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Effects of Distracter Novelty on Attentional Orienting in Healthy Aging and Parkinson's Disease

Permanent Link: http://ufdc.ufl.edu/UFE0022707/00001

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Title: Effects of Distracter Novelty on Attentional Orienting in Healthy Aging and Parkinson's Disease An Event-Related Potential (ERP) Study
Physical Description: 1 online resource (105 p.)
Language: english
Creator: Stigge-Kaufman, David
Publisher: University of Florida
Place of Publication: Gainesville, Fla.
Publication Date: 2009

Subjects

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

Notes

Abstract: Novel events are preferentially processed in the brain in order to facilitate adaptive responses to a dynamic, changing world. However, much is still unknown about the mechanisms that give rise to attentional orienting toward novel events in the brain. Healthy aging and Parkinson?s disease (PD) have been previously associated with deficits in novelty processing, which is mediated by neural networks that give rise to preferential processing for novel distracters. In order to better characterize the nature of these attentional mechanisms, two event-related potential (ERP) experiments were conducted in young adults, older adults, and PD patients. The experiments manipulated the novelty characteristics of task-irrelevant distracters that were presented in the context of a three-stimulus oddball task. This task allowed for the examination of both distracter- and target-related processing as a function of distracter novelty. As expected, novel distracters differentially engaged the visual attention system in ways that were not seen for non-novel distracters. However, older adults and PD patients showed impairments in their attentional orienting responses toward novel stimuli. These deficits in distracter processing were associated with a number of other cognitive and emotional symptoms, and further gave rise to impairments in target-related processing. Notably, older adults and PD patients exhibited weaker processing of attentional targets and a frontal shift in their ERP reflections of target processing, which is consistent with a frontally-mediated deficit in memory updating for the targets. Taken together, the results of these experiments provide strong evidence that novel events receive preferential neural processing in ways that are influenced by the stimulus features that characterize the event, as well as the functional integrity of specialized attentional orienting networks in the brain. Older adults and PD patients appear to be less engaged with new information, yet more susceptible to the interfering effects of novel distracters. These findings help to clarify the ways in which stimulus characteristics affect attentional orienting to unexpected events, along with the impacts that healthy aging and PD have on this process.
General Note: In the series University of Florida Digital Collections.
General Note: Includes vita.
Bibliography: Includes bibliographical references.
Source of Description: Description based on online resource; title from PDF title page.
Source of Description: This bibliographic record is available under the Creative Commons CC0 public domain dedication. The University of Florida Libraries, as creator of this bibliographic record, has waived all rights to it worldwide under copyright law, including all related and neighboring rights, to the extent allowed by law.
Statement of Responsibility: by David Stigge-Kaufman.
Thesis: Thesis (Ph.D.)--University of Florida, 2009.
Local: Adviser: Perlstein, William.
Electronic Access: RESTRICTED TO UF STUDENTS, STAFF, FACULTY, AND ON-CAMPUS USE UNTIL 2011-08-31

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Source Institution: UFRGP
Rights Management: Applicable rights reserved.
Classification: lcc - LD1780 2009
System ID: UFE0022707:00001

Permanent Link: http://ufdc.ufl.edu/UFE0022707/00001

Material Information

Title: Effects of Distracter Novelty on Attentional Orienting in Healthy Aging and Parkinson's Disease An Event-Related Potential (ERP) Study
Physical Description: 1 online resource (105 p.)
Language: english
Creator: Stigge-Kaufman, David
Publisher: University of Florida
Place of Publication: Gainesville, Fla.
Publication Date: 2009

