complete listing of all picture stimuli and

their associated normative valence and arousal ratings can be found in Appendix A.

Pictures were presented in a fixed, pseudo-random order, with the constraint that no more

than two trials of the same picture type could occur in a row. Two different picture orders were

created by repositioning the pictures so that pictures occurring in the first half of Order 1 were

presented in the second half of Order 2. Administration of the two orders was counterbalanced to

minimize potential effects of order of presentation.









Psychophysiology Procedure

Upon arrival at the laboratory, surface Ag-AgCl electrodes filled with an isotonic

electrolyte were positioned under the participants' left and right eyes to record

electromyographic (EMG) activity from the orbicularis oculi muscle. Electrode placement

followed recommendations by Fridlund & Cacioppo (1986). Participants were then asked to sit

in a comfortable chair, located in a sound-attenuated and electrically shielded 12'x12' room.

Participants were told that throughout of the experiment they could communicate with the

experimenter via an intercom. Startle eyeblink responses were elicited by a single 50 ms burst of

white noise (95 db, instantaneous rise time) produced by a Colbourn S81-02 module and

delivered binaurally through Telephonics (TD-591c) stereo headphones. The session began with

twelve probes delivered in the absence of any other stimulus (blank startles). These initial probes

were designed to ensure appropriate elicitation of the startle responses, correct any potential

problems with electrodes' functioning or placement, and assess group differences in blank startle

characteristics.

Picture stimuli for the emotion-modulated startle task were displayed on a 21-inch

computer monitor located directly two feet in front of the participant. After the participant was

familiarized with the procedure (including use of the emotion rating scale, described below) and

practiced using the rating scale with four sample pictures, the experiment commenced.

Participants were presented with 64 pictures that included 48 startle probe trails and 16 "filler"

trials, during which no startle probe was presented. The 64 pictures were arranged in four blocks

of 16 pictures each. Each block consisted of 12 startle probe trials plus 4 interspersed filler

trials. This ratio of startle to no-startle probe trials (approximately 75% of trials associated with a

startle probe) is consistent with the majority of past studies examining emotional modulation of









the startle reflex using picture stimuli (Bradley, 2000; Cuthbert, Bradley, & Lang, 1996; Vrana et

al., 1988).

Each picture was presented on the computer monitor for six seconds. During this time, a

white noise burst (startle probe) was randomly presented at one of three time intervals following

picture onset (4200, 5000, or 5800 ms). Startle probe onset was counterbalanced across the

different picture categories. The use of three different time points after picture onset was

designed to prevent participants from developing expectancy of the startle probe. After the

presentation of each picture, participants completed subjective ratings as described below. This

was followed by a variable 10-15 second inter-trial interval before the onset on the next trial.

Valence and Arousal Ratings of Pictures

Approximately 8 to 12 seconds following the presentation of each picture, the Self

Assessment Manikin (SAM) appeared on the computer screen. SAM is a graphic display

depicting a cartoon figure that varies along the dimensions of valence and arousal (Greenwald,

Cook, & Lang, 1989; Lang, 1980). For valence, different versions of the cartoon figure depict

the cartoon's level of pleasantness. The scale goes from highly unpleasant to neutral to highly

pleasant. Each figure has a number (1-9) associated with it. For arousal, different versions of the

cartoon figure are shown ranging from sleepy/calm/bored to neutral to highly excited or

energized. Again, each figure has a number associated with it, ranging from 1-9. During the

experiment, participants were asked to rate their reactions to each picture immediately after

viewing it by referring to the SAM rating scale. Participants spoke their ratings aloud, and

ratings were transmitted via intercom to an examiner in another room, who recorded all

responses. Participants were given as long as needed to make their ratings.









Post Hoc Ratings of Basic Emotions

Following completion of the entire psychophysiology experiment, electrodes were

removed and each participant was reshown the 48 primary picture stimuli on an Apple iBook

laptop and asked to make additional ratings. Participants rated how much happiness, fear,

disgust, and sadness they felt while viewing each picture using a 1-9 rating scale. These post hoc

basic emotion ratings served as a manipulation check to determine if the targeted emotion (i.e.,

"disgust" for the contamination and mutilation pictures, "fear" for the threat pictures,

"happiness" for the pleasant pictures) was produced at both the group and the individual level.

Participants were told that this rating scale was different from the one using during the

psychophysiology experiment, and that their ratings with this new scale would not correspond to

ratings with the previous scale. The rating scale was depicted visually as a vertical line labeled

with the numbers one through nine. The number "1" was accompanied by the text "I did not feel

any of this emotion at all," the number "5" was accompanied by the text "I moderately felt this

emotion," and the number "9" was accompanied by the text "I strongly felt this emotion."

Participants advanced through the pictures by pressing a touchpad, and were instructed to move

through the pictures at their own pace. Participants wrote down their ratings on a separate

response sheet.

The pictures were presented in a different order than during the psychophysiology

experiment, and two alternate orders were created. Administration of these two orders was

counterbalanced across group and sex.

Psychophysiology Data Reduction

The raw EMG signal was amplified (30,000 gain) and frequencies below 90 Hz and above

1000 Hz were filtered using Colbourn bioamplifiers. The raw signal was then rectified and

integrated using a Colbourn Contour Following Integrator with a nominal time constant of 100









milliseconds. Digital sampling at 1000 Hz began 50 ms before presentation of the acoustic startle

probe and continued for 250 ms after startle probe offset. Data from each participant were

visually examined, and trials with clear artifacts (e.g., eyeblink movements before probe onset)

were rejected. Subsequent data reduction was completed using a custom software program for

data condensing. Latency and amplitude of the peak response within 20 ms to 120 ms after probe

onset were determined. Trials with a peak latency outside of the specified latency range were

discarded, as were trials with a peak amplitude more than 3 standard deviations above or below

each participant's mean magnitude for a given picture category. In order to minimize the effects

of inter-subject variability in overall magnitude, raw scores were converted into T-scores (mean

of 50, standard deviation of 10) for each participant's left and right eyes separately. For each

picture category, average T-scores were computed using all valid trials from both eyes. When

data from one eye were invalid, only the valid eye was used. Only participants who had at least

two valid trials for each picture category were retained for subsequent analyses.

Primary Statistical Analyses

Prior to proceeding with the analyses outlined below, data were checked to ensure

assumptions of univariate normality were met. Significance tests were two-tailed and set at the

conventional levels for significance (p < .05). When post hoc t-tests were used to further

examine significant effects, Bonferroni correction for multiple comparisons was employed. All

analyses were performed using SPSS for Windows statistical software (Version 13.0, Lead

Technologies, Inc., Chicago, IL). The statistical analyses used to test primary study predictions

are described below.

Specific Aim 1

It was predicted that Parkinson patients would demonstrate reduced emotional reactivity,

as indexed by emotional modulation of startle, specific to threatening pictures. To test this









prediction, data were subjected to 2 Group (PDs, controls) x 5 A Priori Picture Category

(pleasant, neutral, threat, disgust- contamination, disgust-mutilation) repeated measures Analysis

of Variance (ANOVA) with eyeblink magnitude T-scores as the dependent variable. A main

effect of picture category and a group-by-picture-category interaction was predicted. The

interaction was decomposed by five planned one-way ANOVAs (one for each apriori picture

category) with group as the between-subjects factor.

Specific Aim 2

A secondary aim of the study was to explore the relationship between emotional reactivity

deficits in Parkinson's disease and self-report measures as well as spousal-report measures of

mood. First, the relationship between self-reported depression and eyeblink magnitudes was

examined through five separate linear regressions (one for each picture category: neutral,

pleasant, threat, disgust- contamination, and disgust- mutilation). BDI-II scores, diagnostic

group, and the BDI-II x diagnostic group interaction term were entered simultaneously as the

independent variables. Eyeblink magnitude T-scores served as the dependent variable. Based on

previous literature (Allen et al., 1999; Bowers, Miller, Mikos, et al., 2006), it was predicted that

BDI-II scores and eyeblink magnitude would not have a significant linear relationship.

Next, Surrogate BDI-II data were analyzed via repeated measures ANOVA with diagnosis

as a between-subjects factor and self-report/ Surrogate BDI-II score as a two-level within-

subjects factor. Because not all participants had a spouse or partner, the sample size for this

analysis consisted of 21 PD patients and their partners and 18 controls and their partners. We

were interested in the main effect of self-/ surrogate BDI-II scores to determine whether a

discrepancy exists between ratings of depression completed by oneself versus a spouse.

Additionally, the diagnosis x self/spousal-report interaction allowed for examination of the

prediction that the difference between self- and surrogate BDI-II ratings would be greater for the









PD group compared to the control group (i.e., a significant diagnosis x self/spousal-report

interaction). It was predicted that spouses of PD patients would perceive them as being more

depressed than they truly are, due to misattribution of PD symptoms (e.g., masked facies) to

depression.

The relationship between BDI-II scores, Surrogate BDI-II scores, group membership, and

startle eyeblink magnitudes was examined using five separate linear regressions (one per apriori

picture category) to determine the contribution these variables may have to total eyeblink

magnitude variance. BDI-II self-report scores, Surrogate BDI-II scores, diagnostic group, and the

BDI-II x Surrogate BDI-II interaction term were simultaneously entered into the regression

equation as independent variables. There were no specific apriori predictions as to whether

Surrogate BDI-II scores or the discrepancy between self- and spousal- report level of depression

(represented by the BDI-II x Surrogate BDI-II interaction term) would contribute to eyeblink

magnitude variance.









CHAPTER 3
RESULTS

Participant Characteristics

A summary of participant demographic variables and patient disease characteristics are

presented in Table 3-1. As shown, the two groups did not statistically differ with respect to age,

education, or gender distribution. Overall, the sample was well educated, ranged in age from 50

to 80 years, and contained slightly more males than females. The PD patients were generally in

the middle stages of their disease (Hoehn and Yahr stage of 2 or 3 [Hoehn and Yahr, 1967]) and

all were on L-DOPA and/or dopamine agonists. Seven of the PD patients were on anti-

depressant medications (three on Wellbutrin, two on Lexapro, one on Zoloft, and one on

Effexor). One PD patient on Lexapro was also taking on clozepam to aid in sleep at night. None

of the controls were on any psychotropic medications.

Cognitive and Mood Measures

Parkinson patients and controls did not significantly differ with respect to Dementia Rating

Scale-II, Boston Naming Test, California Verbal Learning Test-II, or Wechsler Memory Scales-

II Logical Memory I and II scores. In contrast, Parkinson patients obtained significantly higher

scores than controls on the BDI-II (t[46] = 2.99, p = .005), although both groups had mean scores

in the non-depressed range (PD = 6.17 [SD = 4.76], control = 2.58 [SD = 3.45]). Three PD

patients and one control had BDI-II scores falling within the mildly depressed range, defined as

scores between 14 and 19 (Beck et al., 1996). All other participants scored within the non-

depressed range. Group means and standard deviations for cognitive and mood measures are

shown in Table 3-2.









Baseline Startle Eyeblink

An initial analysis examined whether the PD patients and controls differed in terms of their

basic unprimedd" startle eyeblink responses. This was done by analyzing the twelve initial

unprimed baseline trials (i.e., no picture presented). Results of independent t-tests showed no

group differences in peak eyeblink magnitude (controls = 6.59 mV [SD = 6.78], PD = 5.38 mV

[SD = 4.45]; t[46] = .73,p > .1). Similarly, there was no difference in baseline startle latency

(controls = 74.19ms [SD = 8.26], PD = 72.86ms [SD = 11.64]; t[46] = .45, p > .1). Thus, the PD

patients displayed unprimed startle eyeblink responses that were similar in both size and latency

to those of the control group.

Emotion-Modulated Startle Eyeblink

Discarded Trials

The total percentage of discarded trials was 9.9%. Discarding was based on eye

movement artifact (determined by visual inspection; 5.1% of all discarded trials), peak latency

out of range (2.8%), peak amplitude out of range (1.5%), and no peak maximum amplitude

found (0.6%). A 2 (Group) x 2 (Stimulus Presentation Order) x 5 (A Priori Picture Category:

pleasant, neutral, fear, disgust- contamination, disgust- mutilation) repeated measures ANOVA

with number of discarded trials as the dependent variable did not yield any significant main

effects or interactions (all p's > .1).

Latency

A 2 (Group) x 2 (Stimulus Presentation Order) x 5 (A Priori Picture Category: pleasant,

neutral, fear, disgust- contamination, disgust- mutilation) repeated measures ANOVA was

conducted to determine whether latency was affected by any of these variables. Results revealed

no significant main effects or interactions (all p's > .1). Thus, the latency to peak did not appear

to vary as a function of group, stimulus presentation order, or apriori picture category.









Magnitude

An initial analysis was conducted in order to determine whether the two stimulus

presentation orders resulted in different findings. This involved a 2 (Group) x 2 (Stimulus

Presentation Order) x 5 (A Priori Picture Category: pleasant, neutral, fear, disgust-

contamination, disgust- mutilation) repeated measures ANOVA with startle magnitude (T-score)

as the dependent variable. No significant main effect or interactions with stimulus presentation

order were found, and thus for the remaining analyses the two orders were combined to increase

power.

The role of startle probe onset latency was also examined to determine whether startle

magnitude was influenced by the timing of probe presentation. A 3 (Probe Onset Latency: 4200

ms, 5000 ms, 5800 ms) x 3 (Valence: pleasant, neutral, unpleasant) repeated measures ANOVA

was conducted for the controls and PD patients separately. For both groups, no significant main

effect of startle probe onset latency or interaction with valence was found (all p's > .6).

Additionally, a 3 (Latency) x 3 (Valence) x 2 (Group) repeated measures ANOVA revealed no

significant interactions (all p's > .1). Thus, the remaining analyses are collapsed across the three

different startle probe onset latencies.

Verification of typical pattern of startle modulation

Before examining the primary aim of the study, emotion-modulated startle eyeblink

magnitudes were checked to verify that the typical pattern of emotion modulation did in fact

occur. Typically, magnitudes for pleasant pictures are smaller compared to neutral pictures,

whereas magnitudes for unpleasant pictures are larger. To examine whether this pattern held true

for the current study, the threat, disgust- contamination, and disgust- mutilation pictures were

collapsed into a general "unpleasant" category. Eyeblink magnitude t-scores were then subjected

to 2 (Group) x 3 (Valence: pleasant, neutral, unpleasant) repeated measures ANOVA. Results









revealed a significant main effect of valence (F[2,92] = 9.37, p < .001, rl2p = .17). No other

effects were significant. Bonferroni-corrected post hoc comparisons indicated that the pleasant

pictures were associated with significantly smaller eyeblink magnitudes than both neutral and

unpleasant pictures (p < .05). The comparison between unpleasant pictures and neutral pictures

was not statistically significant; however, mean eyeblink magnitudes were larger for unpleasant

pictures than neutral pictures. These results indicate that the typical pattern of emotional

modulation was observed for both controls as well as PD patients. Mean eyeblink magnitudes by

group and valence are shown in Figure 3-1.

Primary analysis

To examine the hypothesis that PD patients would should display decreased startle

eyeblink magnitude to threat pictures, a 2 (Group) x 5 (A Priori Picture Category: pleasant,

neutral, threat, disgust- contamination, disgust- mutilation) repeated measures ANOVA was

conducted. This yielded a significant main effect of A Priori Picture Category (F[4,184] = 9.18,

p < .001, rl2p= .17) and a Group x A Priori Picture Category interaction (F[4,184] = 2.49, p <

.05, r12p = .05). Bonferroni-corrected post hoc comparisons indicated that the main effect of A

Priori Picture Category was driven by the threat pictures, which were associated with

significantly larger startle magnitudes (collapsing across both groups) than those for the neutral,

pleasant, disgust- contamination, and disgust- mutilation pictures (all p's < .02). No other

comparisons were significant. When results were examined for controls and PD patients

separately, controls showed significantly larger eyeblink magnitudes to threat pictures compared

to neutral and pleasant pictures (p's < .05). Additionally, eyeblink magnitudes to mutilation

pictures magnitudes tended to be larger compared to pleasant pictures, but this comparison was

no longer significant after Bonferroni corrections were made (p = .1). In contrast, PD patients









showed significantly larger eyeblink magnitudes for threat pictures compared to neutral,

pleasant, and mutilation pictures (p's < .05).

The Group x A Priori Picture Category interaction was decomposed by conducting five

separate univariate ANOVAs (one for each apriori picture category) with Group as the between-

subjects factor. Only the comparison for disgust- mutilation pictures was significant (F[1, 46] =

6.66, p < .02), l2p = .13), with controls showing significantly larger startle eyeblink magnitudes

than PD patients (means: PD = 48.34 [SD = 3.91], controls = 51.09 [SD = 3.47]). Thus, the

prediction that eyeblink magnitudes in response to threat pictures would be reduced in PD

patients compared to controls was not supported; instead, it was the disgust-mutilation pictures

that resulted in attenuated startle eyeblink magnitude in the PD group. Mean eyeblink

magnitudes for each group for pleasant, neutral, threat, disgust- contamination, and disgust-

mutilation pictures are shown in Figure 3-2.

Habituation Pattern

To follow-up on the finding of decreased startle eyeblink magnitude in the PD group in

response to the disgust- mutilation pictures, each group's eyeblink magnitudes to mutilation

pictures was examined on a trial-by-trial basis. The purpose of this analysis was to determine if

group differences in eyeblink magnitudes can be accounted for by differential patterns of

habituation to the mutilation stimuli. For example, one possibility is that controls and PD patients

initially showed similar eyeblink magnitudes to the pictures, but PD patients habituated more

quickly. To examine this possibility, a 2 (Group) x 7 (Trial Number) repeated measures ANOVA

was conducted for the mutilation pictures. Overall, both groups showed habituation of startle

eyeblink magnitude over time (F[11, 506] = 4.55, p < .001), rl2p= .09), as is typically found with

this paradigm. However, the Group x Trial Number interaction was nonsignificant (F[11, 506] =









0.88, p > .5). This indicates that differences in eyeblink magnitude habituation do not explain the

group difference in responsivity to mutilation pictures.

Valence and Arousal Ratings

One explanation for the attenuated startle eyeblink magnitude observed in the PD group in

response to the disgust- mutilation pictures may be that these pictures were considered less

aversive or less arousing by the patients. Thus, subjective ratings of valence and arousal were

analyzed through two separate 2 (Group) x 5 (A Priori Picture Category: pleasant, neutral, threat,

disgust- contamination, and disgust- mutilation) repeated measures ANOVAs. For valence

ratings, results yielded a significant main effect of A Priori Picture Category (F[4,184] = 49.24,

p < .001, r2p= .52). The effect of Group was nonsignificant [F(1,46) = .34, p > .1], as was the

Group x Emotion Category interaction [F(4,184) = .07, p > .1]. Bonferroni-corrected post hoc

comparisons collapsing across the two groups revealed that pleasant pictures were rated as

significantly more pleasant than all other picture types (all p's < .001). Neutral pictures were

rated as significantly more pleasant than contamination, mutilation, and threat pictures (all p's <

.001). Looking at just the unpleasant picture categories (threat, disgust- contamination, and

disgust- mutilation pictures), the mutilation pictures were rated as significantly more pleasant

than the threat pictures (p < .05). No other comparisons were significant.

For arousal ratings, results once again yielded a significant main effect of A Priori Picture

Category (F[4,184] = 56.00, p < .001, q2p= .55), and no other significant effects or interactions

(all p's > .1). Bonferroni-correctedpost hoc comparisons collapsing across the two groups

revealed that the neutral pictures were rated as significantly less arousing than all other picture

types (p's < .001). No other comparisons were significant, indicating that pleasant, threat,

disgust- contamination, and disgust- mutilation pictures were perceived as equally arousing by

subjects. Table 3-3 shows mean valence and arousal ratings for each emotion category by group.









In summary, PD patients did not rate the mutilation pictures as being less unpleasant or

less arousing than controls; thus, these self-report ratings cannot explain the finding of reduced

eyeblink magnitude to mutilation pictures in Parkinson group.

Post Hoc Basic Emotion Ratings

An alternate explanation is that mutilation pictures were not effective in evoking a strong

disgust reaction in the PD group, or perhaps even a strong negative reaction of any type. Because

emotion-modulated startle potentiation is dependent on participants experiencing the pictures as

aversive, this could explain the PD patients' diminished eyeblink magnitudes to mutilation

pictures. To explore this possibility, the post hoc basic emotion ratings made by all participants

after the psychophysiology portion of the experiment were examined. As previously described,

each participant rated each picture in terms of how happy, disgusted, fearful, and sad he or she

felt while viewing the picture. These ratings served as a manipulation check to ensure that the

pictures did in fact evoke the emotions they were intended to. Specifically, it was expected that

contamination and mutilation pictures would be associated with the highest "disgust" ratings,

threatening pictures would be associated with the highest "fear" ratings, and pleasant pictures

would be associated with the highest "happiness" ratings.

First, a 2 (Group) x 2 (Stimulus Presentation Order) x 5 (A Priori Picture Category) x 4

(Post hoc Basic Emotion) repeated measures ANOVA was conducted to confirm that order of

stimulus presentation during the post hoc rating portion of the experiment did not effect results.

The main effect and interactions with presentation order were all non-significant. As such, data

from the two presentation orders were combined. Next, a series of four 2 (Group) x 5 (A Priori

Picture Category: neutral, pleasant, threat, disgust- contamination, disgust- mutilation) repeated

measures ANOVAs were conducted (one for eachpost hoc basic emotion rating: happiness,

disgust, fear, and sadness). Post hoc emotion ratings by group and apriori picture category are









shown in Table 3-4. For the happiness ratings, results yielded a main effect of A Priori Picture

Category (F[4,184] = 463.02, p < .001, 2p = .91), with no other significant effects. Bonferroni-

corrected pairwise comparisons collapsing across the two groups revealed that pleasant pictures

had significantly higher happiness ratings than all other types of pictures (all p's < .001).

Additionally, neutral pictures had significantly higher happiness ratings than threat, mutilation,

and contamination pictures, while threat pictures had significantly higher happiness ratings than

mutilation pictures (p's < .001).

For disgust ratings, the repeated measures AVOVA showed a main effect of A Priori

Picture Category (F[4,184] = 274.23, p < .001, r2p= .86) as well as an A Priori Picture Category

x Group interaction (F[4,184] = 3.19, p < .02, r12p= .07). Bonferroni-corrected pairwise

comparisons collapsing across the two groups revealed that both mutilation and contamination

pictures were rated as significantly more disgusting than all other picture types (p's < .001),

whereas mutilation and contamination pictures did not differ from one another in subjective

disgust ratings. Both the neutral and pleasant pictures were rated as significantly less disgusting

than threat, contamination, and mutilation pictures (all p's < .001). The Group x A Priori Picture

Category interaction was decomposed by conducting five separate univariate ANOVAs (one for

each a priori picture category) with Group as the between-subjects factor. Only the comparison

for threat pictures was significant (F[1, 46] = 7.93, p < .01), 12p = .15), with PD patients rating

these pictures as eliciting more disgust compared to controls (means: PD = 5.55 [SD = 1.99],

controls = 4.81 [SD = 1.94]).

Turning to fear ratings, results yielded a main effect of A Priori Picture Category

(F[4,184] = 162.57, p < .001, r12p= .78); no other effects were significant. Bonferroni- corrected

pairwise comparisons showed that neutral pictures were rated as significantly less fear- evoking









than all other picture categories, whereas threat pictures were rated as significantly more fear-

evoking than all other picture types (p's < .001). Additionally, mutilation pictures were

associated with significantly higher fear ratings than neutral, pleasant, and contamination

pictures (p's < .001).

In summary, each apriori picture category was effective in evoking the intended emotional

reaction. Participants rated pleasant pictures as significantly higher in happiness than all other

pictures types, mutilation and contamination pictures as significantly higher in disgust compared

to all other picture types, and threat pictures as significantly higher in fear compared to all other

picture types. While PD patents rated the threatening pictures as higher in disgust compared to

controls, no group differences were found with respect to degree of happiness, disgust, fear, or

sadness in response to the mutilation pictures. Overall, the self-report data suggest that group

differences in valence, arousal, or basic emotional reactions cannot account for the reduced

eyeblink magnitude to mutilation pictures observed in PD patients.

Arousal Level as Measured by Skin Conductance Response

A potential problem with self-report data is that it is possible that participants rated

pictures based on how they thought they were expected to respond, as opposed to based on how

they truly felt. Recently, studies from two different laboratories reported that PD patients rated

highly arousing negative pictures as less arousing than controls (Bowers, Miller, Mikos, et al,

2006; Wieser et al., 2006); however, this was not observed in the present study. Thus, it is

important to consider the possibility that demand characteristics may have played a role in self-

report ratings.

One way to address concerns about the veracity of subjective ratings of arousal level is to

examine an objective index of physiological arousal. For this reason, apost hoc analysis of skin

conductance response (SCR) was conducted. SCR is an index of sympathetic arousal that is









difficult to consciously control. Changes in SCR are relatively independent of valence; thus, an

increase in SCR is typically observed in response to any type of highly arousing picture, whether

it is positive or negative in valence(Bradley, 2000). In a large study using pictures from the

International Affective Picture System, Bradley, Codispoti, Cuthbert, et al. (2001) found that

erotica, mutilations, and human and animal attacks were associated with the largest SCR.

With regards to the present study, an examination of SCR to mutilation pictures for

controls and PD patients is of particular interest. A finding of reduced SCR to these pictures in

the PD patients compared to controls would suggest that the PD group did not find the mutilation

pictures as arousing as controls. This, in turn, could account for the reduced eyeblink magnitudes

observed in the PD patients in response to this category of pictures, since both valence and

arousal play a role in emotion-modulated startle eyeblink response.

Before conducting this key analysis of interest, the general pattern of SCR to pleasant,

neutral, and unpleasant pictures was examined. For a full description of the SCR data collection

and reduction procedures, please refer to Appendix B. Threat, disgust- contamination, and

disgust- mutilation pictures were collapsed into a general "unpleasant" category. SCR data were

then subjected to 2 (Group) x 3 (Valence: pleasant, neutral, unpleasant) repeated measures

ANOVA. Results revealed no significant effects or interactions, although the main effect of

valence approached significance (F[2,92] = 2.79, p = 0.06, r12p= .06). Group means for each

valence category are depicted in Figure 3-3. Although not statistically significant, the pattern of

SCR in controls versus PDs was of theoretical interest, and thus t-tests comparing neutral to

pleasant pictures as well as neutral to unpleasant pictures were conducted for each group. For the

control group, both pleasant and unpleasant pictures resulted in significantly greater SCR

compared to neutral pictures (pleasant vs. neutral: t(23) = 2.63, p < .02; unpleasant vs. neutral:









t(23) = 2.94, p < .01). In contrast, neither pleasant nor unpleasant pictures differed significantly

from neutral pictures for the Parkinson group (p's > .3).

Next, a 2 (Group) x 5 (A Priori Picture Category: pleasant, neutral, threat, disgust-

contamination, disgust- mutilation) repeated measures ANOVA was conducted so that pictures

within the unpleasant pictures subcategory could be examined separately. As would be expected

based on the non-significant results of the previous repeated measures ANOVA, no significant

effects were found; however, examination of the observed power suggested this analysis was

insufficiently powered to investigate differences within this many different picture categories

(power = .28). Means and standard deviations for control and PD skin conductance response to

each pictures category are shown in Table 3-4.

In sum, the control group displayed a typical pattern of emotion-modulated skin

conductance response, with larger SCR to pleasant and unpleasant pictures compared to neutral

pictures, whereas PD patients did not show any modulation. The analysis that included the

different unpleasant picture subcategories (threat, disgust- contamination, disgust- mutilation)

did not reveal any significant group difference, although it was hindered by low power. These

results do not support the idea that PD patients found mutilation pictures less arousing than

controls; however, they do suggest that PD patients show an absence of emotion-modulated skin

conductance response overall.

Re-Examination of Eyeblink Magnitude via Idiographic Analysis

Although previous analyses indicated that apriori picture categorizations were consistent

with overall post hoc basic discrete emotion ratings at the group level (i.e., pictures generally

evoked the intended emotion), inter-subject differences in emotional reactions to pictures could

potentially influence eyeblink magnitudes at an individual level. As an example, a picture of a

man hiking atop a mountain that is designed to be pleasant in valence may actually evoke









feelings of fear for an individual who is scared of heights. Similarly, although pictures of animal

attacks were intended to evoke fear, some animal-lovers reported feelings of happiness for these

pictures. For this reason, eyeblink magnitude data were reanalyzed via an idiographic approach

based on the post hoc basic emotion ratings (happy, fear, disgust, and sad) made by each

participant.

Individual Categorization of Pictures

For each participant, post hoc ratings for each picture were examined and the picture was

categorized in terms of the basic emotion with the highest rating (e.g., if a picture of a mutilation

had a higher disgust rating compared to happiness, fear, and sadness ratings, the picture would be

categorized as eliciting disgust for that participant).

Pictures with ratings less than a "4" (on a 1-9 scale, with 9 indicating highest emotional

intensity) on all of the basic emotions were categorized as "neutral," since they were rated as

eliciting very little of any emotion. Pictures with similarly high ratings on two contradictory

emotions (e.g., happy and disgust or happy and fear) were excluded due to difficulty in

appropriately categorizing these pictures.

Initial inspection of ratings revealed that many participants frequently rated aversive

pictures (e.g., the apriori fear and disgust pictures) as similarly high in disgust and fear. Thus,

pictures with less than a 2-point difference in ratings of disgust and fear were categorized as

"general aversive" for purposes of idiographic analysis. Initial inspection of ratings also showed

that participants rarely rated a picture as higher in "sadness" than any other basic emotion;

instead, sadness typically co-occurred with either a high disgust or fear rating, or both. For this

reason, sadness was considered to be a "secondary" emotion, at least within the context of the

present study, and when a high sadness rating occurred the picture was categorized under the

"primary" emotion (disgust, fear, or general aversive) that also received a high rating. Thus,









"sad" was not used as a discrete category within the idiographic analysis of eyeblink magnitude

data. The basic emotions examined with respect to eyeblink magnitude were neutral, happy, fear,

and disgust, as well as "general aversive."

Emotion-Modulated Startle Eyeblink Magnitude

Next, mean eyeblink T-scores for the neutral, happy, fear, disgust, and general aversive

categories were calculated for each participant. These T-scores were then subjected to a 2

(Group) x 5 (Post hoc Emotion Category) repeated measures ANOVA. Results yielded a

significant main effect of Post hoc Emotion Category (F[4,184] = 4.83, p < .001, l2p= .10). The

Group x Post hoc Emotion Category interaction was nonsignificant (F[4,184] = 0.38, p > .01).

Bonferroni-corrected pairwise comparisons collapsing across groups indicated that eyeblink

magnitudes in response to pictures categorized as "fear" and "general aversive" were

significantly larger than for "happy" pictures (p < .001 for fear vs. happy; p < .05 for general

aversive vs. happy). No other pairwise comparisons were significant. Mean eyeblink magnitudes

for each group based onpost hoc basic emotion categorization are shown in Figure 3-5.

In summary, the idiographic analysis based on post hoc basic emotion categorization

yielded similar results as the apriori categorization analysis with respect to the main effect: for

both methods of analysis, fear-evoking pictures were associated with a significantly larger startle

eyeblink magnitude than happy pictures. This held true for both the PD and control groups. Thus,

the prediction that PD patients would show reduced eyeblink magnitude to pictures rated highest

in fear was not confirmed. Additionally, the idiographic analysis showed that pictures that were

rated as very high in both disgust and fear (the "general aversive" pictures) were also associated

with significantly larger startle eyeblink magnitude than happy pictures. In contrast, the

idiographic analysis did not yield a significant Group x Emotion Category interaction like the a

priori categorization analysis.









Influence of Trait Positive and Negative Affectivity and Trait Anxiety on Startle Eyeblink
Magnitude

One potential explanation for the observed differences in eyeblink magnitudes to

mutilation pictures between PD patients and controls may be that the individuals within the two

groups systematically differed on certain personality traits. Recent research suggests that

individual personality differences may influence emotion-modulated startle. Specifically, some

studies have found that people with extremely low levels of trait anxiety, neuroticism, and

negative affect do not demonstrate emotion-modulation of the startle reflex for some categories

of affective pictures (Caseras et al., 2006; Corr et al., 1995; Hawk and Kowmas, 2003; Wilson,

Kumari, Gray, & Corr, 2000). These findings suggest that certain individuals may not be

sensitive to the emotion-modulated startle paradigm.

Although the present study did not include assessment of these personality traits, fifteen of

the twenty-four PD patients had recently participated in another study within the laboratory that

included self-report measures of state and trait anxiety (State- Trait Anxiety Inventory [STAI];

Spielberger, 1977) as well as trait positive and negative affectivity (Positive and Negative Affect

Schedule [PANAS], Watson, Clark, & Tellegen, 1988). Although these data were not available

for control participants, the relationship between scores on the negative affect scale of the

PANAS and the trait anxiety scale of the STAI and emotion-modulated startle magnitudes were

examined to determine whether emotion-modulated startle magnitudes systematically varied as a

function of different levels of these traits. For the negative affect scale of the PANAS, scores for

the fifteen PD patients who completed the questionnaire ranged from 10 to 28 (maximum score

is 50, indicating very high trait negative affectivity). The mean was 14.40 (SD = 5.87), indicating

that overall patients were fairly low in negative affect. For the trait anxiety scale of the STAI,

scores ranged from 15 to 59 (the maximum possible score is 60, indicating extremely high trait









anxiety), with a mean of 29.47 (SD = 11.04). This mean score is in the average range for trait

anxiety. A series of multiple regressions with negative affect score and trait anxiety score

simultaneously entered as the independent variable and eyeblink magnitude T-score as the

dependent variable produced nonsignificant results for neutral, pleasant, threat, disgust-

contamination, and disgust- mutilation pictures (p's > .1). Thus, within the PD group, personality

trait differences do not account for a significant portion of the variance in emotion-modulated

eyeblink magnitude. The lack of a significant relationship suggests that at the between-groups

level, personality differences are unlikely to account for the finding of reduced eyeblink

magnitude to mutilation pictures.

Influence of Depression on Eyeblink Magnitude

Next, the relationship between BDI-II scores and eyeblink magnitudes in response to each

apriori picture category was examined through a series of five separate linear regressions (one

for each apriori picture category: neutral, pleasant, threat, disgust- contamination, disgust-

mutilation). BDI-II scores, diagnostic group, and the BDI-II x diagnostic group interaction term

were entered simultaneously as the independent variables, whereas eyeblink magnitude T-scores

served as the dependent variable. The BDI-II x diagnostic group interaction term was included in

the equation because the two groups differed with respect to mean BDI-II scores. None of the

resulting regression models were statistically significant, although the model for disgust-

mutilation pictures approached significance (p = .06). Within this model, the regression

coefficient for "group" was significant (B = -3.13, SE B = 1.18, f= 0.40; t[44] = -2.64, p = .01),

as would be expected based on the known between-groups difference for eyeblink magnitudes in

response to these pictures. Otherwise, none of the regression coefficients for the independent

variables entered into the neutral, pleasant, threat, or disgust- contamination models were

significant. Thus, the prediction that BDI-II scores and startle eyeblink magnitudes would not









have a significant linear relationship was confirmed. Table 3-5 displays the unstandardized and

standardized beta- weights, associated standard error, and t-tests for significance associated with

each independent variable in each model, as well as the overall R2 and adjusted R2 for each

model.

Influence of Psychotropic Medications

Because anti-depressants and anxiolytics may dampen startle reactivity in healthy

individuals (Davis and Gallagher, 1988; Harmer, Reid, Ray, Goodwin, & Cowin, 2006), the

influence of psychotropic medications on startle reactivity was examined. To do so, the seven

PD patients on antidepressants and/or anxiolytics were removed from the sample and a 2 (Group)

x 5 (A priori picture category) repeated measures ANOVA was conducted with the data from

this smaller sample. As with the analysis including the full sample, there was a significant main

effect of A Priori Picture Category (F[4,156] = 10.77, p< .001, fr2p = .22) as well as a significant

Group xA Priori Picture Category interaction (F[4,156] = 3.31, p < .03, f2p= .08).

