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DIMINISHED AFFECTIVE MODULATION OF STARTLE TO THREATENING
STIMULI IN PARKINSON' S DISEASE
KIMBERLY M. MILLER
A THESIS PRESENTED TO THE GRADUATE SCHOOL
OF THE UNIVERSITY OF FLORIDA IN PARTIAL FULFILLMENT
OF THE REQUIREMENTS FOR THE DEGREE OF
MASTER OF SCIENCE
UNIVERSITY OF FLORIDA
Kimberly M. Miller
I would like to acknowledge my research mentor, Dawn Bowers, for her constant
availability and support. I would like to thank the graduate students and research
assistants in the Cognitive Neuroscience Laboratory who helped in the collection of this
data. I would like to thank Michael Okun and his colleagues at the Movement Disorders
Center for providing access to patients, and the patients themselves who endured many
long hours of testing.
TABLE OF CONTENTS
ACKNOWLEDGMENT S ................. ................. iii...___ ....
LIST OF TABLES ....___ ................ ........___.........v
LI ST OF FIGURE S .............. .................... vii
AB S TRAC T ......_ ................. ..........._..._ viii..
1 INTRODUCTION ................. ...............1.......... ......
Motor and Cognitive Symptoms in Parkinson's Disease .............. .....................
Emotional Processing in Parkinson's Disease ................. .............. ......... .....4
Mood Disturbance in Parkinson' s Disease ................ .. ............ ................ ..4
Expression and Perception of Emotion in Parkinson' s Disease ................... .........5
Physiologic Reactivity ................. ............. ... .... ........ ..........7
Pathophysiology of Emotional Changes in Parkinson' s Disease ................ ...............9
Neural Circuitry Involved in Emotional Behavior ..........._.._. ........_.. ........10
Amygdala Pathology ........._.._.. ...._... ...............11....
Rationale for the Present Study .............. ...............12....
Hypotheses and Predictions ........._..... ...._... ...............14....
Hypothesis 1 .............. ............... 14....
Hypothesis 2 ........._.._.. ...._... ...............14....
Exploratory Questions ........._..... ...._... ...............15.....
2 METHODS ........._.._.. ...._... ...............17....
Participants .............. ...............17....
Materials ........._.._........ .. ....._... .... .._... .... .. .........1
International Affective Picture System Slides............... ...............19.
Self Assessment Manikin (SAM) ................. ...............21................
Proc edure s ................ ...............21........... ....
Data Collection ................. ........ ........ ... ............. ....................2
Data Reduction of the Eyeblink Component of the Startle Response .................22
Statistical Analyses............... ...............23
3 RE SULT S .............. ...............26....
Startle Eyeblink .............. .. ........... ...........2
Pleasant versus Unpleasant Pictures .....___._ ........_. .....__. ...........2
Threatening versus Other Unpleasant Pictures ....._.__._ ........___ ..............27
Subj ective Ratings: Valence and Arousal ....__ ......_____ ...... ...___.........2
Pleasant versus Unpleasant Pictures ....__ ......_____ .......___ ............2
Threatening versus Other Unpleasant Pictures ....._____ .........__ ...............30
Eyeblink Magnitude and BDI Correlations ................ ...............31......_... ...
4 DI SCUS SSION ....._.._................. ........_.._.........3
Basic Acoustic Startle in PD Patients ........._._. ............. ... ....._. ...........3
Possible Effects of Depression on the Present Findings .................. .. ............ .......3 8
The Role of the Amygdala in Response to Threatening/Fearful Stimuli .................. .39
Dissociation of Subj ective Ratings and Physiological Response ............... ... ............40
Limitations of the Present Study ................. ...............42........... ...
Directions for Future Research ................. ...............44................
LIST OF REFERENCES ................. ...............47........... ....
BIOGRAPHICAL SKETCH .............. ...............56....
LIST OF TABLES
1-1 Patient and Control Characteristics .................._____ ......... ...........2
3-1 Means and SDs of Pleasantness and Arousal Ratings for Unpleasant and
Pleasant Pictures. ........... ..... .._ ...............30......
3-2 Means and SDs of Pleasantness and Arousal Ratings for Threatening and Other
Unpleasant Pictures. ............. ...............3 1....
3-3 Correlations Between Number of Years with Parkinson' s Disease, BDI Score,
Hoehn and Yahr Stage, and UPDRS Motor Subscale Score............... ..................3
LIST OF FIGURES
1-1 Simplified Direct Loop in the PD patient's Dysfunctional Motor System. ..............3
1-2 Two Hypothesized Striato-Thalamo-Cortical Loops Involved in Emotion. ............11
3-1 Peak Eyeblink Amplitudes for Unpleasant versus Pleasant Pictures ................... ....28
3-2 Peak Eyeblink Amplitude for Threat versus Other Unpleasant Pictures .................29
Abstract of Thesis Presented to the Graduate School
of the University of Florida in Partial Fulfillment of the
Requirements for the Degree of Master of Science
DIMINISHED AFFECTIVE MODULATION OF STARTLE TO THREATENING
STIMULI IN PARKINSON' S DISEASE
Kimberly M. Miller
Chair: Dawn Bowers
Major Department: Clinical and Health Psychology
Rationale. Studies of patients with Parkinson's disease have suggested various
deficits in emotional processing. These impairments may be linked to a decrease in
dopamine levels regulating key limbic circuitry, and pathology of the amygdala in
Parkinson's patients. In the present study, the issue as to whether patients with
Parkinson's disease display normal emotional modulation of startle to unpleasant and
pleasant pictures was examined. Furthermore, within the category of unpleasant pictures,
reactivity to threat-eliciting versus other types of aversive pictures was investigated. It
was hypothesized that Parkinson' s patients would show diminished emotional reactivity
in general to the emotional pictures, based on suggestions of amygdala and limbic
circuitry dysfunction. Additionally, it was hypothesized that Parkinson' s patients would
exhibit reduced emotional reactivity, relative to controls, to threat-eliciting pictures
specifically, due to the role of the amygdala in processing of threatening stimuli.
Methods. To test this hypothesis, twenty Parkinson's patients and fifteen age-
matched healthy Controls viewed standard sets of pleasant, unpleasant, and neutral
pictures for six seconds each. During this time white noise bursts were binaurally
presented to elicit startle eyeblinks. Subj ective ratings of valence and arousal were also
obtained. The Parkinson's patients were tested while "on" dopaminergic medication.
Results. Data were analyzed using 2 X 2 repeated measures Analyses of
Variance. Both the Parkinson's patients and Controls showed significantly larger startle
amplitude during unpleasant versus pleasant pictures, which is the normal pattern of
emotion modulation. This effect was significantly weaker and less robust in the
Parkinson's patients than the Controls, as revealed by a Group X Affect interaction.
Specifically, startles to negative pictures were significantly smaller in Parkinson's than
Controls, with no group differences for pleasant pictures. Within the unpleasant pictures,
Controls showed a significantly larger startle amplitude during threatening versus other
types of unpleasant pictures, whereas the Parkinson' s patients did not. The Parkinson' s
and controls rated the emotional pictures similarly.
Conclusions. The current study found that Parkinson' s patients were less
emotionally reactive than controls to aversive pictures, specifically with regards to threat-
eliciting pictures. The basis for this diminished reactivity is unknown, but may reflect
pathological changes in the amygdala of PD patients, a structure consistently implicated
in processing of fearful stimuli, as well as a reduction in dopamine levels within limbic
Parkinson's disease (PD) is the second most common neurodegenerative disorder
next to Alzheimer' s disease, affecting approximately half a million to a million people in
the United States (McDonald, Richard, & DeLong, 2003). About 50,000 new cases are
reported annually, and this figure is rising as the average age of the population increases
(National Institute of Neurological Disorders and Stroke, 2001). Slightly more males than
females suffer from Parkinson's disease. The average age of onset is approximately 60-
65 years old, although a small proportion of PD patients (5-10%) display symptoms
before age 40 (Fahn, 2003; Lang & Lozano, 1998). The likelihood of developing PD
increases with age, with a lifetime risk of about 2% (Fahn, 2003).
Although the motor and cognitive symptoms of Parkinson' s disease have been
well studied over the years, relatively few studies have specifically examined changes in
emotional reactivity. This is surprising in light of the fact that aspects of the neural
circuitry affected by dopaminergic depletion in PD involve "limbic" regions that are
known to be important in emotional behavior (i.e., amygdala, nucleus accumbens,
orbitofrontal region). Thus, the goal of the present study was to investigate emotional
reactivity in Parkinson's disease by using experimental measures that assessed
physiologic reactivity to emotional pictures. To do this, patients' physiological responses
to pictures of varying valence and arousal levels were measured and compared to the
responses of control subj ects. Before turning to a review of the literature on emotional
processing in PD, the core symptoms of Parkinson' s disease will be briefly discussed.
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. This dopaminergic depletion then affects a
whole cascade of structures involved in the production of voluntary movement,
particularly the basal ganglia. A diagram of the neural circuitry involved in Parkinson' s
disease is depicted in Figure 1-1. It has been estimated that patients with PD have an
approximately 60-85% 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 maj or 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' 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., globus pallidus internus, subthalamic
nucleus). The basic 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).
SNC (VA, VL)
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).
Although the motor symptoms of Parkinson' s disease are the primary focus of
pharmacotherapy and surgical treatments, various nonmotor symptoms also occur and
can be particularly disturbing and disabling. These include insomnia, autonomic
dysfunction, mood disturbance, psychosis, and cognitive changes. Common cognitive
sequalae are 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 20%
of Parkinson' s patients develop a frank dementia (Brown & Marsden, 1984), which is
most common in PD patients with a later age of onset. When a patient suffers from both
dementia and PD, they are referred to as having "Parkinson's plus syndrome" (Fahn,
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
sections, a brief overview of some of the emotional changes that accompany Parkinson' s
disease will be presented.
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 Parkinson's patients may exhibit difficulties in
at least three of these domains. Each of these will be briefly reviewed below.
Mood Disturbance in Parkinson's Disease
A variety of studies have consistently found mood disturbances among patients
with Parkinson' s disease, with an average of 40-50% of PD patients experiencing
depressive symptoms (Cummings, 1992; McDonald et al., 2003; Zgaljardic et al., 2003).