Subjects

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

Notes

Abstract: Novel events are preferentially processed in the brain in order to facilitate adaptive responses to a dynamic, changing world. However, much is still unknown about the mechanisms that give rise to attentional orienting toward novel events in the brain. Healthy aging and Parkinson?s disease (PD) have been previously associated with deficits in novelty processing, which is mediated by neural networks that give rise to preferential processing for novel distracters. In order to better characterize the nature of these attentional mechanisms, two event-related potential (ERP) experiments were conducted in young adults, older adults, and PD patients. The experiments manipulated the novelty characteristics of task-irrelevant distracters that were presented in the context of a three-stimulus oddball task. This task allowed for the examination of both distracter- and target-related processing as a function of distracter novelty. As expected, novel distracters differentially engaged the visual attention system in ways that were not seen for non-novel distracters. However, older adults and PD patients showed impairments in their attentional orienting responses toward novel stimuli. These deficits in distracter processing were associated with a number of other cognitive and emotional symptoms, and further gave rise to impairments in target-related processing. Notably, older adults and PD patients exhibited weaker processing of attentional targets and a frontal shift in their ERP reflections of target processing, which is consistent with a frontally-mediated deficit in memory updating for the targets. Taken together, the results of these experiments provide strong evidence that novel events receive preferential neural processing in ways that are influenced by the stimulus features that characterize the event, as well as the functional integrity of specialized attentional orienting networks in the brain. Older adults and PD patients appear to be less engaged with new information, yet more susceptible to the interfering effects of novel distracters. These findings help to clarify the ways in which stimulus characteristics affect attentional orienting to unexpected events, along with the impacts that healthy aging and PD have on this process.
General Note: In the series University of Florida Digital Collections.
General Note: Includes vita.
Bibliography: Includes bibliographical references.
Source of Description: Description based on online resource; title from PDF title page.
Source of Description: This bibliographic record is available under the Creative Commons CC0 public domain dedication. The University of Florida Libraries, as creator of this bibliographic record, has waived all rights to it worldwide under copyright law, including all related and neighboring rights, to the extent allowed by law.
Statement of Responsibility: by David Stigge-Kaufman.
Thesis: Thesis (Ph.D.)--University of Florida, 2009.
Local: Adviser: Perlstein, William.
Electronic Access: RESTRICTED TO UF STUDENTS, STAFF, FACULTY, AND ON-CAMPUS USE UNTIL 2011-08-31

Record Information

Source Institution: UFRGP
Rights Management: Applicable rights reserved.
Classification: lcc - LD1780 2009
System ID: UFE0022707:00001


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1 EFFECTS OF DISTRACTER NOV ELTY ON ATTENTIONAL ORIENTING IN HEALTHY AGING AND PARKINSONS DISEASE: AN EVENT-RELATED POTENTIAL (ERP) STUDY By DAVID ANDREW STIGGE KAUFMAN A DISSERTATION PRESENTED TO THE GRADUATE SCHOOL OF THE UNIVERSITY OF FLOR IDA IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY UNIVERSITY OF FLORIDA 2009

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2 2009 David Andrew Stigge Kaufman

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3 ACKNOWLEDGMENTS I wish to acknowledge my chair and ment or, William M. Perlstein, Ph.D. for his professional mentorship and enthusia stic support of this project. I also wish to express gratitude to my other dissertation committee members, Dawn Bowers, Ph.D., David Loring, Ph.D., Lori Altmann, Ph.D., and Christina McCrae, Ph.D., for th eir constructive feedback. I would also like to thank Michelle Blanco and Allen Sirizi for their assistance with participant recruitment and data collection. This research was supported by a pre-doctoral National Institute of Health Fellowship, #T32 AG020499.

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4 TABLE OF CONTENTS page ACKNOWLEDGMENTS...............................................................................................................3 LIST OF TABLES................................................................................................................. ..........6 LIST OF FIGURES................................................................................................................ .........8 ABSTRACT....................................................................................................................... ............10 CHAPTER 1 GENERAL INTRODUCTI ON AND METHODS................................................................12 General Introduction........................................................................................................... ....12 Scalp-Recorded Event-Rela ted Potentials (ERPs)..........................................................13 Novelty Processing and the P300....................................................................................14 Novelty Processing and the N2.......................................................................................16 Novelty Processing and Ea rly Sensory Potentials...........................................................17 A Neuroanatomical Model of Attentional Orienting.......................................................18 Summary and Implications of Novelty Processing.........................................................20 ERP Studies of Novelty in Healthy Aging......................................................................21 ERP Studies of Novelty in Parkinsons Disease.............................................................23 Summary and Rationale for the Current Project.............................................................25 General Methods................................................................................................................ .....27 ERP Stimuli and Task.....................................................................................................27 Neuropsychological Measures.........................................................................................28 Emotional Measures........................................................................................................29 EEG Acquisition and Reduction.....................................................................................29 Data Analysis.................................................................................................................. .31 2 EXPERIMENT 1: THE IMPACT OF HEALTHY AGING ON PREFERENTIAL NOVELTY PROCESSING....................................................................................................37 Overview and Predictions.......................................................................................................37 Methods........................................................................................................................ ..........38 Participants................................................................................................................... ...38 Procedures..................................................................................................................... ..38 Results........................................................................................................................ .............38 Behavioral Data...............................................................................................................38 Oddball task performance........................................................................................38 Cognitive and emotional functioning.......................................................................39 Event-Related Potential Data..........................................................................................39 SN component..........................................................................................................40 P2 component...........................................................................................................40 N2 component..........................................................................................................41