Decomposition of the interaction with separate one-way ANOVAs for each apriori picture

category revealed that the PD group had significantly smaller eyeblink magnitudes in response to

mutilation pictures as compared to controls (F[1,39] = 98.33, p < .01 means: PD = 47.95 [SD =

3.39], controls = 51.10 [SD = 3.47]). Between-groups differences for neutral, pleasant, threat,

and contamination pictures were all non-significant. Thus, diminished reactivity to mutilation

pictures by PD patients was maintained when excluding patients on psychotropics. This finding

suggests that psychotropic medication is not responsible for the effect.

Spousal Perception of Depression: Relationship to Self-Reported Depression and Startle
Eyeblink Magnitude

A secondary aim of the current study was to examine the congruency between self- and

spousal- report ratings of depression. It was predicted that spouses of PD patients would









perceive them as being more depressed than they truly are, due to misattributing symptoms of

PD (such as masked facies) to depression. Thus, it was predicted that there would be a larger

discrepancy between self- and surrogate- BDI-II scores for the PD patients as compared to the

controls. Additionally, the relationship between discrepancy in self- versus spousal- depression

ratings and emotion-modulated startle eyeblink magnitudes was examined. The purpose of this

analysis was to determine whether decreased physiological emotional reactivity in PD was

associated with misattribution of mood state by spouses.

Surrogate BDI-II: Comparison with Self-Report BDI-II

A 2 (Group) x 2 (Self-report BDI-II, Surrogate BDI-II) repeated measures ANOVA

yielded a main effect of Group (F[1,37] = 4.66, p < .05, r2p = .11), reflecting higher mean BDI-

II scores in the PD group on both the self-report and surrogate measure. The main effect of self-

report BDI-II vs. Surrogate BDI-II was not significant, nor was the Group x Self-/Surrogate BDI-

II interaction (p's > .1). The lack of significant Group x Self-/Surrogate BDI-II interaction does

not support the prediction that spouses of PD patients would perceive them as being more

depressed than they truly are. To further explore the accuracy of spousal ratings of participants'

level of depression, Pearson's bivariate correlations between self-report and surrogate- report

BDI-II scores were computed. Interestingly, the two measures were significantly correlated for

PD patients, whereas they were not for controls. Although the difference between the two

correlation coefficients is not statistically significant, these findings further bolster the finding

that spouses of PD patients can perceive their partner's mood quite well, contrary to study

predictions. Mean self-report BDI-II and Surrogate BDI-II scores, as well as the correlation

coefficients between the two, are shown in Table 3-6.









Relationship between Surrogate BDI-II and Startle Eyeblink Magnitude

A series of five multiple regressions (one per apriori picture category) with BDI-II self-

report scores, Surrogate BDI-II scores, diagnostic group, and BDI-II x Surrogate BDI-II

interaction term entered simultaneously as independent variables and eyeblink magnitude T-

score as the dependent variable did not yield any significant models. Once again, other than the

significant regression coefficient for "group" in the disgust- mutilation model, none of the

independent variables contributed a significant amount of variance. This suggests that neither

Surrogate BDI-II scores nor degree of discrepancy between self versus surrogate ratings are

associated with emotion-modulated startle magnitude. Table 3-7 shows the unstandardized and

standardized beta- weights, associated standard error, and t-tests for significance associated with

each independent variable in each model, as well as the overall R2 and adjusted R2 for each

model.

Influence of Disease Severity and Duration on Startle Eyeblink Magnitude

To determine whether disease duration or severity were associated with the finding of

decreased startle reactivity to mutilation pictures in the PD patients, the variables "years with

PD" and "UPDRS Motor score" were entered as independent variables simultaneously into a

regression model with eyeblink T-score to disgust- mutilation pictures as the dependent variable.

The overall model was not significant, indicating that neither of these disease-related variables

account for a significant portion of the variance in eyeblink magnitudes (F[2,21]= 47.02, p = .22;

R2 = 0.13, adjusted R2 = 0.05.)









Table 3-1. Demographic and clinical characteristics by group
Characteristic Parkinson (N= 24)


Control (N= 24)


Statistical test


Age (years) 68.00 (6.92) 68.38 (7.73) t(46) = .18
Sex ratio (men: women) 14:10 14:10 X2(1) = 0
Education (yrs) 16.21 (3.16) 16.33 (2.88) t(46) =.14
Disease duration (yrs) 5.54 (3.63)
Hoehn and Yahr stage 2.27 (0.42)
UPDRS Motora 23.46 (8.49)
Levodopa equivalent dose (mg) 682.43 (323.26)


Note: Values are expressed as mean (SD). UPDRS Motor = motor scale of the Unified Parkinson
Disease Rating Scale (Fahn & Elton, 1987).
a Scores obtained in the "on" medication state










Table 3-2. Scores on cognitive and mood measures scores by group
Measure Parkinson (N= 24) Control (N= 24) Statistical test


Dementia Rating Scale-II raw score
(/144)
Dementia Rating Scale-II scaled score

Boston Naming Test raw score (/60)

Boston Naming Test t-score

CVLT-II trials 1-5 total raw score
(/80)
CVLT-II trials 1-5 total t-score

CVLT-II short delay free recall raw
score (/16)
CVLT-II short delay free recall z-
score
CVLT-II short delay cued recall raw
score (/16)
CVLT-II short delay cued recall z-
score
CVLT-II long delay free recall raw
score (/16)
CVLT-II long delay free recall z-score

CVLT-II long delay cued recall raw
score (/16)
CVLT-II long delay cued recall z-
score
WMS-III Logical Memory I raw score
(/75)
WMS-III Logical Memory I scaled
score
WMS-III Logical Memory II raw
score (/50)
WMS-III Logical Memory II scaled
score
Beck Depression Inventory-II


140.92 (2.83)

12.04 (2.40)

56.48 (5.43)

58.96 (10.50)

45.92 (10.75)

55.58 (12.10)

10.21 (3.09)

0.65 (1.18)

11.63 (2.73)

0.50(1.18)

9.88 (3.31)

0.25 (1.15)

11.38(2.67)

0.42 (1.07)

40.19 (9.01)

11.52 (2.96)

25.10 (7.72)

12.57 (3.00)

6.17 (4.76)


141.13 (1.30)

11.79 (1.56)

57.21 (3.61)

59.17 (12.57)

50.38 (6.72)

60.29 (6.66)

10.71 (2.26)

0.81 (0.93)

11.88 (1.96)

0.62 (0.86)

11.04 (2.26)

0.60 (0.85)

11.63 (2.18)

0.54 (0.85)

41.75 (7.70)

12.35 (2.21)

26.80 (6.14)

13.25 (2.65)

2.58 (3.45)


t(46)

t(46)

t(46)

t(46)

t(46) =

t(46)

t(46)

t(46)

t(46)

t(46)

t(46) =

t(46) =

t(46)

t(39)

t(39)a

t(39)a =

t(39)a

t(39)a


=.33

=.43

=.55

=.06

1.72

1.67

=.64

=.54

=.36

=.42

1.43

1.21

=.36

=.45

=.59

1.00

=.78

= .77


**t(46)= 2.99


Note: Values are expressed as mean (SD). CVLT-II= California Verbal Learning Test 2nd
Edition; WMS-III= Wechsler Memory Scales, 3rd Edition.
a Three PD patients and four controls were not administered this test
**p <.01









Table 3-3. Valence and arousal ratings of affective pictures by apriori picture category and
group
Valence Arousal
A Priori Picture Category Parkinson Control Parkinson Control
Neutral 4.71 (0.68) 4.61 (0.65) 3.93 (1.79) 3.36 (1.67)
Pleasant 6.07 (1.72) 5.96 (1.70) 6.67 (0.99) 6.41 (0.90)
Threat 2.60(1.17) 2.62(1.29) 6.79(1.54) 6.53 (1.56)
Disgust- contamination 2.68 (0.95) 2.43 (0.90) 6.46 (1.47) 6.36 (1.36)
Disgust- mutilation 3.04 (2.02) 3.07 (2.15) 6.92 (1.59) 6.74 (1.56)
Note: Values are expressed as mean (SD). Valence ratings are on a 1-9 scale, with 9 being most
pleasant. Arousal ratings are on a 1-9 scale, with 9 being most arousing. No between- groups
differences for valence or arousal were found.

Table 3-4. Post hoc basic emotion ratings by group
A priori picture category
Post hoc Disgust- Disgust-
emotion Group Neutral Pleasant Threat contam. mutil.
Happy Parkinson 2.48 (1.33) 7.03 (1.05) 1.20 (0.27) 1.53 (0.82) 1.07 (0.21)
Control 2.44 (1.57) 6.89 (1.34) 1.20 (0.55) 1.27 (0.66) 1.12(0.47)
Disgust Parkinson 1.32 (0.66) 1.21(0.73) 5.55 (1.99) 6.78 (1.56) 6.85 (1.88)
Control 1.09 (0.18) 1.03 (0.09) 4.08 (1.62) 6.88 (1.65) 6.59 (2.13)
Fear Parkinson 1.18(0.37) 2.27(1.07) 6.81(2.04) 2.38(1.83) 4.55(2.82)
Control 1.04(0.13) 1.92(1.12) 6.83 (1.74) 1.83(0.92) 3.74(1.99)
Sad Parkinson 1.25 (0.43) 1.14(0.50) 3.44 (2.07) 2.59 (1.92) 5.27 (2.63)
Control 1.08(0.18) 1.12(0.35) 3.40(1.90) 2.38(1.71) 5.98(1.99)
Note: Values are expressed as mean (SD). Post hoc basic emotion ratings were all based on a 1-9
scale in which 1 indicates no emotion was felt and 9 indicates the emotion was strongly felt.
Numbers in bold indicate that Parkinson patients rated threat pictures to be significantly higher in
disgust compared to controls, p < .01. Disgust- contam. = contamination pictures; Disgust-
mutil.= mutilation pictures.









Table 3-5. Regression analysis of contributions of group membership and BDI-II scores upon
eyeblink magnitudes
A priori picture Model
category Variable B SE B l t- statistics R2 Adj. R2
Neutral group 0.83 0.74 0.18 1.13 0.03 -0.03
BDI-II -0.01 0.09 -0.01 -0.03
BDI-II x group 0.02 0.4 0.01 0.04
Pleasant group 0.10 0.87 0.02 0.12 0.02 -0.05
BDI-II -0.06 0.10 -0.09 -0.53
BDI-IIx group 0.39 0.47 0.13 0.83
Threat group 0.88 0.88 0.16 1.01 0.08 0.02
BDI-II 0.08 0.10 0.13 0.76
BDI-IIx group -0.62 0.47 -0.20 -1.33
Disgust- group 0.08 1.20 0.01 0.07 0.04 -0.03
contamination BDI-II -0.15 0.14 -0.18 -1.05

BDI-IIx group -0.13 0.64 -0.03 -0.21
Disgust- group -3.13 1.181 -0.40 **-2.64 0.15 0.10
mutilation BDI-II 0.10 0.14 0.12 0.75

BDI-IIx group 0.40 0.63 0.10 0.62
a For all t-tests, df = 44.
**p< .01

Table 3-6. BDI-II self- and surrogate- report scores by group
Surrogate Correlation
Group BDI-II BDI-II coefficient p -value
Parkinson 6.00(5.00) 5.1 (5.34) r= 0.41 0.01
Control 2.67 (3.91) 3.00 (3.24) r= 0.55 0.09










Table 3-7. Regression analysis of contributions of group membership, self-report BDI-II scores,
and Surrogate BDI-II scores upon startle eyeblink magnitudes

A priori picture
category Variable B SE B l t- statistics Model R2 Adj. R2


Neutral


Pleasant


Threat


Disgust-
contamination


Disgust-
mutilation


a For all t-tests, df
*p<.05


group
BDI-II
Surrogate BDI-II
BDI-II x
Surrogate BDI-II

group
BDI-II
Surrogate BDI-II
BDI-II x
Surrogate BDI-II
group
BDI-II
Surrogate BDI-II
BDI-II x
Surrogate BDI-II
group
BDI-II
Surrogate BDI-II
BDI-II x
Surrogate BDI-II
group
BDI-II
Surrogate BDI-II
BDI-II x
Surrogate BDI-II


0.90
0.09
-0.18
0.17


0.02
-0.10
0.11
0.12


1.00
0.06
-0.03
-0.11

-0.12
-0.11
0.01
-0.86


-3.16
0.04
0.13
0.30


0.81
0.10
0.12
0.45


0.99
0.13
0.55
0.55


0.20
0.18
-0.37
0.07


0.00
-0.16
0.04
0.04


1.02 0.18


0.13
0.14
0.57

1.34
0.17
0.18
0.75


0.10
-0.06
-0.04

-0.02
-0.13
0.01
-0.22


1.33 -0.41
0.17 0.04


0.18
0.74


0.16
0.07


1.12
0.84
-1.70
0.37


0.02
-0.75
0.82
0.21


1.00
0.46
-0.25
-0.19

-0.09
-0.62
0.05
-1.15


* -2.37
0.22
0.75
0.40


0.11


0.01


0.03 -0.08


0.05 -0.06


0.08 -0.03


0.18 0.08











52

-51

S50

SO4 Controls

S48 U Parkinson

47

S46

45
Pleasant Neutral Unpleasant
Valence

Figure 3-1. Pattern of emotion- modulated startle eyeblink magnitudes by valence and group. A
main effect of valence was found, with eyeblink magnitudes to pleasant pictures
being significantly smaller than to neutral and unpleasant pictures. Error bars indicate
standard errors of means.













54
53

Z 52

S51
0 Controls
50
5 Parkinson
49
48

47
46

45
Neutral Pleasant Threat Disgust- Disgust-
Contamination Mutilation
A priori picture category

Figure 3-2. Startle eyeblink magnitudes by a priori picture category and group. A main effect of
picture category was found, with eyeblink magnitudes to pleasant pictures greater
than to threat pictures. The picture category x group interaction was also significant,
with eyeblink magnitudes to mutilation pictures smaller for PD patients than controls.
Error bars indicate standard errors of means.











0.12


0.1
+

0.08

EO Controls
0.06









Pleasant Neutral Unpleasant

Valence


Figure 3-3. Skin conductance response by valence and group. Error bars indicate standard errors
of means.











0.12


0.1

+ --
0.08

U 0 Controls
S0.06
0 Parkinson

0 0.04
.C

0.02


0
Neutral Pleasant Threat Disgust- Disgust-
contamination mutilation
A priori emotion category

Figure 3-4. Skin conductance response by a priori picture category and group. Error bars
indicate standard errors of means.













S53

51

0] Controls
49 -
U Parkinson
4 47

45

43
Neutral Happy General Fear Disgust
Aversive
Post hoc emotion category

Figure 3-5. Startle eyeblink magnitudes by post hoc emotion category and group. A main effect
of post hoc emotion category was found, with "fear" and "general aversive" pictures
associated with larger eyeblink magnitudes than "happy" pictures. Error bars indicate
standard errors of means.









CHAPTER 4
DISCUSSION

Summary of Findings

The primary aim of the present study was to test the hypothesis that Parkinson patients

would demonstrate reduced emotional reactivity specific to threatening pictures. Emotion-

modulated startle eyeblink magnitude was used as an index of emotional reactivity. This

hypothesis was based on evidence that the amygdala appears to play a specific role in the

processing of threatening stimuli, coupled with prior findings of amygdala atrophy in

Parkinson's disease. This hypothesis was not supported. Instead, PD patients demonstrated

significantly smaller eyeblink magnitudes to another class of unpleasant pictures, those involving

mutilations. Eyeblink magnitudes to pictures of contaminations (e.g., body products, spoiled

food) did not differ from controls, suggesting that results were not due to generalized diminished

physiological reactivity to disgust-eliciting stimuli. Thus, PD patients showed diminished

reactivity, relative to controls, in the context of pictures showing the effects of bodily harm (i.e.,

mutilations) but not during pictures of threat (i.e., pointed guns, animals ready to attack) or

contamination.

A secondary aim of the study was to examine self- and surrogate-report ratings of

depression and their association with emotion-modulated startle eyeblink magnitude. First, it was

important to determine if any between-groups difference in emotion-modulated startle eyeblink

magnitudes could be accounted for by differential levels of depression. Based on findings from

prior research (Allen et al., 1999; Bowers, Miller, Mikos et al., 2006), a linear relationship

between eyeblink magnitudes and self-reported level of depression was not expected. The data

confirmed this prediction, indicating that PD patients' reduced eyeblink magnitudes to mutilation

pictures could not be attributed to their higher levels of depression.









Next, we examined the prediction that discrepancy between self- and surrogate-report

depression ratings would be larger for PD patients and their spouses compared to controls and

their spouses. This prediction was based on the idea that spouses of PD patients would perceive

them as being more depressed than they truly are, due to misattributing symptoms of PD (e.g.,

masked facies) to depression. This prediction was not supported. Instead, spouses of both

controls and PD patients were fairly accurate at assessing their loved one's mood. Additionally,

no linear relationship between discrepancy in self- versus surrogate-report depression ratings and

emotion-modulated startle eyeblink magnitudes was found. Each of these key findings are

discussed in turn below.

Aim 1

Emotion-Modulated Startle Eyeblink Magnitude: Comparison of Present and Prior Study
Findings

In the present study, Parkinson patients displayed diminished eyeblink magnitudes to

disgusting pictures involving mutilations, while eyeblink magnitudes to threatening pictures

were comparable to those of the control group. This finding is in contrast to the pilot study, in

which startle hyporeactivity in PD patients appeared to be due to decreased magnitudes to threat

pictures (human and animal attacks) as compared to other types of unpleasant pictures (Miller,

2004). One possible explanation for the inconsistency between the current study and the pilot

study may be that in the pilot study, the number of threat pictures and "other unpleasant' pictures

was so small (seven threat pictures; five "other unpleasant" pictures) that the results were not

generalizable to pictures outside those specifically used in the study. For example, an extremely

large eyeblink in response to just one of the pictures in a category could inflate an individual

participant's mean for that category. Another possible explanation for the discrepancy between

the two studies may be that order of stimulus presentation was not carefully controlled in the









pilot study. Only one stimulus order was used, and because the study was post hoc in nature, the

"threat" and "other unpleasant" pictures were not equally distributed with respect to number of

stimuli per category in the first half of the stimulus set versus the second half. Thus, any pictures

associated with a strong emotional response that were located at the beginning of the set could

disproportionately affect the overall mean due to habituation of the startle response over time.

Because the present study overcame both of these methodological limitations of the pilot study,

it is more likely to be a valid reflection of true between-groups differences.

Reduced Startle Eyeblink Magnitude to Mutilation Pictures in Parkinson's Disease:
Proposed Mechanisms

There are several factors that should be considered in interpreting the finding of decreased

startle reactivity to mutilation pictures in PD. First, there is the possibility that the basic startle

eyeblink itself may be compromised or altered in PD patients due to dysfunction of the brainstem

reflex circuitry involved. The existing evidence suggests this is highly unlikely. In both the

previous study (Bowers, Miller, Mikos, et al., 2006; Miller, 2004) and in the current study,

latency and magnitude of the basic, unprimed startle eyeblink was similar for PD patients and

controls. Additionally, other laboratories have investigated startle eyeblink in PD and reported

magnitudes comparable to those of controls (Kofler et al., 2001; Vidaihet et al., 1992 [although

both found increased latency to peak eyeblink, which was not observed in the present study]).

A second possibility is that compared to controls, PD patients may have tended to close

their eyes in response to the mutilation pictures due to the unpleasant content. This concern was

addressed via installation of a video camera in the psychophysiology testing chamber. Overall,

both controls and PD patients rarely closed their eyes in response to a picture. When a participant

closed his/ her eyes (and thus was not viewing the picture when the startle probe was presented),









this trial was discarded from analysis. Thus, the finding of decreased startle eyeblink magnitudes

in PD is not accounted for by deliberate closing of the eyes.

Influence of individual personality differences on emotion-modulated startle eyeblink
magnitude

Another possibility is that reduced startle eyeblink magnitudes to mutilation pictures in the

PD group is not due to disease statusper se, but due to systematic group differences in

personality variables not measured within the current study. The issue of whether individual

personality traits influence emotion-modulated startle has been a topic of recent debate in the

literature. It arises from the fact that while startle potentiation to fear/threat pictures has been

consistently observed, potentiation to disgust pictures is not always found. For example, Balaban

& Taussig (1994) reported that even though disgust pictures were rated as equally arousing and

more unpleasant than fear-evoking pictures, the fear pictures produced startle potentiation but the

disgust pictures did not. In a study using film clips, Kaviani, Gray, Checkley, Kumari, & Wilson

(1999) reported that startle magnitudes were potentiated for clips evoking fear, yet were inhibited

for a film clip of a graphic toe surgery. In contrast, Bradley et al. (2001) and Yartz and Hawk

(2002) found no differences in startle magnitudes to pictures of attack, contamination, or

mutilations (all three potentiated startle). Examination of control data from the current study only

adds to the complexity of interpreting existing findings. Threatening pictures strongly potentiated

startle compared to pleasant pictures, mutilation pictures somewhat potentiated startle (although

this was not significant after Bonferroni correction), but contamination pictures did not. Thus,

the variability in reactions to disgusting pictures across studies begs the question of whether

individual differences in personality traits lead to startle potentiation for some participants, but

not others.









Studies that have examined the relationship between individual differences in emotion-

modulated startle reactivity and personality traits have produced conflicting results. Several

studies have approached the issue by dividing subjects into two groups based on self-reported

personality traits. One group is characterized by high levels of neuroticism, negative affectivity,

and propensity to experience anxiety in the face of punishment or nonreward; the other group is

characterized by low levels of these traits. Using this approach, several studies have reported an

absent or diminished effect of emotion-modulated startle in response to affective pictures or film

clips for the group that has low neuroticism, negative affectivity, and anxiety (Caseras et al.,

2006; Corr et al., 1995; Hawk & Kowmas, 2003; Wilson et al., 2000; although for an exception,

see Kumari et al., 1996). Thus, it is possible that systematic differences in personality traits

between the PD and controls groups could account for the between-groups difference found in

eyeblink magnitudes to mutilation pictures. Although the present study did not include

administration of measures designed to assess the personality traits described above, fifteen of

the PD patients had completed measures of trait anxiety (STAI) and negative affectivity

(PANAS) as part of another study. There appeared to be no relationship between scores on either

of these personality traits and emotion-modulated startle eyeblink magnitudes. Clearly, this

analysis was limited by the fact that these measures were not available for all PD patients or for

the control group; additionally, the small number of participants did not allow for subdivision of

participants into "extremely high" versus "extremely low" negative affect and anxiety groups.

Nonetheless, this limited analysis suggests that startle reactivity did not systematically vary as a

function of these personality variables. As such, it is unlikely that any overall group differences

in trait anxiety or negative affectivity are responsible for the finding of reduced reactivity to

mutilation pictures in the PD group.









Reduced emotional reactivity in PD: Specific to "horror"?

An examination of brain regions putatively involved in the processing of disgust-inducing

pictures may aid in interpretation of startle eyeblink data. The fact that the PD group displayed

diminished emotional modulation of the startle response to mutilation pictures but not

contamination pictures, yet rated both as equally disgusting, suggests that Parkinson patients do

not display hyporeactivity to disgust-eliciting stimuli in general. This conclusion is further

bolstered by the results of the idiographic analysis, in which patients and controls did not differ

in startle reactivity to stimuli they rated as disgusting. Instead, the data suggest that there is a

distinct difference between emotional processing of mutilation and contamination pictures, even

though both types of pictures are typically thought of as eliciting disgust.

Evidence from lesion case reports and fMRI studies suggests that the insula is selectively

involved in processing facial expressions of disgust (Adolphs, Tranel, & Damasio, 2002; Calder,

Keane, Manes, Antoun, Young, 2000; Murphy, Nimmo-Smith, and Lawrence, 2003) as well as

complex visual scenes evoking disgust (Phillips et al., 2000; Shapira et al., 2003; Wright et al.,

2004). Not all investigators have replicated these findings; however, with some studies reporting

equal activation of the insula in response to both disgust- and fear- eliciting pictorial stimuli

(Schienle et al., 2002; Stark et al., 2003). These authors have interpreted their results as an

indication of a common affective circuitry shared between different emotions. Recently, Wright

et al. (2004) noted that some studies used contamination pictures (such as bodily waste products

and spoiled food) along with mutilated bodies to elicit disgust, whereas other studies used only

contamination pictures. In a subsequent fMRI study, they examined the neural substrates

associated with viewing contamination pictures versus mutilation pictures (a comparison with

neutral and fear pictures was also included). These authors found that both contamination and

mutilation pictures significantly activated the insula, whereas fear pictures (human attacks) did









not; moreover, strength of activation was correlated with subjective ratings of disgust. They

interpreted their findings as evidence that the insula is selectively involved in processing disgust.

They also found that mutilation pictures caused greater activation of the occipito-temporal cortex

as compared to contamination pictures, which appeared to be due to the greater arousal

associated with the mutilation pictures, as well as unique activation of the right superior parietal

cortex. This unique area of activation for mutilation pictures indicates that the neural substrates

involved in processing mutilation and contamination pictures are slightly different. Wright et al.

(2004) posed the question of whether this indicates that mutilation pictures evoke a distinct

emotion, such as "horror." Further investigation of whether the "horror" reaction is a specific

discrete emotional response and replications of the neural circuitry involved in this emotional

response are needed before determining if PD patients have a selective deficit in physiological

reactivity to horror.

Subjective ratings of valence, arousal, and basic discrete emotions

Another explanation for the emotion-modulated startle eyeblink finding is that Parkinson

patients found mutilation pictures to be less unpleasant, less arousing, or less disgusting

compared to controls. This could be due to visuoperception problems, resulting in misperception

of pictures, or due to misappraisal of the emotional meaning behind the pictures (Bowers, Miller,

Mikos, et al., 2006). These concerns were addressed by examining the valence and arousal

ratings made by each participant during the psychophysiology experiment, as well as the post

hoc basic emotion ratings made afterwards. The two groups did not significantly differ with

regards to their valence or arousal ratings for mutilation pictures or for any of the a priori picture

categories (neutral, pleasant, threat, disgust- contamination, disgust- mutilation). Additionally, in

theirpost hoc ratings of degree of happiness, disgust, fear, and sadness associated with

mutilation pictures, PD patients' ratings were comparable to controls. Together, these findings









suggest that the lack of startle potentiation to mutilation pictures is not due to a) decreased

subjective unpleasantness or arousal from the standpoint of a dimensional model of emotion; or

b) decreased subjective disgust from a discrete categorical approach to emotion. It is, however,

possible that participants responded to demand characteristics while making their ratings; that is,

they rated pictures based on perceived social norms as opposed to based on how they truly felt.

For example, a participant may have rated a picture of a man attacking a woman as very high in

arousal because that is the socially expected rating even though he may have not felt highly

negatively aroused when viewing the picture. The concern about demand characteristics in the

present study is particularly relevant in light of findings from two different laboratories

indicating that PD patients rate highly arousing negative pictures as less arousing than controls

(Bowers, Miller, Mikos, et al, 2006; Wieser et al., 2006). One fact that may have increased

participant's bias to respond in line with social norms is the fact that most participants were

aware that the current study is the experimenter's dissertation. Thus, some participants may have

been particularly motivated to "perform well" to help a student in school.

Arousal as measured by skin conductance response

To address the concern of potential between-groups differences in arousal level that may

not be detected by examining self-report ratings alone, skin conductance response (SCR) was

examined. Unlike self-report ratings, SCR is an objective measure, and is known to be a strong

index of sympathetic nervous system arousal (Bradley, 2000). In the present study, controls

showed a trend towards increased SCR for unpleasant and pleasant pictures compared to neutral

pictures. In contrast, PD patients showed similar SCR for all categories of pictures; that is, they

did not display emotional modulation of SCR. While results indicated that controls and PD

patients did not significantly differ with respect to SCR to mutilation pictures, this analysis was

hindered by extremely low power. Thus, overall, arousal as measured objectively by SCR did not









correspond to self-report ratings of arousal in PD patients due to a lack of emotional modulation

of SCR. Additionally, prior SCR results from a different sample of PD patients also showed a

lack of emotional modulation (Bowers, unpublished data), as well as an overall pattern of

hyporeactivity. While this finding does not explain why startle eyeblink magnitude was reduced

in response to mutilation pictures specifically (indeed, it only complicates data interpretation), it

clearly suggests that physiological reactivity is aberrant in PD, as indexed by two different

measures of physiological response to emotional stimuli.

Reduced physiological arousal: A translational deficit?

Recently, Bowers, Miller, Mikos, et al. (2006) suggested that PD patients' lack of apparent

physiological arousal in response to pictures that evoke high levels of arousal in controls may be

due to faulty communication between the amygdala and prefrontal cortical areas, putatively due

to low levels of dopamine in PD. More specifically, these authors hypothesized that PD patients

are able to analyze the emotional significance of a stimulus, but the amygdala is unable to

"translate" the results of this emotional appraisal into a physiological response. This hypothesis

is based on a series of animal studies that elucidate the key role played by dopamine in

modulating amygdala activity via cortically- controlled inhibition and disinhibition. The

basolateral nucleus of the amygdala is normally under inhibitory control from the prefrontal

cortex (PFC) due to GABAergic intemeurons (Rosenkranz and Grace, 1999, 2002)1. This

inhibition is thought to be essential to emotional homeostasis, as selective blocking of the

inhibition produces an acute anxiety-like state in rats (Sanders and Shekhar, 1995). In response

to sensory-driven stress (e.g., viewing an aversive picture), dopamine is released in the



1 In the introduction, reference was made to decreased amygdala volume and structural changes to the integrity of
the amygdala in Parkinson's disease (Harding, Stimson, Henderson, & Halliday, 2002; Braak & Braak, 2000). The
basolateral complex of the amygdala is not one of the specific nuclei in which these changes have been reported,
thus it is assumed this nucleus is generally intact.









basolateral amygdala (Inglis and Moghaddam, 1999). This results in suppression of the PFC's

inhibition of the amygdala (net effect: excitation) via feedforward interneurons (Marowsky,

Yanagawa, Obata, and Vogt, 2005). Thus, dopamine acts to modulate PFC-controlled inhibition

and disinhibition of the amygdala in response to stress-inducing stimuli.

According to Bowers, Miller, Mikos, et al. (2006), one can speculate that in Parkinson's

disease, dopaminergic depletion would reduce the extent to which amygdalar disinhibition would

occur in response to a highly-arousing, stress-evoking stimulus. Because the amygdala projects

to basic startle circuitry within the brainstem as well as the hypothalamus, which mediates

sympathetic nervous system arousal (Amaral, Price, Pitkanen, & Carmichael, 1992) the net effect

would potentially be reduced physiologic reactivity, as indexed by measures such as emotion-

modulated startle eyeblink or skin conductance response. While this theory explains a general

reduction in physiological reactivity to aversive pictures in PD, it does not explain why

decreased startle eyeblink magnitudes were found specific to mutilation pictures. One possible

explanation, although mere speculation at this point, is that the mutilation pictures are actually

more arousing than the threat and contamination pictures, even though participants rated them as

equally arousing and SCR in controls was equivalent for all three negative picture categories. In

fact, in a recent large-scale study, Bradley, Codispoti, Cuthbert, et al. (2001) found that

mutilation and animal attack pictures were associated with significantly higher SCR and arousal

ratings than other negative picture contents (such as pictures of vehicular accidents or

contamination). Following this line of reasoning, a significant difference in eyeblink magnitude

between controls and PD may have been found for the mutilation pictures specifically because

they were the only category of aversive pictures sufficiently arousing to detect the muted

responsivity in PD. Thus, reduced physiological reactivity in PD may vary as a function of









arousal level in response to a negative stimulus, with those stimuli eliciting higher arousal being

sensitive enough to detect between-groups differences. The potential significance of decreased

physiological reactivity to arousing aversive stimuli will be addressed later on in this section.

First, the findings with regards to Aim 2 are discussed.

Aim 2

Influence of Depression on Emotion-Modulated Startle Eyeblink Magnitude

A secondary aim of the present study was to examine the influence of depression upon

startle eyeblink magnitudes. This aim tested the possibility that between-groups differences in

startle eyeblink magnitudes may simply be due to differences in level of depression. As

predicted, results indicated that depression was not associated with startle reactivity. This finding

is consistent with prior reports that mild depression does not affect emotion-modulated startle,

although severe depression has been associated with a lack of modulation in response to

emotional stimuli (Allen et al., 1999). Furthermore, a reanalysis of the data removing all

participants on psychotropic medications produced the same findings as with the full sample.

These results indicate that the decreased eyeblink magnitude to mutilation pictures in the PD

group was not due to depression or the influence of psychotropic medications.

Accurately Assessing Depression: Comparison of Self- and Surrogate Report Measures

An additional goal was to determine if symptoms of Parkinson's disease (e.g., masked

facies, rigidity) lead spouses of PD patients to perceive of them as being more depressed than

they truly are. This prediction was not supported; that is, spouses of patients did not misattribute

disease symptoms to depression. In fact, spousal ratings and self-ratings of depression were

highly correlated, suggesting that in general spouses of PD patients are well-attuned to how their

loved ones are feeling. These spousal-report results are in contrast to prior studies using health

care professionals and laypersons as raters, which found that negative traits were often









misattributed to PD patients. For example, PD patients were rated as more anxious, unhappy, and

hostile than controls (Pentland et al.,1987, 1988; Pitcairn et al., 1990). This present study is the

first to examinefamily member perceptions of mood states in Parkinson's patients, and findings

suggest that spouses do not tend to make the misattributions that people who do not know the

patient very well may make. These findings further suggest that spouses may adequately serve as

surrogate reporters of a patient's mood in clinical settings when the patient is unable or unwilling

to report his or her own mood.

Alternatively, the significant correlation between self- and spousal- report of depression

symptoms in PD could be interpreted as an indication that cognitively intact PD patients do not

exhibit self-awareness deficits (often referred to as aosaganosia, or denial of the illness) in the

domain of assessing their own mood. This is relevant when examined in the context of literature

suggesting that PD patients may show self-awareness deficits with regard to other aspects of

their functioning. For example, Leritz, Loftis, Crucian, Friedman, & Bowers (2004) found that

PD patients rated themselves as more independent in their ability to carry out activities of daily

living compared to their caregiver's ratings. In this study, as with the present study, the caregiver

was often a spouse. Similarly, Seltzer, Vasterling, Mathias, & Brennan (2001) found that PD

patients rated themselves as less impaired than their caregivers did in terms of their motoric

functioning, self-care, and social skills. Leritz et al. (2004) proposed that damage to frontal-

subcortical connections in PD (Alexander et al., 1986) may account for these awareness deficits.

In contrast, a recent examination of self- and caregiver- ratings of affect found that PD patients

were generally aware of their reduced facial expressivity (Mikos et al., 2007). One explanation

for this discrepancy between studies may be that self-awareness deficits may be specific to

certain domains of the functioning, with awareness of emotional functioning and mood being









spared. A more likely explanation is that global self-awareness deficits may be related to severity

of cognitive impairment. Future studies are needed to address whether self- and spousal mood

ratings correlate for PD patients that are cognitively impaired.

Relationship between Surrogate-Report Depression and Emotion-modulated Startle
Eyeblink Magnitude

Relating these finding back to the primary startle paradigm data, neither spousal-completed

Surrogate BDI-II scores or self- vs. spousal- discrepancy were significantly associated with

emotion-modulated startle eyeblink magnitude. This is not surprising, given that self- and

spousal- BDI-II scores were correlated and self-report BDI-II scores were found to be unrelated

to eyeblink magnitude.

Study Limitations

There are several limitations to the current study that should be acknowledged. First, the

patient sample may not be representative of the typical person with Parkinson's disease. The

sample had an average of 16 years of education, with many individuals having obtained master's

degrees, Ph.D.s, and medical degrees. Although it is unlikely that educational status influences

the emotion-modulated startle eyeblink, as it is thought to be a fairly automatic reaction

(Bradley, 2000), it is possible that education could potentially influence subjective emotion

ratings in terms of participants "overthinking" their responses or trying to anticipate the desired

response from the examiner.