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 cortical and subcortical pathways (Burn, 2002; Mayberg et
al., 1990). In addition to decreasing quality of life, depression and other psychiatric
disturbance in Parkinson's patients appear to exacerbate motoric symptoms (Cummings,
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 subj ective sense of indifference (Marin, 1991). Between 40 and 50% of Parkinson' s
patients have been described as meeting criteria for apathy, based on various "apathy"
scales (Isella et al., 2002; Starkstein, Mayberg, Preziosi, Andrezejewski, Leiguarda, &
Robinson, 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 (Pluck & Brown, 2002). Instead, apathy has been correlated with
increasing cognitive impairments. 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,
Expression and Perception of Emotion in Parkinson's Disease
In addition to mood disturbances, patients with Parkinson's disease also have
difficulty communicating emotion using various 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). In fact, one of the common 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 in the disease course and is
unrelated to depression (Katiskitis & Pilowsky, 1991; Smith, Smith, & Ellgring, 1996).
Recent studies 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 et al., in press). Unfortunately, diminished use of
nonverbal communication signals by Parkinson patients poses significant problems,
ranging from misdiagnosis of depression to the misattribution of negative emotion states
by family members and health care providers.
The research literature regarding the perception of emotional information (faces,
scenes, prosody) is inconsistent at best. Some investigators have found that Parkinson' s
disease patients 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 and Tranel,
1998; Madeley, Ellis, & Mindham, 1995). Some possibilities that may account for these
discrepancies are methodologic inconsistencies regarding the stage of 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 difficulties with processing of specific emotions such as
"fear" 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 and colleagues (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).
Another approach for examining emotional behavior involves monitoring
patients' physiological reactivity to emotional materials. To date, there are no published
studies of psychophysiologic reactivity to emotional materials in patients with
Parkinson's disease. This is surprising, since using physiology as an index of emotional
reactivity in a Parkinson's sample has several advantages. First, it does not require a
voluntary motor response (as measurements of facial expressivity or vocal prosody do),
thereby eliminating 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 do), and thus the demand characteristics associated with it are
minimal. Finally, because the response that is being measured is near impossible to
voluntarily control, it does not rely on the subj ect' s attention, motivation, or cooperation
Skin conductance. One type of physiological reaction frequently measured in
psychological research is skin conductance response (SCR) to emotional stimuli. This is
accomplished by applying electrodes that essentially measure "palm sweat" to the inside
of the hands. The larger the SCR, the larger the physiological arousal the subject has
experienced in response to the emotional stimuli. Although measurement of SCR can be
useful, it does have serious 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 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.
Startle eyeblink response. Another widely used index of emotional reactivity is
the affective modulation of the startle eyeblink response (Lang, Bradley, & Cuthbert,
1990; Vrana, Spence, & Lang, 1988). It is this measure that was chosen to serve as the
index of emotional reactivity in the present study. In order to understand the mechanism
of this phenomenon, it is first necessary to describe the basic startle response 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. It is characterized by limb
and trunk movements of the body, as well as a reflexive eyeblink (Bradley & Vrana,
1993). A variety of studies over the past decade have documented that size of the startle
eyeblink is directly modulated by an individual's affective state (i.e., negative, positive).
In humans, startle response magnitude (as indexed by reflexive eyeblink) is augmented
during emotionally aversive tasks and attenuated during more pleasant tasks. This
valence modulation of startle is observed across a variety of tasks involving slide
viewing, imagining emotional situations, and anticipation of shock (Bradley, Cuthbert, &
Lang, 1990, 1991; Grillon, Ameli, Woods, & Merikangas, 1991; Lang, Bradley, &
Cuthbert, 1990). Lang et al. (1990) proposed that startle response magnitude reflects the
valence of the individual's central motivational state (appetitive versus aversive), rather
than being a tactical response in a specific affective context.
The neural circuitry underlying the startle response has been exquisitely mapped
out by Mike Davis and colleagues (Davis, 1992; Davis, Gendelman, Tischler, &
Gendelman, 1982). Davis' group has shown that the basic startle circuitry is mediated
entirely subcortically (at the level of the brainstem-spinal cord), and can be directly
modulated by the amydal (at least in rodents) via its proj section 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 while leaving the basic startle intact (Hitchcock & Davis, 1991; Hitchcock,
Sananes, & Davis, 1989). Further, lesions at some cortical sites that relay information to
the amygdala appear to attenuate fear potentiated startle in rodents (Rosen, Hitchcock,
Miserendino, Falls, Campeau, & Davis, 1992). In humans, temporal lobe ablations
involving the amygdala are associated with reduced startle potentiation during the
viewing unpleasant pictures.
Taken together, these findings suggest that increases in the startle response during
negative emotional states may reflect the amygdala's role in both threat detection and in
modulating subcortical startle circuitry.
Pathophysiology of Emotional Changes in Parkinson's Disease
Before turning to the rationale for the current study, the question arises as to the
basis for changes in emotional behavior in Parkinson's disease. There appears to be at
least two possible mechanisms that might potentially affect emotional processing in
Parkinson's disease. First, the reduction in nigrostriatal dopamine found in PD influence
neural circuits that have been implicated in emotion. Secondly, evidence has been found
that the amygdala, a key limbic structure, exhibits significant pathological changes in
Parkinson's disease. Each of these possible mechanisms will be discussed below.
Neural Circuitry Involved in Emotional Behavior
The deficits in emotional processing described previously may be linked to limbic
circuitry subserved by the neurotransmitter dopamine. There are three main systems
through which dopamine may affect emotional processing in PD: 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 Hyve 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 depicted 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
A) B) Lateral
Anterior Cingulate Cortex ObtfotlCre
Ventral Striatum Caudate
(Nucleus Accumbens) (ventromedial)
G.P. rostrolateral/ G.P. mdm/
SThalamus I Thalamus
MD & VA AID
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
reticulata, mdm = medial dorsomedial.
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).
In summary, there are myriad hypothesized dopamine-mediated circuits that
connect the limbic system to the frontal cortex and thus allow for emotional modulation
of cognitive processes. The depletion of dopamine that characterizes Parkinson's disease
may affect regulation of these circuits, potentially leading to dysfunction in emotional
One of the key limbic structures involved in emotion is the amygdala, a small
almond-shaped structure located within the anterior temporal lobe. The amygdala has
consistently been implicated in the recognition of fearful stimuli and responding to
threatening situations. Monkeys with lesions of the amygdala do not display normal fear
reactions to threatening stimuli, such as snakes (Amaral, 2003; Kltiver & Bucy, 1939). In
humans, lesions of the amygdala have been associated with behavioral placidity,
diminished physiologic reactivity, and impairments in recognizing fearful faces
(Aggleton, 1992; Calder, Young, Rowland, Perrett, Hodges, & Etcoff, 1996; Young,
Aggleton, Hellawell, Johnson, Broks, & Hanley, 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
Recently, several investigators have found evidence of pathological changes in
the amygdala of Parkinson' s patients. In a post-mortem study, Harding and colleagues
(Harding, Stimson, Henderson, & Halliday, 2002) found a 20% reduction in the
amygdala volumes of PD patients compared to normal controls. Ouchi and colleagues
(1999) found a 30-45% reduction of dopamine agonist binding in the amygdala of PD
patients, which they speculated might be due to a loss of pre-synaptic dopamine terminals
in this region. Additionally, post-mortem studies have found the presence of Lewy
bodies in the amygdala of PD patients (Braak & Braak, 2000).
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.
The findings thus far with respect to these questions are reviewed below.
Rationale for the Present Study
To date, there are no published studies that have used psychophysiology as a
marker of emotional responsiveness in Parkinson' s disease. Because of the symptoms of
PD include motor rigidity and slowing, using facial expressivity or vocal prosody as an
index of emotional reactivity (as has been done in past studies) may potentially confound
motoric deficits with emotional deficits. Thus, measurement of affective startle eyeblink
magnitude may provide a clearer methodological approach to investigating emotional
reactivity in this patient group. Seignorel and colleagues (Seignorel, Miller, Bowers, &
Okun, 2003) found no significant differences in either latency or magnitude of startle
eyeblink responses in a group of PD patients compared to controls, suggesting that
despite motor impairments, basic eyeblink startle startle remain intact in Parkinson's
patients. Similar findings with respect to the magnitude of basic startle responses have
also been described by other researchers (Koffer et al., 2001; Vidailhet, Rothwell,
Thompson, Lees, & Marsden, 1992).
The primary purpose of the present study was twofold: 1) To determine if PD
patients and controls differ in degree of startle modulation produced by positive and
negative stimuli; and 2) To determine if PD patients exhibit less startle potentiation to
threatening stimuli, relative to controls. To date, no studies have investigated PD
patients' reaction (as opposed to ability to recognize) to non-facial threat-evoking
stimuli. For this reason, the issue of whether PD patients exhibit a normal response to
threatening stimuli is unknown, although observations of amygdala pathology raise the
possibility that threat responding may potentially be disrupted. The only existing studies
that address threat processing in PD patients have focused on the ability to recognize
fearful facial expressions. Findings from these studies have been mixed. In a task
involving recognition of prototypical emotional facial expressions, Sprengelmeyer et al.
(2003) found that medicated PD patients were specifically impaired at recognizing anger
and fear, compared to controls. However, when these same patients were tested on a
different emotion recognition task (involving morphed images of emotional expressions),
they demonstrated no deficit. Kan et al. (2003) found that PD patients were impaired in
the recognition of fear and disgust when moving facial stimuli were used. Thus, these
studies raise the possibility that recognition of fearful faces may be impaired in PD
patients, but do not address the issue of whether an abnormal reaction to a threat-eliciting
stimulus exists at the physiologic or subj ective level in Parkinson' s.
Hypotheses and Predictions
In healthy subjects, unpleasant stimuli are consistently associated with larger blinks
compared to pleasant stimuli. Keeping this in mind, the following hypotheses were
Parkinson's disease patients will display diminished emotional reactivity relative to
normal controls, as indexed by startle modulation during affective pictures. Thus, it was
predicted that PD patients would exhibit a significantly smaller eyeblink magnitude than
controls while viewing unpleasant slides, and a significantly larger eyeblink magnitude
than controls while viewing pleasant slides. This prediction is based on the observations
that PD patients show 1) reduced striatal dopamine, which may affect dopamine-
mediated limbic circuits; and 2) amygdala neuropathology, which may affect the ability
of the amygdala to modulate the basic startle response.