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5 P3 component...........................................................................................................42 Difference waves......................................................................................................43 Relationship with neuropsychological performance................................................44 Discussion..................................................................................................................... ..........45 3 EXPERIMENT 2: THE IMPACT OF PARKINSONS DISEASE ON PREFERENTIAL NOVELTY PROCESSING......................................................................63 Overview and Predictions.......................................................................................................63 Methods........................................................................................................................ ..........64 Participants................................................................................................................... ...64 Procedures..................................................................................................................... ..65 Results........................................................................................................................ .............65 Behavioral Data...............................................................................................................65 Oddball task performance........................................................................................65 Cognitive and emotional functioning.......................................................................66 Event-Related Potential Data..........................................................................................66 SN component..........................................................................................................66 P2 component...........................................................................................................67 N2 component..........................................................................................................68 P3 component...........................................................................................................68 Difference waves......................................................................................................69 Relationship with neuropsychological performance................................................69 Discussion..................................................................................................................... ..........71 4 GENERAL DISCUSSION.....................................................................................................91 LIST OF REFERENCES............................................................................................................. ..97 BIOGRAPHICAL SKETCH.......................................................................................................105

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6 LIST OF TABLES Table page 2-1 Mean and standard deviation ( SD ) demographic and neuropsychological data for young and older participants..............................................................................................49 2-2 Mean reaction time and accuracy data from the oddball task............................................50 2-3 Peak amplitudes (V) from young participan ts for each stimulus type across novel and non-novel distra cter blocks.........................................................................................50 2-4 Peak latencies (ms) from young participants for each stimulus type across novel and non-novel distracter blocks................................................................................................51 2-5 Peak amplitudes (V) from older particip ants for each stimulus type across novel and non-novel distra cter blocks.........................................................................................52 2-6 Peak latencies (ms) from older participan ts for each stimulus type across novel and non-novel distracter blocks................................................................................................53 2-7 Summary of the 2-Group x 3-Stimulus x 3-Site x 2-Distract er ANOVAs performed on P3 peak amplitude data.................................................................................................53 2-8 Summary of the 2-Group x 3-Stimulus x 3-Site x 2-Block ANOVAs performed on P3 peak latency data...........................................................................................................54 2-9 Significant correlations between P3 di fference waves and neuropsychological measures for young and older groups combined...............................................................54 2-10 Summary of hierarchical regr ession analysis for variables predicting the amplitude of the target-standard difference wave from novel distracter trials.......................................55 2-11 Summary of hierarchical regression analysis for variables predicting the amplitude of the target-standard difference wave from non-novel distracter trials................................55 3-1 Mean and standard deviation ( SD ) demographic and neuropsychological data for controls and PD participants..............................................................................................75 3-2 Behavioral data fr om the oddball task...............................................................................76 3-3 Peak amplitudes (V) from the control gr oup for each stimulus type across novel and non-novel distracter blocks................................................................................................76 3-4 Peak amplitudes (V) from PD patients for each stimulus type across novel and nonnovel distracter blocks.......................................................................................................77 3-5 Peak latencies (ms) from controls for each stimulus type across novel and non-novel distracter blocks.............................................................................................................. ...78

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7 3-6 Peak latencies (ms) from PD patients for each stimulus type across novel and nonnovel distracter blocks.......................................................................................................79 3-7 Summary of the 2-Group x 3-Stimulus x 3-Site x 2-Distract er ANOVAs performed on P3 peak amplitude data.................................................................................................79 3-8 Summary of the 2-Group x 3-Stimulus x 3-Site x 2-Distract er ANOVAs performed on P3 peak latency data......................................................................................................80 3-9 Significant correlations between differen ce waves and neuropsychological measures for control and PD groups separately.................................................................................81 3-10 Summary of hierarchical re gression analysis for variable s predicting the amplitude of the novel Distracter-Standard difference wave..................................................................82 3-11 Summary of hierarchical re gression analysis for variable s predicting the amplitude of the novel Distracter-Standard difference wave..................................................................82 3-12 Summary of hierarchical re gression analysis for variable s predicting the amplitude of the non-novel Distracter-Standard difference wave..........................................................83