The sample also had an imbalance of men and women (14 men and 10 women per group).

Although preliminary analyses including "sex" as a dependent variable revealed no significant

effect of sex for any of the key study aims, the study was not designed to be sufficiently powered

to examine sex differences. In a large study of sex differences in physiologic reactivity, Bradley,

Codispoti, Sabatinelli, et al. (2001) reported that in general, women tend to respond with greater









defense activation to aversive pictures whereas men show greater reactivity to erotic pictures.

This raises the possibility that sex may interact with startle potentiation to the fear, disgust-

contamination, or disgust- mutilation pictures. Additionally, studies of women with PD are

surprisingly lacking in the existent literature. Most studies include only men, or a significantly

greater proportion of men that women. Thus, there is a need for studies that examine the unique

effects that Parkinson's disease may have upon women.

The present study is also limited by the fact that participants were limited to PD patients in

Hoehn and Yahr stage 2 or 3, and the majority of patients had on-medication UPDRS motor

scores falling in the 20s (range: 4-41). Although startle eyeblink magnitudes were not

significantly associated with UPDRS motor score, this finding is limited by the fact that persons

with severe PD were not included in the study. It is possible that a linear relationship between

disease severity and eyeblink magnitude exists (as was found by Bowers, Miller, Mikos, et al.,

2006), but was not detected by the restricted range in the current study. Future studies should

include patients with a broader range of disease severity in order to more fully examine the

impact of disease progression upon emotion-modulated startle.

A major limitation of the spousal Surrogate-BDI-II rating portion of the study was that it

was not sufficiently powered to detect any interaction with group membership. The observed

power for the Surrogate BDI-II x Group interaction was .14, which is clearly inadequate. Thus,

the finding that spouses of controls and PD patients can serve as adequate surrogate reporters of

mood should be interpreted with caution. Larger scale studies are needed to confirm that spouses

are adequate surrogate reporters, and to examine the potential practical clinical utility of a

surrogate mood measure for use with PD patients.









This study included a unique idiographic approach to startle eyeblink data analysis, in

which each participant's emotion-modulated startle eyeblink magnitude T-scores were created

based on his or her post hoc ratings of the amount of happiness, disgust, fear, and sadness felt for

each picture. This rating system had several important limitations. First, ratings of all six

"primary" discrete emotions (happy, sad, disgusted, fearful, angry, and surprise; Ekman &

Friesen, 1976) were not included. This was due to concerns that requiring patients to make such

a large number of ratings for each picture would be exhausting or confusing. Thus, anger and

surprise were eliminated from the rating process, as these emotions were not directly relevant to

study aims. "Sad" was retained so that participants would not be biased to rate all aversive

pictures as simply disgusting or fearful. Clearly, ratings of all six primary discrete emotions

could more fully capture the subjective experiences of participants. Secondly, the post hoc rating

scale used for indicating degree of emotion experienced was anchored on one end with a

descriptor that was relative, as opposed to absolute. Specifically, the highest rating on the scale

had the descriptor "I strongly felt this emotion." In a critique of psychophysical measurement,

Bartoshuk, Fast, & Snyder (2005) pointed out that a vague intensity descriptor such as "strongly"

can vary in interpretation from person to person, creating invalid comparisons. A more

appropriate descriptor for the high end of the rating scale would have been "This emotion was

the strongest imaginable," particularly since the low end of the scale was anchored with an

absolute descriptor ("I did not feel any of this emotion"). Thirdly, although the pictures chosen to

evoke specific emotions were generally effective in doing so, the negatively-valenced pictures

often evoked more than one emotion. This finding is hardly unusual; indeed, other investigators

(Bradley, Codispoti, Sabatinelli, et al., 2001; Yartz & Hawk, 2002) have also observed that

pictorial stimuli tend to produce "blends" of emotions. However, this created difficulty in









categorizing individual stimuli for the idiographic analysis of eyeblink magnitudes. Because the

apriori fear and disgust- mutilation pictures often were rated as high in disgust and fear, it was

necessary to create a "general aversive" emotion category when analyzing startle eyeblink

magnitude data from an idiographic approach. The lack of a significant group x post hoc

emotion category interaction in the idiographic analysis was likely due to the fact that mutilation

pictures were subsumed by either the "disgust" or "general aversive" category, effectively

masking group differences specific to the mutilation pictures. Additionally, some participants

interpreted the meaning of "disgust" in a way not intended. For example, PD patients rated fear

pictures (pictures of animal and human attacks) significantly higher in disgust than controls. It

appears that in this case they were not referring to disgust as a visceral reaction to grotesque

stimuli, but as a moral judgement within the context of a social situation (i.e., "I am disgusted by

your behavior"). Although the purpose behind the idiographic approach was to account for

individual differences in emotional reactions, the possibility that participants might interpret the

emotion labels differently that the experimenter intended was not anticipated. Clearly, individual

differences in conceptualization of what makes a stimulus "disgusting" can affect overall results.

These issues complicate the interpretation of the present data, but also raise important questions

about methodological and conceptual concerns within emotion research in general.

Conceptual and Methodological Issues in Emotion Research

Taken together, the data from the post hoc ratings portion of the study suggests that

laboratory experiments attempting to parse apart emotional reactions based on a discrete

categorical approach to emotions may be overly simplistic. Unfortunately, many studies in the

emotion literature ask participants to "pick a label" amongst the choices of happy, sad, disgusted,

fearful, angry, or surprised in response to presentation of a facial expression, prosodic utterance,

or to describe how they are feeling. This approach is understandable and often necessary to









make sense of the data; however, in reality discrete emotions do not occur in relative isolation of

all other emotions. Similarly, it may not be easy for participants to decompose their emotional

reactions into their basic discrete components. For example, asking participants how happy, sad,

disgusted, fearful, angry, or surprised they feel may not fully capture the complex emotional

reactions associated with certain interpersonal situations, such as seeing a gun held to a person's

head or a disfigured body. As stated by Lang, (1995) "emotional judgments, physiology, and

behavior can present a confusing rock pile that resists a simple classification by specific

emotional states." Future studies may benefit from a taking a dimensional approach to emotional

experiences, as suggested by Lang (1995), in which emotional response to an aversive stimulus

is classified by an action tendency to withdraw, and emotional response to an appetitive stimulus

is classified by a tendency to approach. Alternatively, future studies may benefit from having

participants rate emotions from both discrete emotion and dimensional approaches, as was done

in the current study, then examining results from both perspectives. Finally, it may be fruitful to

ask participants to describe in their own words their emotional reactions, rather than forcing

them to choose from a pre-determined set of responses. Although this poses problems in

quantitative data analysis, it more fully captures the complexity of human emotional experience.

This same problem also exists with respect to classifying emotion-eliciting stimuli when

designing an experiment. As previously mentioned, Wright et al. (2004) pointed out that some

authors have used only contamination pictures to induce a disgust response, whereas others used

both contamination and mutilation pictures. While this raises the issue of how to best classify

mutilation pictures (should they be with the other "disgust" pictures, or in their own category?),

further exploration of this issue is unlikely to advance scientific knowledge of emotional

reactions. A more productive direction to take might be an examination of the emotional









significance behind mutilation pictures. At a more primitive level, a mutilated body represents

destruction of the victim's bodily integrity, and thus could be perceived by the viewer as a threat

to his or her own bodily integrity. From this perspective, it is clear that mutilations evoke a

strong aversive emotional reaction, regardless of whether the semantic label of'disgust' or

'horror' is given to the reaction.

Significance of the Study

The present research has two important findings that add to the literature on emotion in

Parkinson's disease. First, PD patients showed diminished reactivity, as measured by emotion-

modulated startle eyeblink, to pictures of mutilations. While it might be tempting to propose that

this finding represents a "mutilation-specific" emotional processing deficit in PD, such an

interpretation is overly simplistic and does not take into consideration other relevant factors. For

example, one possibility is that the diminished reactivity in PD is not emotion- or content-

specific, but represents a deficit in physiological responsivity to highly arousing negative stimuli

in general. Mutilation pictures are highly arousing stimuli because they represent a threat to

bodily integrity; as such, it may be that the mutilation pictures were the only category of pictures

sufficiently arousing to detect a between-groups difference in physiological reactivity. In the

present study, we attempted to further investigate the issue of reduced physiological arousal in

PD by examining skin conductance response (SCR) data; however, this was problematic because

PD patients did not appear to exhibit emotional modulation of SCR for any of the picture

categories. The interpretation of skin conductance data is further complicated by the fact that

autonomic nervous system dysfunction is often found in patients with PD as a result of cell loss

and Lewy bodies within the sympathetic ganglion (for a review, see Chauduri, 2001). Thus, the

abnormalities in SCR observed in the present study may be due to general autonomic

dysregulation. One possible way to bypass this problem in future studies is to examine other









variables associated with arousal level. For example, an important area for future research is

examination of cortisol levels in responses to stress in PD. Because measurement of cortisol

levels provides a neuroendocrine marker of reactions to stressful stimuli, this method could

approach the problem of decreased reactivity to arousing, aversive stimuli from a new angle.

Although the literature on cortisol levels in PD is sparse, one study found that PD patients

showed overall elevations in plasma cortisol levels, yet a "flattening" of cortisol variations

typically observed throughout the day (Hartmann, Veldhuis, Deuschle, Standhardt, & Heuser,

1997). Interesting, this pattern of flattened amplitude variations in cortisol has been found in

depressed patients (Deuschle et al., 1997; Halbreich, Asnis, Shindldecker, Zumoff, & Nathan,

1985; Linkowski et al., 1985). Clearly, future research is needed to explore cortisol levels in PD

and their potential association with depression in this patient population.

The second important finding from the present study is that a strong convergence emerged

between spousal and PD patient ratings of the patient's mood. Although the evidence is limited

by inadequate statistical power, the issue of surrogate mood reporting is particularly important in

the later stages of Parkinson's, when patients may be unable to report upon their own mood due

to dementia or speech deficits. Logsdon & Teri (1995) have already reported that spouses served

as valid surrogate reporters of mood for patients with Alzheimer's disease. A similar validation

of the Surrogate BDI-II for use with caregivers of PD patients may lead to useful clinical

applications. Such a measure could be used with spouses of patients unable to report upon their

mood, or unwilling to discuss mood due to embarrassment or concerns about social stigma.

Recognizing that spouses can serve as important sources of information concerning a patient's

mood may lead to improved detection of depression in Parkinson's disease.









Although studies of emotion have many methodological challenges to overcome, this study

represents an attempt at further characterizing changes in emotional reactivity that may occur

with Parkinson's disease. Hopefully, future studies will continue to explore these changes not

simply in isolation, but from the framework of an integrated model that considers how emotion,

cognition, and motor symptoms interact to affect the well-being of the whole person.










APPENDIX A
NORMATIVE VALENCE AND AROUSAL RATINGS FOR PICTURE STIMULI

Table A-1. International Affective Picture System (IAPS) Normative Valence and Arousal
Ratings

Picture
Category IAPS # Picture Description Valencea Arousala
Neutral


7100
7235
7080
7050
7020
7211
7035
7038
7950
7150
7175
7233


Pleasant


8501
8034
5260
4599
8370
4653
4626
8170
5621
5629
8470
8200


firehydrant
chair
fork
hairdryer
fan
clock
mug
shoes
tissue
umbrella
lamp
plate
Average

money
snowskier
waterfall
romantic couple
rafting
couple
wedding
sailboat
skydivers
hiker
gymnast
waterskier
Average


5.24(1.20)
4.96(1.18)
5.27 (1.09)
4.93 (0.81)
4.97 (1.04)
4.81 (1.78)
4.98 (0.96)
4.82(1.2)
4.94 (1.21)
4.72(1.00)
4.87 (1.00)
5.09(1.46)
4.97 (1.16)

7.91 (1.66)
7.06(1.53)
7.34(1.74)
7.12(1.48)
7.77 (1.29)
6.56 (1.65)
7.6 (1.66)
7.63 (1.34)
7.57 (1.42)
7.03 (1.55)
7.74(1.53)
7.54 (1.37)
7.41 (1.52)


2.89(1.70)
2.83 (2.00)
2.32(1.84)
2.75(1.80)
2.17(1.71)
4.20 (2.40)
2.66(1.82)
3.01 (1.96)
2.28(1.81)
2.61 (1.76)
1.72(1.26)
2.77 (1.92)
2.68 (1.83)

6.44 (2.29)
6.30 (2.16)
5.71 (2.53)
5.69 (1.94)
6.73 (2.24)
5.83 (2.07)
5.78 (2.42)
6.12(2.30)
6.99 (1.95)
6.55(2.11)
6.14(2.19)
6.35 (1.98)
6.22 (2.18)









Table A-1. Continued

Picture
Category IAPS # Picture Description Valencea Arousala
Threat


6313
3500
6510
6242
6260
6821
6243
1120
1052
1525
1932
1300


3000
3071
3110
3400
3150


knife attack
gun pointed at man
masked man
gang with gun
aimed gun
gang attacking car
man pointing gun
snake
snake
attackdog
shark attack
dog with teeth bared
Average


mutilated face
mutilated body
bum victim
severed hand
bloody chopped
fingers


1.98 (1.38)
2.21 (1.34)
2.46(1.58)
2.69 (1.59)
2.44(1.54)
2.38(1.72)
2.33 (1.49)
3.49 (1.93)
3.5 (1.87)
3.09(1.72)
3.85 (2.11)
3.55 (1.78)
2.83 (1.67)

1.59 (1.35)
1.88 (1.39)
1.79(1.30)
2.35 (1.90)
2.26 (1.57)


6.94 (2.23)
6.99 (1.68)
6.96 (2.23)
5.43 (1.93)
6.93 (1.98)
6.29(2.19)
5.99 (2.23)
6.93 (2.20)
6.52 (2.02)
6.51 (2.25)
6.47 (2.09)
6.79(1.84)
6.56 (2.07)

7.34 (2.27)
6.86(2.05)
6.70(2.16)
6.91 (2.22)
6.55 (2.20)


3060 mutilated body 1.79 (1.56) 7.12 (2.09)
6415 dead bloody tiger 2.21 (1.51) 6.2(2.31)
9300 dirty toilet 2.26 (1.76) 6.00(2.41)
7359 bug on pie 3.38 (1.75) 5.07(2.09)
9301 dirty toilet 2.26 (1.56) 5.28 (2.46)
9373 vomit 3.38 (1.48) 5.01(2.16)
1274 roaches 3.17(1.53) 5.39 (2.39)
Average 2.36 (1.56) 6.20 (2.23)
Note: Values are expressed as mean (SD). Valence ratings are on a 1-9 scale, with 9 being most
pleasant. Arousal ratings are on a 1-9 scale, with 9 being most arousing.
aFrom Lang et al., 2001b


Disgust









APPENDIX B
SKIN CONDUCTANCE RESPONSE DATA ACQUISITION AND REDUCTION
PROCEDURES

Data Acquisition

The skin on the palm of the hand was prepared by washing the hands with a mild soap,

then wiping the skin with rubbing alcohol. Next, surface Ag-AgCl electrodes were filled with an

isotonic eylectrolyte gel and positioned on the thenar and hypothenar eminence of left and right

palm. During the psychophysiology experiment, SCR was sampled at 20 Hz using two

Coulbourn Isolated Skin Conductance couplers in DC mode.

Data Reduction

Each picture trial was scored for the largest change in SCR between 0.9 and 6.0 seconds

after picture onset. Raw values for the left and right palms were averaged into a composite score

for each trial. A value of"1" was added to these composite scores to eliminate negative values.

This new value was then subjected to a log transformation to reduce skewness (Bradley,

Codispoti, Cuthbert, et al., 2001). Because SCR habituates rapidly, only responses to the first

half of the entire stimulus set (i.e., responses to the first 32 pictures) were included in the data

analyses reported. Because SCR habituates rapidly, only responses to the first half of the entire

stimulus set (i.e., responses to the first 32 pictures) were included in the data analyses reported.









LIST OF REFERENCES

Adolphs, R., Schul, R., & Tranel, D. (1998). Intact recognition of facial emotion in Parkinson's
disease. Neuropsychology, 12(2), 253-258.

Adolphs, R., Tranel, D., & Damasio, A. R. (2003). Dissociable neural systems for recognizing
emotions. Brain and Cognition, 52(1), 61-69.

Alexander, G.E., DeLong, M.R., & Strick, P.L. (1986). Parallel organization of functionally
segregated circuits linking basal ganglia and cortex. Annual Review ofNeuroscience, 9,
357-381.

Allen, N.B., Trinder, J., & Brennan, C. (1999). Affective startle modulation in clinical
depression: preliminary findings. Biological Psychiatry, 46, 542-550.

Amaral, D.G. (2003). The Amygdala, Social Behavior, and Danger Detection. Annals of the New
York Academy of Sciences, 1000, 337-347.

Amaral, D.G., Price, S., Pitkanen, A., & Carmichael, S. (1992). Anatomical organization of the
primate amygdaloid complex. In J. Aggleton (Ed.), The amygdala (pp. 1-66). New York:
Wiley.

Balaban, M.T., & Taussig, H.N. (1994). Salience of fear/threat in the affective modulation of the
human startle blink. Biological Psychology, 38, 117-131.

Bartoshuk, L.M., Fast, K., & Snyder, D.J. (2005). Differences in our sensory worlds: invalid
comparisons with labeled scales. Current Directions in Psychological Science, 14(3), 122-
125.

Beck, A.T.(1996). The Beck Depression Inventory-II. San Antonio, TX: The Psychological
Corporation.

Beck, A.T., Steer, R., & Brown, G. (1996). The Beck Depression Inventory-IIManual. San
Antonio, TX: The Psychological Corporation.

Benabid, A.L. (2003). Deep brain stimulation for Parkinson's disease. Current Opinion in
Neurobiology, 13(6), 696-706.

Blonder, L.X., Gur, R.E., & Gur, R.C. (1989). The effects of right and left hemiparkinsonism on
prosody. Brain andLanguage, 36, 193-207.

Borod, J.C., Welkowitz, J., Alpert, M., Brozgold, A.Z., Martin, C., Peselow, E., et al. (1990).
Parameters of emotional processing in neuropsychiatric disorders: conceptual issues and a
battery of tests. Journal of Communication Disorders, 23, 247-271.

Bowers, D. (2007). [Emotion-modulated skin conductance response in Parkinson's disease].
Unpublished raw data.









Bowers, D., Gilmore, R., Gokcay, D., Roper, S., Rogish, M., & Kortenkamp, S. (2001).
Laterality effects in verbal-emotional modulation of startle following temporal lobectomy
[Abstract]. Journal of the International Neuropsychological Society, 7(2), 199.

Bowers, D., Miller, K., Bosch, W., Gokcay, D., Pedraza, O., Springer, U., et al. (2006). Faces of
emotion in Parkinson's disease: Micro-expressivity and bradykinesia during voluntary
facial expressions. Journal of the International Neuropsychological Society, 12(6), 765-
73.

Bowers, D., Miller, K., Mikos, A., Kirsch-Darrow, L., Springer, U., Fernandez, H., et al. (2006).
Startling facts about emotion in Parkinson's disease: blunted reactivity to aversive stimuli.
Brain, 129(pt 12), 3356-65.

Braak, H., & Braak, E. (2000). Pathoanatomy of Parkinson's disease. Journal ofNeurology,
247(Suppl. 2), 1I/3-11/10.

Bradley, M. (2000). Emotion and motivation. In L. Tassinary, J. Cacioppo, & G. Berntson
(Eds.), Handbook ofpsychophysiology. New York, NY: Cambridge University Press.

Bradley, M.M., Codispoti, M, Cuthbert, B., & Lang, P. (2001). Emotion and Motivation I:
Defensive and Appetitive Reactions in Picture Processing. Emotion, 1(3), 276-298.

Bradley, M.M., Codispoti, M., Sabatinelli, D., & Lang, P.J. (2001). Emotion and motivation II:
sex differences in picture processing. Emotion, 1(3), 300-319.

Bradley, M.M., & Vrana, S.R. (1993). In N. Birbaumer, & A. Ohman (Eds.), The structure of
emotion: Psychophysiological, cognitive, and clinical aspects (pp. 270-287). Seattle, WA:
Hogrefe & Huber.

Brown, R.G., & Pluck, G. (2000). Negative symptoms: the 'pathology' of motivation and goal-
directed behaviour. Trends in Neuroscience, 23, 412-417.

Buck, R., & Duffy, R.J. (1980). Nonverbal communication of affect in brain-damaged patients.
Cortex, 16, 351-362.

Burn DJ. (2002). Beyond the iron mask: Towards better recognition and treatment of depression
associated with Parkinson's disease. Movement Disorders, 17(3), 445-454.

Calder, A.J., Young, A.W., Rowland, D., Perrett, D.I., Hodges, J.R., & Etcoff, N.L. (1996).
Facial emotion recognition after bilateral amygdala damage: differentially severe
impairment of fear. Cognitive Neuropsychology, 13, 699-745.

Calder, A. J., Keane, J., Manes, F., Antoun, N., & Young, A. W. (2000). Impaired recognition
and experience of disgust following brain injury. Nature Neuroscience, 3(11), 1077-1078.









Caseras, F. X., Fullana, M. A., Riba, J., Barbanoj, M. J., Aluja, A., & Torrubia, R. (2006).
Influence of individual differences in the Behavioral Inhibition System and stimulus
content (fear versus blood-disgust) on affective startle reflex modulation. Biological
Psychology, 72(3), 251-256.

Chaudhuri, K.R. (2001). Autonomic dysfunction in movement disorders. Current Opinions in
Neurology, 14(4), 505-511.

Cools, R., Barker, R.A., Sahakian, B.J., & Robbins, T.W. (2001). Mechanisms of cognitive set
flexibility in Parkinson's disease. Brain, 124, 2503-2512.

Corr, P.J., Wilson, G.D., Fotiadou, M., Kumari, V., Gray, N.S., Checkley, S., et al. (1995).
Personality and affective modulation of the startle reflex. Personality andIndividual
Differences, 19, 543-553.

Cummings, J.L. (1992). Depression and Parkinson's disease: A review. American Journal of
Psychiatry, 149, 443-454.

Cuthbert, B., Bradley, M., & Lang, P. (1996). Probing picture perception: Activation and
emotion. Psychophysiology, 33, 103-111.

Davis, M. (1992). The role of the amygdala in conditioned fear. In J. Aggleton (Ed.), The
Amygdala: Neurobiological aspects of emotion, memory, and mental dysfunction (pp. 255-
305). New York, NY: Wiley Publishers.

Davis, M., & Gallagher, D.W. (1988). Continuous slow release of low levels of diazepam
produces tolerance to its depressant and anxiolytic effects on the startle reflex. European
Journal ofPharmacology, 150, 23-33.

Davis, M., Genderlman, D.S., Tischler, M.D., & Gendelman, P.M. (1982). A primary acoustic
startle circuit: lesion and stimulation studies. Journal ofNeuroscience, 2(6), 791-805.

Delis, D., Kramer, J., Kaplan, E., & Ober, B. (2000). The California VerbalLearning Test, 2nd
Edition Manual. San Antonio, TX: Psychological Corporation.

Deuschle, M., Schweiger, U., Weber, B., Gotthardt, U., Korner, A., Schmider, J., et al. (1997).
Diurnal activity and pulsatility of the hypothalamus-pituitary-adrenal system in male
depressed patients and healthy controls. Journal of Clinical Endocrinology and
Metabolism, 82(1), 234-238.

Dimitrov, M, Grafman, J., Soares, A.H., Clark, K. (1999). Concept formation and concept
shifting in frontal lesion and Parkinson's disease patients assessed with the California card
sorting task. Neuropsychology, 13, 135-143.

Dooneief, G., Mirabello, E., Bell, K., Marder, K., Stern, Y., & Mayeux. R. (1992). An estimate
of the incidence of depression in idiopathic Parkinson's disease. Archives ofNeurology,
49, 305-307.









Ekman, P., & Friesen, W.V. (1976). Pictures of Facial Affect. Washington, D.C.: Consulting
Psychologists Press, Inc.

Fahn, S., Elton, R.L. (1987). Unified Parkinsons Disease Rating Scale. In S. Fahn, C.D.
Marsden, M. Goldstein, D.B. Calne (Eds.), Recent developments in Parkinson's disease,
Volume 2 (pp. 153-163). Florham Park, NJ: Macmillan Healthcare Information.

Fahn, S. (2003). Description of Parkinson's disease as a clinical syndrome. Annual New York
Academy of Sciences, 991, 1-14.

Fridlund, A. J., & Cacioppo, J. T. (1986). Guidelines for human electromyographic research.
Psychophysiology, 23(5), 567-589.

Gauntlett-Gilbert, J., Roberts, R.C., Brown, V.J. (1999). Mechanisms underlying attentional set-
shifting in Parkinson's disease. Neuropsychologia, 37, 605-616.

German, D. C., Manaye, K. F., White, C. L., 3rd, Woodward, D. J., McIntire, D. D., Smith, W.
K., et al. (1992). Disease-specific patterns of locus coeruleus cell loss. Annals of
Neurology, 32(5), 667-676.

Greenwald, M., Cook, E., & Lang, P. (1989). Affective judgment and psychophysiological
response dimensional covariation in the evaluation of pictorial stimuli. Journal of
Psychophysiology, 3, 51-64.

Halbreich, U., Asnis, G. M., Shindledecker, R., Zumoff, B., & Nathan, R. S. (1985). Cortisol
secretion in endogenous depression. II. Time-related functions. Archives of General
Psychiatry, 42(9), 909-914.

Harding, A.J., Stimson, E., Henderson, J.M., & Halliday, G.H. (2002). Clinical correlates of
selective pathology in the amygdala of patients with Parkinson's disease. Brain, 125, 2431-
2445.

Hariri, A.R., Mattay, V.S., Tessitore, A., Fera, F., & Weinberger, D.R. (2003). Neocortical
Modulation of the amygdala response to fearful stimuli. Biological Psychiatry, 53, 494-
501.

Harmer, C., Shelley, N., Cowen, P., & Goodwin, G. (2006). 5HT(3) antagonism abolishes the
emotion potentiated startle effect in humans. Psychopharmacology (Berl), 186, 8-24.

Hartmann, A., Veldhuis, J. D., Deuschle, M., Standhardt, H., & Heuser, I. (1997). Twenty-four
hour cortisol release profiles in patients with Alzheimer's and Parkinson's disease
compared to normal controls: ultradian secretary pulsatility and diurnal variation.
Neurobiology ofAging. 18(3), 285-289.

Hawk, L. W., Jr., & Kowmas, A. D. (2003). Affective modulation and prepulse inhibition of
startle among undergraduates high and low in behavioral inhibition and approach.
Psychophysiology, 40(1), 131-138.









Hitchcock, J.M., & Davis, M. (1991). Efferent pathway of the amygdala involved in conditioned
fear as measured with the fear-potentiated startle paradigm. Behavioral Neuroscience,
105(6), 826-842.

Hitchcock, J.M., Sananes, C.B., Davis, M. (1989). Sensitization of the startle reflex by
footshock: Blockade by lesions of the central nucleus of the amygdala or its efferent
pathway to the brainstem. Behavioral Neuroscience, 103(3), 509-518.

Hoehn, M., & Yahr, M. (1967). Parkinsonism: onset, progression, and mortality. Neurology, 17,
427-442.

Hughes, A.J., Ben-Shlomo, Y., Daniel, S.E., & Lees, A.J. (1992). What features improve the
accuracy of clinical diagnosis in Parkinson's disease: a clinicopathologic study. Neurology,
42, 1142-1146.

Hughes, A.J., Daniel, S.E., Kilford, L., & Lees, A.J. (1992). Accuracy of clinical diagnosis of
idiopathic Parkinson's disease: A clinicopathological study of 100 cases. Journal of
Neurology, Neurosurgery, and Psychiatry, 55, 181-184.

Isella, V., Melzi, P., Grimaldi, M., Iurlaro, S., Piolti, R., Ferrarese, C., et al. (2002). Clinical,
neuropsychological, and morphometric correlates of apathy in Parkinson's disease.
Movement Disorders, 17(2), 366-371.

Inglis, F. M., & Moghaddam, B. (1999). Dopaminergic innervation of the amygdala is highly
responsive to stress. Journal ofNeurochemistry, 72(3), 1088-1094.

Jacobs, D.H., Shuren, J., Bowers, D., & Heilman, K.M. (1995). Emotional facial imagery,
perception, and expression in Parkinson's disease. Neurology, 45, 1696-1702.

Jacobs, D.M., Stern, Y., & Mayeux, R. (2000). Dementia in Parkinson's disease, Huntington's
disease, and other degenerative conditions. In M.J. Farah & T.E. Feinberg (Eds.), Patient-
basedapproaches to cognitive neuroscience (pp. 375-384). Cambridge, MA: MIT Press.

Jurica, P.J., Leitten, C.L., & Mattis, S. (2001). Dementia Rating Scale-2 Professional Manual.
Lutz, FL: Psychological Assessment Resources, Inc.

Kan, Y., Kawamura, M., Hasegawa, Y., Mochizuki, S., & Nakamura, K. (2002). Recognition of
emotion from facial, prosodic, and written verbal stimuli in Parkinson's disease. Cortex,
38(4), 623-630.

Kaplan, E.F., Goodglass, H., & Weintraub, S. (2001). The Boston Naming Test, 2nd edition.
Philadelphia: Lea & Febiger.

Katsikitis, B.A., & Pilowsky, M.D. (1988). A study of facial expression in Parkinson's disease
using a novel microcomputer-based method. Journal ofNeurology, Neurosurgery, and
Psychiatry, 51, 362-366.









Katsikitis, B.A., & Pilowsky, M.D. (1991). A controlled quantitative study of facial expression
in Parkinson's disease and depression. The Journal of Nervous andMental Disease,
179(11), 683-688.

Kaviani, H., Gray, J. A., Checkley, S. A., Kumari, V., & Wilson, G. D. (1999). Modulation of
the acoustic startle reflex by emotionally-toned film-clips. International Journal of
Psychophysiology, 32(1), 47-54.

Kaviani, H., Gray, J. A., Checkley, S. A., Raven, P. W., Wilson, G. D., & Kumari, V. (2004).
Affective modulation of the startle response in depression: influence of the severity of
depression, anhedonia, and anxiety. Journal of Affective Disorders, 83(1), 21-31.

Kirsch-Darrow, L., Fernandez, H.H., Marsiske, M., Okun, M.S., & Bowers, D. (2006).
Dissociating apathy and depression in Parkinson's disease. Neurology, 11(67), 33-38.

Kltiver, H., & Bucy, P.C. (1939). Preliminary analysis of the temporal lobes in monkeys.
Archives ofNeurology and Psychiatry, 42, 979-1000.

Kofler, M., Muller, J., Wenning, G.K. Reggiani, L., Hollosi, P., Bosch, S., et al. (2001). The
auditory startle reaction in parkinsonian disorders. Movement Disorders, 16(1), 62-71.

Kumari, V., Corr, P.J., Wilson, G.D., Kaviani, H., Thornton, J.C., Checkely, S.A., et al. (1996).
Personality and modulation of the startle reflex by emotionally toned film clips.
Personality and Individual Differences, 21, 1029-1041.

Lang, P.J. (1980). Behavioral treatment and biobehavioral assessment: Computer applications. In
J.B. Sidowski, J.H. Johnson, & T.A. Williams (Eds.). Technology in mental health care
delivery. Norwood, NJ: Albex Publishing Corporation.

Lang, P.J. (1995). The Emotion Probe: studies of motivation and attention. The American
Psychologist, 50(5), 372-385.

Lang, P.J., Bradley, M.M., & Cuthbert, B.N. (1990). Emotion, attention, and the startle reflex.
Psychological Review, 97(3), 377-395.

Lang, P., Bradley, M., & Cuthbert, B. (2001a). The International Affective Picture System
(photographic slides). Gainesville, FL: The Center for Research in Psychophysiology,
University of Florida.

Lang, P., Bradley, M., & Cuthbert, B. (2001b). International affective picture system (IAPS):
Instruction manual and affective ratings: Technical Report A-5. Gainesville, FL: The
Center for Research in Psychophysiology, University of Florida.

Lezak, M.D., Howieson, D.B., & Loring, D.W. (2004). Neuropsychological Assessment (Fourth
Edition). Oxford: Oxford University Press.

Leritz, E., Loftis, C., Crucian, G., Friedman, W., & Bowers, D. (2004). Self-awareness of
deficits in Parkinson disease. The Clinical Neuropsychologist, 18(3), 352-361.









Linkowski, P., Mendlewicz, J., Leclercq, R., Brasseur, M., Hubain, P., Golstein, J., et al. (1985).
The 24-hour profile of adrenocorticotropin and cortisol in major depressive illness. Journal
of Clinical Endocrinology andMetabolism, 61(3), 429-438.

Logsdon, R., & Teri, L. (1995). Depression in Alzheimer's disease patients: Caregivers as
surrogate reporters. Journal of the American Geriatric Society, 43, 150-155.

Lucas, J.A., Ivnik, R.J., Smith, G.E., Bohac, D.L., Tangalos, E.G., Kokmen, E., et al. (1998).
Normative Data for the Mattis Dementia Rating Scale. Journal of Clinical and
Experimental Neuropsychology, 20(4), 536-47.

Madeley, P., Ellis, A.W., & Mindham, R.H.S. (1995). Facial expressions and Parkinson's
disease. Behavioural Neurology, 8, 115-119.

Marin, R.S. (1991). Apathy: A neuropsychiatric syndrome. Journal ofNeuropsychiatry and
Clinical Neuroscience, 3, 243-254.

Marowsky, A., Yanagawa, Y., Obata, K., & Vogt, K. E. (2005). A specialized subclass of
interneurons mediates dopaminergic facilitation of amygdala function. Neuron, 48(6),
1025-1037.

Mattis, S. (2001). Dementia Rating Scale-2. Odessa, FL: Psychological Assessment Resources.

Mayberg, H.S., Starkstein, S.E., Sadzot, B., Preziosi, T., Andrezejewski, P.L., Dannals, R.F., et
al. (1990). Selective hypometabolism in the inferior frontal lobe in depressed patients with
Parkinson's disease. Annals ofNeurology, 28(1), 57-64.

McDonald, W.M., Richard, I.H., & DeLong, M.R. (2003). Prevalence, etiology, andtreatment of
depression in Parkinson's disease. BiologicalPsychiatry, 54(3), 363-75.

Mikos, A., Skoblar, B., Springer, U., Kellison, I., Nisenzon, A., Fernandez, H., et al. (2007,
June). Behind the maskedface: Emotion self-perception and apathy in PD. Poster session
to be presented at the Movement Disorder Society's 11th International Congress of
Parkinson's Disease and Movement Disorders, Istanbul, Turkey.

Miller, K.M. (2004). Diminished affective modulation of startle to threatening stimuli in
Parkinson's disease. Unpublished master's thesis, University of Florida, Gainesville.

Murphy, F. C., Nimmo-Smith, I., & Lawrence, A. D. (2003). Functional neuroanatomy of
emotions: a meta-analysis. Cognitive, Affective, and Behavioral Neuroscience, 3(3), 207-
233.

National Institute of Neurological Disorders and Stroke (2001, July 1). Parkinson's disease
backgrounder. Retrieved February 9, 2004, from
http://www.ninds.nih.gov/healthandmedical/pubs/parkinson's-disease-backgrounder.ht
ml.









O'Gorman, J.R. (1990). Individual differences in the orienting response: Nonresponding in
nonclinical samples. Pavlovian Journal ofBiological Science, 25(3), 104-108.

Ouchi, Y., Yoshikawa, E., Okada, H., Futatsubashi, M., Sekine, Y., Iyo, M., et al. (1999).
Alterations in binding site density of dopamine transporter in the striatum, orbitofrontal
cortex, and amygdala in early Parkinson's disease: Compartment analysis for 3-CFT
binding with positron emission tomography. Annals ofNeurology, 45, 601-610.