Parkinson's patients will show a more diminished emotional response to
threatening pictures as compared to other categories of unpleasant pictures. Specifically,
it was predicted that PD patients would display a significantly smaller eyeblink
magnitude than controls in response to threatening slides, whereas their eyeblink
magnitude during other unpleasant pictures would not significantly differ from that of
controls. This prediction is based on the fact that the amygdala is known to play a key
role in responding to threatening stimuli, is implicated in the fear-potentiated startle, and
exhibits pathology in PD patients.
In addition to the maj or hypotheses described above, several exploratory questions
were addressed. For example, would Parkinson patients rate the affective pictures as
intensely emotional as the controls in terms of valence? This is an important question for
several reasons. First, if PD patients rated the emotional pictures as less intense, then this
might be due to perceptual problems in appraising the stimuli, which could potentially
influence emotional reactivity. Alternatively, reduced ratings might be due to some
alteration in emotional appraisal. As mentioned previously, approximately 40% of PD
patients experience apathy (Marin, 1996). One component of apathy is diminished
emotional response to both positive and negative events. Whether this holds true for
positive and negative pictures in an experimental setting, which is obviously much
different from the natural environment, is unknown. If it does indeed hold true, then
patients with PD should find unpleasant pictures less unpleasant than controls, and
pleasant pictures should be rated as less pleasant than control' ratings. On the other hand,
Smith et al. (1996) found that PD patients rated emotional scenes from movies no
differently from healthy controls. This raises the possibility that patients in the current
study might rate pictures similarly to controls, yet nevertheless show differences in
emotional reactivity as indexed by startle. This situation would suggest a decouplingg"
between appraisal and the translation of the results of this appraisal into a motivational
state. The amygdala is thought to play a pivotal role in this translational process based
on lesion studies of patients who have undergone resection of the mesial temporal region
including the amygdala (Bowers et al., 1998). Should a decoupling be found in
Parkinson's patients, this finding would be consistent with some abnormality in the
translationall" process, possibly related to alterations in amygdala functioning. An
additional question was whether controls and PD patients would find the pictures
similarly arousing. If PD patients are experiencing emotional "blunting", one might
expect them to find the emotional stimuli less arousing than controls. Finally, it was
important to determine if any differences between patients' and controls' emotional
startle modulation could be attributed to differences in level of depression. Therefore, an
additional exploratory goal was to investigate any possible association between
depressive symptoms and startle eyeblink magnitude.
Participants included twenty patients with idiopathic Parkinson's disease and
fifteen healthy age-matched controls. The Parkinson's patients were recruited through
the Movement Disorders Center of the University of Florida and had been evaluated
within the preceding three months by a movement disorders neurologist (Dr. Okun or Dr.
Fernandez). As part of their routine workup in the Movement Disorders Clinic, the
Parkinson' s patients received standard measures for staging the severity of their motor
symptoms and disease course. These included: the thrited'Parkinson Disease Rating
Scale-ThirdEdition' (motor subscale [Fahn & Elton, 1987]), a modified Hoehn-Y ahrYYYY~~~~~~YYYYY
scale (Hoehn & Yahr, 1967), and the Scinvab andEnglandActivities ofDaily Living3
(Schwab & England, 1969). Patients were evaluated on these scales "off" medication (12
hours after last levodopa dose) and again one hour after taking their medication ("on"
state). During this clinical evaluation, PD patients were also screened for dementia
(M~ini-M~entalState Exam [Folstein, Folstein, & McHugh, 2001]), depressed mood (Beck
SThis is a rating tool designed to assess the severity of various motor symptoms over the course of the
disease. Higher scores indicate greater severity. Patients were assessed while on and off dopaminergic
2 This scale is used to rate the "stage" of severitv/disability in the PD patient. Stages range from 1-5, with
five being the most severe (cannot walk without assistance, or is confined to wheelchair). Patients were
assessed while on and off dopaminergic medication.
3 This rating scale is an index of the PD patient' s level of functioning in activities of daily life. Scores
range from 0-100%, with 100% indicating complete independence, and 0% indicating that the patient is
Depression Inventory [Beck, 1978]), and decreased quality of life (Parkinson Disease
Quality of Life Scale-39 [Peto, Jenkinson, & Fitzpatrick, 1998]).
To be included in the PD group, patients had to meet stringent diagnostic criteria
for Parkinson' s disease, be free of other neurologic or medical illness that would
compromise their participation (or interpretation of findings), and be free of dementia and
significant psychological distress (i.e., a psychiatric disorder). The clinical diagnosis of
idiopathic PD was based on: (a) the presence of at least two of four cardinal motor
signals (i.e., akinesia, bradykinesia, resting tremor, rigidity [Hughes, Ben-Shlomo, et al.,
1992; Hughes, Daniel, et al., 1992]); and (b) a demonstrated therapeutic response to
dopamine replacement therapy, as defined by a marked improvement in Parkinsonian
motor signs, based on the motor subscore of the United Parkinson Disease Rating Scale
(UPDRS) following administration of levodopa during their screening neurologic
examination. A demonstrated good response to levodopa therapy was required in order
to exclude patients with Parkinson's plus syndromes (e.g., Shy-Drager, multiple system
atrophy, Lewy body disease, corticobasal degeneration). Only Parkinson patients who
scored in the nondemented range on the Mini-Mental State Exam (>26) were invited to
participate in the present study.
The PD patients included sixteen men and four women, who ranged in age from 43
to 85 (X = 61.9, SD = 10.0). As a group, they had been treated for Parkinson' s disease
for eleven years and were in the mid-stages of their disease, based on staging criteria
from the Hoehn and Yahr scale. This information is depicted in Table 1-1. In order to
assess depressive symptomatology, all patients received the Beck Depression Inventory
(BDI) on the same day they received the experimental emotional tasks. The BDI scores
for the PD patients included in the present study ranged from two to nineteen (means and
standard deviations are shown in Table 1-1). Two patients met criteria for Mild
Depression (BDIs = 14 and 19), as defined by Beck, Steer, & Brown (1996).
Control participants included fifteen healthy individuals (ten men, five women)
who had been recruited from the community. Any control participant with reported
psychiatric disorder, head previous head injury, learning disability, or neurological
disorder was excluded. Controls were also given the BDI. There were no instances in
which Control participants produced BDI scores that exceeded thirteen (the
recommended cutoff score for Mild Depression; Beck et al., 1996).
A comparison of patient and control demographic variables is presented in Table 1-
1. As shown, the PD and Control groups did not significantly differ with respect to age
(t(33)= 1.90, p = .40), although the mean age of the PD patients was about ten years
greater than that of the controls. The reason for this discrepancy related to the young age
of two of the control subj ects (these subj ects were twenty-five and twenty-nine years old,
respectively). Additionally, the PD patients were slightly more educated than the controls
(t (28.7)= 2.04, p = .05). The PD patients had a mean of fifteen years of education,
whereas controls had a mean of 13.5 years of education. Finally, PD patients and
controls significantly differed with respect to their mean BDI scores (t(31) = 3.06, p<
005), with BDI scores of the PD group (X = 8.5) being significantly higher than those of
the Controls (X = 4. 1).
International Affective Picture System Slides
Participants viewed a subset of forty-four pictures (twelve pleasant, twelve
unpleasant, twelve neutral, and eight "filler") taken from the International Affective
Table 1-1. Patient and Control Characteristics
PD patients Controls
(N = 2 0) (N- = 5)
Men: Women 16:4 10: 5
Age 62.9 (10) 53.8 (15.2) ns
Yrs. Ed 15. (2.9) 13.5 (1.3) p =.05
Hoehn-Yahr* 2.7 (.52) -
UPDRS motor* 27.2 (10.2) -
Yrs. with PD 10.8 (6.0) -
BDI 8.5 (4.0) 4.1 (4.0) p .005
* Assessed while on dopaminergic medication.
Picture System (Lang, Bradley, & Cuthbert, 2001a). Efforts were made to equate
the pleasant and unpleasant pictures on the basis of normative ratings of arousal (Lang,
Bradley, & Cuthbert, 2001Ib); however, a t-test revealed that the normative sample of men
and women found the unpleasant pictures to be more arousing on average than the
pleasant pictures, t(1 1) = 2.73, p < .05 (mean of Unpleasant pictures = 6.6, SD = .664;
mean of Pleasant pictures = 5.8, SD = 1.03 [ratings range from one to nine, with nine
being the most arousing]).4 The experiment began with two filler slides for practice,
followed by six blocks of seven trials. Each block contained two unpleasant slides, two
pleasant slides, two neutral slides, and one filler slide, presented in randomized order.
In order to investigate the impact of threatening pictures on emotional reactivity,
the negative pictures were further divided into two additional categories: "Threat" versus
"other unpleasant" pictures. "Threat" slides were defined as any slide suggesting
imminent attack, such as a snake preparing to bite, a gun pointed at the viewer, or a dog
with saliva-dripping fangs spread open. All remaining unpleasant pictures were then
SThese normative ratings were obtained from a large sample of college students, and thus may not be
applicable to older participants. Additionally, the male to female ratio of the normative sample differs from
that of the current study.
categorized as "other unpleasant" pictures. This post-hoc division resulted in seven
"threat" pictures and Hyve "other unpleasant" pictures. The IAPS numbers for the threat
pictures are: 1090, 2120, 1300, 3000, 3530, 6230, 6370). The IAPS numbers for the
"other unpleasant" pictures are: 3010, 3100, 3130, 9040, 9050). "Threat" pictures had a
mean normative arousal rating of 6.40 (SD = 0.862) and "other unpleasant" pictures had a
mean normative arousal rating of 6.56 (SD = 0.52 [Lang, Bradley, & Cuthbert, 2001b]).
Self Assessment Manikin (SAM)
Each participant rated the pictures for valence (pleasant, unpleasant) and arousal
using the Self Assessment Manikin (SAM). SAM is a graphic display depicting a
cartoon Eigure that varies along the dimensions of valence and arousal (Greenwald, Cook,
& Lang, 1989; Lang, 1980). For valence, nine versions of the cartoon Eigure were shown,
ranging from positive to neutral to negative. For arousal, nine versions of the cartoon
Eigure were shown ranging, from sleepy to neutral to highly excited. During the
experiment, participants were asked to rate their reactions to each IAPS picture
immediately after viewing it by referring to the SAM figures. The SAM Eigures were
vertically displayed on a computer screen in front of the participants. The participants
verbally gave their valence and arousal ratings which were heard, via an intercom, by an
investigator in an adj acent room.