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8 LIST OF FIGURES Figure page 1-1 Schematic illustration of diffe rent paradigms that elicit the P300.....................................33 1-2 Sample fractal design used as a novel distracter in the oddball task.................................34 1-3 Examples of planned comparisons used in ERP data analysis..........................................35 1-4 Montage used for the EEG analys es, showing interna tional 10 positions interpolated from the 64-channel geodes ic sensor net (EGI; Eugene, Oregon)................36 2-1 Grand-averaged standard, target, and di stracter ERPs from the midline electrodes for young adults................................................................................................................... ....56 2-2 Grand-averaged standard, target, and di stracter ERPs from the midline electrodes for older adults................................................................................................................... ......57 2-3 Mean amplitudes and latencies for th e SN component as a function of stimulus condition and distracter type..............................................................................................58 2-4 Mean amplitudes and latencies for th e P2 component as a function of stimulus condition and distracter type for the two participant groups.............................................58 2-5 Mean amplitudes for the N2 componen t as a function of stimulus condition and distracter type for the two participant groups....................................................................59 2-6 Mean amplitudes for the P3 component as a function of stimulus condition for young and older participants.........................................................................................................59 2-7 Normalized (z-score) ERP amplitudes for the P3 as a function of electrode site and stimulus condition for young and older participants..........................................................60 2-8 Spherical spline voltage maps for the difference wave s of distracter standard stimulus across participant groups, taken at 400 ms..........................................................61 2-9 Spherical spline voltage maps for the difference waves of target standard stimulus across participant groups taken at 400 ms........................................................................62 3-1 Grand-averaged standard, target, and di stracter ERPs from the midline electrodes for healthy controls............................................................................................................... ...84 3-2 Grand-averaged standard, target, and di stracter ERPs from the midline electrodes for PD patients.................................................................................................................... .....85 3-3 Mean amplitudes for the SN componen t as a function of stimulus condition and distracter type................................................................................................................ .....86

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9 3-4 Mean amplitudes for the P2 component as a function of stimulus condition and distracter type................................................................................................................ .....86 3-5 Normalized (z-score) ERP amplitudes for the P3 as a function of electrode site and stimulus condition for both groups combined...................................................................87 3-6 ERP latencies for the P3 as a functio n of electrode site and stimulus condition for both groups combined........................................................................................................88 3-7 Spherical spline voltage maps for the difference wave s of distracter standard stimulus across participant groups, taken at 400 ms..........................................................89 3-8 Spherical spline voltage maps for the difference waves of target standard stimulus across participant groups taken at 400 ms........................................................................90

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10 Abstract of Dissertation Pres ented to the Graduate School of the University of Florida in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy EFFECTS OF DISTRACTER NOV ELTY ON ATTENTIONAL ORIENTING IN HEALTHY AGING AND PARKINSONS DISEASE: AN EVENT-RELATED POTENTIAL (ERP) STUDY By David Andrew Stigge Kaufman August 2009 Chair: William M. Perlstein Major: Psychology Novel events are preferentially processed in the brain in order to facilitate adaptive responses to a dynamic, changing world. However, much is still unknown about the mechanisms that give rise to attentional orienting toward novel events in the brain. Healthy aging and Parkinsons disease (PD) have been previously associated with defic its in novelty processing, which is mediated by neural networks that give rise to preferential processing for novel distracters. In order to better characterize the nature of these attentional mechanisms, two eventrelated potential (ERP) experiments were condu cted in young adults, older adults, and PD patients. The experiments manipulated the novelt y characteristics of task -irrelevant distracters that were presented in the cont ext of a three-stimulus oddball tas k. This task allowed for the examination of both distractera nd target-related processing as a function of distracter novelty. As expected, novel distracters differentially engage d the visual attention system in ways that were not seen for non-novel distracters. Howe ver, older adults and PD patients showed impairments in their attentional orienting respons es toward novel stimuli. These deficits in distracter processing were associated with a nu mber of other cognitive and emotional symptoms, and further gave rise to impairments in target -related processing. Notably, older adults and PD

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11 patients exhibited weaker proces sing of attentional targets and a frontal shift in their ERP reflections of target processing, which is consiste nt with a frontally-mediated deficit in memory updating for the targets. Taken together, the results of these expe riments provide strong evidence that novel events receive preferential neural processing in ways that are influenced by the stimulus features that charac terize the event, as well as the functional integrity of specialized attentional orienting networks in the brain. Ol der adults and PD patie nts appear to be less engaged with new information, yet more sus ceptible to the interf ering effects of novel distracters. These findings help to clarify the ways in which stimulus characteristics affect attentional orienting to unexpected events, al ong with the impacts that healthy aging and PD have on this process.