Pell, M.D. & Leonard, C.L. (2005). Facial expression decoding in early Parkinson's disease.
Brain Research. Cognitive Brain Research, 23(2-3), 327-340.

Pentland, B, Pitcarin, T., Gray, J., & Riddle, W. (1987). The effects of reduced expression in
Parkinson's disease on concept formation by health professionals. Clinical Rehabilitation,
1,307-131.

Pentland, B, Pitcarin, T., Gray, J., & Riddle, W. (1988). The effects of reduced non-verbal
communication in Parkinson's disease. British Journal of Disorders of Communication,
23, 31-34.

Phillips, M. L., Marks, I. M., Senior, C., Lythgoe, D., O'Dwyer, A. M., Meehan, O., et al. (2000).
A differential neural response in obsessive-compulsive disorder patients with washing
compared with checking symptoms to disgust. Psychological Medicine, 30(5), 1037-1050.

Pitcairn, T., Clemie, S., Gray, J., & Pentland, B. (1990a). Non-verbal cues in the self-
presentation of Parkinson patients. British Journal of Clinical Psychology, 29, 177-184.

Pitcairn, T., Clemie, S., Gray, J., & Pentland, B. (1990b). Impressions of parkinsonian patients
from their recorded voices. British Journal of Disorders of Communication, 25(1), 85-92.

Pluck,G., & Brown, R.G. (2002). Apathy in Parkinson's disease. Journal ofNeurology,
Neurosurgery, and Psychiatry, 73(6), 636-42.

Pogarell, O., & Oertel, W.H. (1999). Parkinsonian syndromes and Parkinson's disease:
Diagnosis and differential diagnosis. In P.A. LeWitt & W.H. Oertel (Eds.), Parkinson 's
disease: The treatment options (pp. 1-10). London, UK: Martin Dunitz.

Remy P, Doder, M., Lees, A., Turjanski. N., & Brooks, D. (2005). Depression in Parkinson's
disease: loss of dopamine and noradrenaline innervation in the limbic system. Brain,
128(Pt 6), 1314-1322.

Rosen, J.B., & Davis, M. (1988). Enhancement of acoustic startle by electrical stimulation of the
amygdala. Behavioral Neuroscience, 102(2), 195-202, 324.

Rosenkranz, J.A., & Grace, A.A. (1999). Modulation ofbasolateral amygdala neuronal firing and
afferent drive by dopamine receptor activation in vivo. Journal ofNeuroscience, 19(24),
11027-11039.









Rosenkranz, J.A., & Grace, A.A. (2002). Cellular mechanisms of infralimbic and prelimbic
prefrontal cortical inhibition and dopaminergic modulation of basolateral amygdala
neurons in vivo. Journal ofNeuroscience, 22(1), 324-337.

Sanders, S.K., & Shekhar, A. (1995). Regulation of anxiety by GABAA receptors in the rat
amygdala. Pharmacolog, Biochemistry, and Behavior, 52(4), 701-706.

Schienle, A., Stark, R., Walter, B., Blecker, C., Ott, U., Kirsch, P., et al. (2002). The insula is not
specifically involved in disgust processing: an fMRI study. Neuroreport, 13(16), 2023-
2026.

Scott, S., Caird, F., & Williams, B. (1984). Evidence for an apparent sensory speech disorder in
Parkinson's disease. Journal ofNeurology, Neurosurgery, and Psychiatry, 47, 840-843.

Seltzer, B., Vasterling, J. J., Mathias, C. W., & Brennan, A. (2001). Clinical and
neuropsychological correlates of impaired awareness of deficits in Alzheimer disease and
Parkinson disease: a comparative study. Neuropsychiatry, Neuropsychology, and
Behavioral Neurology, 14(2), 122-129.

Shapira, N. A., Liu, Y., He, A. G., Bradley, M. M., Lessig, M. C., James, G. A., et al. (2003).
Brain activation by disgust-inducing pictures in obsessive-compulsive disorder. Biological
Psychiatry, 54(7), 751-756.

Simons, G., Pasqualini, M.C., Reddy, V., & Wood, J. (2004). Emotional and nonemotional facial
expressions in people with Parkinson's disease. Journal of the International
Neuropsychological Society, 4(10), 521-535.

Slaughter, J.R., Slaughter, K.A., Nichols, D., Holmes, S.E., & Martens M.P. (2001). Prevalence,
clinical manifestations, etiology, and treatment of depression in Parkinson's disease.
Journal ofNeuropsychiatry and Clinical Neuroscience, 13, 187-196.

Smith, M.C., Smith, M.K., & Ellgring, H. (1996). Spontaneous and posed facial expression in
Parkinson's disease. Journal of the International Neuropsychological Society, 2, 383-391.

Spielberger, C.D. (1977). State- Trait Anxiety Inventory. Palo Alto, CA: Consulting
Psychologists Press, Inc.

Sprengelmeyer, R., Young, A. W., Mahn, K., Schroeder, U., Woitalla, D., Buttner, T., et al.
(2003). Facial expression recognition in people with medicated and unmedicated
Parkinson's disease. Neuropsychologia, 41(8), 1047-1057.

Stark, R., Schienle, A., Walter, B., Kirsch, P., Sammer, G., Ott, U., et al. (2003). Hemodynamic
responses to fear and disgust-inducing pictures: an fMRI study. International Journal of
Psychophysiology, 50, 225-234.

Starkstein, S.E., Mayberg, H.S., Preziosi, T.J., Andrezejewski, P., Leiguarda, R., & Robinson,
R.G. (1992). Reliability, validity, and clinical correlates of apathy in Parkinson's disease.
Journal ofNeuropsychiatry and Clinical Neuroscience, 4, 134-139.









Tessitore, A., Hariri, A.R., Fera, F., Smith, W.G., Chase, T.N., Hyde, T.M., et al. (2002).
Dopamine modulates the response of the human amygdala: A study in Parkinson's disease.
The Journal ofNeuroscience, 22(20), 9099-9103.

van Spaendonck, K.P., Berger, H.J., Horstink, M.W., Borm, G.F., & Cools, A.R. (1993). Card
sorting performance in Parkinson's disease: A comparison between acquisition and
shifting performance. Journal of Clinical Experimental Neuropsychology, 17, 918-925.

Vidailhet, M., Rothwell, J.C., Thompson, P.D., Lees, A.J., & Marsden, C.D. (1992). The
auditory startle response in the Steele-Richardson-Olszewski syndrome and Parkinson's
disease. Brain, 115(4), 1181-1192.

Vrana, S.R., Spence, E.L., & Lang, P.J. (1988). The startle probe response: A new measure of
emotion? Journal ofAbnormal Psychology, 97(4), 487-491.

Watson, D., Clark, L. A., & Tellegen, A. (1988). Development and validation of brief measures
of positive and negative affect: The PANAS scales. Journal of Personality and Social
Psychology, 54, 1063-1070.

Wechsler, D. (1997). Wechsler Memory Scale- Third Edition Manual. San Antonio, TX:
Psychological Corporation.

Wieser, M. J., Muhlberger, A., Alpers, G. W., Macht, M., Ellgring, H., & Pauli, P. (2006).
Emotion processing in Parkinson's disease: dissociation between early neuronal processing
and explicit ratings. Clinical Neurophysiology, 117(1), 94-102.

Wilson, G.D., Kumari, V., Gray, J.A., & Corr, P.J. (2000). The role of neuroticism in startle
reactions to fearful and disgusting stimuli. Personality and Individual Differences, 29,
1077-1082.

Wright, P., He, G., Shapira, N.A., Goodman, W.K., & Liu, Y. (2004). Digust and the insula:
fMRI responses to pictures of mutilation and contamination. Neuroreport, 15(15), 2347-
2351.

Yartz, A.R., & Hawk, L.W. (2002). Addressing the specificity of affective startle modulation:
fear versus disgust. Biological Psychology, 59, 55-68.

Yoshimura N, K. M., Masaoka Y, Homma I. (2005). The amygdala of patients with Parkinson's
disease is silent in response to fearful facial expressions. Neuroscience, 131(2), 523-534.

Young, A.W., Aggleton, J.P., Hellawell, D.J., Johnson, M., Broks, P., & Hanley, J.R. (1995).
Face processing impairments after amygdalotomy. Brain, 118, 15-24.









BIOGRAPHICAL SKETCH

Kimberly Miller was born in San Jose, California. She received her B.A. in psychology

from the University of California at Berkeley. She has been a graduate student in Clinical &

Health Psychology student at the University of Florida for the past five years, where she is

specializing in neuropsychology. This dissertation is an extension of the ideas originating from

her master's thesis, completed in 2004 under the mentorship of Dawn Bowers. Outside of

psychology, Kim enjoys reading, running, and spending time at the beach.





PAGE 1

1 EMOTIONAL REACTIVITY IN PARKINSO NS DISEASE: PSYCHOPHYSIOLOGICAL AND PSYCHOSOCIAL CORRELATES By KIMBERLY M. MILLER A DISSERTATION PRESENTED TO THE GRADUATE SCHOOL OF THE UNIVERSITY OF FLOR IDA IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY UNIVERSITY OF FLORIDA 2008

PAGE 2

2 2008 Kimberly M. Miller

PAGE 3

3 To my parents for teaching me the value of pers everance, self-confidence, and a sense of humor.

PAGE 4

4 ACKNOWLEDGMENTS I would like to thank Dawn Bowers for he r mentorship, Michael Okun and all those affiliated with the UF Movement Disorders Cent er for help in participant recruitment, and Michael Marsiske for statistical guidance. I w ould like to specially thank the many people who made my dissertation possible by participating in this study. I gratefully acknowledge NIH/ National Institute of Neurological Di sorders and Stroke for grant support

PAGE 5

5 TABLE OF CONTENTS page ACKNOWLEDGMENTS...............................................................................................................4 LIST OF TABLES................................................................................................................. ..........8 LIST OF FIGURES................................................................................................................ .........9 ABSTRACT....................................................................................................................... ............10 CHAPTER 1 INTRODUCTION..................................................................................................................12 Statement and Overview of the Problem................................................................................12 Motor and Cognitive Symptoms in Parkinsons Disease.......................................................14 Emotional Processing in Parkinsons Disease........................................................................16 Mood Disturbance...........................................................................................................16 Emotional E xpression......................................................................................................17 Perception of Emotion.....................................................................................................18 Physiological Reactivity..................................................................................................19 Mechanisms of Emotional Changes.......................................................................................20 Changes to Neurotransmitters Implicated in Emotion....................................................20 Limbic System Neuropathology......................................................................................22 Emotional Modulation of the Startle Eyeblink Response.......................................................24 Basic Startle in Parkinsons Disease.......................................................................................26 Psychosocial Effects of Emotional Changes in Parkinsons Disease.....................................26 Preliminary Findings........................................................................................................... ...27 Specific Aims.................................................................................................................. ........28 Specific Aim 1.................................................................................................................29 Specific Aim 2.................................................................................................................29 2 MATERIALS AND METHODS...........................................................................................34 Overview....................................................................................................................... ..........34 Participants................................................................................................................... ..........34 Session 1 (Screening): Mate rials and Procedures...................................................................36 Session 2 (Psychophysiology): Ma terials and Procedures.....................................................38 Medication Wash-Out for Parkinson Patients.................................................................38 Picture Stimuli................................................................................................................ .39 Psychophysiology Procedure...........................................................................................41 Valence and Arousal Ratings of Pictures........................................................................42 Post Hoc Ratings of Basic Emotions...............................................................................43 Psychophysiology Data Reduction..................................................................................43 Primary Statistical Analyses...................................................................................................44 Specific Aim 1.................................................................................................................44

PAGE 6

6 Specific Aim 2.................................................................................................................45 3 RESULTS........................................................................................................................ .......47 Participant Characteristics.................................................................................................... ..47 Cognitive and Mood Measures...............................................................................................47 Baseline Startle Eyeblink...................................................................................................... ..48 Emotion-Modulated Startle Eyeblink.....................................................................................48 Discarded Trials...............................................................................................................48 Latency........................................................................................................................ ....48 Magnitude...................................................................................................................... ..49 Verification of typical patte rn of startle modulation................................................49 Primary an alysis.......................................................................................................50 Habituation Pattern............................................................................................................ .....51 Valence and Arousal Ratings..................................................................................................52 Post Hoc Basic Emotion Ratings............................................................................................53 Arousal Level as Measured by Skin Conductance Response.................................................55 Re-Examination of Eyeblink Magnit ude via Idiographic Analysis........................................57 Individual Categoriz ation of Pictures..............................................................................58 Emotion-Modulated Startle Eyeblink Magnitude...........................................................59 Influence of Trait Positive and Negative Affectivity and Trai t Anxiety on Startle Eyeblink Magnitude............................................................................................................60 Influence of Depression on Eyeblink Magnitude...................................................................61 Influence of Psychotropic Medications..................................................................................62 Spousal Perception of Depression: Relationshi p to Self-Reported De pression and Startle Eyeblink Magnitude............................................................................................................62 Surrogate BDI-II: Comparison with Self-Report BDI-II................................................63 Relationship between Surrogate BDI-II and Startle Eyeblink Magnitude......................64 Influence of Disease Severity and Duration on Startle Eyeblink Magnitude.........................64 4 DISCUSSION..................................................................................................................... ....75 Summary of Findings............................................................................................................ .75 Aim 1.......................................................................................................................... ............76 Emotion-Modulated Startle Eyeblink Magnitu de: Comparison of Present and Prior Study Findings.............................................................................................................76 Reduced Startle Eyeblink Magnitude to Mutilation Pictures in Parkinsons Disease: Proposed Mechanisms.................................................................................................77 Influence of individual personality di fferences on emotion-modulated startle eyeblink magnitude...............................................................................................78 Reduced emotional reactivity in PD: Specific to horror?.....................................80 Subjective ratings of valence, arou sal, and basic discrete emotions........................81 Arousal as measured by skin conductance response................................................82 Reduced physiological arousal: A translational deficit?..........................................83 Aim 2.......................................................................................................................... ............85 Influence of Depression on Emotion-M odulated Startle Eyeblink Magnitude...............85

PAGE 7

7 Accurately Assessing Depression: Comp arison of Selfand Surrogate Report Measures......................................................................................................................85 Relationship between Surrogate-Report De pression and Emotion-modulated Startle Eyeblink Magnitude.....................................................................................................87 Study Limitations.............................................................................................................. ......87 Conceptual and Methodological Issues in Emotion Research................................................90 Significance of the Study...................................................................................................... ..92 APPENDIX A NORMATIVE VALENCE AND AROUSAL RATINGS FOR PICTURE STIMULI.........95 B SKIN CONDUCTANCE RESONSE DAT A ACQUISITION AND REDUCTION PROCEDURES..................................................................................................................... .97 Data Acquisition............................................................................................................... ......97 Data Reduction................................................................................................................. ......97 LIST OF REFERENCES............................................................................................................. ..98 BIOGRAPHICAL SKETCH.......................................................................................................108

PAGE 8

8 LIST OF TABLES Table page 3-1 Demographic and clinical characteristics by group...........................................................65 3-2 Scores on cognitive and mood measures scores by group.................................................66 3-3 Valence and arousal ratings of affective pictures by a priori picture category and group.......................................................................................................................... ........67 3-4 Post hoc basic emotion ratings by group...........................................................................67 3-5 Regression analysis of contributions of group membership and BDI-II scores upon eyeblink magnitudes..........................................................................................................68 3-6 BDI-II selfand surrogatereport scores by group............................................................68 3-7 Regression analysis of c ontributions of group membersh ip, self-report BDI-II scores, and Surrogate BDI-II scores upon startle eyeblink magnitudes........................................69 A-1 International Affective Picture Syst em (IAPS) Normative Valence and Arousal Ratings........................................................................................................................ .......95

PAGE 9

9 LIST OF FIGURES Figure page 1-1 Simplified direct loop in the PD patients dysfunctional motor system...........................31 1-2 Two hypothesized striato-thalamo-co rtical loops involved in emotion.............................32 1-3 Preliminary findings of emotion-modulate d startle eyeblink magnitude in PD patients and controls................................................................................................................... .....33 3-1 Pattern of emotionmodulated startl e eyeblink magnitudes by valence and group..........70 3-2 Startle eyeblink magnitudes by a priori picture category and group.................................71 3-3 Skin conductance response by valence and group.............................................................72 3-4 Skin conductance response by a priori picture category and group...................................73 3-5 Startle eyeblink magnitudes by post hoc emotion category and group.............................74

PAGE 10

10 Abstract of Dissertation Pres ented to the Graduate School of the University of Florida in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy EMOTIONAL REACTIVITY IN PARKINSO NS DISEASE: PSYCHOPHYSIOLOGICAL AND PSYCHOSOCIAL CORRELATES By Kimberly M. Miller August 2008 Chair: Dawn Bowers Major: Psychology Preliminary work in our laboratory suggests th at patients with Parkinsons disease (PD) may demonstrate diminished physiological reactivity to threatening pictures. This may be due to the fact that the amygdala is known to exhibit pa thology in PD, and is a neural structure that plays a key role in processing threat signals in the environment. Our primary aim was to further explore the possibility of reduced emotional reac tivity to threatening s timuli in PD, as indexed by emotional modulation of the startle eyeblink reflex. Our secondary aim was to examine the psychosocial impact of any reactivity deficits by determining whether they are associated with depression and with the misattributio n of depression by patients spouses. Twenty-four non-demented PD patients in th e off medication state and 24 ageand education-matched controls viewed neutral, pleasant, disgusting (mutilations and contaminations), and threatening (human and an imal attack) pictures. During this time, white noise bursts were binaurally presen ted to elicit startle eyeblinks. Participants also completed the Beck Depression Inventory, 2nd edition (BDI-II) and spouses completed a surrogate-report version of this measure. Contrary to predictions, PD patients did not display reduced startle potentiation to threatening pictures depicting att ack. Instead, diminished reactivity to pictures of mutilations was

PAGE 11

11 found. Neither selfnor surrogate-r eport ratings of depression we re associated with eyeblink magnitude. Additionally, spousal an d PD patient depression ratings were significantly correlated, indicating that spouses do not appear to misattribute PD symptoms to depression. We hypothesized that PD patients may have a general deficit in physiological responsivity to highly arousing negative stimuli, as opposed to an emotion-specific deficit. Mutilation pictures are particularly arousing because th ey represent a threat to bodily integrity; as such, it may be that mutilation pictures were the only category of pictures sufficiently arousing to detect a between-groups difference in physio logical reactivity. A secondary finding suggests that spouses may serve as accurate surrogate reporters of mood when PD patients are unable to report upon their own mood. In sum, results s uggest that PD patients have ab errant physiological emotional reactivity, but this does not appear to be related to spousal perceptions of mood.

PAGE 12

12 CHAPTER 1 INTRODUCTION Statement and Overview of the Problem Parkinsons disease (PD) is a neurodegenerative disease that affects approximately half a million to one million people in the United St ates (McDonald, Richard, & DeLong, 2003), with 50,000 new cases diagnosed each year (National Ins titute of Neurological Disorders and Stroke, 2001). PD involves progressive depletion of dopami nergic neurons within the substantia nigra and is characterized by bradyki nesia (slowed movements), ri gidity, tremor, and postural instability. While these motor symptoms are th e defining feature of Parkinsons disease, neuropsychiatric symptoms are prevalent and can be the most dist urbing, disabling, and misunderstood aspects of the disease. Distur bances of mood and motivation are common and include depression, anxiety, and apathy. In addition to neuropsychiatric symptoms, patie nts with Parkinsons disease have difficulty communicating emotion using nonverbal signals such as facial expression and emotional tone of voice (Blonder, Gur, & Gur, 1989; Borod et al ., 1990; Buck & Duffy, 1980; Jacobs, Shuren, Bowers, & Heilman, 1995; Smith, Smith, & Ellgri ng, 1996). One of the prot otypical clinical features of Parkinsons disease is masked facies, a term that refers to the expressionless facial demeanor of PD patients. Diminished facial expr essivity occurs relatively early on in the disease course and appears to be unrel ated to depression (Katiskitis & Pilowsky, 1991; Smith et al., 1996). Findings of reduced facial expressivity in PD raise the possibility of impairments in emotional reactivity (how an individual re sponds physiologically, subjectively, or overtly). To date few studies have investigat ed the topic of emotional reactiv ity in Parkinson disease from a multicomponential framework.

PAGE 13

13 Although Parkinson patients are not as facially or prosodically expressive as their healthy counterparts, they typically repor t subjective feelings that are comparable in intensity during tasks such as viewing emotional pictures (Bowers, Miller, Bosch, et al., 2006; Simons, Pasqualini, Reddy, & Wood, 2004; Smith et al., 1 996). However, self-report ratings are potentially unreliable because they are subjec t to demand characteristics, meaning that the participant may simply respond in the fashi on that is expected of him or her. Our study measured emotional reactivity in Park inson patients with a method that does not rely on facial expression, prosody (both of which ar e known to be affected in PD), or self-report. Instead, emotional modulation of th e startle eyeblink reflex was us ed as an index of emotional reactivity. This paradigm rests on the well-documented principle that the size of the startle eyeblink is directly modulated by an individuals emotional stat e. Additionally, because the response that is being measured is near impossible to voluntarily control, it does not rely on the participants explicit attention, trai ning, or cooperation (Bradley, 2000). The overall aims of our study were twofold. The primary aim was to examine whether emotional reactivity deficits in Parkinsons dise ase differentially affect specific emotions. A recent study in our laboratory found that PD patients demonstrated significantly reduced reactivity in response to viewi ng unpleasant pictures, but not pleasant or neutral pictures (Bowers, Miller, Mikos, et al., 2006). In a post hoc analysis, this finding was parsed apart by comparing PD patients emotiona l reactivity to threat-inducing pictures (i.e., pictures suggesting imminent attack, such as a snake preparing or bi te or a gun pointed at the viewer) versus other types of unpleasant pictures (i.e., mutilated bodies a plane crash, a starving person; Miller, 2004). The threat-inducing pictures appeared to account for the di minished startle reactivity in the PD patients. The current study aimed to re plicate this finding wh ile addressing several

PAGE 14

14 methodological limitations of the initial study. Name ly, the present study used a larger number of pictures, an a priori design, and specifically compared th reat -inducing pict ures to another discrete emotional category of unpl easant stimuli that are similarl y high in arousal level: disgustinducing pictures. Additionally, PD patients were tested while off their dopaminergic medication (unlike in the previous study) so that any potentially restorativ e effect dopaminergic medication may have on emotional reactivity would not confound the interpretation of results. The second aim of the present study was to examine the relationship between emotional reactivity deficits in PD patients and fam ily members percepti ons of depressive symptomatology in the patient. Th is aim is fuelled by findings from previous research that diminished use of nonverbal communication sign als by Parkinson patients poses significant psychosocial problems, particularly in terms of incorrect attribu tions of negative mood state or depression by family members and health care providers (Pentland, Pitcairn, Gray, & Riddle, 1987, 1988; Pitcairn, Clemie, Gray, & Pentland, 1990a, 1990b). The distinct contribution of this study is its focus on measuring emotional reactivity in Parkinsons disease via a method that is not conf ounded by deficits in faci al/vocal expression or self-report reliability issues. Furthermore, increased understa nding of emotional reactivity deficits accompanying PD may prove to be clini cally useful in reducing healthcare providers and family members attributions that the patien t is apathetic, depressed, or uninterested due to lack of overt emotional reaction. Before desc ribing the hypotheses in further detail, a brief overview of Parkinsons disease will be presen ted, followed by a discussion of changes in emotional functioning associated with the disease. Motor and Cognitive Symptoms in Parkinsons Disease Behaviorally, Parkinsons disease is charac terized by motor symptoms including resting tremor, bradykinesia (slo wed movement), rigidity (increas ed muscle tone), and akinesia

PAGE 15

15 (difficulty initiating or main taining a body movement [Hughes, Ben-Shlomo, Daniel, & Lees, 1992; Hughes, Daniel, Kilford, & Lees, 1992]). Additionally, Parkinsons patients may experience diminished facial expressivity (mask ed facies), loss of postural reflexes, and/or motoric freezing when attempting to walk (F ahn, 2003). These motoric symptoms are thought to be caused primarily by a depletion of dopamine rgic neurons in the substantia nigra, which then affects a cascade of stru ctures involved in the produc tion of voluntary movement, particularly the basal ganglia. The neural circuitry i nvolved in Parkinsons disease is shown in Figure 1-1. It has been estimated that patients with PD have a 60-85% cell loss of dopaminergic neurons in the substantia ni gra (Pogarell & Oertel, 1999). As such, dopamine replacement therapy (using levodopa, a dopamine pr ecursor that is able to cro ss the blood-brain barrier) is the major medical approach to treat ing the motor symptoms of Pa rkinsons (Fahn, 2003). Initially, the motor symptoms of Parkinsons disease are dramatically improved by dopaminergic therapy. Over time, however, medications become less eff ective and are associated with dramatic on and off medication fluctuations in symptoms. This has led to recent surgical treatments for Parkinsons disease, including the implantation of small stimulating micro-electrodes into specific brain regions within the basal ganglia (i.e., internal segment of the globus pallidus, subthalamic nucleus). The conceptual idea behi nd deep brain stimulation and other surgical treatments for Parkinsons disease is to change the imbalance of activation and inhibition that results from dopaminergic depletion (Benabid, 2003). Although the motor symptoms of Parkins ons disease are the primary focus of pharmacotherapy and surgical treatments, various nonmotor symptoms (e.g., cognitive problems, dementia, psychosis, anxiety, insomnia, autonom ic dysfunction, and mood disturbances) also occur and can be particularly disturbing and disabling. Common cognitive sequalae include

PAGE 16

16 slowed thinking (bradyphrenia), impaired set-shifting, reduced working memory, and forgetfulness (Cools, Barker, Sahakian, & R obbins, 2001; Dimitrov, Grafman, Soares, & Clark, 1999; Fahn, 2003; Gauntlett-Gilbert, Robert s, & Brown, 1999; van Spaendonck, Berger, Horstink, Borm, & Cools, 1995). Moreover, about is it estimated that 30-50% of Parkinsons patients eventually develop frank de mentia (Jacobs, Stern, & Mayeux, 2000). Myriad studies have investigated the pattern of motoric and cognitive deficits found in Parkinsons disease. Fewer have delved into the domain of emotional changes that accompany Parkinsons disease, the focus of the current study. In the followi ng section, the literature concerning emotional changes in PD is reviewed. Emotional Processing in Parkinsons Disease Emotional processing can be broadly conceptu alized as encompassing four domains: mood (subjective emotional experien ce), perception, expression, and physiology. Research to date suggests that PD patients may exhibit difficulties in at least three of th ese domains, each of which are considered in turn below. Mood Disturbance Depression is a significant problem in Parkins ons disease, with onethird to onehalf of all patients suffering from a depression syndr ome (Cummings, 1992; Dooneief et al., 1992; McDonald et al., 2003; Slaughter, Slaughter, Nichol s, Holmes, & Martens, 2001). In addition to decreasing quality of life, depr ession and other psychiatric dist urbance in Parkinson patients appear to exacerbate motoric symptoms (Cu mmings, 1992). Accumulating evidence over the years suggests that depression in PD may be secondary to the underlying neuroanatomical degeneration, rather than simply a reaction to psychosocial stress and di sability, although the latter may clearly play a role as well. The inci dence of depression is co rrelated with changes in central serotonergic function a nd neurodegeneration of specific dopaminergic-, serotonergic-,

PAGE 17

17 and noradrenergicmediated cortical and subcor tical pathways (Burn, 2002; German et al., 1992; Mayberg et al., 1990; Remy, Doder, Lees Turjanski, & Brooks, 2005). Other common psychiatric disturbances in Pa rkinsons disease are anxiety and apathy (Fahn, 2003). Apathy refers to diminished emo tional reactivity to both positive and negative events, lack of motivation to engage in goal-di rected behavior or cognition, and a subjective sense of indifference (Marin, 1991). Approximately 40 to 50% of Parkinsons patients have been described as meeting criteria for apathy, based on assessment through various apathy rating scales (Isella et al., 2002; Kirsch-Darrow, Fernandez, Marsiske, Okun, & Bowers, 2006; Starkstein et al., 1992), with higher levels of ap athy in Parkinsons patien ts relative to equally disabled patients with severe osteoarthritis (Pluck & Brown, 2002). Those patients with high levels of apathy are not more likely to be depressed or anxiou s than those with the lowest levels of apathy (Kirsch-Darrow et al., 2006; Pluc k & Brown, 2002). Like depression, it has been argued that apathy is more likely a direct consequence of diseas e-related physiological changes than a psychological reaction or adaptation to disability (Brown & Pluck, 2000; Pluck & Brown, 2002). Emotional Expression In addition to mood disturbances, patients w ith Parkinsons disease also have impaired ability to communicate emotion us ing various nonverbal signals su ch as facial expression (the masked facies of Parkinsons disease) and prosody (Blonder et al., 1989; Borod et al., 1990; Buck & Duffy, 1980; Jacobs et al.; Smith et al., 1996). Diminished facial expressivity occurs relatively early in the disease cour se and has been found to be unrel ated to depression (Katiskitis & Pilowsky, 1991; Smith et al., 1996). Recent studies from our laboratory using sophisticated computer imaging techniques have found that the facial movements in Parkinsons disease are actually smaller in amplitude, slower to initiate occur less frequently, and correlate with other

PAGE 18

18 motor symptoms of Parkinsons disease such as bradykinesia (Bowers, Miller, Bosch, et al., 2006). Diminished use of nonverbal communicati on signals by Parkinson patients can create a host of psychosocial problems, ranging from misdia gnosis of depression to the misattribution of negative emotion states by family members and health care providers. These problems will be discussed in greater detail in subsequent sections. Perception of Emotion Research literature regarding the percepti on of emotional information (faces, scenes, prosody) in PD is inconsistent at best. Some investigators ha ve found that individuals with Parkinsons disease are impaired when asked to identify emotional faces, emotional prosody, or emotional scenes (Blonder et al., 1989; Jac obs et al., 1995; Scott, Caird & Williams, 1984; Sprengelmeyer et al., 2003). Others, however have not documented differences between Parkinsons disease patients and healthy c ontrols (Adolphs, Schul, & Tranel, 1998; Madeley, Ellis, & Mindham, 1995). Some possibilities that may account for these discrepancies are methodological inconsistencies regarding the severi ty of Parkinsons disease, whether patients are tested on versus off medications, and the extent of co-existing cognitive impairment or mood disturbance. Recently, a particular interest has emerged with respect to the possibility that Parkinsons patients may have specific difficulties with pro cessing of negatively-valenced emotions such as fear and/or disgust relative to other emotions. Some research ers have found that PD patients appear to be more impaired at recognizing aversi ve facial expressions (i.e ., anger, disgust, fear) than other expressions. For example, Ka n, Kawamura, Hasegawa, Mochizuki, & Nakamura (2002) found that PD patients were selectively imp aired at recognizing fear and disgust facial expressions. However, not all researchers have found impairments in recognition of emotional facial expressions (Adolphs, et al ., 1998; Madeley et al., 1995).

PAGE 19

19 Physiological Reactivity A fourth domain within the multicomponen tial framework of emotion processing is physiological reactivity, which can be studied in the laboratory via measuring subjects physiological reactivity to emotional materials. There are several methods commonly used in the measurement of psychophysiologic reactivity. On e method is skin conductance response (SCR) to emotional stimuli. This is accomplished by applying electrodes that essentially measure palm sweat on the inside of the hands. In ge neral, the larger the SCR, the greater the physiological arousal the subjec t has experienced in response to the emotional stimulus. Although measurement of SCR can be useful, it has limitations. First, individuals vary considerably in how their SCR to emotional st imuli habituates over time. Some individuals habituate after a few trials, whereas others do not appear to habituate much at all. Secondly, 1520% of healthy people are nonresponders; that is, they to do not exhibit a discernable difference in SCR to varying types of emo tional stimuli (Bradley, 2000; OGorman, 1990). Finally, excess motor activity (such as tremor in the hands) can dramatically interfere with skin conductance recordings (Bradley, 2000). For th ese reasons, SCR data do not always produce consistent results, may not dete ct subtle between-groups differe nces in physiological responding, and may not be the most appropriate physiologic measure for patients with a movement disorder. Another widely used index of emotional react ivity is emotional modulation of the startle eyeblink response (Lang, Bradley, & Cuthbert, 1 990; Vrana, Spence, & Lang, 1988). This index takes advantage of the reflexive eyeblink that natu rally occurs in response to an abrupt, jarring stimulus. In essence, a priming effect occurs whereby negatively-valenced stimuli augment the size of the eyeblink and positively-valenced stimuli decrease the size of the eyeblink. It is this measure that served as the index of emotional re activity in the present st udy and is described in

PAGE 20

20 detail in a later section. Howe ver, first the potential mechanis ms for the emotional processing deficits just review ed will be discussed. Mechanisms of Emotional Changes There are at least two mechanisms that may affect emotional processing in Parkinsons disease. First, research suggests that PD patients experience changes (decreased neurotransmitter production or reduced binding) to several neurotransmitters involved in emotion. It has been proposed that the emo tional changes observed in PD patients may be a consequence of the loss of nigro-striatal dopamine and/or the loss of mesolimbic and mesocortical dopamine, which in turn may a ffect serotonin and norepinephrine-producing regions of the brain (the dorsa l raphe nuclei and the locus coer uleus, respectively). Secondly, evidence of pathological changes to the structur al integrity of key limbic structures has been found in the brains of individuals with Parkins ons disease. Both of these mechanisms are discussed in turn below. Changes to Neurotransmitters Implicated in Emotion It is thought that some of the emotional ch anges found in PD may be in part linked to limbic circuitry subserved by the neurotransmitter dopamine. There are three main systems through which dopamine depletion may affect emotional processing in PD by disrupting modulation of these systems: the striat o-thalamo-cortico loops, the mesolimbic circuit, and the mesocortical circuit. Beginni ng with the first of these, Al exander, DeLong, & Strick (1986) proposed a network of five paralle l striato-thalamo-cortical circui ts that allow frontal cortical activity to be modulated by ascending input from the basal ganglia/thalamus through direct and indirect pathways. Two of these circuits involve key limbic areas such as the orbitofrontal cortex (OFC), the anterior cingulate cortex (ACC), a nd the nucleus accumbens. General schematas of these two circuits are shown in Figure 1-2.