Prior to beginning the study, informed consent was obtained from each participant
according to University and Federal guidelines. All testing took place in the Cognitive
Neuroscience Laboratory of the UF Brain Institute. The session began with completion
of various questionnaires, including the BDI. This was followed by a detailed
description of the study and attachment of electrodes over the face and hands. (For the
purpose of the present study, only the startle component will be described). After
cleaning the area under the eye, two 3 mm Ag/AgCl electrodes were filled with a
conducting gel (Medical Associates, Inc., Stock # TD-40, Lot # 70204) and were
positioned under the left and right eyes to record EMG activity from the orbicularis oculi
muscle. Electrodes were affixed to the skin surface with adhesive collars. During the
experiment, participants sat in a reclining chair that was located in a sound-attenuated and
electrically shielded 12'xl2' room. Visual stimuli were displayed on a 21" computer
monitor located directly in front of the participant. After the participant was taught how
to use SAM and practiced with two sample slides, the experiment commenced. Each trial
began by presentation of the picture for six seconds. During this time, startle eyeblinks
were elicited by a 50 ms burst of white noise (95dB, instantaneous rise time) that was
delivered binaurally via Telephonics (TD-591c) headphones. A Colbourn S81-02
module generated the white noise bursts that were gated through a Colbourn S82-24
amplifier. These white noise bursts (startle probes) were randomly presented at various
points following picture onset (i.e., 4200, 5000, or 5800 ms) and counterbalanced across
valence category. Following each picture, the SAM figure appeared on the computer
screen and the participant verbally rated his/her subj ective level of valence and arousal.
Data Reduction of the Eyeblink Component of the Startle Response
The eyeblink component of the startle response was measured by recording EMG
activity from the orbicularis oculi muscle beneath each eye. The raw EMG signal was
amplified and frequencies below 90 Hz and above 1000 Hz were filtered using a
Colbourn bioamplifier. Amplification of acoustic startle was set at 30,000. The raw
signal was then rectified and integrated using a Colbourn Contour Following Integrator
with a time constant of 200 ms. This information was sent to a Scientific Solutions A/D
board interconnected with a custom personal computer. Digital sampling at 1000 Hz
began 50ms prior to startle probe onset and continued at this rate for 250 ms after the
probe onset. The startle data were reduced off-line using custom software programs.
These programs automatically eliminate trials with an unstable baseline and derive
baseline, peak, and blink amplitude values in arbitrary A-D units for each trial. Each trial
was scored for amplitude (i.e., peak baseline in microvolts) during the 25-130 ms
interval following startle onset. Trials that failed to reach peak during this interval were
rej ected. Latency to peak blink magnitude (in ms) was also derived on a trial-by-trial
To test the first prediction (PD patients will exhibit a significantly smaller
eyeblink magnitude than controls while viewing unpleasant slides, and a significantly
larger eyeblink magnitude than controls while viewing pleasant slides), valence-
modulation of startle was evaluated by conducting a 2 (PDs, controls) X 2 (pleasant,
unpleasant) Repeated Measures Analysis of Variance with eyeblink magnitude T-scores
as the dependent variable. The eyeblink magnitudes in response to neutral pictures were
not included in the analysis for several reasons. First, although the neutral pictures have
normative subjective valence ratings that fall midway between ratings of pleasant and
unpleasant pictures, individuals' physiologic responses to these pictures vary widely.
One subj ect may respond to an ostensibly neutral picture as if it is somewhat negative in
valence, while another may respond to the same picture as if it is positive in valence.
Furthermore, research suggests that individual differences in current state anxiety levels
can affect startle modulation while viewing emotionally valenced pictures (Grillon,
Ameli, & Davis, 1993). Potentially, the same subject could respond differently to the
same "neutral" picture on two separate occasions, depending on factors such as the
individual's mood and the situation. Finally, the inclusion of only strongly valenced
pictures in the analysis, as opposed to more ambivalent pictures, increased the chances of
detecting any potential differences between the PD and Control groups.
To test the second prediction (PD patients will display a significantly smaller
eyeblink magnitude than controls in response to threatening slides), a 2 (PDs, controls) X
2 (threat, other unpleasant) Repeated Measures Analysis of Variance was conducted, with
eyeblink magnitude as the dependent variable once again.
Next, to investigate whether PD patients and controls rated pleasant and
unpleasant slides similarly with respect to valence, a 2 (PDs, controls) X 2 (pleasant,
unpleasant) Repeated Measures ANOVA was conducted, with subj ective valence ratings
as the dependent variable. This analysis was then repeated with "threat" and "other
unpleasant" pictures as the independent variables.
To investigate whether PD patients and controls differed in their arousal ratings of
pleasant and unpleasant pictures, a 2 (PDs, controls) X 2 (pleasant pictures, unpleasant
pictures) Repeated Measures ANOVA was conducted with subj ective arousal ratings as
the dependent variable. This analysis was then repeated with "threat" and "other
unpleasant" pictures as the independent variables.
A final set of analyses examined the relationship between emotional reactivity, as
indexed by startle magnitude, and scores on the Beck Depression Inventory. Although
only two of the PD patients scored below the clinical cutoff for depression on the Beck
Depression Inventory, the PD patients did obtain significantly higher scores on the BDI
(X = 8.5) than the Controls (X = 4.1). Thus, correlational analyses were performed in
order to learn whether BDI scores varied in any systematic way with emotional reactivity,
as indexed by startle. A startle reactivity index score was derived using the following
formula: [Unpleasant T-score] [Pleasant T-score]. This index score is a measure of
overall emotional reactivity; the larger the difference between the eyeblink peak
magnitudes for pleasant and unpleasant pictures, the greater reactivity to the stimuli the
participant is displaying. A second correlational analysis was performed using an index
score derived from the Threat and Other Unpleasant pictures (i.e., [Threat T-score] -
[Other Unpleasant T-score]).
Startle eyeblink responses were converted to T-scores (X=50, SD=10) following
the procedures of Bradley & Vrana (1993). This was done order to minimize between-
subj ect variability in the absolute size of startle responses that might otherwise obfuscate
the pattern of the relationship among pleasant, neutral, and unpleasant conditions. For
each participant an overall mean startle magnitude (and standard deviation) was derived
from the values of that subj ect' s individual trials. T-scores for each subj ect were
computed on a trial-by-trial basis, based on the unique array of values for a particular
subject. From these data, average startle responses (T-scores) were derived for the
unpleasant, neutral and pleasant pictures. Because startle values were similar for the left
and right eyes, a composite score was created (by averaging the left and right eye T-
scores) and used as the dependent value in the analyses described below. Since left and
right eye startle values did not significantly differ, for instances in which one eye
contained greater than 50% invalid trials, values from the other eye were used instead of
a composite score. Valid trials were defined as blinks that reached peak amplitude during
the 25-130 ms interval following startle onset.
Pleasant versus Unpleasant Pictures
The initial analysis examined whether Parkinson patients differed from Controls in
their emotional reactivity during pleasant versus unpleasant pictures. A repeated
measures Analysis of Variance (ANOVA) was conducted, with Group (PDs, Controls) as
the between-subj ects factor and Type Affect (pleasant, unpleasant) as the within-subj ects
factor. Results revealed a significant main effect for Type Affect (F(1, 33) = 31.39,
p<.001). Consistent with previous findings (Bradley & Vrana, 1993), startle eyeblinks
during unpleasant pictures (X = 51.4, SD = 2.41) were significantly larger than those
during pleasant pictures (X = 48.1, SD = 2.10). Additionally, there was significant Type
Affect X Group interaction (F(1,33)= 4.60, p<.05). This is depicted in Figure 3-1. Post
hoc t-tests indicated that: (a) for the PD group, startle eyeblinks were significantly larger
during unpleasant (X = 50.62, SD = 2.67) than pleasant pictures (X = 48.60, SD = 2.23;
t(19) = 2.35, p < .05); (b) for the Control group, startle eyeblinks were significantly
larger during unpleasant (X = 52.17, SD = 1.71) than pleasant pictures (X = 47.67, SD =
1.80; t(14) = 6.43, p < .001); (c) for unpleasant pictures, the Controls (X = 52.17, SD =
1.71) exhibited significantly larger eyeblinks than the Parkinson's patients (X = 50.62,
SD = 2.67; t(33) = -2. 11, p < .05; (d) for pleasant pictures, Controls (X = 47.67, SD =
1.80) and Parkinson's patients (X = 48.60, SD = 2.23) did not significantly differ with
respect to peak eyeblink amplitude (t(33) = 1.33, p > .19).
In summary, these findings indicate that both groups displayed greater emotional
reactivity, as indexed by startle modulation, during unpleasant versus pleasant picture
viewing. However, the Controls' reactivity was significantly greater than the Parkinson's
patients' during presentation of unpleasant pictures.
Threatening versus Other Unpleasant Pictures
A second ANOVA was conducted in order to determine whether Parkinson' s
patients were less reactive to "threat" versus other types of unpleasant emotional pictures.
One control and four PD patients were excluded from this analysis due to the fact that
55 f I U pleasant rlctures
Figure 3-1. Peak Eyeblink Amplitudes for Unpleasant versus Pleasant Pictures
these participants had less than 50% valid trials for either the "threat"or"other
unpleasant" category.A repeated measures ANOVA was conducted with Group (PD,
Controls) as the between-subject factor and Type Affect (Threat, Other unpleasant) as the
within-subj ect factor. Results of this ANOVA revealed a significant main effect for Type
Affect (F(1, 28)= 15.4, p<.001), indicating that startle eyeblink responses were larger
during threatening pictures (X = 53.36, SD = .612) as compared to other types of
unpleasant pictures (X = 49.21, SD = .696). Again, the Condition X Group interaction
was significant (F(1, 28)= 5.31, p<.05). Post hoc t-tests indicated that: (a) for the PD
group, startle eyeblinks did not significantly differ with respect to peak eyeblink
amplitude for "threat" (X = 51.91, SD = 4.10; t(15) = -1.05, p >.30) versus "other
unpleasant" pictures (X = 50.20, SD = 3.84); (b) for the Control group, startle eyeblinks
were significantly larger while viewing "threat" (X = 54.80, SD = 2. 17) versus "other
unpleasant" pictures (X = 48.22, SD = 3.76; t(13) = -5.13, p <.001); (c) for "threat"
pictures, the Controls exhibited significantly larger eyeblinks (X = 54.80, SD = 2. 17) than
the Parkinson's patients (X = 51.91, SD = 4.10; t(30) = -2.74, p < .05); (d) for "other
unpleasant" pictures, Controls (X = 48.22, SD = 3.76) and Parkinson's patients (X =
50.20, SD = 3.84) did not significantly differ with respect to peak eyeblink amplitude
(t(30) = 1.20, p >.20).