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12 CHAPTER 1 GENERAL INTRODUCTION AND METHODS General Introduction Flexible allocation of attenti on is a vital c ognitive process th at facilitates adaptation to changing environmental demands. Novel events can serve as either potential sources of engagement, irrelevant distracter s that are ignored, or obstacles that block the achievement of ones goals. Adaptive responding to novel events is necessary to successfully navigate through unexpected cognitive and emotional challenges. Unfortunately, life is wrought with factors that can interfere with our ability to efficiently process novelty. Healthy aging brings about neurophysiological changes that are associated with compromised cognitive processing. Alterations in the dopaminergic systems in healthy aging may be responsible in part for some of the executive functioning deficits that preferenti ally impact frontal lobe functioning and complex attentional processing in old age (Raz, 2000; Woodruff-Pak, 1997). As a result, it has been suggested that neurodegen erative diseases like Parkinsons disease (PD) may provide a useful clinical model for understanding some of the co gnitive deficits of healthy aging, primarily because the dopamine deficits that characterize PD may disrupt frontal-stria tal circuitry in ways that are similar to age-related frontal dysfunc tion (Cabeza, 2001). Declines in attentional processing have been observed in healthy ag ing (McDowd & Shaw, 2000) and PD (Poliakoff et al., 2003), yet the nature of these attentional impair ments is not always consistent (Kingstone et al., 2002). In PD, emotional symptoms frequent ly accompany cognitive and motor deficits, and there is suggestion that some of these problems are associated with impairments in novelty processing. Because of these reasons, PD provide s a unique clinical opportunity to examine the relationships between novelty processing, executive functioning, emotional dysfunction, and the underlying neuropathology within this clinical condition.

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13 The overall goals of this dissertation rese arch are to better und erstand how novelty is processed in the brain, and how h ealthy aging and PD affect the ability to respond appropriately to novel events. Specifically, I will address three research questions: 1. At what point(s) during atte ntional processing do novel ev ents receive preferential engagement? 2. How does healthy aging and/or Parkinsons dise ase impact the preferential processing of novelty? 3. How is novelty processing related to other forms of cognitive and emotional functioning in young adults, healthy aging, and Parkinsons disease? In order to address my first research question, it is necessary to utilize a tool that is able to index neural activity with rapid (millisecond) fidelity in a non-invasive manner. Of current psychophysiological methodologies, one of the best approaches for charact erizing rapid changes of this sort is to measure scalp-based event-rela ted potentials (ERPs). Not surprisingly, there is a rich history of ERP research on the topic of novelty pro cessing. After a revi ew of ERPs and how they can be used to study attentional proces sing of novelty, I will discuss specific impairments that have been observed in the way that older ad ults and PD patients process novel events. This chapter will then conclude with an overview of the general methods used in the two experiments that follow. Scalp-Recorded Event-Related Potentials (ERPs) Over the last forty years, advances in electrophysiology have enabled new kinds of questions to be addressed about the neural systems and processe s that underlie many forms of cognition. The electroencephalo gram (EEG) is the record of the volume-conducted electrical activity of the brain measured by scalp el ectrodes (Davidson, Jackson, & Larson, 2000). Electrical activity recorded from the EEG can be averaged in asso ciation with the presentation of specific events of interest. In itially, the event-related response associated with the presentation