PAGE 21

21 Outside of these striato-thalamo-cortical circuits, the dopamine-mediated mesolimbic pathway is implicated in emotional processing as well. The ventral tegmental area has dopaminergic connections to the ventral striatum (which consists of the nucleus accumbens and olfactory tubercle) of th e basal ganglia. Changes in dopaminerg ic input to the ventral striatum can then affect the associated striato-thalamo-cortical circuits and thus depletion of dopamine may affect the ability of limbic structures to influence frontal cortical activity. Finally, the mesocortical circuit connects the ventral tegmenta l area to the cortex, and provides yet another way in which dopamine depletion may affect em otional functioning. Cortical dopamine release modulates the descending cortico-stri atal fibers, potentially influenc ing the activity of the striatothalamo-cortico circuits (Brown & Pluck, 2000). With respect to mood changes in PD, Maybe rg et al. (1990) found reduced metabolic activity in the inferior-orbitofrontal cortex and cauda te of depressed PD patients, with severity of depression having an inverse relationship with orbitofrontal metabolism. This suggests that depression in PD is associated with dysfuncti on of these areas. Mayberg and colleagues have proposed the following explana tion of how serotonin is affected by loss of dopamine: dopaminergic efferents from the ventral tegmenta l area project to the OFC (mesocortical) which then project to limbic structures such as the dor sal raphe nuclei, where se rotonin is produced. In this way, disruption to the meso-cortico-limbic dopamine circuitry may a ffect the serotonergic cell bodies in the dorsal raphe. Dysfunction of dopaminergic pathways may pot entially disrupt noradrenergic cells in a similar way. In a recent PET study, Remy et al. (2005) used a tracer th at binds with strong affinity to epinephrine and dopamine transporters but with much weaker affinity to serotonin transporters. They found that non-depressed PD patients had significantly higher binding of this

PAGE 22

22 tracer in the locus coeruleus, mediodorsal thalamus, ventral stri atum, ACC, and right amygdala. These authors pointed out the lo cus coeruleus sends noradreneri c projections to the ventral striatum. Thus, a loss of dopamine to the ACC/ MOFC limbic loop may indirectly affect norephinephrine cells in the same way that serotonin is proposed to be affected. In sum, depletion of dopamine in PD (in bot h the Alexander loops and the mesolimbic and mesocortical loops) may in turn affect norepinep hrine and serotonin through connected circuitry. Changes in the dopaminergic, noradrenergic, and se rotonergic systems may then lead to changes in mood and emotional processing. Limbic System Neuropathology Recently, several investigators have found ev idence of neuropathological changes to limbic structures in Parkinson patients. In a post-mortem study, Harding and colleagues (Harding, Stimson, Henderson, & Halliday, 2002) found a 20% reduction in amygdalar volume of PD patients compared to normal controls, in addition to the presence of Lewy bodies in many subjects amygdali. Ouchi and colleagues (1999) found a 30-45% reduction of dopamine agonist binding in the amygdali of PD patients, as well as a 48% reduction in dopamine agonist binding in the orbitofrontal cortex, anot her key limbic region. They speculate d this might be due to a loss of pre-synaptic dopamine terminals in these regi ons. A histological study of brains of deceased PD patients (Braak & Braak, 2000) found cytoskeletal damage to neurons in the amygdala, anterior cingulate cortex, raphe nucleus and locus coeruleus. Evidence of pathology of the amygdala is part icularly relevant to the current study. The amygdala is a small, almond-shaped structure loca ted in the anterior te mporal lobe. It has consistently been implicated in the recognition of fearful stimuli and the response to fearful or threatening situations. Monkeys with lesions of the amygdala do not display normal fear reactions to threatening stimuli, such as snakes (Amaral, 2003; Klver & Bucy, 1939). In

PAGE 23

23 humans, lesions of the amygdala have been asso ciated with behavioral placidity, diminished physiologic reactivity, and impairments in recogn izing fearful faces (Calder et al., 1996; Young et al., 1995). Electrical st imulation of the amygdala elicits many of the behaviors used to define the state of fear, such as tac hycardia, increased galvanic skin response, corticosteroid release, and increased startle (Davis, 1992). The fact that the amygdala has been shown to exhibit neuropathology in PD brings up the issue as to whether Parkinsons patients might have a diminished emotional reactivity to threatening stimuli, or difficulty interpreting ex pressions of fear in others. Although researchers have investigated the ability of PD patients to recognize fearful faces, no published study to date has examined physiologic reactions to fear-e voking stimuli. However, preliminary work suggests that PD patients may show diminished emotional reactivity spec ific to threat-inducing materials (Miller, 2004). With rega rds to the facial r ecognition literature, Kan et al. (2002) found that PD patients were selectivel y impaired at recognizing fear and disgust facial expressions; however, neither Adolphs et al. (1998), Madele y et al. (1995), nor Pell and Leonard (2005) found consistent impairments in PD patients ability to recognize emotional facial expressions. Importantly, these studies involved recognition of faces as opposed to viewing emotion-eliciting pictures as will be the case in the current study. In an fMRI experiment using threat-inducing pictures from the International Affective Pictur e System (which will be used in the current study), Hariri, Mattay, Tessitore, Fera, & We inberger (2003) found a significant bilateral amygdala BOLD response when healthy subjects were asked to simply match a threatening picture to a picture identical to it. This suggests that amygdala is involved in processing of threat-inducing pictures, although it is unknown whether pathology to its structure would result in deficits in emotional processing and emotiona l reactivity specifically. Tessitore et al. (2002)

PAGE 24

24 reported that viewing of facial expressions of f ear was associated with robust bilateral amygdala response in healthy subjects, but absent in PD patients who had been withdrawn from levodopa. Administration of levodopa partiall y restored amygdala BOLD re sponse, but not to the degree present in healthy subjects. This raises the pos sibility that the loss of dopamine characterizing PD may affect processing of emotional material s by neural circuitry th at includes the amygdala, and bolsters the argument for the withdrawal of all dopaminergic medications from PD participants in the current study. Recentl y, Yoshimura, Kawamura, Masaoka, & Homma (2005) reported an absence of event-related potentials from the amygdali of PD patients while viewing fearful faces. Thus, the literatur e clearly suggests abnormal amygdala responsivity in PD patients during the processing of fearor threatinducing stimuli. Emotional Modulation of the Startle Eyeblink Response The current study employs emotional modulati on of the startle eyeblink response as a means through which to measure emotional reacti vity. In order to understand the mechanism of the phenomenon of emotional modulation of the star tle eyeblink response, it is first necessary to describe the basic startle reflex and how it is neurally mediated. In mammals, an automatic startle response occurs at the abr upt onset of a stimulus, such as a jarring noise or flash of light. This response is protective for the organism and is characterized by limb and trunk movements of the body, as well as a reflexiv e eyeblink (Bradley & Vrana, 1993). In humans, the eyeblink has been used to measure the startle reflex re sponse because it is the most reliable, easily recorded, and quickest component of the startle response. A variety of studies over the past decade have documented that the size of the startle eyeblink is directly modulated by an individuals emotional state. In humans, startle response magnitude (as indexed by reflexive eyeblink) is au gmented when an individual is involved in an emotionally aversive task. C onversely, startle responses are a ttenuated during more pleasant

PAGE 25

25 tasks. This valence modulation of startle is ob served across a variety of tasks involving picture viewing, imagining emotional situations, and anticipation of shock (Bradley, 2000; Bradley, Codispoti, Cuthbert, & Lang, 2001; Lang et al., 1 990). The enhancement of startle has been viewed as a priming effect, whereby the pr otective withdrawal reflex is primed during unpleasant emotional states and inhibited during pleasant emoti onal states. The neural circuitry of startl e and its modulation has been ex quisitely detailed in studies by Davis and colleagues using a rodent model (Davis, 1992; Davis, Gendelman, Tischler, & Gendelman, 1982). In brief, the basic startle circ uitry is mediated enti rely at the level of brainstem. However, startle responses can be di rectly modulated (i.e., potentiated or inhibited) by input from the central nucleus of the amygdala via its projection to the brainstem. Electrical stimulation of the amygdala in rats facilitates st artle (Rosen & Davis, 19 88), while lesions of the amygdala diminish fear-potentiated and shock-sensitized startle re sponses but leave basic startle intact (Hitchcock & Davis, 1991; Hitchcock, Sana nes, & Davis, 1989). Thus, dysfunction of the amygdala does not eliminate the basic startle response per se Rather, it eliminates potentiation of startle reactivity during aversive emotional st ates. In humans, for example, temporal lobe ablations involving the amygdala are associated with reduced startle modulation during viewing of aversive pictures or while listening to negativ e sentences (Bowers et al., 2001). The use of the startle response as an index of emotional reacti vity in a Parkinsons sample has several advantages. First, because it does not require a voluntary motor response (as measurements of facial expre ssivity or vocal prosody do), it e liminates the confounding problem that the movements being used as an index of expressivity may be affected by the motor symptoms of PD. Secondly, measurement of physiological reaction do es not depend on selfreport (as many paper-and-pencil measures of mood and emotion do), and thus the demand

PAGE 26

26 characteristics associated with it are minima l since the eyeblink response is difficult to voluntarily control (Bradley, 2000). Basic Startle in Parkinsons Disease Relevant to the present study is the questi on of whether PD patients might have a basic defect in startle eyeblink reactivity per se Conceivably, Parkinsons patients could have motor abnormalities that reduce or minimize the size of the eyeblink response. This, in turn, would result in reduced startle eyeblink magnitudes in response to negative emotional pictures, giving rise to the impression of diminished emotional reactivity to unpleasant s timuli. However, two studies have reported that while th e latency of startle is slightly delayed in PD, the magnitude or size of the basic startle eyeblink response to acoustic stimuli does not differ significantly between PD patients and controls (Kofler et al ., 2001; Vidailhet, Rothwell, Thompson, Lees, & Marsden, 1992). Similarly, we recently found no significant difference in startle magnitude between PD patients and age-matched controls test ed in our laboratory (Bowers, Miller, Mikos, et al., 2006). Taken together, th ese findings suggest that Parkins on patients do NOT have a basic defect in basic startle reac tivity, as indexed by size of the eyeblink response. Psychosocial Effects of Emotiona l Changes in Parkinsons Disease As described, Parkinsons disease is ch aracterized by overt affective changes including a reduction in facial and vocal expressivity. Th ese changes have the pot ential to effect the perception and treatment of PD pa tients by those closest to them, and are the focus of the second aim of the current study. In an investigation dire cted at testing the obser vation that PD patients tend to be interpreted as co ld or unfeeling, Pentland et al. (1987, 1988) found that when silent video footage of PD patients was shown to health professionals, the patients were rated as being significantly more hostile, anxious, susp icious, unhappy, and bored than controls with heart disease. In a follow-up st udy, tape recordings of interviews with PD patients and heart

PAGE 27

27 disease controls were presented to nave listen ers and produced similar findings (Pitcairn et al., 1990b). In both these studies th ere was no measurable differe nce between the two subject groups with regard to affect or personality measures, and none of the patients were suffering from depression. These authors suggested that the non-verbal behavi or of PD patients, characterized by upper body rigidity and a lack of hand movement contributes greatly to the misattribution of depression. To date, no study has examined the effect of emotional changes on family members perceptions of the PD patient. Thus, the second specific aim of the current study is to obtain spousal ratings of perception of depression sympto ms in their relative with PD and compare these to the PD patients self-re port ratings of depressi on. This will allow for investigation of whether emotional reactivity deficits are associated with greater misperception of depression in PD patients by family members. Preliminary Findings Bowers, Miller, Mikos, et al. (2006) recently completed a study of emotional modulation of startle in 23 PD patients wh ile on dopaminergic medication and 17 age-matched controls. All participants were presented with 44 pictures from the International Affective Picture System (Lang, Bradley, & Cuthbert, 2001a), with one-third of the pictures being unpleasant in valence, one-third being pleasant, and one -third neutral. Data analysis revealed a significant Emotion Category x Group interaction ( F (1,33)= 4.60, p <.05), with PD patients exhibiting significantly smaller eyeblink magnitudes than controls wh ile viewing unpleasant pictures. In contrast, eyeblink magnitudes during viewing of pleasant pictures were comparable to that of controls. These data suggest that PD pa tients may have a selective defi cit in emotional reactivity to unpleasant stimuli. To determine whether certain types of unpleas ant pictures were more contributory to diminished startle reac tivity than others, a post hoc exploratory analysis was conducting by

PAGE 28

28 categorizing the unpleasant pictur es into threatening versus other types of unpleasant pictures (Miller, 2004). This post hoc division was partially determined by the fact that the stimulus set contained several pi ctures designed to induce feelings of fear or threat (i.e., a gun pointed at the subject, a dog with fangs open ready to bite), but fewer pictures representative of other negative emotions (i.e., disgust, sadne ss, etc.). Again, the Emotion Category x Group interaction was significant ( F (1, 28)= 5.31, p <.05), with Parkinsons patients displaying smaller eyeblinks than controls in res ponse to the threat-induc ing slides (Figure 1-3). However, this exploratory analysis had seve ral limitations, including the fa ct that the analyses were post hoc in nature and the total number of t hreat pictures was small. T hus, the current study was designed to better control for these limitations. This was done by using a larger number of unpleasant pictures, an a priori design, and by specifically comparing threat-inducing pict ures to another discrete emotional category of unpl easant stimuli that are similarl y high in arousal level: disgustinducing pictures. This allowed for an examination of whether th e deficits previously observed in PD patients were due to aversive stimuli in general, stimuli that ar e extremely arousing or upsetting, or stimuli that are threatening in nature. Additionally, PD patients underwent an overnight (12-hour) anti-parkins onian medication wash-out so that presence of symptomalleviating medication would not confound the inte rpretation of emotional reactivity results. Specific Aims Although much research has pointed to emotional expressivity deficits in Parkinsons disease, few studies have examined possible emotional reactivity deficits in PD. Preliminary work suggests that Parkinson patients may demons trate a significantly diminished reactivity to threatening or fear-inducing emotional materials, compared to their healthy counterparts. This may be due to the fact that th e amygdala has been known to exhibit pathology in PD, and is a

PAGE 29

29 neural structure that plays a key role in pro cessing and interpreting threat signals in the environment. As such, the present study has the following specific aims: Specific Aim 1 The first aim tested the hypothesis that Pa rkinson patients would demonstrate reduced emotional reactivity, as indexed by emotional mo dulation of startle, to threatening pictures. This aim was based on the view that the amygdala appear s to play a specific role in the processing of threat-inducing stimuli coupled w ith prior findings of amygdala atrophy in Parkinsons disease. Therefore, startle eyeblink magn itudes while viewing th reat-inducing pictures were directly compared against eyeblink magnitudes while view ing another category of similarly arousing and unpleasant stimuli (i.e., disgust pict ures). It was predicted that PD patients would demonstrate reduced startle potentiation in response to threat-inducing stimuli compared to healthy agematched controls, whereas they would not differ fr om controls in eyeblink magnitudes to disgust pictures. This aim examined the possibility of an emotion-specific re activity deficit in PD. Specific Aim 2 The second aim was to explore the relationshi p between emotional re activity deficits in Parkinsons disease and spousaland self-report measures of mood. This aim consisted of two key aspects. The first involved determining whet her emotional reactivity deficits are correlated with depressive symptomatology. Based on prio r work, it was predicted that depression and startle eyeblink magnitudes would not be significantly associated (Bowers, Miller, Mikos, et al., 2006). This prediction was further supported by Allen, Trinder, & Brennans (1999) study, which found that severe depression affected em otional modulation of startle eyeblink, whereas mild to moderate depression did not. The second asp ect involved examination of spousal ratings of perception of depression for bot h PD patients and controls. A gr eater discrepancy between self and spousal ratings of depression for PD patients than for contro ls was predicted. Specifically, it

PAGE 30

30 was predicted that spouses of PD patients would perceive their si gnificant other as being more depressed than they truly are. Ostensibly, this would be due to their mi sattributing symptoms of PD (e.g., masked facies) to depr ession. Finally, the re lationship between discrepancy in selfversus spousaldepression ratings and emo tion-modulated startle eyeblink magnitude was examined to determine whether misattribution of mood state by others is associated with reduced physiological emotional reactivity.

PAGE 31

31 Figure 1-1. Simplified direct l oop in the PD patients dysfunctional motor system. The striatum receives excitatory projections from the co rtex, but input from the SNc is impaired due to a reduction of dopamine. This re sults in the striatum not receiving enough excitatory input to exert its inhibitory influence over the MGP and SNr. The MGP and SNr, free of inhibition from the striat um, provide inhibitory influence over the thalamus, thus preventing the thalamus from providing excitatory output to the cortex. The inhibition of the thalamus and l ack of cortical activa tion results in poverty of movement. (SNc = substant ia nigra pars compacta, MGP = medial globus pallidus, SNr = substantia nigra pars reticularis, VA= ventral anterior nucleus, VL= ventral lateral nucleus).

PAGE 32

32 A B Figure 1-2. Two hypothesized st riato-thalamo-cortical loops involved in emotion. A) ACC loop. B) OFC loop. (G.P.= globus pallidus, SN r = substantia nigra pars reticularis, mdm = medial dorsomedial nucleus, DM= dor somedial nucleus, VA= ventral anterior nucleus). Ventral Striatum (Nucleus Accumbens) G.P. rostrolateral/SNr Thalamus DM & V A Anterior Cingulate Cortex Caudate (ventromedial) G.P. mdm / SNr Thalamus DM Lateral Orbitofrontal Cortex

PAGE 33

33 42 44 46 48 50 52 54 56 58ThreatOther unpleasant pictures Emotion CategoryMean blink magnitude (t-score ) Controls Parkinson Figure 1-3. Preliminary findings of emotionmodulated startle eyeblink magnitude in PD patients and controls. PD patients showed significantly smaller eyeblink magnitudes in response to threat pictures. Error bars indicate standard errors of means.

PAGE 34

34 CHAPTER 2 MATERIALS AND METHODS Overview All participants came to the laboratory on tw o separate occasions, spaced no more than two weeks apart. The first session was a sc reening session, during which cognitive and mood measures were administered and a medical and psychiatric history was taken. The second session consisted of the psychophysiology experiment a nd emotion ratings. Addi tionally, participants with significant others were given the Surr ogate BDI-II to take home for their partner to complete. Participants All study participants were be tween 50 and 85 years old. Parkin son patients were recruited from the Movement Disorders Center at the Un iversity of Florida as well as from ongoing studies within the Cognitive Neuroscience laborato ry. Controls were recruited via flyers posted in the community and in newspapers, as well as fro m a list of participants from prior experiments who had indicated an interest in being contacted for future studies. Informed consent to participate in this research was obtained fo llowing University of Florida IRB guidelines. Exclusion criteria for the control group included History of head injury, neurol ogical disease, lear ning disability, substance abuse, or major psychiatric disorder Current use of psychotropic medications Current medical illness that could potent ially affect cognition (e.g., cancer or HIV) Less than nine years of formal education Possible dementia or disturbance in cognition. This was determined by a score greater than 1.5 standard deviations below ageand e ducation-appropriate norms (i.e., below 7th percentile) on either the Dementia Ra ting Scale, 2nd Edition (DRS-II) total score or on the delayed recall portions of Calif ornia Verbal Learning Test, 2nd Edition (CVLT-II) and

PAGE 35

35 Logical Memory II total recall score fr om the Wechsler Memory Scales, 3rd Edition (WMS-III) Significant depression symptoma tology. This was determined by a score > 19 (the cut score for moderate depression recomme nded by Beck, Steer, and Brown, 1996) on the Beck Depression Inventory, 2nd Edition. Previous research ha s found that individuals with severe levels of depression symptoms have a different pattern of st artle modulation relative to healthy controls (Allen et al., 1999; Kaviani et al., 2004). As such, high levels of depression symptoms may a ffect startle modulation. All Parkinson patients included in the study were diagnosed by a fellowship-trained movement disorders neurologist. Pa rkinson patients were subject to the same exclusion criteria as controls. The only exception wa s that PD patients were not excl uded if they were currently taking antidepressants or anti-anxiety medications. Additional exclusion criteria specific to the PD group included Evidence of secondary or atypical parkins onism (as suggested by history of stroke, exposure to toxins or neurol eptics, history of encephalitis neurological signs or upper motor neuron disease, cerebellar involvement, or lack of response to levodopa therapy) Presence of a co-morbid movement disorder Unstable medication regime resulting in severe dyskinesias or freezing Hoehn and Yahr stage greater than three (due to safety concerns in the off-medication condition Prior neurosurgical treatments including deep brain stimulation or lesion surgery. The initial sample of participants consis ted of 28 Parkinson patients and 27 healthy controls. Three PD patients were excluded afte r the screening session due to BDI-II scores over 19, indicating moderate-to-severe depression. One was excluded for double vision due to its potential influence on perception of affectiv e pictures. One control was excluded due to diagnosis of ADHD and l earning disorder revealed during th e screening session, and one due to substance abuse and apparent in toxication during the screening se ssion. Another control decided

PAGE 36

36 against participating in the expe rimental session due to sensitiv ity to seeing blood. Thus, a total of 24 PD patients and 24 controls completed all study procedures. Session 1 (Screening): Materials and Procedures During the screening sessi on, all participants were admi nistered the Dementia Rating Scale, 2nd Edition (DRS-II; Mattis, 2001), the Ca lifornia Verbal Learning Test, 2nd Edition (CVLT-II; Delis, Kramer, Kaplan, & Ober, 2000), the Wechsler Memory Scales, 3rd Edition (WMS-III) Logical Memory I and II subtests (Wechsler, 1997), the Boston Naming Test (BNT; Kaplan, Goodglass, and Weintraub, 2001), and the Beck Depression Inventory, 2nd Edition (BDIII; Beck, 1996). The PD patients were tested wh ile on their normal dopaminergic medications so that test performance would estimate their t ypical level of cognitive and motoric functioning. Measures administered are descri bed briefly below. At the comp letion of Session 1, participants with a spouse were asked to bring home a copy of the Surrogate BDI-II for their spouse to complete and bring or mail back to the laboratory. The Dementia Rating Scale, 2nd Edition is a screening measure for dementia that yields a total score, as well as subscale scores in the domains of attention, in itiation/ perseveration, construction, conceptualization, and memory. The authors report a test-rete st reliability of .97 and a split-half reliability of .90 (Jurica, Leitten, & Mattis, 2001). The DRS-II has been validated for use on various neurological popula tions, including patien ts with Parkinsons disease. For screening purposes, total raw scores were converted to ageand education-corrected MOANS (Mayo Older American Normative Studies ; Lucas et al., 1998) scaled scores, then percentiles, to determine study eligibility. The California Verbal Learning Test, 2nd Edition is a verbal memory task that involves repeated presentations of a list of sixteen wo rds. The words can be grouped into semantic categories, allowing for assessmen t of voluntary and cued use of strategy in learning. The test

PAGE 37

37 includes both immediate and delayed recall of list material. Test-retest and split-half reliabilities for subscores of the various CVLT-II indices ar e generally above .80 (Delis et al., 2000). The Wechsler Memory Scales, 3rd Edition (WMS-III) Logical Memory I and II subtests assess ability to recall information presented in narrative format. Two stories are read by an examiner, and immediate and delayed recall for story details are tested. The second story is presented twice, allowing for analysis of learni ng slope. Test-retest and split-half reliabilities for Logical Memory I total recall and Logical Memory II total recall subscores are above .80 (Wechsler, 1997). The Boston Naming Test, 2nd Edition (BNT) is a confronta tion naming task consisting of 60 ink drawings varying in degree of familiarity (Kaplan et al., 2001). The test has been shown to effectively elicit naming impairments in aphasic patients, and has been found to be significantly correlated w ith tests of verbal knowledge a nd reading ability (Lezak, Howieson, and Loring, 2004). The Beck Depression Inventory, 2nd Edition (BDI-II) is a self-report questionnaire presented in multiple choice format designed to measure presence and degree of symptoms of depression. It consists of twenty-one items, each sc ored from 0 to 3. This widely used measure of depression symptomatology has internal consistency and test-retest reliability both above .9 (Beck, Steer, and Brown, 1996). The BDI-II manu al recommends the following cut score guidelines: 0-13 minimal depression, 14-19 mild depression, 20-28 moderate depression, and 29 and above severe depression (Beck et al., 1996). The Surrogate BDIII is a measure created explicitly for use in the current study. It is identical to the BDI-II, with th e exception that the word I was replaced by my family member. Both control and PD participants wi th spouses were asked to bring home this

PAGE 38

38 questionnaire to give to their spouse. The questionnaire was accompan ied by a letter that included instructions and a descri ption of the purpose of the questi onnaire. This letter, as well as the Surrogate BDI-II, was approved by the Univer sity of Florida IRB. The Surrogate BDI-II included the following instructions for spouses: This questionnaire cons ists of 21 groups of statements. Please read each group of statements carefully and choose the one statement from each group that best describes your evaluation of how your family member has been thinking, feeling, or acting over the past TWO WEEKS including today. For some statements, you may not know how s/he has been feeling or thinking; this is okay, just make your best guess. If several statements in the group seem to apply equally well, circle the highest number for the group. The spouse was asked to complete the ques tionnaire on the same day that their partner participated in the experiment so that selfand surrogate BDI-II scores would refer to the same time period. Although the concept of a Surrogate BDI-II has not been previously used with a PD population, Logsdon and Teri (1995) have used a surr ogate version of the BD I (first edition) in which caregivers reported depressi ve symptoms in patients with Alzheimers disease. They reported that coefficient alpha leve ls were comparable to levels reported for the traditional selfreport format and concluded that the BDI was appropriate for su rrogate reporting of depression symptoms. Session 2 (Psychophysiology): Materials and Procedures Medication Wash-Out for Parkinson Patients Parkinson participants were asked to withhol d all anti-Parkinson medications for at least twelve hours prior to participating in Sessi on 2. This is because it is unknown how antiParkinson medications may affect emotional reacti vity at the physiological level. Because one aim of the study was to characterize any emoti onal reactivity deficits found in Parkinsons

PAGE 39

39 disease, it was essential that any medication that might alleviate or mask potential deficits be withheld during study participati on. The half-life of the most potent PD medication, levodopa, is about 60-90 minutes, whereas th e most commonly used dopamine agonists, pramipexole and ropinirole, have a half-life between 3-8 hours. Thus, participants with PD were asked to withhold all dopa medications overnight for a pe riod of at least 12 hours. Based on these halflives, it is reasonable to expect that a 12-hour time span would nor mally place the PD participant in the "off" medication state. Picture Stimuli The picture stimuli used in the psychophys iology portion of the study consisted of 48 primary pictures (24 unpleasant (further subdivided into 12 disgust and 12 threat), 12 neutral, and 12 pleasant). Unpleasant pictures were limited to pictures intended to elicit feelings of disgust and threat/fear because other negative emotions, such as anger and sadness, have been shown to be difficult to elicit re liably (Smith et al., 1996) a nd because disgust and fear are emotions associated with similarly high physiolo gical arousal. Pictures were drawn from the International Affective Picture System (IAPS; La ng et al., 2001a) and were chosen based on the normative study data published for the IAPS (La ng, Bradley, & Cuthbert, 2001b) and a study in which 135 subjects were asked to rate IAPS pictur es in terms of the discrete emotions the pictures elicited (Bradley, Codi spotti, Sabatinelli, & Lang, 2001) The latter study found that both men and women rated pictures of contam ination (e.g., dirty toilets, vomit, feces), accidents/injuries, and mutilated bodies as primarily very high in disgust, whereas pictures of animal attacks and humans attacking one another were rated as primarily very high in fear (Bradley, Codispotti, Sabatinelli, et al., 2001). Thus, these types of pictures were selected when creating the disgust and threat pi cture sets for the current study.

PAGE 40

40 The disgust pictures were further subd ivided into 6 mutilation pictures and 6 contamination pictures. This subdivision was based on neuroi maging (fMRI) findings in normal adults indicating that distinct neural responses occurred to mutilation pictures versus contamination pictures (Wright, He, Shapira, Goodman, and Liu, 2004). In brief, both types of pictures (mutilation, contamination) resulted in insula activation; however, the mutilation pictures also caused greater activ ation of the occipital temporal cortex and unique activation of the right superior parietal cort ex relative to the contaminati on pictures. Subdividing the disgust pictures into mutilation and contamination pictures allowed for the examination of potential differences in emotion ratings and startle eyeblink reactivity for these two types of stimuli. The pleasant and unpleasant (i.e., th reat and disgust) pictures we re equivalent with regards to average arousal ratings reported by partic ipants in Lang et al.s (2001b) IAPS normative study. With regards to valence ratings, normativ e ratings placed the pl easant pictures as equidistant from the most pleasant anchor point as the threat and disgust pictures were from the most unpleasant anchor point on the 1-9 rati ng scale. The neutral pictures had an average valence rating that fell in the middle of the rati ng scale and an average arousal rating that was lower than the pleasant, threat, and disgust pictur es. A complete listing of all picture stimuli and their associated normative valence and arous al ratings can be found in Appendix A. Pictures were presented in a fixed, pseudo-rando m order, with the constraint that no more than two trials of the same picture type could o ccur in a row. Two different picture orders were created by repositioning the pictures so that pictur es occurring in the firs t half of Order 1 were presented in the second half of Order 2. Administ ration of the two orders was counterbalanced to minimize potential effects of order of presentation.

PAGE 41

41 Psychophysiology Procedure Upon arrival at the laborator y, surface Ag-AgCl electrode s filled with an isotonic electrolyte were positioned under the participants left and right eyes to record electromyographic (EMG) activity from the orbi cularis oculi muscle. Electrode placement followed recommendations by Fridlund & Cacioppo ( 1986). Participants were then asked to sit in a comfortable chair, located in a sound-attenu ated and electrically shielded 12x12 room. Participants were told that throughout of the experiment th ey could communicate with the experimenter via an intercom. Startle eyeblink re sponses were elicited by a single 50 ms burst of white noise (95 db, instantaneous rise time) produced by a Colbourn S81-02 module and delivered binaurally through Telephonics (TD-5 91c) stereo headphones. The session began with twelve probes delivered in the ab sence of any other stimulus (blank startles). These initial probes were designed to ensure appropriate elicitati on of the startle responses, correct any potential problems with electrodes functioni ng or placement, and assess group differences in blank startle characteristics. Picture stimuli for the emotion-modulated st artle task were displayed on a 21-inch computer monitor located directly two feet in front of the participant. After the participant was familiarized with the procedure (including use of the emotion rating scale, described below) and practiced using the rating scale with four sa mple pictures, the experiment commenced. Participants were presented with 64 pictures th at included 48 startle probe trails and 16 filler trials, during which no startle pr obe was presented. The 64 pictures were arranged in four blocks of 16 pictures each. Each block consisted of 12 startle probe trials plus 4 interspersed filler trials. This ratio of startle to no-startle probe tria ls (approximately 75% of tr ials associated with a startle probe) is consistent with the majority of past studies examining emotional modulation of

PAGE 42

42 the startle reflex using picture stimuli (Bradle y, 2000; Cuthbert, Bradle y, & Lang, 1996; Vrana et al., 1988). Each picture was presented on the computer monitor for six seconds. During this time, a white noise burst (startle probe ) was randomly presented at one of three time intervals following picture onset (4200, 5000, or 5800 ms). Startle pr obe onset was counterbalanced across the different picture categories. The use of thr ee different time points af ter picture onset was designed to prevent participants from developing expectancy of the startle probe. After the presentation of each picture, participants comple ted subjective ratings as described below. This was followed by a variable 10-15 second inter-trial interval before the on set on the next trial. Valence and Arousal Ratings of Pictures Approximately 8 to 12 seconds following th e presentation of each picture, the Self Assessment Manikin (SAM) appeared on the com puter screen. SAM is a graphic display depicting a cartoon figure that va ries along the dimensions of va lence and arousal (Greenwald, Cook, & Lang, 1989; Lang, 1980). For valence, differe nt versions of the cartoon figure depict the cartoons level of pleas antness. The scale goes from high ly unpleasant to neutral to highly pleasant. Each figure has a number (1-9) associated with it. For arousal, different versions of the cartoon figure are shown ranging from sleepy/calm /bored to neutral to highly excited or energized. Again, each figure has a number associated with it, ranging from 1-9. During the experiment, participants were asked to rate th eir reactions to each picture immediately after viewing it by referring to the SAM rating scal e. Participants spoke their ratings aloud, and ratings were transmitted via intercom to an examiner in another room, who recorded all responses. Participants were given as long as needed to make their ratings.

PAGE 43

43 Post Hoc Ratings of Basic Emotions Following completion of the entire psyc hophysiology experiment, electrodes were removed and each participant was reshown the 48 primary picture stimuli on an Apple iBook laptop and asked to make additional ratings. Participants rated how much happiness, fear, disgust, and sadness they felt while viewing each picture using a 1-9 rating scale. These post hoc basic emotion ratings served as a manipulation ch eck to determine if the targeted emotion (i.e., disgust for the contamination and mutilation pictures, fear for the threat pictures, happiness for the pleasant pi ctures) was produced at both the group and the individual level. Participants were told that this rating scale was different from the one using during the psychophysiology experiment, and that their ratings with this ne w scale would not correspond to ratings with the previous scale. The rating scale was depicted visually as a vertical line labeled with the numbers one through nine. The number was accompanied by the text I did not feel any of this emotion at all, the number was accompanied by the text I moderately felt this emotion, and the number was accompanied by th e text I strongly felt this emotion. Participants advanced through th e pictures by pressing a touchpad, and were instructed to move through the pictures at their ow n pace. Participants wrote down their ratings on a separate response sheet. The pictures were presented in a diffe rent order than dur ing the psychophysiology experiment, and two alternate or ders were created. Administra tion of these two orders was counterbalanced across group and sex. Psychophysiology Data Reduction The raw EMG signal was amplified (30,000 gain ) and frequencies below 90 Hz and above 1000 Hz were filtered using Colbourn bioamplif iers. The raw signal was then rectified and integrated using a Colbourn Contour Following In tegrator with a nominal time constant of 100

PAGE 44

44 milliseconds. Digital sampling at 1000 Hz began 50 ms before presentation of the acoustic startle probe and continued for 250 ms after startle pr obe offset. Data from each participant were visually examined, and trials with clear artif acts (e.g., eyeblink moveme nts before probe onset) were rejected. Subsequent data reduction was completed using a custom software program for data condensing. Latency and amplitude of the peak response within 20 ms to 120 ms after probe onset were determined. Trials with a peak late ncy outside of the specifi ed latency range were discarded, as were trials with a peak amplitude more than 3 standard deviations above or below each participants mean magnitude for a given pict ure category. In order to minimize the effects of inter-subject va riability in overall magnitude, raw scores were converted into T-scores (mean of 50, standard deviation of 10) for each particip ants left and right ey es separately. For each picture category, average T-scores were computed using all valid trials from both eyes. When data from one eye were invalid, only the valid eye was used. Only participants who had at least two valid trials for each pi cture category were retained for subsequent analyses. Primary Statistical Analyses Prior to proceeding with the analyses outlin ed below, data were checked to ensure assumptions of univariate normality were met. Si gnificance tests were two-tailed and set at the conventional levels for significance ( p < .05). When post ho c t-tests were used to further examine significant effects, Bonferroni correctio n for multiple comparisons was employed. All analyses were performed using SPSS for Windows statistical software (Version 13.0, Lead Technologies, Inc., Chicago, IL). Th e statistical analyses used to test primary study predictions are described below. Specific Aim 1 It was predicted that Parkinson patients would demonstrate reduced emotional reactivity, as indexed by emotional modulation of startle, sp ecific to threatening pictures. To test this

PAGE 45

45 prediction, data were subjected to 2 Group (PDs, controls) x 5 A Priori Picture Category (pleasant, neutral, threat, dis gustcontamination, disgust-mutilati on) repeated measures Analysis of Variance (ANOVA) with eyeblink magnitude Tscores as the dependent variable. A main effect of picture category and a group-by-pi cture-category interaction was predicted. The interaction was decomposed by five planned one-way ANOVAs (one for each a priori picture category) with group as the between-subjects factor. Specific Aim 2 A secondary aim of the study was to explore th e relationship between emotional reactivity deficits in Parkinsons disease and self-report measures as well as spousal-report measures of mood. First, the relationship be tween self-reported depression and eyeblink magnitudes was examined through five separate linear regressi ons (one for each pictur e category: neutral, pleasant, threat, disgustcontamination, a nd disgustmutilation). BDI-II scores, diagnostic group, and the BDI-II x diagnostic group interaction term were entered simultaneously as the independent variables. Eyeblink magnitude T-scor es served as the dependent variable. Based on previous literature (Allen et al ., 1999; Bowers, Miller, Mikos, et al., 2006), it was predicted that BDI-II scores and eyeblink magnitude would not have a significant linear relationship. Next, Surrogate BDI-II data we re analyzed via repeated m easures ANOVA with diagnosis as a between-subjects factor a nd self-report/ Surrogate BDI-II score as a two-level withinsubjects factor. Because not all participants had a spouse or part ner, the sample size for this analysis consisted of 21 PD patie nts and their partners and 18 c ontrols and their partners. We were interested in the main effect of self-/ surrogate BDI-II scores to determine whether a discrepancy exists between ratings of depr ession completed by oneself versus a spouse. Additionally, the diagnosis x self /spousal-report interaction al lowed for examination of the prediction that the difference between selfand surrogate BDI-II ratings would be greater for the

PAGE 46

46 PD group compared to the control group (i.e ., a significant diagnosis x self/spousal-report interaction). It was predicted th at spouses of PD patients would perceive them as being more depressed than they truly are, due to misattribution of PD sy mptoms (e.g., masked facies) to depression. The relationship between BDI-II scores, Surrogate BDI-II scores, group membership, and startle eyeblink magnitudes was examined using five separate linear regressions (one per a priori picture category) to determine the contribution these variable s may have to total eyeblink magnitude variance. BDI-II self-report scores, Surrogate BDI-II scores, diagnostic group, and the BDI-II x Surrogate BDI-II interaction term were simultaneously entered into the regression equation as independent variab les. There were no specific a priori predictions as to whether Surrogate BDI-II scores or the discrepancy betwee n selfand spousalreport level of depression (represented by the BDI-II x Surrogate BDI-II inte raction term) would contribute to eyeblink magnitude variance.