60 M Threat Pictures
O Other Unpleasant Pictures
Figure 3-2. Peak Eyeblink Amplitude for Threat versus Other Unpleasant Pictures
In summary, Controls demonstrated greater emotional reactivity to "threat" pictures
in comparison to the "other unpleasant" pictures, where as the Parkinson's patients did
not. However, both groups responded similarly to the "other unpleasant" pictures.
Subjective Ratings: Valence and Arousal
Pleasant versus Unpleasant Pictures
A third set of analyses was conducted to examine subj ective ratings of the
emotional pictures by the Parkinson's patients and Controls. The mean valence and
arousal ratings for the pleasant and unpleasant pictures are depicted in Table 3-1. Two
PD patients and two controls were excluded due to missing data. The valence ratings and
the arousal ratings were independently analyzed in separate Group X Type Affect
(Pleasant, Unpleasant) repeated measures ANOVAs. Results of the valence ANOVA
indicated a main effect for Type Affect (F(1,29) = 54.2, p<.001). Namely, unpleasant
pictures (X = 2.85, SD = 1.68) were rated as significantly more negative than the pleasant
pictures (X = 6.80, SD = 1.48). The Group X Type Affect interaction was not
significant, F(1,29) = 2.08, p = .16. Results of the ANOVA for the arousal ratings
revealed no significant main effects or interactions. Taken together, these findings
indicate that the pleasant and unpleasant pictures elicited ratings that differed in terms of
Table 3-1. Means and SDs of Pleasantness and Arousal Ratings for Unpleasant and
Unpleasant Pleasant Unpleasant Pleasant
Valence* Valence* Arousal~ Arousal~
PD Patients 2.57 (1.70) 7.14 (1.16) 5.22 (2.01) 6.10 (1.36)
Controls 3.24 (1.65) 6.32 (1.77) 5.78 (1.66) 5.47 (1.67)
* Valence ratings ranged from 1 (highly negative) to 9 (highly pleasant).
SArousal ratings ranged from 1 (low arousal) to 9 (high arousal)
valence. However, both the Controls and PD groups found the negative and positive
pictures to be similar in terms of how "arousing" they found them.
Threatening versus Other Unpleasant Pictures
A fourth set of analyses was conducted to examine subj ective ratings of the "threat"
and "other unpleasant" pictures by the Parkinson' s patients and Controls. The mean
valence and arousal ratings for these categories are shown in Table 3-1. As with the
analyses of subj ective ratings for pleasant and unpleasant pictures, two PD patients and
two controls were excluded from the analyses due to missing data. The valence ratings
and the arousal ratings were independently analyzed in separate Group X Type Affect
(Pleasant, Unpleasant) repeated measures ANOVAs. Results of the valence ANOVA
indicated a main effect for Type Affect, F(1,29) = 10.3, p<.005. Suprisingly, participants
subjectively found the "other unpleasant" pictures (X = 2.49, SD = 1.93) to be more
unpleasant than the "threatening" pictures (X = 3.11, SD = 1.62), even though both
groups showed greater startle eyeblink potentiation for the threatening pictures. The
Group X Type Affect interaction was not significant, F(1,29) = 0.308, p= .58. Results of
the ANOVA for the arousal ratings revealed no significant main effects or interactions.
Taken together, these findings indicate that both groups found the "other unpleasant"
pictures more unpleasant the "threat" pictures, although greater startle potentiation was
Table 3-2. Means and SDs of Pleasantness and Arousal Ratings for Threatening and
Other Unpleasant Pictures.
Threatening Other Unpleasant Threatening Other Unpleasant
Valence* Valence* Arousal+ Arousal+
PD Patients 2.86 (1.71) 2.16 (1.80) 5.42 (2.15) 4.94 (2.33)
Controls 3.45 (1.47) 2.95 (2.01) 5.76 (1.74) 5.80 (1.89)
* Valence ratings ranged from 1 (highly negative) to 9 (highly pleasant).
SArousal ratings ranged from 1 (low arousal) to 9 (high arousal)
demonstrated for "threat" pictures. However, participants did not find the two categories
of pictures to differ in terms of level of arousal they evoked.
Eyeblink Magnitude and BDI Correlations
A final set of analyses examined the relationship between emotional reactivity, as
indexed by startle magnitude, and scores on the Beck Depression Inventory. Although all
but two Parkinson' s patients and none of the Controls scored below the cutoff for Mild
Depression on the BDI, the PD patients did obtain significantly higher scores (X = 8.5)
than the Controls (X = 4.1). Thus, correlational analyses were performed in order to
learn whether BDI scores varied in any systematic way with emotional reactivity, as
indexed by startle. A "startle reactivity index score" was computed ([Unpleasant T-
score] [Pleasant T-score], see Chapter 2 for an explanation of this formula) to serve as a
measure of overall emotional reactivity. The Pearson's product-moment correlation
between this index score and the BDI score was nonsignifieant (r = -0. 167, p = .3 52).
Two control subjects were excluded from the analysis due to missing BDI scores. A
second correlational analysis was performed using an index score derived from the
"threat" and "other unpleasant" pictures (i.e., [Threat T-score] [Other Unpleasant] T-
score). The results of this analysis indicated that the Pearson' s correlation between this
difference score and BDI scores was again nonsignifieant (r = -0.304, p = .102). In
summary, these Eindings suggest that level of depressive symptomatology, as indexed by
the BDI, does not vary in any systematic fashion with emotional modulation of startle.
Next, correlational analyses were performed in the Parkinson's disease group to
examine the relationships among the Hoehn and Yahr stage (assessed while on
medication), UPDRS motor subscale score (assessed while on medication), duration of
illness, and BDI score. These analyses were performed in order to determine if severity or
duration of Parkinson' s disease is associated with depression symptomatology. The
correlations between these variables are displayed in Table 3-3. The correlation between
Hoehn and Yahr stage and BDI score was nonsignifieant (r = -.008, p > .97), as was the
correlation between number of years with Parkinson' s disease and BDI score (r = .089, p
> .62). However, UPDRS score and BDI score were significantly positively correlated,
r= .518, p < .05. Although the UPDRS and Hoehn and Yahr both measure level of motor
impairment, the UPDRS assesses impairment at the level of highly specific motor
symptoms and has a greater range of possible scores. This may be why a significant
correlation was found between the UPDRS and the BDI, but not Hoehn and Yahr Stage
and BDI. Finally, UPDRS score and Hoehn and Yahr stage were highly significantly
correlated in the positive direction (as would be expected since they both assess level of
motor impairment in the PD patient), r = 67, p < .005, and Hoehn and Yahr stage and
years with PD were significantly positively correlated, r = .44, p = .05. In sum, these
analyses demonstrate that a) degree of motor impairment (as assessed by Hoehn and Yahr
stage) increases with duration of illness; and b) greater motor limitation is associated with
greater depression severity.
Correlational analyses were also performed between the general index of startle
reactivity ([Unpleasant T-score] [Pleasant T-score]) and UPDRS motor subscale score,
Hoehn and Yahr stage, and years with PD in order to determine if severity or duration of
Parkinson's disease is associated with reduced startle reactivity. Hoehn and Yahr stage
and startle reactivity index were significantly negatively correlated, r = -0.70, p < .005, as
Table 3-3. Correlations Between Number of Years with Parkinson's Disease, BDI Score,
Hoehn and Yahr Stage, and UPDRS Motor Subscale Score.
Yrs. PD BDI Hoehn &Yahr UPDRS
Yrs. PD 1.00 0.089 0.444* 0.107
BDI -- 1.00 -.008 .518*
Hoehn & Yahr -- -- 1.00 .665**
UPDRS motor subcale -- -- -- 1.00
*. Correlation is significant at the .05 level (two-tailed).
**. Correlation is significant at the .01 level (two-tailed).
were number of years with illness and startle reactivity index, r = -0.36, p < .05.
Additionally, the correlation between UPDRS score and startle reactivity approached
significance, r = -0.48, p = .053. Taken together, these findings suggest that greater
motor impairment and longer disease duration in Parkinson's patients are associated with
reduced emotional reactivity, as indexed by startle modulation.
The present study sought to examine two hypotheses. The first hypothesis was that
Parkinson's patients would show diminished emotional reactivity to effectively valenced
pictures. This led to the specific prediction that PD patients would exhibit a significantly
smaller eyeblink magnitude than controls while viewing unpleasant slides, and a
significantly larger eyeblink magnitude than controls while viewing pleasant slides. This
prediction was based on previous findings that PD patients show reduced striatal
dopamine, which may affect dopamine-mediated limbic circuits; as well as amygdala
neuropathology, which may affect the amygdala' s modulation of the basic startle
response. The second hypothesis was that Parkinson's patients would exhibit greater
emotional blunting for threatening pictures, as opposed to other categories of negative
pictures. Specifically, it was predicted that PD patients would display a significantly
smaller eyeblink response than controls in response to threatening slides, whereas their
eyeblink responses during other unpleasant pictures would not differ from that of
controls. This prediction was based on the fact that the amygdala is known to play a key
role in responding to threatening stimuli, is implicated in fear-potentiated startle, and
exhibits pathology in PD patients.
Hypothesis 1 was partially supported by the data. Parkinson's patients exhibited
significantly smaller eyeblink responses than controls while viewing the unpleasant
pictures; however, their eyeblink responses during pleasant pictures did not differ from
those of controls. Thus, the PD patients demonstrated diminished emotional reactivity to
negatively valenced pictures but not positively valenced pictures.