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14 of a stimulus is embedded in the ongoing EEG ac tivity. Extracting an ERP waveform associated with a specific stimulus is accomplished by aver aging multiple samples of the EEG that are timelocked to repeated occurrences of the stimulus (Fabiani, Gratton, & Coles, 2000). Assuming that the underlying brain activity remains constant duri ng the same conditions of an experiment, there is a benefit of averaging in that the ERPs should remain somewhat consistent from trial to trial, while the ongoing background EEG is random and is averaged out of the resulting waveform (Otten & Rugg, 2005). ERPs are highly sensitive to changes in neur al activity on the level of milliseconds (ms), making them the gold standard among noninvasive imaging methods in terms of temporal resolution (Fabiani et al., 2000). ERP waveforms us ually consist of discrete voltage deflections that can either be positiveor negative-going. Specific com ponents of ERP waveforms are usually named in accordance with their polarity ( positive or negative) and peak latency (in ms). A common example is P300, which refers to an ERP component with a positive peak that has latency of approximately 300 ms post-stimulus onset. Since the P300 is typically the third positive peak after a stimulus, this component is also frequently called the P3, particularly when specific subcomponents of this potential are examined. Novelty Processing and the P300 The P300 was first described over four decad es ago (Sutton, Braren, Zubin, & John, 1965), and it has become one of the most highly studied components in the ERP literature. Various experimental paradigms elicit th e P300, including simple paradigm s when a participant responds to a single target stimulus (Fi gure 1-1A). A traditional two-stim ulus oddball task presents an infrequent target in the backgr ound of a more frequent standard stimulus (Figure 1-1B). A larger P300 is evoked by the infrequent target compared to the standa rd background stimulus. Additionally, P300 amplitude varies systematically with the proportion of infrequent events (e.g.,

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15 Duncan-Johnson & Donchin, 1977). These two-stimulus oddball finding s are frequently taken to suggest that subjective probability (i.e., expectancy ) controls the amplitude of the P300 (Fabiani et al., 2000). Three-stimulus oddball tasks present an infreque nt target in the bac kground of a frequently occurring standard stimulus and an infrequently o ccurring distracter stimul us (Figure 1-1C). In these three-stimulus oddball paradigms, two subc omponents of the P300 are typically seen. The P3a is evoked most prominently by infrequent, task-irrelevant distracter stimuli when the stimulus discrimination between target and stan dard stimuli is difficult (Polich & Comerchero, 2003). In these paradigms, distracter stimuli ar e contextually novel, meaning that they are not expected given the parameters (i.e ., attentional goals) of the tas k, and participants are typically instructed to not respond to them. The stimulus features of the distracters may either be novel (i.e., unfamiliar stimuli that are unique for each tria l) or non-novel (i.e., repeating across trials). The P3a has often been interpreted as reflecting an orienting reflex toward unexpected events (Simons & Perlstein, 1997), which is believed to be a fundamental biological mechanism that influences exploratory behavior and is critical for survival and evolution (Sokolov, 1963). The P3a component reflects attentional orienting to ward distracters with a frontocentral maximum amplitude distribution, while a different compone nt called the P3b is t ypically evoked most prominently by task-relevant target stimuli, with a more posterior parietal distribution (Snyder & Hillyard, 1976; Squires, Squires, & Hillyard, 1975). By manipulating the nature of stimulus feat ures of distracters in three-stimulus oddball tasks, some researchers have concluded that di stracter stimuli that are more novel and complex elicit a P3a component with a greater frontal distri bution compared to distracters that are simple and repeating (Cycowicz & Friedman, 2004). Ho wever, others have compared novel and non-

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16 novel distracter effects and concluded that the resulting P3a components are virtually indistinguishable from each other (Simons, Gr aham, Miles, & Chen, 2001; Simons & Perlstein, 1997). However, it is important to note that ex periment-specific variab les (e.g., task difficulty, perceptual distinctivenes s of stimuli, etc.) play a large ro le in dictating P3 responses during oddball tasks (e.g., Comerchero & Polich, 1998), making some cross-study comparisons difficult. In order to best inte grate findings from different rese archers and methodologies in this paper, P3 responses will generally be identified as distracter-related or target-related, rather than P3a or P3b. Novelty Processing and the N2 For several decades, the N2 has been comm only observed in association with the P3 component. This N2 response (sometimes called N2b) typically has front ocentral distribution and occurs prior to a P3 response to a distracter (J. R. Folstein & Van Petten, 2008). Early threestimulus oddball studies found that the N2 is imp acted by the complexity of novel stimuli, such that simple novel distracters elicited a smaller N2 response than those that are more complex (Courchesne, Hillyard, & Galambos, 1975). More recent studies often overlook the effects of novelty on N2 amplitude, in favor of focusing exclusively on P3 responses. For example, when examining the difference between novel and no n-novel distracters, Polich and Comerchero (2003) did not discuss any impact on the N2 compone nt. However, analysis of the figures from this study suggests that the N2 was enhanced by di stracter novelty features to a greater degree than the P3 component, which showed nearly identical amplitudes from novel and non-novel distracters. One study found interesting effects on N2 respons es by utilizing different variants of the three-stimulus oddball paradigm that manipulated the degree of stimulus complexity in the targets, distracters, and standard stimuli (Daffn er, Mesulam, Scinto, Calvo et al., 2000). These