PAGE 47

47 CHAPTER 3 RESULTS Participant Characteristics A summary of participant demographic vari ables and patient disease characteristics are presented in Table 3-1. As shown, the two groups did not statistically differ with respect to age, education, or gender distribution. Overall, the sa mple was well educated, ranged in age from 50 to 80 years, and contained slightly more males th an females. The PD patients were generally in the middle stages of their disease (Hoehn and Ya hr stage of 2 or 3 [Hoehn and Yahr, 1967]) and all were on L-DOPA and/or dopa mine agonists. Seven of th e PD patients were on antidepressant medications (thr ee on Wellbutrin, two on Lexapro, one on Zoloft, and one on Effexor). One PD patient on Lexapr o was also taking on clozepam to aid in sleep at night. None of the controls were on any psychotropic medications. Cognitive and Mood Measures Parkinson patients and controls did not signifi cantly differ with respect to Dementia Rating Scale-II, Boston Naming Test, California Verbal Learning Test-II, or Wechsler Memory ScalesII Logical Memory I and II scores. In contrast, Parkinson patients obtai ned significantly higher scores than controls on the BDI-II ( t [46] = 2.99, p = .005), although both groups had mean scores in the non-depressed range (PD = 6.17 [SD = 4.76], control = 2.58 [SD = 3.45]). Three PD patients and one control had BDI-II scores falling within the mildly depressed range, defined as scores between 14 and 19 (Beck et al., 1996). A ll other participants sc ored within the nondepressed range. Group means and standard devi ations for cognitive and mood measures are shown in Table 3-2.

PAGE 48

48 Baseline Startle Eyeblink An initial analysis examined whether the PD pa tients and controls differed in terms of their basic unprimed startle eyeblink responses. This was done by analyzing the twelve initial unprimed baseline trials (i.e., no picture presented). Results of independent t-tests showed no group differences in peak eyeblink magnitude (controls = 6.59 mV [S D = 6.78], PD = 5.38 mV [SD = 4.45]; t [46] = .73, p > .1). Similarly, there was no diffe rence in baseline startle latency (controls = 74.19ms [SD = 8.26] PD = 72.86ms [SD = 11.64]; t [46] = .45, p > .1). Thus, the PD patients displayed unprimed startle eyeblink responses that were si milar in both size and latency to those of the control group. Emotion-Modulated Startle Eyeblink Discarded Trials The total percentage of discarded tria ls was 9.9%. Discarding was based on eye movement artifact (determined by vi sual inspection; 5.1% of all di scarded trials), peak latency out of range (2.8%), peak amplitude out of range (1.5%), and no peak maximum amplitude found (0.6%). A 2 (Group) x 2 (Stimulus Presentation Order) x 5 ( A Priori Picture Category: pleasant, neutral, fear, disgustcontaminati on, disgustmutilation) repeated measures ANOVA with number of discarded trials as the depende nt variable did not yi eld any significant main effects or interactions (all p s > .1). Latency A 2 (Group) x 2 (Stimulus Presentation Order) x 5 ( A Priori Picture Category: pleasant, neutral, fear, disgustcont amination, disgustmutilation) repeated measures ANOVA was conducted to determine whether latency was affected by any of these variables. Results revealed no significant main effect s or interactions (all p s > .1). Thus, the latency to peak did not appear to vary as a function of group, s timulus presentation order, or a priori picture category.

PAGE 49

49 Magnitude An initial analysis was conducted in orde r to determine whether the two stimulus presentation orders resulted in different findings. This i nvolved a 2 (Group) x 2 (Stimulus Presentation Order) x 5 ( A Priori Picture Category: pleasant neutral, fear, disgustcontamination, disgustmutilati on) repeated measures ANOVA with startle magnitude (T-score) as the dependent variable. No significant main eff ect or interactions with stimulus presentation order were found, and thus for the remaining analyses the two orders were combined to increase power. The role of startle probe onset latency was also examined to determine whether startle magnitude was influenced by the timing of probe presentation. A 3 (Probe Onset Latency: 4200 ms, 5000 ms, 5800 ms) x 3 (Valence: pleasant, ne utral, unpleasant) repeated measures ANOVA was conducted for the controls and PD patients separately. For both groups, no significant main effect of startle probe onset latency or interaction with valence was found (all p s > .6). Additionally, a 3 (Latency) x 3 (Valence) x 2 (Group) repeated measures ANOVA revealed no significant interactions (all p s > .1). Thus, the remaining analyses are collapsed across the three different startle probe onset latencies. Verification of typical pa ttern of startle modulation Before examining the primary aim of the study, emotion-modulated startle eyeblink magnitudes were checked to verify that the typi cal pattern of emotion modulation did in fact occur. Typically, magnitudes for pleasant pictur es are smaller compared to neutral pictures, whereas magnitudes for unpleasant pictures are larger To examine whether this pattern held true for the current study, the threat, disgustcontam ination, and disgustmutilation pictures were collapsed into a general unpleas ant category. Eyeblink magnitude t-scores were then subjected to 2 (Group) x 3 (Valence: pleasant, neutral, unpleasant) repeated measures ANOVA. Results

PAGE 50

50 revealed a significant main effect of valence ( F [2,92] = 9.37, p < .001, 2 p = .17). No other effects were significant. Bonferroni-corrected post hoc comparisons indicate d that the pleasant pictures were associated with significantly smaller eyeblink magnitudes than both neutral and unpleasant pictures ( p < .05). The comparison between unpleasa nt pictures and neutral pictures was not statistically significant; however, mean ey eblink magnitudes were larger for unpleasant pictures than neutral pictures. These results indicate that th e typical pattern of emotional modulation was observed for both c ontrols as well as PD patients. Mean eyeblink magnitudes by group and valence are shown in Figure 3-1. Primary analysis To examine the hypothesis that PD patient s would should display decreased startle eyeblink magnitude to threat pictures, a 2 (Group) x 5 ( A Priori Picture Category: pleasant, neutral, threat, disgustc ontamination, disgustmutilation) repeated measures ANOVA was conducted. This yielded a signi ficant main effect of A Priori Picture Category ( F [4,184] = 9.18, p < .001, 2 p = .17) and a Group x A Priori Picture Category inte raction (F[4,184] = 2.49, p < .05, 2 p = .05). Bonferroni-corrected post hoc comparisons indicated that the main effect of A Priori Picture Category was driven by the threat pictures, which were associated with significantly larger startle magnitudes (collapsing across both groups) than those for the neutral, pleasant, disgustcontamination, a nd disgustmutilation pictures (all p s < .02). No other comparisons were significant. When results we re examined for cont rols and PD patients separately, controls showed signi ficantly larger eyeblink magnitude s to threat pictures compared to neutral and pl easant pictures ( p s < .05). Additionally, eyebli nk magnitudes to mutilation pictures magnitudes tended to be larger compared to pleasant pictures, but this comparison was no longer significant after Bonferro ni corrections were made ( p = .1). In contrast, PD patients

PAGE 51

51 showed significantly larger ey eblink magnitudes for threat pict ures compared to neutral, pleasant, and mutilation pictures ( p s < .05). The Group x A Priori Picture Category interaction wa s decomposed by conducting five separate univariate ANOVAs (one for each a priori picture category) with Group as the betweensubjects factor. Only the comparison for disgustmutilation pictures was significant ( F [1, 46] = 6.66, p < .02), 2 p = .13), with controls showing significan tly larger startle eyeblink magnitudes than PD patients (means: PD = 48.34 [SD = 3.91 ], controls = 51.09 [SD = 3.47]). Thus, the prediction that eyeblink magnitude s in response to threat pictur es would be reduced in PD patients compared to controls was not supported; instead, it was the disgust-mutilation pictures that resulted in attenuated startle eyeblink magnitude in the PD group. Mean eyeblink magnitudes for each group for pleasant, neutral, threat, disgustcontamination, and disgustmutilation pictures are shown in Figure 3-2. Habituation Pattern To follow-up on the finding of decreased star tle eyeblink magnitude in the PD group in response to the disgustmutilation pictures, each groups eyeblink magnitudes to mutilation pictures was examined on a trial-by-trial basis. Th e purpose of this analysis was to determine if group differences in eyeblink magnitudes can be accounted for by differential patterns of habituation to the mutilation stimuli. For example, one possibility is that controls and PD patients initially showed similar eyeblink magnitudes to the pictures, but PD patients habituated more quickly. To examine this possibi lity, a 2 (Group) x 7 (Trial Nu mber) repeated measures ANOVA was conducted for the mutilation pictures. Overall, both groups showed habituation of startle eyeblink magnitude over time ( F [11, 506] = 4.55, p < .001), 2 p = .09), as is typically found with this paradigm. However, the Group x Tria l Number interaction was nonsignificant ( F [11, 506] =

PAGE 52

52 0.88, p > .5). This indicates that di fferences in eyeblink magnitude habituation do no t explain the group difference in responsivity to mutilation pictures. Valence and Arousal Ratings One explanation for the attenuated startle ey eblink magnitude observe d in the PD group in response to the disgustmutilation pictures may be that these pictures were considered less aversive or less arousing by the patients. Thus, subjective ratings of valence and arousal were analyzed through two separate 2 (Group) x 5 ( A Priori Picture Category: pleas ant, neutral, threat, disgustcontamination, and di sgustmutilation) repeated measures ANOVAs. For valence ratings, results yielded a si gnificant main effect of A Priori Picture Category ( F [4,184] = 49.24, p < .001, 2 p = .52). The effect of Group was nonsignificant [ F (1,46) = .34, p > .1], as was the Group x Emotion Category interaction [ F (4,184) = .07, p > .1]. Bonferroni-corrected post hoc comparisons collapsing across the two groups rev ealed that pleasant pictures were rated as significantly more pleasant than all other picture types (all p s < .001). Neutral pictures were rated as significantly more plea sant than contamination, mutila tion, and threat pictures (all p s < .001). Looking at just the unpleasant picture cate gories (threat, disgus tcontamination, and disgustmutilation pictures), the mutilation pictures were rated as significantly more pleasant than the threat pictures ( p < .05). No other comparisons were significant. For arousal ratings, results once again yielded a significant main effect of A Priori Picture Category ( F [4,184] = 56.00, p < .001, 2 p = .55), and no other significant effects or interactions (all p s > .1). Bonferroni-corrected post hoc comparisons collapsing across the two groups revealed that the neutral pictur es were rated as significantly le ss arousing than all other picture types (ps < .001). No other comparisons were significant, indicating th at pleasant, threat, disgustcontamination, and disgustmutilation pi ctures were perceived as equally arousing by subjects. Table 3-3 shows mean valence and arou sal ratings for each emotion category by group.

PAGE 53

53 In summary, PD patients did not rate the mu tilation pictures as being less unpleasant or less arousing than controls; thus, these self-repor t ratings cannot explain the finding of reduced eyeblink magnitude to mutilation pictures in Parkinson group. Post Hoc Basic Emotion Ratings An alternate explanation is that mutilation pi ctures were not effective in evoking a strong disgust reaction in the PD group, or perhaps even a strong negative reaction of any type. Because emotion-modulated startle potentia tion is dependent on participants experiencing the pictures as aversive, this could explain the PD patients diminished eyeblink magnitudes to mutilation pictures. To explore this possibility, the post hoc basic emotion ratings made by all participants after the psychophysiology portion of the experiment were examined. As previously described, each participant rated each pictur e in terms of how happy, disgusted, fearful, and sad he or she felt while viewing the picture. These ratings serv ed as a manipulation check to ensure that the pictures did in fact evoke the emotions they we re intended to. Specifically, it was expected that contamination and mutilation pictures would be associated with the highest disgust ratings, threatening pictures would be a ssociated with the highest fear ratings, and pleasant pictures would be associated with the highest happiness ratings. First, a 2 (Group) x 2 (Stimulus Presentation Order) x 5 ( A Priori Picture Category) x 4 ( Post hoc Basic Emotion) repeated measures ANOV A was conducted to confirm that order of stimulus presentation during the post hoc rating portion of the experi ment did not effect results. The main effect and interactions with presentati on order were all non-significant. As such, data from the two presentation orders were combin ed. Next, a series of four 2 (Group) x 5 ( A Priori Picture Category: neutral, pleasa nt, threat, disgustcontamination, disgustmutilation) repeated measures ANOVAs were conducted (one for each post hoc basic emotion rating: happiness, disgust, fear, and sadness). Post hoc emotion ratings by group and a priori picture category are

PAGE 54

54 shown in Table 3-4. For the happiness rati ngs, results yielded a main effect of A Priori Picture Category ( F [4,184] = 463.02, p < .001, 2 p = .91), with no other signifi cant effects. Bonferronicorrected pairwise comparisons collapsing across th e two groups revealed th at pleasant pictures had significantly higher happiness ratings than all other types of pictures (all p s < .001). Additionally, neutral pictures had significantl y higher happiness ratings than threat, mutilation, and contamination pictures, while threat pictures had significan tly higher happiness ratings than mutilation pictures ( ps < .001). For disgust ratings, the repeated m easures AVOVA showed a main effect of A Priori Picture Category ( F [4,184] = 274.23, p < .001, 2 p = .86) as well as an A Priori Picture Category x Group interaction ( F [4,184] = 3.19, p < .02, 2 p = .07). Bonferroni-co rrected pairwise comparisons collapsing across the two groups revealed that both mutilation and contamination pictures were rated as signi ficantly more disgusting than all other picture types ( ps < .001), whereas mutilation and contamination pictures did not differ from one another in subjective disgust ratings. Both the neutra l and pleasant pictures were rate d as significantly less disgusting than threat, contamination, and mutilation pictures (all p s < .001). The Group x A Priori Picture Category interaction was decomposed by conducti ng five separate univariate ANOVAs (one for each a priori picture category) with Group as the betw een-subjects factor. Only the comparison for threat pictures was significant ( F [1, 46] = 7.93, p < .01), 2 p = .15), with PD patients rating these pictures as eliciting more disgust comp ared to controls (means: PD = 5.55 [SD = 1.99], controls = 4.81 [SD = 1.94]). Turning to fear ratings, results yielded a main effect of A Priori Picture Category ( F [4,184] = 162.57, p < .001, 2 p = .78); no other effects were si gnificant. Bonferronicorrected pairwise comparisons showed that neutral pictures were rated as significan tly less fearevoking

PAGE 55

55 than all other picture categories, whereas threat pictures were rated as significantly more fearevoking than all other picture types (ps < .001). Additionally, mutilation pictures were associated with significantly higher fear ratin gs than neutral, pleasant, and contamination pictures (ps < .001). In summary, each a priori picture category was effective in evoking the intended emotional reaction. Participants rated pleas ant pictures as significantly hi gher in happiness than all other pictures types, mutilation and contamination pictures as significantly higher in disgust compared to all other picture types, and threat pictures as significantly higher in fear compared to all other picture types. While PD patents rated the threaten ing pictures as higher in disgust compared to controls, no group differences were found with resp ect to degree of happine ss, disgust, fear, or sadness in response to the mutilation pictures. Ov erall, the self-report data suggest that group differences in valence, arousal, or basic em otional reactions cannot account for the reduced eyeblink magnitude to mutilation pi ctures observed in PD patients. Arousal Level as Measured by Skin Conductance Response A potential problem with self-repo rt data is that it is possi ble that participants rated pictures based on how they thought they were expected to respond, as opposed to based on how they truly felt. Recently, studies from two differe nt laboratories reported that PD patients rated highly arousing negative pictures as less arousing than controls (B owers, Miller, Mikos, et al, 2006; Wieser et al., 2006); however, this was not observed in the present study. Thus, it is important to consider the possibility that demand characteristics may have played a role in selfreport ratings. One way to address concerns about the veracity of subjective ratings of arousal level is to examine an objective index of physiol ogical arousal. For this reason, a post hoc analysis of skin conductance response (SCR) was conducted. SCR is an index of sympathe tic arousal that is

PAGE 56

56 difficult to consciously control. Changes in SCR are relatively independent of valence; thus, an increase in SCR is typically observed in response to any type of highly ar ousing picture, whether it is positive or negative in valence(Bradley, 2000). In a large study us ing pictures from the International Affective Picture System, Bradley, Codispoti, Cuthbert, et al. (2001) found that erotica, mutilations, and human and animal attacks were associated with the largest SCR. With regards to the present study, an examination of SCR to mutilation pictures for controls and PD patients is of pa rticular interest. A finding of re duced SCR to these pictures in the PD patients compared to controls would s uggest that the PD group did not find the mutilation pictures as arousing as controls This, in turn, could account fo r the reduced eyeblink magnitudes observed in the PD patients in re sponse to this category of pi ctures, since both valence and arousal play a role in emotion-m odulated startle eyeblink response. Before conducting this key analysis of intere st, the general pattern of SCR to pleasant, neutral, and unpleasant pictures was examined. Fo r a full description of the SCR data collection and reduction procedures, please refer to Append ix B. Threat, disgustcontamination, and disgustmutilation pictures were collapsed into a general unpleasant category. SCR data were then subjected to 2 (Group) x 3 (Valence: pleas ant, neutral, unpleasant) repeated measures ANOVA. Results revealed no signi ficant effects or interactions, although the main effect of valence approached significance ( F [2,92] = 2.79, p = 0.06, 2 p = .06). Group means for each valence category are depicted in Figure 3-3. Although not statistically signifi cant, the pattern of SCR in controls versus PDs was of theoretical interest, and thus t-test s comparing neutral to pleasant pictures as well as neutral to unpleasan t pictures were conducted for each group. For the control group, both pleasant and unpleasant pict ures resulted in signi ficantly greater SCR compared to neutral pictur es (pleasant vs. neutral: t (23) = 2.63, p < .02; unpleasant vs. neutral:

PAGE 57

57 t (23) = 2.94, p < .01). In contrast, neithe r pleasant nor unpleasant pictur es differed significantly from neutral pictures for the Parkinson group ( p s > .3). Next, a 2 (Group) x 5 ( A Priori Picture Category: pleasant, neutral, threat, disgustcontamination, disgustmutilati on) repeated measures ANOVA was conducted so that pictures within the unpleasant pictures s ubcategory could be examined separately. As would be expected based on the non-significant results of the prev ious repeated measures ANOVA, no significant effects were found; however, examination of th e observed power suggested this analysis was insufficiently powered to investigate differences within this many different picture categories (power = .28). Means and standard deviations for control and PD skin conductance response to each pictures category are shown in Table 3-4. In sum, the control group displayed a t ypical pattern of emotion-modulated skin conductance response, with larger SCR to pleasan t and unpleasant pictures compared to neutral pictures, whereas PD patients did not show any modulation. The analysis that included the different unpleasant picture subcategories (threat disgustcontamination, disgustmutilation) did not reveal any significant group difference, although it wa s hindered by low power. These results do not support the idea that PD patient s found mutilation pictures less arousing than controls; however, they do suggest that PD patie nts show an absence of emotion-modulated skin conductance response overall. Re-Examination of Eyeblink Magnitude via Idiographic Analysis Although previous analyses indicated that a priori picture categorizatio ns were consistent with overall post hoc basic discrete emotion ratings at the group level (i.e., pictures generally evoked the intended emotion), inter-subject differen ces in emotional reactions to pictures could potentially influence eyeblink magnitudes at an in dividual level. As an example, a picture of a man hiking atop a mountain that is designed to be pleasant in valence may actually evoke

PAGE 58

58 feelings of fear for an individua l who is scared of heights. Similarly, although pictures of animal attacks were intended to evoke f ear, some animal-lovers reported feelings of happiness for these pictures. For this reason, eyeblink magnitude data were reanalyzed via an idiographic approach based on the post hoc basic emotion ratings (happy, fear disgust, and sad) made by each participant. Individual Categorization of Pictures For each participant, post hoc ratings for each picture were examined and the picture was categorized in terms of the basi c emotion with the highest rating (e.g., if a picture of a mutilation had a higher disgust rating compared to happiness, fear, and sadness ratings, the picture would be categorized as eliciting dis gust for that participant). Pictures with ratings less than a (on a 1-9 scale, with 9 indi cating highest emotional intensity) on all of the basic emo tions were categorized as neutr al, since they were rated as eliciting very little of any emotion. Pictures w ith similarly high rati ngs on two contradictory emotions (e.g., happy and disgust or happy and fear) were excluded due to difficulty in appropriately categorizing these pictures. Initial inspection of ratings revealed that many participants frequently rated aversive pictures (e.g., the a priori fear and disgust pictures) as sim ilarly high in disgust and fear. Thus, pictures with less than a 2-point difference in ratings of disgus t and fear were categorized as general aversive for purposes of idiographic an alysis. Initial inspection of ratings also showed that participants rarely rated a picture as hi gher in sadness than any other basic emotion; instead, sadness typically co-occurred with either a high disgust or fear ra ting, or both. For this reason, sadness was considered to be a secondary emotion, at le ast within the context of the present study, and when a high sadness rating oc curred the picture was categorized under the primary emotion (disgust, fear, or general aver sive) that also receiv ed a high rating. Thus,

PAGE 59

59 sad was not used as a discrete category within the idiographic analysis of eyeblink magnitude data. The basic emotions examined with respect to eyeblink magnitude were neutral, happy, fear, and disgust, as well as general aversive. Emotion-Modulated Startle Eyeblink Magnitude Next, mean eyeblink T-scores for the neutral, happy, fear, disgust, and general aversive categories were calculated for each participant. These T-scores were then subjected to a 2 (Group) x 5 ( Post hoc Emotion Category) repeated m easures ANOVA. Results yielded a significant main effect of Post hoc Emotion Category ( F [4,184] = 4.83, p < .001, 2 p = .10). The Group x Post hoc Emotion Category interaction was nonsignificant (F[4,184] = 0.38, p > .01). Bonferroni-corrected pairwise comparisons co llapsing across groups i ndicated that eyeblink magnitudes in response to pictures categori zed as fear and general aversive were significantly larger than for happy pictures ( p < .001 for fear vs. happy; p < .05 for general aversive vs. happy). No other pairwise comparis ons were significant. Mean eyeblink magnitudes for each group based on post hoc basic emotion categorizatio n are shown in Figure 3-5. In summary, the idiogr aphic analysis based on post hoc basic emotion categorization yielded similar results as the a priori categorization analysis with re spect to the main effect: for both methods of analysis, fear-evoking pictures were associated with a significantly larger startle eyeblink magnitude than happy pictures. This held true for both the PD and control groups. Thus, the prediction that PD patients would show reduc ed eyeblink magnitude to pictures rated highest in fear was not confirmed. Additionally, the idiogra phic analysis showed that pictures that were rated as very high in both disgust and fear (the general aversive pictures) were also associated with significantly larger startle eyeblink magn itude than happy pictures. In contrast, the idiographic analysis did not yield a significant Group x Emoti on Category interaction like the a priori categorization analysis.

PAGE 60

60 Influence of Trait Positive and Negative Aff ectivity and Trait Anxiety on Startle Eyeblink Magnitude One potential explanation for the observe d differences in eyeblink magnitudes to mutilation pictures between PD patients and controls may be that the individuals within the two groups systematically differed on certain pers onality traits. Recent research suggests that individual personality differences may influenc e emotion-modulated star tle. Specifically, some studies have found that people with extremely lo w levels of trait anxiety, neuroticism, and negative affect do not demonstrate emotion-modula tion of the startle refl ex for some categories of affective pictures (Caseras et al., 2006; Corr et al., 1995; Hawk and Kowmas, 2003; Wilson, Kumari, Gray, & Corr, 2000). These findings su ggest that certain individuals may not be sensitive to the emotion-m odulated startle paradigm. Although the present study did not include assessment of these pe rsonality traits, fifteen of the twenty-four PD patients had re cently participated in another study within the laboratory that included self-report measures of state and trait anxiety (StateTrait A nxiety Inventory [STAI]; Spielberger, 1977) as well as trait positive and ne gative affectivity (Posit ive and Negative Affect Schedule [PANAS], Watson, Clark, & Tellegen, 1988). Although thes e data were not available for control participants, the relationship between scores on the negative affect scale of the PANAS and the trait anxiety scale of the STAI and emotion-modulated startle magnitudes were examined to determine whether emotion-modulated startle magnitudes systematically varied as a function of different levels of these traits. For the negative affect scale of the PANAS, scores for the fifteen PD patients who completed the ques tionnaire ranged from 10 to 28 (maximum score is 50, indicating very high tra it negative affectivity). The mean was 14.40 (SD = 5.87), indicating that overall patients were fairly low in negative affect. For the trait anxiety scale of the STAI, scores ranged from 15 to 59 (the maximum possi ble score is 60, indicatin g extremely high trait

PAGE 61

61 anxiety), with a mean of 29.47 (SD = 11.04). This m ean score is in the average range for trait anxiety. A series of multiple regressions with negative affect score and trait anxiety score simultaneously entered as the independent vari able and eyeblink magn itude T-score as the dependent variable produced nons ignificant results for neutral, pleasant, threat, disgustcontamination, and disgustmutilation pictures ( p s > .1). Thus, within the PD group, personality trait differences do not account for a significant portion of the variance in emotion-modulated eyeblink magnitude. The lack of a significant re lationship suggests that at the between-groups level, personality differences are unlikely to account for the finding of reduced eyeblink magnitude to mutilation pictures. Influence of Depression on Eyeblink Magnitude Next, the relationship between BDI-II scores and eyeblink magnitudes in response to each a priori picture category was examined through a series of five separate lin ear regressions (one for each a priori picture category: neutral, pleasant, threat, disgustcontamination, disgustmutilation). BDI-II scores, diagnostic group, and the BDI-II x diagnostic group interaction term were entered simultaneously as the independent variables, wher eas eyeblink magnitude T-scores served as the dependent variable. The BDI-II x di agnostic group interaction term was included in the equation because the two groups differed with respect to mean BDI-II scores. None of the resulting regression models were statistically significant, although the model for disgustmutilation pictures approached significance ( p = .06). Within this model, the regression coefficient for group was significant ( B = -3.13, SE B = 1.18, = 0.40; t [44] = -2.64, p = .01), as would be expected based on the known betw een-groups difference for eyeblink magnitudes in response to these pictures. Otherwise, none of the regression coefficients for the independent variables entered into the neutra l, pleasant, threat, or disgus tcontamination models were significant. Thus, the prediction that BDI-II scor es and startle eyeblink magnitudes would not

PAGE 62

62 have a significant linear relati onship was confirmed. Table 3-5 displays the unstandardized and standardized betaweights, a ssociated standard error, and t -tests for significance associated with each independent variable in each model, as well as the overall R2 and adjusted R2 for each model. Influence of Psychotropic Medications Because anti-depressants and anxiolytics ma y dampen startle reactivity in healthy individuals (Davis and Galla gher, 1988; Harmer, Reid, Ray, Goodwin, & Cowin, 2006), the influence of psychotropic medications on startle reactivity was examined. To do so, the seven PD patients on antidepressants and/ or anxiolytics were removed from the sample and a 2 (Group) x 5 (A priori picture category) repeated measures ANOVA was conducted with the data from this smaller sample. As with the analysis includ ing the full sample, there was a significant main effect of A Priori Picture Category ( F [4,156] = 10.77, p < .001, 2 p = .22) as well as a significant Group x A Priori Picture Category interaction ( F [4,156] = 3.31, p < .03, 2 p = .08). Decomposition of the interaction wi th separate one-way ANOVAs for each a priori picture category revealed that the PD group had significantly smaller ey eblink magnitudes in response to mutilation pictures as compared to controls (F[1,39] = 98.33, p < .01 means: PD = 47.95 [SD = 3.39], controls = 51.10 [SD = 3.47]). Between-groups differences for neutral, pleasant, threat, and contamination pictures were all non-signifi cant. Thus, diminished reactivity to mutilation pictures by PD patients was maintained when ex cluding patients on psychotropics. This finding suggests that psychotropic medication is not responsible for the effect. Spousal Perception of Depression: Relationship to Self-Reported Depression and Startle Eyeblink Magnitude A secondary aim of the current study was to examine the congruency between selfand spousalreport ratings of depression. It wa s predicted that spouses of PD patients would

PAGE 63

63 perceive them as being more de pressed than they truly are, du e to misattributing symptoms of PD (such as masked facies) to depression. Thus, it was predicted that th ere would be a larger discrepancy between selfand surr ogateBDI-II scores for the PD patients as compared to the controls. Additionally, the relationship between discrepancy in selfversus spousaldepression ratings and emotion-modulated startle eyeblink magnitudes was examined. The purpose of this analysis was to determine whether decreased physiological emotional reactivity in PD was associated with misattribu tion of mood state by spouses. Surrogate BDI-II: Comparison with Self-Report BDI-II A 2 (Group) x 2 (Self-repor t BDI-II, Surrogate BDI-II) repeated measures ANOVA yielded a main effect of Group (F[1,37] = 4.66, p < .05, 2p = .11), reflecting higher mean BDIII scores in the PD group on both the self-report a nd surrogate measure. The main effect of selfreport BDI-II vs. Surrogate BDI-II was not signif icant, nor was the Group x Self-/Surrogate BDIII interaction (ps > .1). The lack of signifi cant Group x Self-/Surrogate BDI-II interaction does not support the prediction that s pouses of PD patients would pe rceive them as being more depressed than they truly are. To further explor e the accuracy of spousal ratings of participants level of depression, Pearsons bi variate correlations between self-report and surrogatereport BDI-II scores were computed. Interestingly, the tw o measures were significantly correlated for PD patients, whereas they were not for c ontrols. Although the diffe rence between the two correlation coefficients is not st atistically significant, these fi ndings further bolster the finding that spouses of PD patients can perceive their partners mood quite well, contrary to study predictions. Mean self-report BDI-II and Surr ogate BDI-II scores, as well as the correlation coefficients between the two, are shown in Table 3-6.

PAGE 64

64 Relationship between Surrogate BDIII and Startle Eyeblink Magnitude A series of five multiple regressions (one per a prior i picture category) with BDI-II selfreport scores, Surrogate BDI-II scores, di agnostic group, and BDI-II x Surrogate BDI-II interaction term entered simultaneously as in dependent variables and eyeblink magnitude Tscore as the dependent variable did not yield any significant m odels. Once again, other than the significant regression coefficient for group in the disgustmutilation model, none of the independent variables contribute d a significant amount of variance This suggests that neither Surrogate BDI-II scores nor degree of discrepancy between self versus surrogate ratings are associated with emotion-modulated startle ma gnitude. Table 3-7 shows the unstandardized and standardized betaweights, associ ated standard error, and t-tests for significance associated with each independent variable in each model, as well as the overall R2 and adjusted R2 for each model. Influence of Disease Severity and Du ration on Startle Eyeblink Magnitude To determine whether disease duration or seve rity were associated with the finding of decreased startle reactivity to mutilation pictures in the PD patients, the variables years with PD and UPDRS Motor score were entered as independent variables simultaneously into a regression model with eyeblink T-score to disgustmutilation pictures as the dependent variable. The overall model was not significan t, indicating that neither of these disease-related variables account for a significant portion of th e variance in eyeblink magnitudes ( F [2,21]= 47.02, p = .22; R2 = 0.13, adjusted R2 = 0.05.)

PAGE 65

65 Table 3-1. Demographic and clin ical characteristics by group Characteristic Parkinson ( N = 24) Control ( N = 24) Statistical test Age (years) 68.00 (6.92)68.38 (7.73) t (46) = .18 Sex ratio (men: women) 14:1014:10 2(1) = 0 Education (yrs) 16.21 (3.16)16.33 (2.88) t (46) = .14 Disease duration (yrs) 5.54 (3.63) __ Hoehn and Yahr stagea 2.27 (0.42) __ UPDRS Motora 23.46 (8.49) __ Levodopa equivalent dose (mg) 682.43 (323.26) __ Note: Values are expressed as mean (SD). UPDR S Motor = motor scale of the Unified Parkinson Disease Rating Scale (Fahn & Elton, 1987). a Scores obtained in th e "on" medication state

PAGE 66

66 Table 3-2. Scores on cognitive and mood measures scores by group Measure Parkinson ( N = 24) Control ( N = 24) Statistical test Dementia Rating Scale-II raw score (/144) 140.92 (2.83)141.13 (1.30) t (46) = .33 Dementia Rating Scale-II scaled score 12.04 (2.40)11.79 (1.56) t (46) = .43 Boston Naming Test raw sc ore (/60) 56.48 (5.43)57.21 (3.61) t (46) = .55 Boston Naming Test tscore 58.96 (10.50)59.17 (12.57) t (46) = .06 CVLT-II trials 1-5 total raw score (/80) 45.92 (10.75)50.38 (6.72) t (46) = 1.72 CVLT-II trials 1-5 total t-score 55.58 (12.10)60.29 (6.66) t (46) = 1.67 CVLT-II short delay free recall raw score (/16) 10.21 (3.09)10.71 (2.26) t (46) = .64 CVLT-II short delay free recall zscore 0.65 (1.18)0.81 (0.93) t (46) = .54 CVLT-II short delay cued recall raw score (/16) 11.63 (2.73)11.88 (1.96) t (46) = .36 CVLT-II short delay cued recall zscore 0.50 (1.18)0.62 (0.86) t (46) = .42 CVLT-II long delay free recall raw score (/16) 9.88 (3.31)11.04 (2.26) t (46) = 1.43 CVLT-II long delay free recall z-score 0.25 (1.15)0.60 (0.85) t (46) = 1.21 CVLT-II long delay cued recall raw score (/16) 11.38 (2.67)11.63 (2.18) t (46) = .36 CVLT-II long delay cued recall zscore 0.42 (1.07)0.54 (0.85) t (39) = .45 WMS-III Logical Memory I raw score (/75) 40.19 (9.01)41.75 (7.70) t (39)a = .59 WMS-III Logical Memory I scaled score 11.52 (2.96)12.35 (2.21) t (39)a = 1.00 WMS-III Logical Memory II raw score (/50) 25.10 (7.72)26.80 (6.14) t (39)a = .78 WMS-III Logical Memory II scaled score 12.57 (3.00)13.25 (2.65) t (39)a = .77 Beck Depression Inventory-II 6.17 (4.76)2.58 (3.45) ** t (46)= 2.99 Note: Values are expressed as mean (SD). CVLT-II= California Ve rbal Learning Test 2nd Edition; WMS-III= Wechsler Memory Scales, 3rd Edition. a Three PD patients and four controls were not administered this test ** p < .01

PAGE 67

67 Table 3-3. Valence and arousal rati ngs of affective pictures by a priori picture category and group Valence Arousal A Priori Picture Category Parkinson Control Parkinson Control Neutral 4.71 (0.68)4.61 (0.65)3.93 (1.79) 3.36 (1.67) Pleasant 6.07 (1.72)5.96 (1.70)6.67 (0.99) 6.41 (0.90) Threat 2.60 (1.17)2.62 (1.29)6.79 (1.54) 6.53 (1.56) Disgustcontamination 2.68 (0.95)2.43 (0.90)6.46 (1.47) 6.36 (1.36) Disgustmutilation 3.04 (2.02)3.07 (2.15) 6.92 (1.59) 6.74 (1.56) Note: Values are expressed as mean (SD). Valen ce ratings are on a 1-9 scale, with 9 being most pleasant. Arousal ratings are on a 1-9 scale, with 9 being most arousing. No betweengroups differences for valence or arousal were found. Table 3-4. Post hoc basic emotion ratings by group A priori picture category Post hoc emotion Group Neutral Pleasant Threat Disgustcontam. Disgustmutil. Parkinson 2.48 (1.33)7.03 (1.05)1.20 (0.27)1.53 (0.82) 1.07 (0.21) Happy Control 2.44 (1.57)6.89 (1.34)1.20 (0.55)1.27 (0.66) 1.12 (0.47) Parkinson 1.32 (0.66)1.21 (0.73) 5.55 (1.99) 6.78 (1.56) 6.85 (1.88) Disgust Control 1.09 (0.18)1.03 (0.09) 4.08 (1.62) 6.88 (1.65) 6.59 (2.13) Parkinson 1.18 (0.37)2.27 (1.07)6.81 (2.04)2.38 (1.83) 4.55 (2.82) Fear Control 1.04 (0.13)1.92 (1.12)6.83 (1.74)1.83 (0.92) 3.74 (1.99) Parkinson 1.25 (0.43)1.14 (0.50)3.44 (2.07)2.59 (1.92) 5.27 (2.63) Sad Control 1.08 (0.18)1.12 (0.35)3.40 (1.90)2.38 (1.71) 5.98 (1.99) Note: Values are expressed as mean (SD). Post hoc basic emotion ratings were all based on a 1-9 scale in which 1 indicates no emotion was felt and 9 indicates the emotion was strongly felt. Numbers in bold indicate that Parkin son patients rated threat pictures to be significantly higher in disgust compared to controls, p < .01. Disgustcontam. = c ontamination pictures; Disgustmutil.= mutilation pictures.