Hypothesis 2 was also supported by the data. That is, PD patients exhibited
significantly smaller eyeblink responses while viewing threatening pictures relative to
controls. The patients and controls did not differ significantly with respect to eyeblink
responses during other types of unpleasant pictures.
In summary, PD patients demonstrated diminished emotional reactivity to
unpleasant pictures compared to healthy controls (as indexed by startle eyeblink
modulation), but did not differ from controls in terms of emotional reactivity to pleasant
pictures. Furthermore, this effect seems to be driven by the PD patients' diminished
emotional reactivity towards threatening stimuli specifically.
Basic Acoustic Startle in PD Patients
Before discussing some possible explanations for the present Eindings, an obvious
question concerns whether the Parkinson's patients might have a basic defect in startle
eyeblink reactivity per se. Conceivably, Parkinson's patients could have motor
abnormalities that might reduce or minimize the size of the eyeblink response itself.
This, in turn, would result in reduced size of startle eyeblink responses during negative
emotional pictures, giving rise to the impression of diminished emotional reactivity to
unpleasant and threatening stimuli. To explore this, it is necessary to look at past
research on the basic startle response in patients with Parkinson's disease. Vidailhet and
colleagues (1992) examined startle eyeblink responses elicited by an abrupt noise in
eleven patients with idiopathic PD and a group of controls. Both the magnitude of the
startle eyeblink response and the pattern of muscles recruited were similar in the PD
patients and controls. However, the latency of the eyeblink response was significantly
delayed in the Parkinson's patients. Similar findings were described by Koffer and
coworkers (2001). In contrast, Seignorel and colleagues (2003) found no significant
differences in either latency or magnitude of startle eyeblink responses in PD patients and
In the present study, basic startle data were available from ten controls and ten
Parkinson's patients. Basic startle eyeblink responses were obtained immediately prior to
presentation of the emotional pictures. These data consisted of twelve startle eyeblink
responses that had been elicited in response to a burst of white noise delivered through
headphones. The results of a one-way ANOVA revealed no significant differences
between the PD and Control groups in terms of latency to peak startle eyeblink, (F(1,18)
= 1.62, p >.20 [Control mean = 73.3 ms, SD = 8.27; PD mean = 66.9 ms, SD = 13.5]).
Similarly, there was no significant difference between the PD patients and Controls with
regard to the magnitude of the startle eyeblink response (F(1,18) = 2.50, p>. 10 [Control
mean = .0170 mV, SD = .009; PD mean = .0113 mV, SD = .008])
Taken together, some inconsistency exists with respect to latency of basic startle
eyeblink responses described in the literature. Some studies report slowed startle
eyeblink responses in Parkinson' s patients (Kofler et al., 2001; Vidailhet et al., 1992),
whereas others have found no difference between PD patients and Controls (Bowers,
Miller, Springer, Foote, & Okun, submitted; Seignorel et al., 2003). Importantly,
however, all studies are consistent with respect to magnitude of startle responses in
Parkinson patients and controls. Specifically, the PD patients appear normal with regards
to the absolute size of the startle eyeblink peak. This, of course, is the variable of interest
in the current study.
Possible Effects of Depression on the Present Findings
One possible explanation for the present findings is that the PD patients had
diminished potentiation of startle eyeblink in response to unpleasant pictures due to
depression and/or apathy. Every attempt was made to exclude PD patients that may be
depressed from the study by only including patients that did not meet criteria for Maj or
Depression. However, two of the twenty PD patients did meet criteria for "mild
depression" as determined by BDI score, and PD patients and controls did significantly
differ with respect to mean BDI scores. Another possibility is that some of the patients
may have experienced depression in the past and abnormal emotional reactivity may have
persisted (even though they were asymptomatic at the time of testing). Findings from a
recent study with depressed patients suggest that this is an unlikely explanation. Using
pictures from the International Affective Picture System, Allen and coworkers (Allen,
Trinder, & Brennan, 1999) found that moderate to severely depressed subjects (BDI
scores ranging from 19 to 29) showed normal emotional startle modulation. Patients who
were extremely depressed (i.e., BDI scores greater than 30) showed a larger startle
potentiation for pleasant versus unpleasant pictures (i.e., they responded to the pleasant
pictures as if they were aversive). Although this study involved a small sample size, it
suggests that abnormal startle modulation is not exhibited by depressed subj ects unless
they are severely depressed; furthermore, the pattern of startle potentiation found was
opposite to that of the current study. Namely, the PD patients in the present study
demonstrated normal startle modulation for pleasant pictures, but diminished startle
modulation for unpleasant pictures.
Similarly, the pattern of responding in the current study does not appear to be due
to a generalized apathy. Since apathy is the diminished reaction to all stimuli, both
positive and negative (Marin, 1996), one would expect a diminished reaction to
emotional pictures of all valence categories if apathy were indeed the driving force
behind the observed responses in PD patients. However, the present study did not
formally test level of apathy by use of standard scales, and thus this possibility cannot be
addressed by the current data.
The Role of the Amygdala in Response to Threatening/Fearful Stimuli
The Einding of reduced emotional responsivity to unpleasant pictures, and more
specifically, threatening pictures, is consistent with previous reports of pathological
changes in the amygdala of patients with Parkinson' s disease (Braak & Braak, 2000;
Harding et al., 2002; Ouchi et al., 1999). Several studies of patients with lesions that
include the amygdala have reported impaired identification of fear facial expressions
(Adophs et al. 1994, 1995; Calder et al. 1996; Young et al. 1995;). Additionally, fMRI
studies have found that the viewing of facial expressions of fear is associated with robust
amygdala activation (Breiter et al., 1996; Davidson & Irwin, 1999; Davis & Whalen,
2001; Morris et al., 1996; Whalen et al., 1998). Importantly, however, amygdala
activation is sometimes found for other negative facial expressions of emotion as well,
including disgust (Schienle et al., 2002) and anger (Tessitore et al., 2002). In an
experiment utilizing threatening pictures from the IAPS series (similar to the current
study), Hariri et al. (2003) found a significant bilateral amygdala BOLD response when
healthy subjects were asked to simply match a picture to a picture identical to it. In light
of this evidence implicating the amygdala in the processing of threatening stimuli, it is
possible that the PD patients in the present study suffer from significant amygdala
pathology that is causing a diminished emotional reactivity to threat-evoking stimuli. The
Parkinson's patients in the current study each received head MRI scans; however, at this
time volumetric measurements of the amygdala have not been performed, and thus this
prediction remains speculative. Additionally, Tessitore et al. (2001) have found evidence
that dopamine may modulate the functioning of the amygdala. The implication of this
finding with regards to the current study is that dopamine modulation of the amygdala
may be disrupted in PD patients due to loss of striatal dopamine.
An alternative or additional explanation for the current findings is that reduced
dopaminerigic innervation (i.e., nigrostriatal, mesolimbic, and/or mesocortical) in PD
patients may be disrupting the neural circuitry involved in emotion processing. Although
the patients in the present study were tested while on dopaminergic medication, it is
unlikely that this makes them similar to healthy people with respect to dopamine levels.
For example, Ouchi and coworkers (1999) found a reduction of dopamine (DA) agonist
binding in the amygdala, striatum, and orbitofrontal cortex of unmedicated PD patients.
The authors suggested that this might be due to a loss of presynaptic DA terminals in
these regions. To relate this back to the present study, a loss of dopaminergic terminals
would decrease levadopa binding in the medicated patients, leaving them with
abnormally low DA levels even when on medication. Additionally, the results from
Ouchi and colleagues' laboratory suggest an alteration in the mesocortical, mesolimbic,
and striato-thalamo-cortico orbitofrontal dopaminergic systems' functioning in PD
patients. As mentioned previously, these are circuits thought to be involved in emotional
Dissociation of Subjective Ratings and Physiological Response
Interestingly, although the PD patients showed diminished modulation of startle in
response to negative stimuli (particularly threatening stimuli) compared to controls, the
two groups did not differ with respect to their subj ective ratings of valence and arousal
levels in response to the pictures. Although the literature is sparse, there is evidence that
decouplingg" of subj ective emotional experience and physiological response can occur in
patients following brain damage. For example, a dissociation between skin conductance
responses (SCRs) and verbal report during anticipatory anxiety of electric shock was
reported by Slomine et al. (1999). Patients with both right and left hemisphere brain
damage exhibited smaller SCRs than healthy controls while anticipating the shock, yet all
groups reported feeling less pleasant, less in control, and more aroused while awaiting
shock as opposed to during a no-shock condition. In contrast, Meadows & Kaplan (1994)
reported that patients with right hemisphere damage showed diminished SCRs to
emotional and neutral slides relative to controls, while patients with left hemisphere brain
damage exhibited increased SCRs to both emotional and neutral slides. The groups did
not differ with respect to subj ective ratings of the slides, or in orienting and habituation to
Decoupling of physiological and subj ective emotional responses in Parkinson' s
disease patients has not been discussed in the literature, and is certainly an area towards
which future research should be directed. Although the mechanism underlying this
decouplingg" is unknown, one possibility is that subj ective emotional experience
typically incorporates feedback from the body's physiological pattern of response. In
Parkinson's disease as well as other neurological disorders, brain abnormalities can cause
a functional disconnect between the two (Slomine et al., 1999). Alternatively, it may be
that patients know the typical valence rating that is expected from them for each slide
(i.e., mutilation pictures should be rated as very unpleasant, puppies as pleasant) and are
conforming to experimenter demand characteristics.
Limitations of the Present Study
Several limitations of the current study must be acknowledged. First, the study
suffers from a small sample size, and thus it is uncertain whether these findings would be
replicated in a larger sample. Secondly, women and men were included together,
although men and women are generally regarded as responding to emotional stimuli
differently, and expressing emotional reactivity to different degrees.' The study also
utilized a rather homogeneous sample of Parkinson patients who were highly educated
and who had moderate motor impairments (mean Hoehn-Yahr stage of 2.7). Further
research is needed to determine whether the same pattern of affective startle modulation
exits in patients with milder or more severe PD.