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17 results included two key findings regarding the natu re of N2 responses to novelty. First, simple distracters elicited larger N2 amplitudes when pr esented in the context of contrasting stimulus features complex targets and standard stimuli relative to targets and standards that were also simple. Furthermore, unusual distracters evoked larger N2s than simple, familiar distracters. These findings suggest that the N2 novelty effect can arise for two different reasons: 1) deviation from a predominant stimulus category, and 2) novel stimulus features (i.e ., departures from longterm familiarity; see J. R. Folstein & Van Petten, 2008). In a recent extension of this paradigm, Chong and colleagues (2008) examined the effect of characterizing nove l designs as taskrelevant items to explore, rather than task-irrel evant distracters to ignore. They found that the N2 processed the novel stimuli equa lly regardless of their task re levancy, suggesting that the N2 reflects a more automatic detection of unfamilia r novel stimuli that is not modulated by topdown influences. Conversely, the P3 and late slow waves evoked by novel stimuli were larger when viewed as a task-relevan t exploration, suggesting that th ese later stages of processing involve more a voluntary allocation of processing resources to novel events. Novelty Processing and Ea rly Sensory Potentials The visual P1 (80-130 ms) is generated by extr astriate visual cort ex and reflects early sensory processing (Clark & Hillyard, 1996). Th e visual N1 (140-200 ms) arises from multiple neural generators in secondary vi sual cortex and downstream associ ation cortices in the temporal and parietal lobes (Di Russo, Martinez, Sereno, Pitzalis, & Hillyard, 2002). Spatial attention leads to amplification of these two early sensor y potentials, yet attent ional selection based on nonspatial features such as colo r and shape is not associated w ith changes in the P1 or N1. Instead, this form of feature se lection is associated with a large negative potential over the occipital lobe called the selec tion negativity (SN) that begins 140-180 ms after stimulus onset and is believed to be generated by the dorsal o ccipital cortex and posterior fusiform gyrus

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18 (Hillyard & Anllo-Vento, 1998). An interesting combination of spa tial and feature detection is reflected in a later, more frontally-distributed P2 response (180-300 ms), which is modulated by both spatial attention as well as feature detection such as co lor processing (O'Donnell, Swearer, Smith, Hokama, & McCarley, 1997). Since oddb all paradigms often manipulate stimulus features based on color or shape, the SN and P2 effects may become relevant for interpreting results about novelty effects. Because of their exogenous nature, however, P1, N1, SN, and P2 responses are rarely reported in studies employing novelty oddball ta sks. Nevertheless, there is evidence that certain kinds of novel distracters elicit enhancements of P2 amplitudes, even in the context of brain injury or h ealthy aging (Czigler & Balazs, 2005; R. T. Knight, 1997). The effects of novelty on these early potentials are likely to vary ac ross studies in accordance with specific stimulus features that have been se lected for experimental novelty manipulations. A Neuroanatomical Model of Attentional Orienting Early investigation of hippocampal activity us ing depth electrodes suggested that the P300 is partly generated by structures of the medial te mporal lobe (Halgren et al., 1980). Patients with lesions to the frontal lobe or hippocampal region have shown di sruptions in P3 potentials to distracter stimuli (Daffner, Mesula m, Scinto, Acar et al., 2000; R. Knight, 1996; R. T. Knight, 1984), suggesting that engagement of both frontal and hippocampal regions is necessary for the mechanisms of attentional processing that give rise to a distracter -related P3 potential. Intracranial electrophysiological recordings in epilepsy patients have shown that P3-like ERP responses to novel distracters are am plified in the regions of the in ferior frontal sulcus, anterior cingulate cortex (ACC), temporopa rietal and inferior temporal cortex, and the posterior hippocampus (Baudena, Halgren, Heit, & Clar ke, 1995; Halgren, Baudena, Clarke, Heit, Liegeois et al., 1995; Halgren, Ba udena, Clarke, Heit, Marinkovic et al., 1995). Interestingly, it has also been proposed that the frontal activity that gives rise to distracter-r elated P3 is mediated