PAGE 68

68 Table 3-5. Regression analysis of contributi ons of group membership and BDI-II scores upon eyeblink magnitudes A priori picture category Variable B SE B t statistica Model R2 Adj. R2 group 0.83 0.74 0.18 1.13 BDI-II -0.01 0.09 -0.01 -0.03 Neutral BDI-II x group 0.02 0.4 0.01 0.04 0.03 -0.03 Pleasant group 0.10 0.87 0.02 0.12 BDI-II -0.06 0.10 -0.09 -0.53 BDI-II x group 0.39 0.47 0.13 0.83 0.02 -0.05 Threat group 0.88 0.88 0.16 1.01 BDI-II 0.08 0.10 0.13 0.76 BDI-II x group -0.62 0.47 -0.20 -1.33 0.08 0.02 group 0.08 1.20 0.01 0.07 BDI-II -0.15 0.14 -0.18 -1.05 Disgustcontamination BDI-II x group -0.13 0.64 -0.03 -0.21 0.04 -0.03 group -3.13 1.181 -0.40 **-2.64 BDI-II 0.10 0.14 0.12 0.75 Disgustmutilation BDI-II x group 0.40 0.63 0.10 0.62 0.15 0.10 a For all t-tests, df = 44. ** p < .01 Table 3-6. BDI-II selfand surrogatereport scores by group Group BDI-II Surrogate BDI-II Correlation coefficient p -value Parkinson 6.00 (5.00) 5.1 (5.34) r = 0.41 0.01 Control 2.67 (3.91) 3.00 (3.24) r = 0.55 0.09

PAGE 69

69 Table 3-7. Regression analysis of contributions of group membership, self-report BDI-II scores, and Surrogate BDI-II scores upon startle eyeblink magnitudes A priori picture category Variable B SE B t statistica Model R2 Adj. R2 group 0.900.810.201.12 BDI-II 0.090.100.180.84 Surrogate BDI-II -0.180.12-0.37-1.70 Neutral BDI-II x Surrogate BDI-II 0.170.450.070.37 0.11 0.01 Pleasant group 0.020.990.000.02 BDI-II -0.100.13-0.16-0.75 Surrogate BDI-II 0.110.550.040.82 BDI-II x Surrogate BDI-II 0.120.550.040.21 0.03 -0.08 Threat group 1.001.020.181.00 BDI-II 0.060.130.100.46 Surrogate BDI-II -0.030.14-0.06-0.25 BDI-II x Surrogate BDI-II -0.110.57-0.04-0.19 0.05 -0.06 group -0.121.34-0.02-0.09 BDI-II -0.110.17-0.13-0.62 Surrogate BDI-II 0.010.180.010.05 Disgustcontamination BDI-II x Surrogate BDI-II -0.860.75-0.22-1.15 0.08 -0.03 group -3.161.33-0.41 -2.37 BDI-II 0.040.170.040.22 Surrogate BDI-II 0.130.180.160.75 Disgustmutilation BDI-II x Surrogate BDI-II 0.300.740.070.40 0.18 0.08 a For all t-tests, df = 44. p < .05

PAGE 70

70 45 46 47 48 49 50 51 52 PleasantNeutralUnpleasant ValenceMean blink magnitude (t-score ) Controls Parkinson Figure 3-1. Pattern of emoti onmodulated startle eyeblink magnitudes by valence and group. A main effect of valence was found, with ey eblink magnitudes to pleasant pictures being significantly smaller than to neutral and unpleasant pictures. Error bars indicate standard errors of means.

PAGE 71

71 45 46 47 48 49 50 51 52 53 54 55 NeutralPleasantThreatDisgustContamination DisgustMutilation A priori picture categoryMean blink magnitude (t-score) Controls Parkinson Figure 3-2. Startle eyeblink magnit udes by a priori picture category and group. A main effect of picture category was found, with eyeblink ma gnitudes to pleasant pictures greater than to threat pictures. The picture categor y x group interaction was also significant, with eyeblink magnitudes to mutilation pictur es smaller for PD patients than controls. Error bars indicate standard errors of means.

PAGE 72

72 0 0.02 0.04 0.06 0.08 0.1 0.12PleasantNeutralUnpleasantValenceSkin conductance (log[ S+1]) Controls Parkinson Figure 3-3. Skin conductance res ponse by valence and group. Error bars indicate standard errors of means.

PAGE 73

73 0 0.02 0.04 0.06 0.08 0.1 0.12NeutralPleasantThreatDisgustcontamination DisgustmutilationA priori emotion categorySkin conductance (log[ S+1] ) Controls Parkinson Figure 3-4. Skin conductance response by a pr iori picture category and group. Error bars indicate standard errors of means.

PAGE 74

74 43 45 47 49 51 53 55 NeutralHappyGeneral Aversive FearDisgust Post hoc emotion categoryMean blink magnitude (t-score ) Controls Parkinson Figure 3-5. Startle eyeblink magnitudes by post hoc emotion category and group. A main effect of post hoc emotion category was found, with fear and general aversive pictures associated with larger eyeblink magnitudes th an happy pictures. Error bars indicate standard errors of means.

PAGE 75

75 CHAPTER 4 DISCUSSION Summary of Findings The primary aim of the present study was to test the hypothesis that Parkinson patients would demonstrate reduced emotional reactivit y specific to threatening pictures. Emotionmodulated startle eyeblink magnitude was used as an index of emotional reactivity. This hypothesis was based on evidence that the amygda la appears to play a specific role in the processing of threatening stimuli, coupled with prior findings of amygdala atrophy in Parkinsons disease. This hypothesis was not supported. Instead, PD patients demonstrated significantly smaller eyeblink magnitudes to anot her class of unpleasant pictures, those involving mutilations. Eyeblink magnitudes to pictures of contaminations (e.g., body products, spoiled food) did not differ from controls suggesting that results were not due to generalized diminished physiological reactivity to disgust-eliciting stim uli. Thus, PD patients showed diminished reactivity, relative to controls, in the context of pictur es showing the effects of bodily harm (i.e., mutilations) but not during pictures of threat (i .e., pointed guns, animals ready to attack) or contamination. A secondary aim of the study was to exam ine selfand surrogate-report ratings of depression and their association with emotion-modulated startle eyeblink magnitude. First, it was important to determine if any between-groups di fference in emotion-modulated startle eyeblink magnitudes could be accounted for by differentia l levels of depression. Based on findings from prior research (Allen et al., 1999; Bowers, Mi ller, Mikos et al., 2006), a linear relationship between eyeblink magnitudes and self-reported leve l of depression was not expected. The data confirmed this prediction, indicating that PD patients reduced eyeblink magnitudes to mutilation pictures could not be at tributed to their higher levels of depression.

PAGE 76

76 Next, we examined the prediction that di screpancy between selfand surrogate-report depression ratings would be larger for PD patient s and their spouses compared to controls and their spouses. This prediction was based on the id ea that spouses of PD patients would perceive them as being more depressed than they truly are, due to misattributing symptoms of PD (e.g., masked facies) to depression. This predicti on was not supported. Instead, spouses of both controls and PD patients were fairly accurate at assessing their loved ones mood. Additionally, no linear relationship between disc repancy in selfversus surroga te-report depres sion ratings and emotion-modulated startle eyeblink magnitude s was found. Each of these key findings are discussed in turn below. Aim 1 Emotion-Modulated Startle Eyeblink Magnitude: Comparison of Present and Prior Study Findings In the present study, Parkinson patients di splayed diminished eyeblink magnitudes to disgusting pictures involving mutilations, while eyeblink magnitudes to threatening pictures were comparable to those of the control group. Th is finding is in contrast to the pilot study, in which startle hyporeactivity in PD patients appeared to be due to decreased magnitudes to threat pictures (human and animal attacks) as compared to other types of unplea sant pictures (Miller, 2004). One possible explanation for the inconsis tency between the current study and the pilot study may be that in the pilot study, the number of threat pictures and oth er unpleasant pictures was so small (seven threat pictures; five other unpleasant pictures) th at the results were not generalizable to pictures outside those specifically used in the study. For example, an extremely large eyeblink in response to ju st one of the pictures in a cat egory could inflate an individual participants mean for that ca tegory. Another possible explanati on for the discrepancy between the two studies may be that order of stimulus presentation was not careful ly controlled in the

PAGE 77

77 pilot study. Only one stimulus order was used, and because the study was post hoc in nature, the threat and other unpleasant pi ctures were not equally distribut ed with respect to number of stimuli per category in the first ha lf of the stimulus set versus the second half. Thus, any pictures associated with a strong emotional response that were located at the beginning of the set could disproportionately affect the overa ll mean due to habituation of the startle response over time. Because the present study overcame both of th ese methodological limitati ons of the pilot study, it is more likely to be a valid reflect ion of true between-groups differences. Reduced Startle Eyeblink Magnitude to Mutila tion Pictures in Parkinsons Disease: Proposed Mechanisms There are several factors that should be cons idered in interpreting the finding of decreased startle reactivity to mutilation pictures in PD. Firs t, there is the possibility that the basic startle eyeblink itself may be compromised or altered in PD patients due to dysfunction of the brainstem reflex circuitry involved. The existing eviden ce suggests this is highl y unlikely. In both the previous study (Bowers, Miller, Mikos, et al ., 2006; Miller, 2004) and in the current study, latency and magnitude of the basic, unprimed startle eyeblink was sim ilar for PD patients and controls. Additionally, other laboratories have investigated startle eyeblink in PD and reported magnitudes comparable to those of controls (K ofler et al., 2001; Vida ihet et al., 1992 [although both found increased latency to peak eyeblink, wh ich was not observed in the present study]). A second possibility is that compared to c ontrols, PD patients may have tended to close their eyes in response to the mutilation pictures due to the unpleasant content. This concern was addressed via installation of a video camera in the psychophysiology testing chamber. Overall, both controls and PD patients rarely closed their eyes in response to a picture. When a participant closed his/ her eyes (and thus was not viewing the picture when the startle probe was presented),

PAGE 78

78 this trial was discarded from analysis. Thus, th e finding of decreased startle eyeblink magnitudes in PD is not accounted for by de liberate closing of the eyes. Influence of individual personality differen ces on emotion-modulated startle eyeblink magnitude Another possibility is that reduced startle ey eblink magnitudes to mutilation pictures in the PD group is not due to disease status per se but due to systematic group differences in personality variables not measur ed within the current study. Th e issue of whether individual personality traits influence emotion-modulated st artle has been a topic of recent debate in the literature. It arises from the f act that while startle potentiation to fear/threat pictures has been consistently observed, potentiation to disgust pictures is not alwa ys found. For example, Balaban & Taussig (1994) reported that ev en though disgust pictur es were rated as equally arousing and more unpleasant than fear-evoking pictures, the fear pictures pr oduced startle potentiation but the disgust pictures did not In a study using film clips, Kavi ani, Gray, Checkley, Kumari, & Wilson (1999) reported that startle magnitudes were potentiated for clips evoking fear, yet were inhibited for a film clip of a graphic to e surgery. In contrast, Bradley et al. (2001) and Yartz and Hawk (2002) found no differences in startle magnitudes to pictures of attac k, contamination, or mutilations (all three potentiated startle). Examina tion of control data from the current study only adds to the complexity of interpreting existing findings. Threatening pictur es strongly potentiated startle compared to pleasant pictures, mutilati on pictures somewhat potentiated startle (although this was not significant after B onferroni correction), but contam ination pictures did not. Thus, the variability in reactions to disgusting pictur es across studies begs the question of whether individual differences in personal ity traits lead to startle potentiation for some participants, but not others.

PAGE 79

79 Studies that have examined the relationship between individual differences in emotionmodulated startle reactivity and personality traits ha ve produced conflicting results. Several studies have approached the i ssue by dividing subjects into tw o groups based on self-reported personality traits. One group is characterized by hi gh levels of neuroticis m, negative affectivity, and propensity to experience anxi ety in the face of punishment or nonreward; the other group is characterized by low levels of these traits. Using this approach, several st udies have reported an absent or diminished effect of emotion-modulated startle in response to aff ective pictures or film clips for the group that has low neuroticism, ne gative affectivity, and anxiety (Caseras et al., 2006; Corr et al., 1995; Hawk & Kowmas, 2003; Wilson et al., 2000; although for an exception, see Kumari et al., 1996). Thus, it is possible that systematic differences in personality traits between the PD and controls groups could acco unt for the between-groups difference found in eyeblink magnitudes to mutilation pictures. Although the present study did not include administration of measures designed to assess th e personality traits desc ribed above, fifteen of the PD patients had completed measures of trait anxiety (STAI) and negative affectivity (PANAS) as part of another study. There appeared to be no relationship between scores on either of these personality traits and emotion-modulat ed startle eyeblink magnitudes. Clearly, this analysis was limited by the fact that these measures were not available for all PD patients or for the control group; additionally, the small number of participants did not allow for subdivision of participants into extremely hi gh versus extremely low nega tive affect and anxiety groups. Nonetheless, this limited analysis suggests that startle reactivity did not systematically vary as a function of these personality variables. As suc h, it is unlikely that any overall group differences in trait anxiety or negative aff ectivity are responsible for the finding of reduced reactivity to mutilation pictures in the PD group.

PAGE 80

80 Reduced emotional reactivity in PD: Specific to horror? An examination of brain regions putatively i nvolved in the processing of disgust-inducing pictures may aid in interpretati on of startle eyeblink data. The fact that the PD group displayed diminished emotional modulation of the star tle response to mutilation pictures but not contamination pictures, yet rated both as equall y disgusting, suggests that Parkinson patients do not display hyporeactivity to disgus t-eliciting stimuli in general. This conclusion is further bolstered by the results of the idiographic analysis, in which pa tients and controls did not differ in startle reactivity to stimuli they rated as dis gusting. Instead, the data suggest that there is a distinct difference between emotional processing of mutilation and contamination pictures, even though both types of pictures are typica lly thought of as eliciting disgust. Evidence from lesion case reports and fMRI studi es suggests that the in sula is selectively involved in processing facial e xpressions of disgust (Adolphs, Tranel, & Damasio, 2002; Calder, Keane, Manes, Antoun, Young, 2000; Murphy, Nimm o-Smith, and Lawrence, 2003) as well as complex visual scenes evoking di sgust (Phillips et al ., 2000; Shapira et al., 2003; Wright et al., 2004). Not all investigators have replicated these findings; howeve r, with some studies reporting equal activation of the insula in response to bot h disgustand fearelic iting pictorial stimuli (Schienle et al., 2002; Stark et al., 2003). These authors have in terpreted their results as an indication of a common affective circuitry shared between different emotions. Recently, Wright et al. (2004) noted that some st udies used contamination pictures (such as bodily waste products and spoiled food) along with mutilated bodies to e licit disgust, whereas other studies used only contamination pictures. In a subsequent fMRI study, they examined the neural substrates associated with viewing contamination pictures versus mutilation pictures (a comparison with neutral and fear pictures was also included). These authors found that both contamination and mutilation pictures significantly activated the insula, whereas fear pictures (human attacks) did

PAGE 81

81 not; moreover, strength of activation was correlate d with subjective ratings of disgust. They interpreted their findings as eviden ce that the insula is selectivel y involved in processing disgust. They also found that mutilation pictures caused great er activation of the occipito-temporal cortex as compared to contamination pictures, which appeared to be due to the greater arousal associated with the mutilation pictures, as well as unique activation of the right superior parietal cortex. This unique area of activation for mutilation pictures indicates that the neural substrates involved in processing mutilation and contamination pi ctures are slightly different. Wright et al. (2004) posed the question of whether this indica tes that mutilation pictures evoke a distinct emotion, such as horror. Furthe r investigation of wh ether the horror r eaction is a specific discrete emotional response and replications of the neural circuitry invol ved in this emotional response are needed before determining if PD pa tients have a selective deficit in physiological reactivity to horror. Subjective ratings of valence, arousal, and basic discrete emotions Another explanation for the emotion-modulated startle eyeblink findi ng is that Parkinson patients found mutilation pictures to be less unpleasant, less arousing, or less disgusting compared to controls. This could be due to visuoperception problems, resulting in misperception of pictures, or due to misappraisal of the emoti onal meaning behind the pictures (Bowers, Miller, Mikos, et al., 2006). These conc erns were addressed by examin ing the valence and arousal ratings made by each participant during the psychophysiology experiment, as well as the post hoc basic emotion ratings made afterwards. The two groups did not significantly differ with regards to their valence or arousal ratings for mutilation pictures or for any of the a priori picture categories (neutral, pleasant, threat, disgustco ntamination, disgustmutilation). Additionally, in their post hoc ratings of degree of happiness, disgus t, fear, and sadness associated with mutilation pictures, PD patients ratings were co mparable to controls. Together, these findings

PAGE 82

82 suggest that the lack of startle potentiation to mutilation pictures is not due to a) decreased subjective unpleasantness or arousal from the standpoint of a dimensional model of emotion; or b) decreased subjective disgust from a discrete categorical approach to emotion. It is, however, possible that participants responde d to demand characteristics while making their ratings; that is, they rated pictures based on perceived social nor ms as opposed to based on how they truly felt. For example, a participant may have rated a pict ure of a man attacking a woman as very high in arousal because that is the socially expected rating even though he may have not felt highly negatively aroused when viewing the picture. Th e concern about demand characteristics in the present study is particularly relevant in light of findings from two different laboratories indicating that PD patients rate highly arousing negative pictures as less arousing than controls (Bowers, Miller, Mikos, et al, 2006; Wieser et al., 2006). One f act that may have increased participants bias to respond in lin e with social norms is the fact that most participants were aware that the current study is th e experimenters dissert ation. Thus, some pa rticipants may have been particularly motivated to perform well to help a student in school. Arousal as measured by skin conductance response To address the concern of potential between-groups differences in arousal level that may not be detected by examining self-report ratings alone, skin conductance response (SCR) was examined. Unlike self-report ratings, SCR is an objective measure, and is known to be a strong index of sympathetic nervous system arousal (B radley, 2000). In the pr esent study, controls showed a trend towards increased SCR for unpleasan t and pleasant pictures compared to neutral pictures. In contrast, PD patients showed similar SCR for all categories of pictures; that is, they did not display emotional modulation of SCR. Wh ile results indicated th at controls and PD patients did not significantly diffe r with respect to SCR to mutilation pictures, this analysis was hindered by extremely low power. Thus, overall, ar ousal as measured objectively by SCR did not

PAGE 83

83 correspond to self-report ratings of arousal in PD patients due to a lack of emotional modulation of SCR. Additionally, prior SCR results from a different sample of PD patients also showed a lack of emotional modulation (Bowers, unpublishe d data), as well as an overall pattern of hyporeactivity. While this finding does not explain why startle eyeblink magnitude was reduced in response to mutilation pictures specifically (i ndeed, it only complicates data interpretation), it clearly suggests that physiologi cal reactivity is aberrant in PD, as indexed by two different measures of physiological res ponse to emotional stimuli. Reduced physiological arousal: A translational deficit? Recently, Bowers, Miller, Mikos, et al. (2006) suggested that PD patients lack of apparent physiological arousal in response to pictures that evoke high levels of arousal in controls may be due to faulty communication betw een the amygdala and prefrontal cortical areas, putatively due to low levels of dopamine in PD. More specifi cally, these authors hypothesized that PD patients are able to analyze the emotional significance of a stimulus, but the amygdala is unable to translate the results of this emotional appraisal into a physio logical response. This hypothesis is based on a series of animal studies that elucidate the key role played by dopamine in modulating amygdala activity vi a corticallycontro lled inhibition and disinhibition. The basolateral nucleus of the amygdala is normally under inhibitory control from the prefrontal cortex (PFC) due to GABAergic intern eurons (Rosenkranz and Grace, 1999, 2002)1. This inhibition is thought to be essential to emoti onal homeostasis, as selective blocking of the inhibition produces an acute anxiet y-like state in rats (Sanders and Shekhar, 1995). In response to sensory-driven stress (e.g., viewing an aver sive picture), dopamine is released in the 1 In the introduction, reference was made to decreased amy gdala volume and structural changes to the integrity of the amygdala in Parkinsons disease (Harding, Stimson, Henderson, & Halliday, 2002; Braak & Braak, 2000). The basolateral complex of the amygdala is not one of the specific nuclei in which these changes have been reported, thus it is assumed this nucleus is generally intact.

PAGE 84

84 basolateral amygdala (Inglis a nd Moghaddam, 1999). This results in suppression of the PFCs inhibition of the amygdala (net effect: excita tion) via feedforward in terneurons (Marowsky, Yanagawa, Obata, and Vogt, 2005). Thus, dopami ne acts to modulate PFC -controlled inhibition and disinhibition of the amygdala in re sponse to stress-inducing stimuli. According to Bowers, Miller, Mikos, et al. (2 006), one can speculate that in Parkinsons disease, dopaminergic depletion would reduce the extent to which amygda lar disinhibition would occur in response to a highly-arousing, stress-e voking stimulus. Because the amygdala projects to basic startle circuitry with in the brainstem as well as th e hypothalamus, which mediates sympathetic nervous system arousal (Amaral, Pric e, Pitkanen, & Carmichael, 1992) the net effect would potentially be reduced phys iologic reactivity, as indexed by measures such as emotionmodulated startle eyeblink or sk in conductance response. While th is theory explains a general reduction in physiological reactivity to aversi ve pictures in PD, it does not explain why decreased startle eyeblink magnitudes were f ound specific to mutilation pictures. One possible explanation, although mere speculation at this po int, is that the mutilation pictures are actually more arousing than the threat and contamination pictures, even though participants rated them as equally arousing and SCR in contro ls was equivalent for all three negative picture categories. In fact, in a recent large-scale study, Bradley, C odispoti, Cuthbert, et al. (2001) found that mutilation and animal attack pictures were associ ated with significantly higher SCR and arousal ratings than other negative picture contents (such as pictures of vehicular accidents or contamination). Following this line of reasoning a significant difference in eyeblink magnitude between controls and PD may have been found for the mutilation pictures specifically because they were the only category of aversive pict ures sufficiently arousing to detect the muted responsivity in PD. Thus, reduced physiological reactivity in PD may va ry as a function of

PAGE 85

85 arousal level in response to a negative stimulus with those stimuli elic iting higher arousal being sensitive enough to detect between-groups differen ces. The potential signif icance of decreased physiological reactivity to arousing aversive stimuli will be addr essed later on in this section. First, the findings with regards to Aim 2 are discussed. Aim 2 Influence of Depression on EmotionModulated Startle Eyeblink Magnitude A secondary aim of the present study was to examine the influence of depression upon startle eyeblink magnitudes. This aim tested the possibility that between-groups differences in startle eyeblink magnitudes may simply be due to differences in level of depression. As predicted, results indicated that depression was not associated with startle reactivity. This finding is consistent with prior reports that mild de pression does not affect emotion-modulated startle, although severe depression has b een associated with a lack of modulation in response to emotional stimuli (Allen et al., 1999). Furtherm ore, a reanalysis of the data removing all participants on psychotropic medi cations produced the same findings as with the full sample. These results indicate that the decreased eyebli nk magnitude to mutilation pictures in the PD group was not due to depression or the influence of psychotropic medications. Accurately Assessing Depression: Comparis on of Selfand Surrogate Report Measures An additional goal was to determine if sy mptoms of Parkinsons disease (e.g., masked facies, rigidity) lead spouses of PD patients to perceive of them as being more depressed than they truly are. This prediction was not supported; that is, spouses of patie nts did not misattribute disease symptoms to depression. In fact, spousal ratings and self-ratings of depression were highly correlated, suggesting that in general spouse s of PD patients are well-attuned to how their loved ones are feeling. These spousal-report results ar e in contrast to prior studies using health care professionals and laypersons as raters, which found that negative traits were often

PAGE 86

86 misattributed to PD patients. For example, PD patients were rated as more anxious, unhappy, and hostile than controls (Pentland et al.,1987, 1988; Pitcairn et al., 1990) This present study is the first to examine family member perceptions of mood states in Parkinsons patients, and findings suggest that spouses do not tend to make the misattributions that people who do not know the patient very well may make. These findings further suggest that spouses may adequately serve as surrogate reporters of a patients mood in clinical settings when the patient is unable or unwilling to report his or her own mood. Alternatively, the significant correlation between selfand spousalreport of depression symptoms in PD could be interpreted as an indi cation that cognitively intact PD patients do not exhibit self-awareness defic its (often referred to as agnosagnosia or denial of the illness) in the domain of assessing their own mood. This is relevant when examined in the context of literature suggesting that PD patients may show self-awarene ss deficits with regard to other aspects of their functioning. For example, Leritz, Loftis, Crucian, Friedm an, & Bowers (2004) found that PD patients rated themselves as more independent in their ability to carry out activities of daily living compared to their caregiver s ratings. In this study, as with the present study, the caregiver was often a spouse. Similarly, Seltzer, Vasterli ng, Mathias, & Brennan (2001) found that PD patients rated themselves as less impaired than their caregivers did in terms of their motoric functioning, self-care, and social skills. Leritz et al. (2004) proposed that damage to frontalsubcortical connections in PD (Alexander et al ., 1986) may account for these awareness deficits. In contrast, a recent examination of selfand care giverratings of affect found that PD patients were generally aware of their reduced facial ex pressivity (Mikos et al., 2007). One explanation for this discrepancy between studies may be that self-awareness deficits may be specific to certain domains of the functio ning, with awareness of emoti onal functioning and mood being

PAGE 87

87 spared. A more likely explanation is that global self-awareness defi cits may be related to severity of cognitive impairment. Future studies are need ed to address whether selfand spousal mood ratings correlate for PD patients that are cognitively impaired. Relationship between Surrogate-Report De pression and Emotion-modulated Startle Eyeblink Magnitude Relating these finding back to the primary star tle paradigm data, neither spousal-completed Surrogate BDI-II scores or selfvs. spousaldisc repancy were significantly associated with emotion-modulated startle eyeblink magnitude. Th is is not surprising, given that selfand spousalBDI-II scores were corre lated and self-report BDI-II scores were found to be unrelated to eyeblink magnitude. Study Limitations There are several limitations to the current study that should be acknowledged. First, the patient sample may not be representative of th e typical person with Pa rkinsons disease. The sample had an average of 16 years of educati on, with many individuals having obtained masters degrees, Ph.D.s, and medical degrees. Although it is unlikely that educati onal status influences the emotion-modulated startle eyeblink, as it is thought to be a fairly automatic reaction (Bradley, 2000), it is possible th at education could potentially influence subjective emotion ratings in terms of participants overthinking their responses or trying to anticipate the desired response from the examiner. The sample also had an imbalance of men and women (14 men and 10 women per group). Although preliminary analyses including sex as a dependent variable re vealed no significant effect of sex for any of the key study aims, th e study was not designed to be sufficiently powered to examine sex differences. In a large study of se x differences in physiolo gic reactivity, Bradley, Codispoti, Sabatinelli, et al. ( 2001) reported that in general, wo men tend to respond with greater

PAGE 88

88 defense activation to aversive pictures whereas men show greater reactivity to erotic pictures. This raises the possibility that sex may interact with startle potentiati on to the fear, disgustcontamination, or disgustmutilation pictures Additionally, studies of women with PD are surprisingly lacking in the existent literature. Most studies include only men, or a significantly greater proportion of men that women. Thus, there is a need for studies that examine the unique effects that Parkinsons disease may have upon women. The present study is also limited by the fact that participants were lim ited to PD patients in Hoehn and Yahr stage 2 or 3, and the major ity of patients had on-medication UPDRS motor scores falling in the 20s (range: 4-41). Although startle eyeblink magnitudes were not significantly associated with UPDRS motor score, this finding is limited by the fact that persons with severe PD were not include d in the study. It is possible that a linear relationship between disease severity and eyeblink magnitude exists (as was found by Bowers, Miller, Mikos, et al., 2006), but was not detected by the restricted ra nge in the current study. Future studies should include patients with a broader range of disease severity in order to more fully examine the impact of disease progression upon emotion-modulated startle. A major limitation of the spousal Surrogate-BDI -II rating portion of the study was that it was not sufficiently powered to detect any in teraction with group membership. The observed power for the Surrogate BDI-II x Group interacti on was .14, which is clearly inadequate. Thus, the finding that spouses of controls and PD patient s can serve as adequate surrogate reporters of mood should be interpreted with ca ution. Larger scale st udies are needed to confirm that spouses are adequate surrogate reporters, and to examine the potential practical clinical utility of a surrogate mood measure for use with PD patients.

PAGE 89

89 This study included a unique id iographic approach to startl e eyeblink data analysis, in which each participants emotion-modulated startl e eyeblink magnitude T-scores were created based on his or her post hoc ratings of the amount of happiness, disgust, fear, and sadness felt for each picture. This rating system had several im portant limitations. First, ratings of all six primary discrete emotions (happy, sad, dis gusted, fearful, angry, and surprise; Ekman & Friesen, 1976) were not included. Th is was due to concerns that re quiring patients to make such a large number of ratings for each picture would be exhausting or confusing. Thus, anger and surprise were eliminated from the rating process, as these emotions were no t directly relevant to study aims. Sad was retained so that participants w ould not be biased to rate all aversive pictures as simply disgusting or fearful. Clearl y, ratings of all six prim ary discrete emotions could more fully capture the subjective e xperiences of particip ants. Secondly, the post hoc rating scale used for indicating degree of emotion e xperienced was anchored on one end with a descriptor that was relative, as opposed to abso lute. Specifically, the highest rating on the scale had the descriptor I strongly felt this emotion. In a critique of psychophysical measurement, Bartoshuk, Fast, & Snyder (2005) pointed out that a vague intensity descript or such as strongly can vary in interpretation from person to person, creating invalid comparisons. A more appropriate descriptor for the high end of the rating scale woul d have been This emotion was the strongest imaginable, partic ularly since the low end of th e scale was anchored with an absolute descriptor (I did not feel any of this emotion). Thirdly, although the pictures chosen to evoke specific emotions were generally effectiv e in doing so, the negativ ely-valenced pictures often evoked more than one emotion. This finding is hardly unusual; inde ed, other investigators (Bradley, Codispoti, Sabatinelli, et al., 2001; Yartz & Hawk, 2002) have also observed that pictorial stimuli tend to produce blends of emo tions. However, this created difficulty in

PAGE 90

90 categorizing individual stimuli for the idiographi c analysis of eyeblink magnitudes. Because the a priori fear and disgustmutilation pictures often we re rated as high in disgust and fear, it was necessary to create a general aversive em otion category when analyzing startle eyeblink magnitude data from an idiographic appr oach. The lack of a significant group x post hoc emotion category interaction in the idiographic anal ysis was likely due to the fact that mutilation pictures were subsumed by either the disgust or general aversive category, effectively masking group differences specific to the mutilati on pictures. Additionally, some participants interpreted the meaning of disgust in a way not intended. For example, PD patients rated fear pictures (pictures of animal and human attacks) significantly higher in dis gust than controls. It appears that in this case they were not referri ng to disgust as a viscer al reaction to grotesque stimuli, but as a moral judgement within the contex t of a social situation (i.e., I am disgusted by your behavior). Although the purpose behind th e idiographic approach was to account for individual differences in emotional reactions, the possibility that participants might interpret the emotion labels differently that the experimenter intended was not anticipate d. Clearly, individual differences in conceptualization of what makes a stimulus disgusting can affect overall results. These issues complicate the interpretation of the present data, but also ra ise important questions about methodological and conceptual concerns within emotion research in general. Conceptual and Methodological Issues in Emotion Research Taken together, the data from the post hoc ratings portion of th e study suggests that laboratory experiments attempting to parse ap art emotional reactions based on a discrete categorical approach to emotions may be overl y simplistic. Unfortunately many studies in the emotion literature ask participants to pick a label amongst the choices of happy, sad, disgusted, fearful, angry, or surprised in response to pres entation of a facial expr ession, prosodic utterance, or to describe how they are feeling. This a pproach is understandable and often necessary to

PAGE 91

91 make sense of the data; however, in reality discre te emotions do not occur in relative isolation of all other emotions. Similarly, it may not be easy for participants to decompose their emotional reactions into their basic disc rete components. For example, asking participants how happy, sad, disgusted, fearful, angry, or surprised they f eel may not fully capture the complex emotional reactions associated with certain interpersonal si tuations, such as seeing a gun held to a persons head or a disfigured body. As stated by La ng, (1995) emotional judgments, physiology, and behavior can present a confusi ng rock pile that resists a simple classification by specific emotional states. Future studies may benefit fr om a taking a dimensional approach to emotional experiences, as suggested by Lang (1995), in which emotional response to an aversive stimulus is classified by an action tendenc y to withdraw, and emotional res ponse to an appetitive stimulus is classified by a tendency to approach. Altern atively, future studies may benefit from having participants rate emotions from both discrete emotion and dime nsional approaches, as was done in the current study, then examining results from both perspectives. Finally, it may be fruitful to ask participants to describe in their own words their emotional reactions, rather than forcing them to choose from a pre-determined set of responses. Although this poses problems in quantitative data analysis, it more fully captures the complexity of human emotional experience. This same problem also exists with respect to classifying emotion-eliciting stimuli when designing an experiment. As previously mentione d, Wright et al. (2004) pointed out that some authors have used only contamination pictures to induce a disgust response, whereas others used both contamination and mutilation pictures. While this raises the issue of how to best classify mutilation pictures (should they be with the other disgust pictures, or in their own category?), further exploration of this issue is unlikely to advance scientific knowledge of emotional reactions. A more productive di rection to take might be an examination of the emotional

PAGE 92

92 significance behind mutilation pictures. At a more primitive level, a mutilated body represents destruction of the victims bodily integrity, and thus could be percei ved by the viewer as a threat to his or her own bodily integrity. From this pe rspective, it is clear that mutilations evoke a strong aversive emotional reaction, regardless of whether the semantic label of disgust or horror is given to the reaction. Significance of the Study The present research has two important findings that add to the literature on emotion in Parkinsons disease. First, PD patients showed diminished reactivity, as measured by emotionmodulated startle eyeblink, to pi ctures of mutilations. While it might be tempting to propose that this finding represents a mutilation-specific em otional processing deficit in PD, such an interpretation is overly simplistic and does not take into consideration other relevant factors. For example, one possibility is that the diminished reactivity in PD is not emotionor contentspecific, but represents a defic it in physiological responsivity to highly arousing negative stimuli in general. Mutilation pictures are highly arousi ng stimuli because they represent a threat to bodily integrity; as such, it may be that the mutilation pictures were the only category of pictures sufficiently arousing to detect a between-groups difference in physiological reactivity. In the present study, we attempted to fu rther investigate the issue of re duced physiological arousal in PD by examining skin conductance response (SCR) data; however, this was problematic because PD patients did not appear to exhibit emoti onal modulation of SCR for any of the picture categories. The interpretation of skin conductance data is furthe r complicated by the fact that autonomic nervous system dysfunction is often found in patients with PD as a result of cell loss and Lewy bodies within the sympathetic ganglio n (for a review, see Chauduri, 2001). Thus, the abnormalities in SCR observed in the present study may be due to general autonomic dysregulation. One possible way to bypass this probl em in future studies is to examine other

PAGE 93

93 variables associated with arousal level. For exam ple, an important area for future research is examination of cortisol levels in responses to stress in PD. Because measurement of cortisol levels provides a neuroendocrine marker of reac tions to stressful stimuli, this method could approach the problem of decrea sed reactivity to arousing, aversi ve stimuli from a new angle. Although the literature on cortis ol levels in PD is sparse, one study found that PD patients showed overall elevations in plasma cortisol leve ls, yet a flattening of cortisol variations typically observed throughout the day (Hartmann, Veldhuis, De uschle, Standhardt, & Heuser, 1997). Interesting, this pattern of flattened amplit ude variations in cortisol has been found in depressed patients (Deuschle et al., 1997; Halbreich, Asnis, Sh indldecker, Zumoff, & Nathan, 1985; Linkowski et al., 1985). Clearl y, future research is needed to explore cortisol levels in PD and their potential association with de pression in this patient population. The second important finding from the present study is that a strong convergence emerged between spousal and PD patient ratings of the patients mood. Although the evidence is limited by inadequate statistical power, th e issue of surrogate mood reporting is particularly important in the later stages of Pa rkinsons, when patients may be una ble to report upon their own mood due to dementia or speech deficits. Logsdon & Teri (1995) have already reported that spouses served as valid surrogate reporters of mood for patients with Alzheimers disease. A similar validation of the Surrogate BDI-II for use with caregivers of PD patients may lead to useful clinical applications. Such a measure could be used with spouses of patients unabl e to report upon their mood, or unwilling to discuss mood due to embarra ssment or concerns about social stigma. Recognizing that spouses can se rve as important sources of in formation concerning a patients mood may lead to improved detection of depression in Parkinsons disease.