Turning to a methodological critique of the study, one limitation is the fact that the
analysis of eyeblink magnitude to threatening versus other types of fearful stimuli was
conducted post-hoc. Thus, the original set of forty-four pictures was designed to measure
emotional reactivity to neutral, pleasant, and unpleasant stimuli; later, pictures depicting
imminent attack were grouped together and labeled as "threatening," and all other
remaining unpleasant pictures were grouped together and labeled "other unpleasant
pictures." Ideally, a larger sample of pictures should be used, expressing a variety of
threatening situations, and designed explicitly to assess startle modulation during viewing
of threatening stimuli versus other specific types of aversive stimuli (for example,
SHowever, separate t-tests conducted on PD and control data yielded no significant differences between
men and women for unpleasant or pleasant blink magnitudes (controls unpleasant: t(13) = -0.038, p >.9;
controls pleasant: t(13) = 0.31, p > .7; PD unpleasant: t(18) = -0.089, p > .9; PD pleasant: t(18) = 0.56, p >
Another limitation of the current study is that startle eyeblink modulation to
unpleasant and pleasant stimuli was assumed to reflect emotional reactivity to the valence
of the pictures. However, the arousal level of a picture also affects startle modulation by
intensifying the magnitude of the eyeblink in the direction of the individual's
motivational activation (i.e., appetitive/pleasant or defensive/unpleasant). Namely, the
more arousing an unpleasant picture is to a participant, the greater the startle potentiation.
Similarly, the more arousing a pleasant picture is to a participant, the more attenuated the
startle eyeblink (Bradley, Codispoti, Cuthbert, & Lang, 2001). It may be that Parkinson's
patients display an overall pattern of "hypoarousal" in response to emotional materials. If
this is true, than Parkinson's patients might have shown a smaller difference between
unpleasant and pleasant picture eyeblink magnitudes relative to controls because they did
not exhibit a level of arousal that would serve to intensify the magnitude of their eyeblink
in line with the direction of the picture valence. Although PD patients reported
experiencing levels of arousal equivalent to those of Controls, they also rated picture
valences similar to Controls, suggesting that their subjective experience and physiologic
reactions are not necessarily congruent. Thus, the possibility that the findings of the
current study were due to a general diminished psychophysiologic reactivity to emotional
material in Parkinson's patients cannot be ruled out.
A further limitation is that analyses in the present study used T-scores, as opposed
to raw eyeblink magnitudes, as a way to measure emotional startle modulation. This was
done to minimize individual differences in eyeblink magnitude modulation, such that all
subjects could be compared on a common metric. However, it is possible that converting
raw scores to T-scores could obscure differences between the PD group and Controls. In
the future, raw startle data should be analyzed as well, to check that it exhibits the same
pattern as the transformed data.
Finally, the current study did not use a manipulation check to determine whether
participants subj ectively felt threatened during presentation of slides categorized as
"threatening." Although PD patients did exhibit diminished startle eyeblink potentiation
for threatening pictures compared to controls, this assumes that threat was indeed the
emotion subj ectively experienced by participants, which may or may not have been the
case. This issue is further confounded by the fact that both groups rated the "other
unpleasant stimuli" as being more unpleasant than the "threatening" stimuli, yet they
displayed larger eyeblink potentiation during viewing of the threatening pictures.
Directions for Future Research
Future directions for research include an exploration as to whether different
subtypes of PD are associated with differential patterns of affective startle eyeblink
modulation. For example, some researchers classify PD patients as either akinetic/rigid
or tremor predominant, depending on the key symptoms of the individual patient
(Ransmayr, Poewe, Ploerer, Birbamer, & Gerstenbrand, 1987; Ransmayr, Poewe, Plorer,
Gerstenbrand, Leidlmair, & Mayr, 1986). It is thought that the akinetic/rigid type
involves greater involvement of the mesolimbic and mesocortical pathways, and thus
these patients may display more aberrant patterns of startle modulation. The emotional
modulation of startle paradigm could also be used in different groups of patients with
basal ganglia disorders, such as those with essential tremor, Progressive Supranuclear
Palsy, and Huntington's Disease, as a way to measure emotional reactivity in these
patient groups without the confounding variable of motor output abnormalities. It may be
that disorders that often appear clinically similar on the behavioral level (such as essential
tremor and PD) may be distinguished from one another by their pattern of emotional
Another important future line of research will be to determine if diminished
reactivity to threatening pictures correlates with measures of amygdala pathology, such as
decreased amygdala volume or decreased BOLD signal (relative to controls) during fMLRI
with concurrent presentation of threatening pictures. The results of the current study,
supported by past literature, suggest that reduced emotional reactivity to threatening
stimuli may be linked to amygdala abnormalities, but this hypothesis is purely
speculative as of now. Additionally, PD patients should be tested off their dopaminergic
medications using the emotional startle modulation paradigm, in order to determine how
dopamine levels affect emotional reactions as assessed by the startle paradigm.
An idea for a future study might include threatening pictures from the IAPS series
intermixed with disgusting pictures. Previous investigators have used pictures such as
body excrement, food contamination, and unsanitary conditions in an attempt to evoke
disgust in participants (e.g., Schienle et al., 2002; Shapira et al., 2003;). Studies have
implicated several structures that are part of the nigrostriatal loop affected in PD as being
involved in the recognition of disgust. For example, in an fMLRI study, Sprengelmeyer
and coworkers (1998) found that viewing pictures of facial expressions of disgust caused
activation of the left anterior insula, right anterior globus pallidus, and putamen in
healthy subjects. Activation of the left anterior insula, bilateral putamen, and right globus
pallidus and caudate nucleus was reported by Phillips et al. (1997), who presented images
of faces depicting different degrees of disgust intensity to normal controls. As such, one
might predict that PD patients presented with disgust-evoking pictures would exhibit
diminished startle potentiation, much as they displayed a diminished startle potentiation
in response to threat-evoking stimuli in the present study.
To conclude, the Einding of reduced emotional reactivity to negative stimuli in PD
patients, and threatening stimuli specifically, does not appear to be an artifact of a motor
output problem or depressive symptomatology. For these reasons, it offers a unique
advantage compared to other measures of emotionality in PD (such as facial expressivity
or vocal prosody), which are wrought with the confounding problem that these
movements may be affected by the motor symptoms of PD. Furthermore, the acoustic
startle is an involuntary physiological reaction that is very difficult, if not impossible, to
inhibit or voluntarily control, and thus does not rely on the participant' s attention or
motivation (Bradley, 2000). These characteristics make measurement of affective
modulation of eyeblink amplitude a paradigm that may afford a purer, more obj ective
method of exploring emotional reactivity in patients with basal ganglia disorders.
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, H., & Damasio, A. (1994). Impaired recognition of
emotion in facial expressions following bilateral damage to the human amygdala.
Nature, 372(6507), 669-772.
Adolphs, R., Tranel, D., Damasio, H., & Damasio, A.R. (1995). Fear and the human
amygdala. The Journal ofNeuroscience, 15, 5879-5892.
Alexander, G.E., DeLong, M.R., & Strick, P.L. (1986). Parallel organization of
functionally segregated circuits linking basal ganglia and cortex. Annual Review of
Neuroscience, 9, 3 57-3 81.
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.
Beck, A.T. (1978). Beck depression inventory. San Antonio, TX: The Psychological
Beck, A.T., Steer, R.A., & Brown, G.K. (1996). Beck depression inventory-Second
edition manual. 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.
Blender, 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., & Diller,
L. (1990). Parameters of emotional processing in neuropsychiatric disorders:
Conceptual issues and a battery of tests. Journal of Conanunication Disorders, 23,
Bowers, D., Bosch, W., Gokcay, D., Peden, C., Pedraza, O., Miller, K., Bongiolatti, S.,
Springer, U., Okun, M. (in press). Faces of emotion in Parkinson's disease: Micro-
expressivity and bradykinesia during voluntary facial expressions. Journal of
Bowers, D. Gilmore, R. Bauer, R., Rogish, M., Kortenkamp, S., Gokay, D., Bradley, M.
& Roper, S. (1998, November) Affect modulation of startle is disrupted by right,
but not left, temporal resections involving the amygdala. Poster session presented at
the meeting of the Society for Neuroscience, Los Angeles, 1998.
Bowers, D., Miller, K., Springer, U., Foote, K., Okun, M. (2003). Startling facts about
emotion in ParkinsonP~~PPP~~~PP~~~PP 's disease. Manuscript submitted for publication.
Braak, H., & Braak, E. (2000). Pathoanatomy of Parkinson' s 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 ofpsychophysiology. New York, NY: Cambridge
Bradley, M.M., Codispoti, M., Cuthbert, B.N., & Lang, P.J. (2001). Emotion and
motivation I: Defensive and appetitive reactions in picture processing. Emotion,
Bradley, M.M., Cuthbert, B.N., & Lang, P.J. (1990). Startle reflex: Emotion or attention?
Psychophysiology, 27, 513-522.
Bradley, M.M., Cuthbert, B.N., & Lang, P.J. (1991). Startle and emotion: Lateral acoustic
probes and the bilateral blink. Psychophysiology, 28, 285-295.
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.
Breiter, H.C., Etcoff, N.L., Whalen, P.J., Kennedy, W.A., Rauch, S.L., Buckner, R.L.,
Strauss, M.M., Hyman, S.E., & Rosen, B.R. (1996). Response and habituation of
the human amygdala during visual processing of facial expression. Neuron, 1 7,
Brown, R.G., & Marsden, C.D. (1984). How common is dementia in Parkinson's
disease? Lancet, 2, 1262-1265.
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. M~ovenzentDisorders, 1 7(3), 445-
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.
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.
Cummings, J.L. (1992). Depression and Parkinson's disease: A review. American
Journal ofPsychiatry, 149, 443-454.
Davidson, R.J., Irwin, W. (1999). The functional neuroanatomy- of emotion and affective
style. Trends in Cognitive Science, 3(1), 11-21.
Davis, M. (1992). The role of the amygdala in conditioned fear. In J. Aggleton (Ed.), The
anzygdala: Neurobiological aspects of emotion, zentory, and mental dys~i~nction
(pp. 255-305). New York, NY: Wiley Publishers.
Davis, M., Genderlman, D.S., Tischler, M.D., & Gendelman, P.M. (1982). A primary
acoustic startle circuit: lesion and stimulation studies. Journal ofNeuroscience,
Davis, M., Whalen, P.J. (2001). The amygdala: Vigilance and emotion. Molecular
Psychiatry, 6(1), 13-34.
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.
Fahn, S. (2003). Description of Parkinson's disease as a clinical syndrome. AnnualNew
York Academy ofSciences, 991, 1-14.