PAGE 94

94 Although studies of emotion have many methodol ogical challenges to overcome, this study represents an attempt at further characterizing changes in emotional reactivity that may occur with Parkinsons disease. Hopefully, future stud ies will continue to explore these changes not simply in isolation, but from the framework of an integrated model that considers how emotion, cognition, and motor symptoms interact to affect the well-being of the whole person.

PAGE 95

95 APPENDIX A NORMATIVE VALENCE AND AROUSAL RATINGS FOR PICTURE STIMULI Table A-1. International Affec tive Picture System (IAPS) Normative Valence and Arousal Ratings Picture Category IAPS # Picture Description Valencea Arousala Neutral 7100 firehydrant 5.24 (1.20)2.89 (1.70) 7235 chair 4.96 (1.18)2.83 (2.00) 7080 fork 5.27 (1.09)2.32 (1.84) 7050 hairdryer 4.93 (0.81)2.75 (1.80) 7020 fan 4.97 (1.04)2.17 (1.71) 7211 clock 4.81 (1.78)4.20 (2.40) 7035 mug 4.98 (0.96)2.66 (1.82) 7038 shoes 4.82 (1.2)3.01 (1.96) 7950 tissue 4.94 (1.21)2.28 (1.81) 7150 umbrella 4.72 (1.00)2.61 (1.76) 7175 lamp 4.87 (1.00)1.72 (1.26) 7233 plate 5.09 (1.46)2.77 (1.92) Average 4.97 (1.16)2.68 (1.83) Pleasant 8501 money 7.91 (1.66)6.44 (2.29) 8034 snowskier 7.06 (1.53)6.30 (2.16) 5260 waterfall 7.34 (1.74)5.71 (2.53) 4599 romantic couple 7.12 (1.48)5.69 (1.94) 8370 rafting 7.77 (1.29)6.73 (2.24) 4653 couple 6.56 (1.65)5.83 (2.07) 4626 wedding 7.6 (1.66)5.78 (2.42) 8170 sailboat 7.63 (1.34)6.12 (2.30) 5621 skydivers 7.57 (1.42)6.99 (1.95) 5629 hiker 7.03 (1.55)6.55 (2.11) 8470 gymnast 7.74 (1.53)6.14 (2.19) 8200 waterskier 7.54 (1.37)6.35 (1.98) Average 7.41 (1.52) 6.22 (2.18)

PAGE 96

96 Table A-1. Continued Picture Category IAPS # Picture Description Valencea Arousala Threat 6313 knife attack 1.98 (1.38)6.94 (2.23) 3500 gun pointed at man 2.21 (1.34)6.99 (1.68) 6510 masked man 2.46 (1.58)6.96 (2.23) 6242 gang with gun 2.69 (1.59)5.43 (1.93) 6260 aimed gun 2.44 (1.54)6.93 (1.98) 6821 gang attacking car 2.38 (1.72)6.29 (2.19) 6243 man pointing gun 2.33 (1.49)5.99 (2.23) 1120 snake 3.49 (1.93)6.93 (2.20) 1052 snake 3.5 (1.87)6.52 (2.02) 1525 attackdog 3.09 (1.72)6.51 (2.25) 1932 shark attack 3.85 (2.11)6.47 (2.09) 1300 dog with teeth bared 3.55 (1.78)6.79 (1.84) Average 2.83 (1.67)6.56 (2.07) Disgust 3000 mutilated face 1.59 (1.35)7.34 (2.27) 3071 mutilated body 1.88 (1.39)6.86 (2.05) 3110 burn victim 1.79 (1.30)6.70 (2.16) 3400 severed hand 2.35 (1.90)6.91 (2.22) 3150 bloody chopped fingers 2.26 (1.57)6.55 (2.20) 3060 mutilated body 1.79 (1.56)7.12 (2.09) 6415 dead bloody tiger 2.21 (1.51)6.2 (2.31) 9300 dirty toilet 2.26 (1.76)6.00 (2.41) 7359 bug on pie 3.38 (1.75)5.07 (2.09) 9301 dirty toilet 2.26 (1.56)5.28 (2.46) 9373 vomit 3.38 (1.48)5.01 (2.16) 1274 roaches 3.17 (1.53)5.39 (2.39) Average 2.36 (1.56) 6.20 (2.23) Note: Values are expressed as mean (SD). Valen ce ratings are on a 1-9 scale, with 9 being most pleasant. Arousal ratings are on a 1-9 scale, with 9 being most arousing. a From Lang et al., 2001b

PAGE 97

97 APPENDIX B SKIN CONDUCTANCE RESONSE DAT A ACQUISITION AND REDUCTION PROCEDURES Data Acquisition The skin on the palm of the hand was prepared by washing the hands with a mild soap, then wiping the skin with rubbing alcohol. Next, surface Ag-AgCl electrodes were filled with an isotonic eylectrolyte gel and positioned on the thenar and hypot henar eminence of left and right palm. During the psychophysiology experiment SCR was sampled at 20 Hz using two Coulbourn Isolated Skin Conducta nce couplers in DC mode. Data Reduction Each picture trial was scored for the larg est change in SCR between 0.9 and 6.0 seconds after picture onset. Raw values for the left and right palms were averaged into a composite score for each trial. A value of was added to thes e composite scores to eliminate negative values. This new value was then subjected to a l og transformation to reduce skewness (Bradley, Codispoti, Cuthbert, et al., 2001). Because SCR habituates rapidly, only responses to the first half of the entire stimulus set (i.e., responses to the first 32 pictures) we re included in the data analyses reported. Because SCR habituates rapidl y, only responses to the fi rst half of the entire stimulus set (i.e., responses to the first 32 pictur es) were included in the data analyses reported.

PAGE 98

98 LIST OF REFERENCES Adolphs, R., Schul, R., & Tranel, D. (1998). Intact recognition of facial emotion in Parkinsons disease. Neuropsychology, 12 (2), 253-258. Adolphs, R., Tranel, D., & Damasio, A. R. (2003) Dissociable neural systems for recognizing emotions. Brain and Cognition, 52 (1), 61-69. Alexander, G.E., DeLong, M.R., & Strick, P.L. (1986). Parallel organi zation of functionally segregated circuits linking basal ganglia and cortex. Annual Review of Neuroscience, 9 357-381. Allen, N.B., Trinder, J., & Brennan, C. (1999) Affective startle modulation in clinical depression: preliminary findings. Biological Psychiatry, 4 6, 542-550. Amaral, D.G. (2003). The Amygdala, Soci al Behavior, and Danger Detection. Annals of the New York Academy of Sciences, 1000 337-347. Amaral, D.G., Price, S., Pitkanen, A., & Carmich ael, S. (1992). Anatomical organization of the primate amygdaloid complex. In J. Aggleton (Ed.), The amygdala (pp. 1-66). New York: Wiley. Balaban, M.T., & Taussig, H.N. (1994). Salience of fear/threat in the aff ective modulation of the human startle blink. Biological Psychology, 38 117-131. Bartoshuk, L.M., Fast, K., & Snyder, D.J. (2005). Differences in our sensory worlds: invalid comparisons with labeled scales. Current Directions in Psychological Science, 14 (3), 122125. Beck, A.T.(1996). The Beck Depression Inventory-II San Antonio, TX: The Psychological Corporation. Beck, A.T., Steer, R., & Brown, G. (1996). The Beck Depression Inventory-II Manual San Antonio, TX: The Psychological Corporation. Benabid, A.L. (2003). Deep brain s timulation for Parkinson's disease. Current Opinion in Neurobiology, 13 (6), 696-706. Blonder, L.X., Gur, R.E., & Gur, R.C. (1989). The effects of right and left hemiparkinsonism on prosody. Brain and Language, 36 193-207. Borod, J.C., Welkowitz, J., Alpert M., Brozgold, A.Z., Martin, C ., Peselow, E., et al. (1990). Parameters of emotional processing in neuropsyc hiatric disorders: conceptual issues and a battery of tests. Journal of Communication Disorders, 23 247-271. Bowers, D. (2007). [Emotion-modulated skin co nductance response in Parkinsons disease]. Unpublished raw data.

PAGE 99

99 Bowers, D., Gilmore, R., Gokcay, D., Roper, S., Rogish, M., & Kortenkamp, S. (2001). Laterality effects in verbal-emotional modulation of star tle following temporal lobectomy [Abstract]. Journal of the Inte rnational Neuropsyc hological Society, 7 (2), 199. Bowers, D., Miller, K., Bosch, W., Gokcay, D., Pedraza, O., Springer, U., et al. (2006). Faces of emotion in Parkinson's disease: Micro-e xpressivity and bradykinesia during voluntary facial expressions. Journal of the Internationa l Neuropsychological Society, 12 (6), 76573. Bowers, D., Miller, K., Mikos, A., Kirsch-Darrow, L., Springer, U., Fernandez, H., et al. (2006). Startling facts about emotion in Parkinsons disease: blunted reactivity to aversive stimuli. Brain, 129 (pt 12), 3356-65. Braak, H., & Braak, E. (2000). Pathoa natomy of Parkinsons disease. Journal of Neurology, 247 (Suppl. 2), II/3-II/10. Bradley, M. (2000). Emotion and motivation. In L. Tassinary, J. Cacioppo, & G. Berntson (Eds.), Handbook of psychophysiology New York, NY: Cambridge University Press. Bradley, M.M., Codispoti, M, Cuthbert, B., & Lang, P. (2001). Emotion and Motivation I: Defensive and Appetitive Reac tions in Picture Processing. Emotion, 1 (3), 276. Bradley, M.M., Codispoti, M., Sabatinelli, D ., & Lang, P.J. (2001). Emotion and motivation II: sex differences in picture pr ocessing. Emotion, 1(3), 300-319. Bradley, M.M., & Vrana, S.R. (1993). In N. Birbaumer, & A. Ohman (Eds.), The structure of emotion: Psychophysiological, c ognitive, and clinical aspects (pp. 270-287). Seattle, WA: Hogrefe & Huber. Brown, R.G., & Pluck, G. (2000). Negative symp toms: the pathology of motivation and goaldirected behaviour. Trends in Neuroscience, 23 412-417. Buck, R., & Duffy, R.J. (1980). Nonverbal communi cation of affect in brain-damaged patients. Cortex, 16 351-362. Burn DJ. (2002). Beyond the iron mask: Towards be tter recognition and treatment of depression associated with Parkinson's disease. Movement Disorders, 17 (3), 445-454. Calder, A.J., Young, A.W., Rowla nd, D., Perrett, D.I., Hodges, J.R., & Etcoff, N.L. (1996). Facial emotion recognition after bilatera l amygdala damage: differentially severe impairment of fear. Cognitive Neuropsychology, 13 699-745. Calder, A. J., Keane, J., Manes, F., Antoun, N., & Young, A. W. (2000). Impaired recognition and experience of disgus t following brain injury. Nature Neuroscience, 3 (11), 1077-1078.

PAGE 100

100 Caseras, F. X., Fullana, M. A., Riba, J., Barba noj, M. J., Aluja, A., & Torrubia, R. (2006). Influence of individual differences in the Behavioral Inhibition System and stimulus content (fear versus blood-disgust) on affective startle reflex modulation. Biological Psychology, 72 (3), 251-256. Chaudhuri, K.R. (2001). Autonomic dys function in movement disorders. Current Opinions in Neurology, 14 (4), 505-511. Cools, R., Barker, R.A., Sahakian, B.J., & Robbins, T.W. (2001). Mechanisms of cognitive set flexibility in Parkinsons disease. Brain, 124 2503-2512. Corr, P.J., Wilson, G.D., Fotiadou, M., Kumari, V., Gray, N.S., Checkley, S., et al. (1995). Personality and affective modul ation of the startle reflex. Personality and Individual Differences, 19 543-553. Cummings, J.L. (1992). Depression a nd Parkinson's disease: A review. American Journal of Psychiatry, 149 443. Cuthbert, B., Bradley, M., & Lang, P. (1996) Probing picture perception: Activation and emotion. Psychophysiology, 33 103-111. Davis, M. (1992). The role of the amygdala in conditioned fear. In J. Aggleton (Ed.), The Amygdala: Neurobiological aspects of emotion, memory, and mental dysfunction (pp. 255305). New York, NY: Wiley Publishers. Davis, M., & Gallagher, D.W. ( 1988). Continuous slow release of low levels of diazepam produces tolerance to its depressant and anxiolytic effects on the startle reflex. European Journal of Pharmacology, 150 23-33. Davis, M., Genderlman, D.S., Tischler, M.D., & Gendelman, P.M. (1982). A primary acoustic startle circuit: lesion an d stimulation studies. Journal of Neuroscience, 2 (6), 791-805. Delis, D., Kramer, J., Kaplan, E., & Ober, B. (2000). The California Verbal Learning Test, 2nd Edition Manual San Antonio, TX: Psyc hological Corporation. Deuschle, M., Schweiger, U., Weber, B., Gotthar dt, U., Korner, A., Schmider, J., et al. (1997). Diurnal activity and pulsatility of the hypot halamus-pituitary-adrenal system in male depressed patients and healthy controls. Journal of Clinical Endocrinology and Metabolism, 82 (1), 234-238. Dimitrov, M, Grafman, J., Soares, A.H., Clark, K. (1999). Concept formation and concept shifting in frontal lesion and Parkinsons disease patients as sessed with the California card sorting task. Neuropsychology, 13 135-143. Dooneief, G., Mirabello, E., Bell, K., Marder, K., Stern, Y., & Mayeux. R. (1992). An estimate of the incidence of depression in idiopathic Parkinsons disease. Archives of Neurology, 49 305-307.

PAGE 101

101 Ekman, P., & Friesen, W.V. (1976). Pictures of Facial Affect. Washington, D.C.: Consulting Psychologists Press, Inc. Fahn, S., Elton, R.L. (1987). Unified Parkinsons Disease Rating Scale. In S. Fahn, C.D. Marsden, M. Goldstein, D.B. Calne (Eds.), Recent developments in Parkinsons disease, Volume 2 (pp. 153-163). Florham Park, NJ: Macmillan Healthcare Information. Fahn, S. (2003). Description of Parkins ons disease as a clinical syndrome. Annual New York Academy of Sciences, 991 1-14. Fridlund, A. J., & Cacioppo, J. T. (1986). Guid elines for human electromyographic research. Psychophysiology, 23(5), 567-589. Gauntlett-Gilbert, J., Roberts, R.C., Brown, V.J. (1999). Mechanisms under lying attentional setshifting in Parkinsons disease. Neuropsychologia, 37 605-616. German, D. C., Manaye, K. F., White, C. L., 3rd, Woodward, D. J., McIntire, D. D., Smith, W. K., et al. (1992). Disease-specific pa tterns of locus coeruleus cell loss. Annals of Neurology, 32 (5), 667-676. Greenwald, M., Cook, E., & Lang, P. (1989). Af fective judgment and psychophysiological response dimensional covariation in th e evaluation of pictorial stimuli. Journal of Psychophysiology, 3 51-64. Halbreich, U., Asnis, G. M., Shindledecker, R., Zumoff, B., & Nathan, R. S. (1985). Cortisol secretion in endogenous depressi on. II. Time-related functions. Archives of General Psychiatry, 42 (9), 909-914. Harding, A.J., Stimson, E., Henderson, J.M., & Ha lliday, G.H. (2002). Clinical correlates of selective pathology in the amygdala of patients with Park insons disease. Brain, 125 24312445. Hariri, A.R., Mattay, V.S., Tessitore, A., Fera F., & Weinberger, D.R. (2003). Neocortical Modulation of the amygdala re sponse to fearful stimuli. Biological Psychiatry, 53 494501. Harmer, C., Shelley, N., Cowen, P., & Goodwin, G. (2006). 5HT(3) antagonism abolishes the emotion potentiated startle effect in humans. Psychopharmacology (Berl), 186 8-24. Hartmann, A., Veldhuis, J. D., Deuschle, M., St andhardt, H., & Heuser, I. (1997). Twenty-four hour cortisol release profiles in patients with Alzheimer's and Parkinson's disease compared to normal controls: ultradian s ecretory pulsatility a nd diurnal variation. Neurobiology of Aging, 18 (3), 285-289. Hawk, L. W., Jr., & Kowmas, A. D. (2003). Aff ective modulation and prepulse inhibition of startle among undergraduates high and low in behavioral inhibition and approach. Psychophysiology, 40 (1), 131-138.

PAGE 102

102 Hitchcock, J.M., & Davis, M. (1991). Efferent pathway of the amygdala involved in conditioned fear as measured with the fea r-potentiated startle paradigm. Behavioral Neuroscience, 105 (6), 826-842. Hitchcock, J.M., Sananes, C.B., Davis, M. (1989 ). Sensitization of the startle reflex by footshock: Blockade by lesions of the central nucleus of the amygdala or its efferent pathway to the brainstem. Behavioral Neuroscience, 10 3(3), 509-518. Hoehn, M., & Yahr, M. (1967). Parkinsoni sm: onset, progression, and mortality. Neurology, 17 427-442. Hughes, A.J., Ben-Shlomo, Y., Daniel, S.E., & Lees, A.J. (1992). What features improve the accuracy of clinical diagnosis in Parkin sons disease: a clinicopathologic study. Neurology, 4 2, 1142-1146. Hughes, A.J., Daniel, S.E., Kilford, L., & Lees, A. J. (1992). Accuracy of clinical diagnosis of idiopathic Parkinsons disease: A clinicopathological study of 100 cases. Journal of Neurology, Neurosurgery, and Psychiatry, 5 5, 181-184. Isella, V., Melzi, P., Grimaldi, M., Iurlaro, S., Piolti, R., Ferrarese, C., et al. (2002). Clinical, neuropsychological, and morpho metric correlates of apat hy in Parkinsons disease. Movement Disorders, 17 (2), 366-371. Inglis, F. M., & Moghaddam, B. (1999). Dopamine rgic innervation of the amygdala is highly responsive to stress. Journal of Neurochemistry, 72 (3), 1088-1094. Jacobs, D.H., Shuren, J., Bowers, D., & Heilm an, K.M. (1995). Emotional facial imagery, perception, and expression in Parkinsons disease. Neurology, 45 1696-1702. Jacobs, D.M., Stern, Y., & Mayeux, R. (2000). Deme ntia in Parkinson's disease, Huntington's disease, and other degenerati ve conditions. In M.J. Fara h & T.E. Feinberg (Eds.), Patientbased approaches to cognitive neuroscience (pp. 375). Cambridge, MA: MIT Press. Jurica, P.J., Leitten, C.L., & Mattis, S. (2001). Dementia Rating Scale-2 Professional Manual Lutz, FL: Psychological Assessment Resources, Inc. Kan, Y., Kawamura, M., Hasegawa, Y., Mochizuki, S., & Nakamura, K. (2002). Recognition of emotion from facial, prosodic, and written verbal stimuli in Parkinsons disease. Cortex, 38 (4), 623-630. Kaplan, E.F., Goodglass, H ., & Weintraub, S. (2001). The Boston Naming Test, 2nd edition Philadelphia: Lea & Febiger. Katsikitis, B.A., & Pilowsky, M.D. (1988). A study of facial expression in Parkinsons disease using a novel microcomputer-based method. Journal of Neurology, Neurosurgery, and Psychiatry, 51 362-366.

PAGE 103

103 Katsikitis, B.A., & Pilowsky, M.D. (1991). A cont rolled quantitative study of facial expression in Parkinsons disease and depression. The Journal of Nervous and Mental Disease, 179 (11), 683-688. Kaviani, H., Gray, J. A., Checkley, S. A., Ku mari, V., & Wilson, G. D. (1999). Modulation of the acoustic startle reflex by emotionally-toned film-clips. International Journal of Psychophysiology, 32 (1), 47-54. Kaviani, H., Gray, J. A., Checkley, S. A., Ra ven, P. W., Wilson, G. D., & Kumari, V. (2004). Affective modulation of the star tle response in depression: in fluence of the severity of depression, anhedonia, and anxiety. Journal of Affective Disorders, 83 (1), 21-31. Kirsch-Darrow, L., Fernandez, H.H., Marsiske, M., Okun, M.S., & Bowers, D. (2006). Dissociating apathy and depressi on in Parkinsons disease. Neurology, 11 (67), 33-38. Klver, H., & Bucy, P.C. (1939). Preliminary an alysis of the temporal lobes in monkeys. Archives of Neurology and Psychiatry, 42 979-1000. Kofler, M., Muller, J., Wenning, G.K. Reggiani, L., Hollosi, P., Bosch, S., et al. (2001). The auditory startle reaction in parkinsonian disorders. Movement Disorders, 1 6(1), 62-71. Kumari, V., Corr, P.J., Wilson, G.D., Kaviani, H., Thornton, J.C., Checkely, S.A., et al. (1996). Personality and modulation of the startle re flex by emotionally toned film clips. Personality and Individual Differences, 21 1029-1041. Lang, P.J. (1980). Behavioral treatment and biobeha vioral assessment: Computer applications. In J.B. Sidowski, J.H. Johnson, & T.A. Williams (Eds.). Technology in mental health care delivery. Norwood, NJ: Albex Publishing Corporation. Lang, P.J. (1995). The Emotion Probe: st udies of motivati on and attention. The American Psychologist, 50 (5), 372-385. Lang, P.J., Bradley, M.M., & Cuthbert, B.N. (19 90). Emotion, attention, and the startle reflex. Psychological Review, 97 (3), 377-395. Lang, P., Bradley, M., & Cuthbert, B. (2001a). The International Affe ctive Picture System (photographic slides). Gainesville, FL: The Center for Research in Psychophysiology, University of Florida. Lang, P., Bradley, M., & Cuthbert, B. (2001b). International affective picture system (IAPS): Instruction manual and affective ratings: Technical Report A-5 Gainesville, FL: The Center for Research in Psychophysiology, University of Florida. Lezak, M.D., Howieson, D.B., & Loring, D.W. (2004). Neuropsychological Assessment (Fourth Edition) Oxford: Oxford University Press. Leritz, E., Loftis, C., Crucian, G., Friedman, W., & Bowers, D. (2004). Self-awareness of deficits in Parkinson disease. The Clinical Neuropsychologist, 18 (3), 352-361.

PAGE 104

104 Linkowski, P., Mendlewicz, J., Leclercq, R., Brasse ur, M., Hubain, P., Gols tein, J., et al. (1985). The 24-hour profile of adrenocorticotropin and cortisol in major depressive illness. Journal of Clinical Endocrinology and Metabolism, 61 (3), 429-438. Logsdon, R., & Teri, L. (1995). De pression in Alzheimers diseas e patients: Caregivers as surrogate reporters. Journal of the American Geriatric Society, 43 150-155. Lucas, J.A., Ivnik, R.J., Smith, G.E., Bohac, D. L., Tangalos, E.G., Kokm en, E., et al. (1998). Normative Data for the Mattis Dementia Rating Scale. Journal of Clinical and Experimental Neuropsychology, 20 (4), 536-47. Madeley, P., Ellis, A.W., & Mindham, R.H.S. (1995). Facial expressions and Parkinsons disease. Behavioural Neurology, 8 115-119. Marin, R.S. (1991). Apathy: A neuropsychiatric syndrome. J o urnal of Neuropsychiatry and Clinical Neuroscience, 3 243-254. Marowsky, A., Yanagawa, Y., Obata, K., & Vogt K. E. (2005). A specialized subclass of interneurons mediates dopaminergic facilitation of amygdala function. Neuron, 48 (6), 1025-1037. Mattis, S. (2001). Dementia Rating Scale-2. Od essa, FL: Psychological Assessment Resources. Mayberg, H.S., Starkstein, S.E., Sadzot, B., Prezi osi, T., Andrezejewski, P.L., Dannals, R.F., et al. (1990). Selective hypometabolis m in the inferior frontal lobe in depressed patients with Parkinson's disease. Annals of Neurology, 28 (1), 57-64. McDonald, W.M., Richard, I.H., & DeLong, M.R. (2003). Prevalence, etiology, andtreatment of depression in Parkinson's disease. Biological Psychiatry, 5 4(3), 363-75. Mikos, A., Skoblar, B., Springer, U., Kellison, I ., Nisenzon, A., Fernandez, H., et al. (2007, June). Behind the masked face: Emotion self-perception and apathy in PD. Poster session to be presented at the Movement Disorder Societys 11th International Congress of Parkinsons Disease and Movement Disorders, Istanbul, Turkey. Miller, K.M. (2004). Diminished affective modulation of startle to threatening stimuli in Parkinsons disease. Unpublished masters thesis, Univ ersity of Florida, Gainesville. Murphy, F. C., Nimmo-Smith, I., & Lawrence, A. D. (2003). Functiona l neuroanatomy of emotions: a meta-analysis. Cognitive, Affective, and Behavioral Neuroscience, 3 (3), 207233. National Institute of Neurological Disorders a nd Stroke (2001, July 1). Parkinsons disease backgrounder. Retrieved February 9, 2004, from http://www.ninds.nih.gov/health_and_medica l/pubs/parkinson's_disease_backgrounder.ht ml.

PAGE 105

105 OGorman, J.R. (1990). Individu al differences in the orient ing response: Nonresponding in nonclinical samples. Pavlovian Journal of Biological Science, 25 (3), 104-108. Ouchi, Y., Yoshikawa, E., Okada, H., Futatsub ashi, M., Sekine, Y., Iyo, M., et al. (1999). Alterations in binding site dens ity of dopamine transporter in the striatum, orbitofrontal cortex, and amygdala in early Parkinson s disease: Compartment analysis for -CFT binding with positron emission tomography. Annals of Neurology, 45 601-610. Pell, M.D. & Leonard, C.L. (2005) Facial expression decoding in early Parkinson's disease. Brain Research. Cognitive Brain Research, 23 (2-3), 327-340. Pentland, B, Pitcarin, T., Gray, J., & Riddle, W. (1987). The effects of reduced expression in Parkinson's disease on concept form ation by health professionals. Clinical Rehabilitation, 1 307-131. Pentland, B, Pitcarin, T., Gray, J., & Riddle, W. (1988). The effects of reduced non-verbal communication in Parkinsons disease. British Journal of Disorders of Communication, 23 31-34. Phillips, M. L., Marks, I. M., Senior, C., Lythgoe D., O'Dwyer, A. M., Meehan, O., et al. (2000). A differential neural response in obsessive-c ompulsive disorder patients with washing compared with checking symptoms to disgust. Psychological Medicine, 30 (5), 1037-1050. Pitcairn, T., Clemie, S., Gray, J., & Pentland, B. (1990a). Non-verbal cues in the selfpresentation of Parkinson patients. British Journal of Clinical Psychology, 29 177-184. Pitcairn, T., Clemie, S., Gray, J ., & Pentland, B. (1990b). Impressi ons of parkinsonian patients from their recorded voices. British Journal of Disorders of Communication, 25 (1), 85-92. Pluck,G., & Brown, R.G. (2002). Apathy in Parkinson's disease. Journal of Neurology, Neurosurgery, and Psychiatry, 73 (6), 636-42. Pogarell, O., & Oertel, W.H. (1999). Parkins onian syndromes and Parkinsons disease: Diagnosis and differential diagnosis. In P.A. LeWitt & W.H. Oertel (Eds.), Parkinsons disease: The treatment options (pp. 1-10). London, UK: Martin Dunitz. Remy P, Doder, M., Lees, A., Turjanski. N ., & Brooks, D. (2005). Depression in Parkinson's disease: loss of dopamine and noradrena line innervation in the limbic system. Brain, 128 (Pt 6), 1314-1322. Rosen, J.B., & Davis, M. (1988). Enhancement of ac oustic startle by electric al stimulation of the amygdala. Behavioral Neuroscience, 102 (2), 195-202, 324. Rosenkranz, J.A., & Grace, A.A. (1999). Modulati on of basolateral amygdala neuronal firing and afferent drive by dopamine receptor activation in vivo. Journal of Neuroscience, 19 (24), 11027-11039.

PAGE 106

106 Rosenkranz, J.A., & Grace, A.A. (2002). Cellula r mechanisms of infralimbic and prelimbic prefrontal cortical inhib ition and dopaminergic modula tion of basolateral amygdala neurons in vivo. Journal of Neuroscience, 22 (1), 324-337. Sanders, S.K., & Shekhar, A. (1995). Regulat ion of anxiety by GABAA receptors in the rat amygdala. Pharmacolog, Biochemistry, and Behavior, 52 (4), 701-706. Schienle, A., Stark, R., Walter, B., Blecker, C., Ott, U., Kirsch, P., et al. (2002). The insula is not specifically involved in disgus t processing: an fMRI study. Neuroreport, 13 (16), 20232026. Scott, S., Caird, F., & Williams, B. (1984). Eviden ce for an apparent sensor y speech disorder in Parkinsons disease. Journal of Neurology, Neurosurgery, and Psychiatry, 47 840-843. Seltzer, B., Vasterling, J. J., Mathias, C. W., & Brennan, A. (2001). Clinical and neuropsychological correlates of impaired awar eness of deficits in Alzheimer disease and Parkinson disease: a comparative study. Neuropsychiatry, Neuropsychology, and Behavioral Neurology, 14 (2), 122-129. Shapira, N. A., Liu, Y., He, A. G., Bradley, M. M., Lessig, M. C., James, G. A., et al. (2003). Brain activation by disgust-i nducing pictures in obse ssive-compulsive disorder. Biological Psychiatry, 54 (7), 751-756. Simons, G., Pasqualini, M.C., Reddy, V., & Wood, J. (2004). Emotional and nonemotional facial expressions in people with Parkinsons disease. Journal of the International Neuropsychological Society, 4 (10), 521-535. Slaughter, J.R., Slaughter, K.A., Nichols, D., Holmes, S.E., & Ma rtens M.P. (2001). Prevalence, clinical manifestations, etio logy, and treatment of depressi on in Parkinsons disease. Journal of Neuropsychiatry and Clinical Neuroscience, 13 187-196. Smith, M.C., Smith, M.K., & Ellgring, H. (1996). Spontaneous and posed facial expression in Parkinsons disease. Journal of the International Neuropsychological Society, 2 383-391. Spielberger, C.D. (1977). St ateTrait Anxiety Inventor y. Palo Alto, CA: Consulting Psychologists Press, Inc. Sprengelmeyer, R., Young, A. W., Mahn, K., Schroe der, U., Woitalla, D., Buttner, T., et al. (2003). Facial expression recognition in people with medicated and unmedicated Parkinson's disease. Neuropsychologia, 41 (8), 1047-1057. Stark, R., Schienle, A., Walter, B., Kirsch, P., Sammer, G., Ott, U., et al. (2003). Hemodynamic responses to fear and disgust-i nducing pictures: an fMRI study. International Journal of Psychophysiology, 50 225-234. Starkstein, S.E., Mayberg, H.S., Preziosi, T.J ., Andrezejewski, P., Leiguarda, R., & Robinson, R.G. (1992). Reliability, validity, and clinical correlates of ap athy in Parkinsons disease. Journal of Neuropsychiatry and Clinical Neuroscience, 4 134-139.

PAGE 107

107 Tessitore, A., Hariri, A.R., Fe ra, F., Smith, W.G., Chase, T.N., Hyde, T.M., et al. (2002). Dopamine modulates the response of the human amygdala: A study in Parkinsons disease. The Journal of Neuroscience, 22 (20), 9099-9103. van Spaendonck, K.P., Berger, H.J., Horstink, M.W ., Borm, G.F., & Cools, A.R. (1993). Card sorting performance in Parkinsons dis ease: A comparison between acquisition and shifting performance. Journal of Clinical Expe rimental Neuropsychology, 17 918-925. Vidailhet, M., Rothwell, J.C., Thompson, P.D ., Lees, A.J., & Marsden, C.D. (1992). The auditory startle response in the Steele-Ri chardson-Olszewski syndr ome and Parkinsons disease. Brain, 11 5(4), 1181-1192. Vrana, S.R., Spence, E.L., & Lang, P.J. (1988). The startle probe respons e: A new measure of emotion? Journal of Abnormal Psychology, 97 (4), 487-491. Watson, D., Clark, L. A., & Tellegen, A. (1988). Development and validation of brief measures of positive and negative affect: The PANAS scales. Journal of Personality and Social Psychology, 54, 1063-1070. Wechsler, D. (1997). Wechsler Memory ScaleThird Edition Manual San Antonio, TX: Psychological Corporation. Wieser, M. J., Muhlberger, A., Alpers, G. W., Macht, M., Ellgring, H., & Pauli, P. (2006). Emotion processing in Parkinson's disease: dissociation between early neuronal processing and explicit ratings. Clinical Neurophysiology, 117 (1), 94-102. Wilson, G.D., Kumari, V., Gray, J.A., & Corr, P.J. (2000). The role of neuroticism in startle reactions to fearful and disgusting stimuli. Personality and Indivi dual Differences, 29 1077-1082. Wright, P., He, G., Shapira, N.A., Goodman, W.K., & Liu, Y. (2004). Digust and the insula: fMRI responses to pictures of mutilation and contamination. Neuroreport, 15 (15), 23472351. Yartz, A.R., & Hawk, L.W. (2002). Addressing the specificity of affectiv e startle modulation: fear versus disgust. Biological Psychology, 59 55-68. Yoshimura N, K. M., Masaoka Y, Homma I. ( 2005). The amygdala of patients with Parkinson's disease is silent in response to fearful facial expressions. Neuroscience, 131 (2), 523-534. Young, A.W., Aggleton, J.P., Hellawell, D.J., J ohnson, M., Broks, P., & Hanley, J.R. (1995). Face processing impairments after amygdalotomy. Brain, 118 15-24.

PAGE 108

108 BIOGRAPHICAL SKETCH Kimberly Miller was born in San Jose, Califor nia. She received her B.A. in psychology from the University of Californi a at Berkeley. She has been a gr aduate student in Clinical & Health Psychology student at the Un iversity of Florida for the pa st five years, where she is specializing in neuropsychology. This dissertation is an extension of the ideas originating from her masters thesis, completed in 2004 under th e mentorship of Dawn Bowers. Outside of psychology, Kim enjoys reading, runni ng, and spending time at the beach.