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 ParkinsonPP~~~PPP~~~PPP~~'s
disease, Voumle 2 (pp. 153-163). Florham Park, NJ: Macmillan Healthcare
Folstein, M.F., Folstein, S.E., & McHugh, P.R. (2001). M~ini-M~entalstate examination.
Odessa, FL: Psychological Assessment Resources.
Gauntlett-Gilbert, J., Roberts, R.C., Brown, V.J. (1999). Mechanisms underlying
attentional set-shifting in Parkinson's disease. Neuropsychologia, 37, 605-616.
Greenwald, M., Cook, E., & Lang, P. (1989). Affective judgment and
psychophysiological response dimensional covariation in the evaluation of pictorial
stimuli. Journal ofPsychophysiology, 3, 51-64.
Grillon, C., Ameli, R., Foot, M., & Davis, M. (1993). Fear-potentiated startle:
Relationship to the level of state/trait anxiety in healthy subj ects. Biological
Psychiatry, 33(8-9), 566-574.
Grillon, C., Ameli, R., Woods, S.W., Merikangas, K., & Davis, M. (1991). Fear-
potentiated startle in humans: Effects of anticipatory anxiety on the acoustic blink
reflex. Psychophysiology, 28(5), 588-595.
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,
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.
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 ofNeurology, Neurosurgery, and Psychiatry, 55, 181-184.
Isella, V., Melzi, P., Grimaldi, M., lurlaro, S., Piolti, R., Ferrarese, C., Frattola, L., &
Appollonio, I. (2002). Clinical, neuropsychological, and morphometric correlates
of apathy in Parkinson' s disease.M2ovement Disorders, 1 7(2), 366-371.
Jacobs, D.H., Shuren, J., Bowers, D., & Heilman, K.M. (1995). Emotional facial
imagery, perception, and expression in Parkinson's disease. Neurology, 45, 1696-
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.
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, andPsychiatry, 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 and
Mental Disease, 1 79(1 1), 683-688.
Kltiver, H., & Bucy, P.C. (1939). Preliminary analysis of the temporal lobes in monkeys.
Archives ofNeurology and Psychiatry, 42, 979-1000.
Koffer, M., Muller, J., Wenning, G.K. Reggiani, L., Hollosi, P., Bosch, S., Ransmayr,
G., Valls-Sole, J., & Poewe, W. (2001). The auditory startle reaction in
parkinsonian disorders. Movement Disorders, 16(1), 62-71.
Lang, P.J. (1980). Behavioral treatment and biobehavioral assessment: Computer
applications. In J.B. Sidowski, J.H. Johnson, & T.A. Williams (Eds.). Technology
in nzental health care delivery. Norwood, NJ: Albex Publishing Corp.
Lang, P.J., Bradley, M.M., & Cuthbert, B.N. (1990). Emotion, attention, and the startle
reflex. Psychological Review, 9 7(3), 3 77-3 95.
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. (2001Ib). International affective picture system
(IAPS): Instruction manual and affective ratings: Technical Report A-5.
Gainesville, FL: The Center for Research in Psychophysiology, University of
Lang, A.E, & Lozano, A.M. (1998). Parkinson's disease: First of two parts. The New
Englan2dJournal of2~edicine, 339(15), 1044-1053.
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.
Marin, R.S., (1996). Apathy: Concept, syndrome, neural mechanisms, and treatment.
Seminars in Clinical Neuropsychiatry, 1, 3 04-3 14.
Mayberg, H.S., Starkstein, S.E., Sadzot, B., Preziosi, T., Andrezejewski, P.L., Dannals,
R.F., Wagner, H.N. Jr., & Robinson R.G. (1990). Selective hypometabolism 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, and
treatment of depression in Parkinson's disease. Biological Psychiatry, 54(3), 363-
Meadows, M.E., & Kaplan, R.F. (1994). Dissociation of autonomic and subj ective
responses to emotional slides in right hemisphere damaged patients.
Neuropsychologia, 32(7), 847-56.
Morris, J.S., Frith, C.D., Perrett, D.I., Rowland, D., Young, A.W., Calder, A.J., & Dolan,
R.J. (1996). A differential neural response in the human amygdala to fearful and
happy facial expressions. Nature, 383, 812-815.
National Institute of Neurological Disorders and Stroke (2001, July 1). Parkinson's
disease backgrounder. Retrieved February 9, 2004, from
p arki nson' s_di seas e~backgrounder. htm
O'Gorman, J.R. (1990). Individual differences in the orienting response: Nonresponding
in nonclinical samples. Pavlovian Journal of Biological Science, 25(3), 104-108.
Ouchi, Y., Yoshikawa, E., Okada, H., Futatsubashi, M., Sekine, Y., lyo, 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 P-CFT binding with positron emission tomography. Annals of
Neurology, 45, 601-610.
Peto, V., Jenkinson, C., & Fitzpatrick, R. (1998). PDQ-39: A review of the development,
validation and application of a Parkinson's disease quality of life questionnaire and
its associated measures. Journal ofNeurology, 245(Supplement 1): S10-S14.
Phillips, M.L., Young, A.W., Scott, S.K., Calder, A.J., Andrew, C., Giampietro, V.,
Williams, S.C.R., Bullmore, E.T., Brammer, M., & Gray, J.A. (1998). Neural
responses to facial and vocal expressions of fear and disgust. Proceedings of the
Royal Society ofLondon, Series B: Biological sciences, 265, 1809-18 17.
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
Ransmayr, G., Poewe, W., Ploerer, S., Birbamer, G., & Gerstenbrand, F. (1987).
Psychometric findings in clinical subtypes of Parkinson's disease. Advances in
Neurology, 45, 409-411.
Ransmayr, G., Poewe, W., Plorer, S., Gerstenbrand, F., Leidlmair, K., & Mayr, U.
(1986). Prognostic implications of the motor symptoms of Parkinson's disease with
respect to clinical, computertomographic and psychometric parameters. Journal of
Neural Transmission, 67(1-2), 1-14.
Rosen, J.B., & Davis, M. (1988). Enhancement of acoustic startle by electrical
stimulation of the amygdala. Behavioral Neuroscience, 102(2), 195-202, 324.
Rosen, J.B., Hitchcock, J.M., Miserendino, M.J., Falls, W.A., Campeau, S., & Davis, M.
(1992). Lesions of the perirhinal cortex but not of the frontal, medial prefrontal,
visual, or insular cortex block fear-potentiated startle using a visual conditioned
stimulus. Journal ofNeuroscience, 12(12), 4624-4633.
Schienle, A., Stark, B., Walter, C., Blecker, U., Ott, P., Kirsch, G., Sammer, G., & Vaitl,
D. (2002). The insula is not specifically involved in disgust processing: A fMLRI
study. Neuroreport, 13, 2023-2026.
Schwab, J.F., & England, A.C. (1969). Unified Parkinson's disease rating scale version
3.0 Schwab and England activities of daily living scale. In F.J. Gillingham & M.C.
Donaldson (Eds.): Third Symposium on Parkinson'sPP~~PP~~~PP~~PP Disease (pp. 152-157).
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.
Seignorel, P., Miller, K., Bowers, D., Okun, M. (2003, October). Startle responses in
patients nI ithr psychogenic movement disorders. Presented at the Psychogenic
Movement Disorders Workshop of the Movement Disorder Society, Atlanta, GA.
Shapira, N.A., Liu, Y., He, A.G., Bradley, M.M., Lessig, M.C., James, G.A., Stein, D.J.,
Lang, P.J., & Goodman, W.K. Brain activation by disgust-inducing pictures in
obsessive-compulsive disorder. Biological Psychiatry, 54(7), 751-756.
Slomine, B., Bowers, D., & Heilman, K.M. (1999). Dissociation between autonomic
responding and verbal report in right and left hemisphere brain damage during
anticipatory anxiety. Neuropsychiatry, Neuropsychology, and Behavioral
Neurology, 12(3), 143-148.
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.
Sprengelmeyer, R., Rausch, M., Eysel, U.T., & Przuntek, H. (1998). Neural structures
associated with recognition of facial expressions of basic emotions. Proceedings of
the Royal Society ofLondon, Series B: Biological sciences, 265, 1927-193 1.
Sprengelmeyer, R., Young, A.W., Mahn, K., Schroeder, U., Woitalla, D., Biittner, T.,
Kuhn, W., & Przuntek, H. (2003). Facial expression recognition in people with
medicated and unmedicated Parkinson's disease. Neuropsychologia, 41, 1047-
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,
Tessitore, A., Hariri, A.R., Fera, F., Smith, W.G., Chase, T.N., Hyde, T.M., Weinberger,
D.R.,& Mattay, V. S. (2002). Dopamine modulates the response of the human
amygdala: A study in Parkinson's disease. The Journal ofNeuroscience, 22(20),
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.
Walker, D.L., & Davis, M. (2002). The role of amygdala glutamate receptors in fear
learning, fear-potentiated startle, and extinction. Pharmacology, Biochemistry, and
Behavior, 71, 379-392.
Whalen, P.J., Rauch, S.L, Etcoff, N.L., McInerney, S.C., Lee, M.B., & Jenike, M.A.
(1998). Masked presentations of emotional facial expressions modulate amygdala
activity without explicit knowledge. Journal ofNeuroscience, 18, 411-418.
Yip, J.T.H., Lee, T.M.C., Ho, S.-L., Tsang, K.-L., & Li, L.S.W. (2003). Emotion
recognition in patients with idiopathic Parkinson's disease. Movement Disorders,
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.
Zgaljardic, D.J., Borod, J.C., Foldi, N.S., & Mattis, P. (2003). A review of the cognitive
and behavioral sequelae of Parkinson' s disease: Relationship to frontostriatal
circuitry. Cognitive and Behavioral Neurology, 16(4), 193-210.
Kimberly Miller was born in San Jose, CA, and received her B.A. in psychology
from the University of California, Berkeley. After gaining research experience in
cognitive neuroscience at the Martinez V.A., she moved to Gainesville to pursue her
doctorate in clinical psychology at the University of Florida, specializing in
neuropsychology. Current clinical interests include learning disorders and speech and
language disorders. Current research interests include the affective modulation of startle
in chronically depressed patients, as well as the effect of psychiatric disorders on