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19 by dopaminergic activity, while the target-relat ed P3 is believed to be mediated by norepinephrine activity in the parietal lobe (P olich & Criado, 2006). The neural generators of novelty N2 effects are largely unclear, as few in formative studies have sought to explicitly examine the neural substrate underlying this component (J. R. Folstein & Van Petten, 2008). Building on the data available from research in humans and animals, Corbetta and Shulman (2002) have proposed that visual attention is mediated by two partially segregated networks in the brain one system includes parietal and superior frontal co rtex and is engaged in top-down selection for stimuli and responses, and another bottom-up system activated by distracters, which includes tempopa rietal and inferior frontal cort ex. According to this model, the bottom-up system is specialized for the de tection of behaviora lly relevant stimuli (particularly when they are unexpected) and can in terrupt the functioning of the top-down system in order to direct attention toward salient events. This model has been partially supported by a recent fMRI study which found that both target and distracters engaged a common ventrola teral frontoparietal network, while distracters alone activated a dorsolateral frontoparietal ne twork (Bledowski, Prvulovic, Goebel, Zanella, & Linden, 2004). Similar evidence was obtained from a bi-field visual selective attention task, which found that novel stimuli engaged activity in a broad network of brain regions, including the superior and middle frontal gyr us, temporal-parietal junction, s uperior parietal lobe, cingulate cortex, hippocampus, and fusiform gyrus (Yam aguchi, Hale, D'Esposito, & Knight, 2004). Interestingly, prefrontal and hippocampal regions were activated regardless of whether these stimuli were presented in the attended hemifi eld, and these regions were the only ones that showed habituation over repeated exposures to the novel stimuli. These imaging findings converge on the clinical data to suggest that prefr ontal and hippocampal regions are critically

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20 involved in attentional orienting and carry out an automatic proce ss of detection and habituation to unexpected distracters, which can occur in the absence of co ntrolled attention, and possibly even disrupt top-down cognitive processes that we re in place prior to the encounter with the distracter. Summary and Implications of Novelty Processing With their excellent temporal resolution, ERPs are well suited for examining rapid changes in brain function that accompany attentional pr ocessing of novelty. Nove lty has been shown to enhance distracter-related N2 and P3 respons es; however, this novelty can arise from two different types of settings. When stimuli are per ceived as unfamiliar, they are judged to be novel as a result of their deviation from a long-term contex t. Novel distracters of this sort elicit larger P3 and N2 amplitudes, presumably reflecting a common attentional or ienting reflex that is driven by a bottom-up visual processing system. This syst em relies in part on long-term memory stores in the brain to maintain a sense of familiarity that can be used as a backdrop on which to evaluate new events that are encountered. One critical qu estion that is not completely resolved in the literature is how much unfam iliarity is necessary to maxi mize the attentional orienting network(s) in the brain. In addition, distracter-related N2 and P3 components can also respond to deviations from a short-term experimental context (i.e., mismatch of expectations), even in the absence of longterm familiarity violations. This has not been explored as much in the literature, but has tremendous relevancy for individuals who fail to show normal levels of preferential processing of novel information. Most studies have found th at older adults have difficulty engaging in attentional orienting, and patient s with frontal lobe deficits typically show even greater impairments. For the benefit of these patients, it is important to understand these alterations in attentional processing and determine if anything ca n be done to improve them. If left unchecked,

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21 these deficits could have many real-world impli cations for these individuals, including a host of negative cognitive and/or emotional problems. Additionally, knowledge gained from studying individuals with novelty processi ng deficits may spark new insight s about neural mechanisms of visual attention and various type s of executive function. With th ese considerations in mind, it is important to appreciate the prev ious research that has investig ated novelty processing in healthy aging and Parkinsons disease, which will be the focus of the remainder of this paper. ERP Studies of Novelty in Healthy Aging ERP studies examining the performance of heal thy older adults in oddball paradigms have found a consistent increase in P3 latency to both ta rget and distracter stimuli in all modalities and across both twoand three-stimulus oddball task s (Anderer, Semlitsch, & Saletu, 1996; Fabiani & Friedman, 1995; Fjell & Walhovd, 2001; Frie dman, Simpson, & Hamberger, 1993; Polich, 1996). These increases in P3 latency are likely to be reflective of age-re lated slowing of memory updating processes that are requir ed to correctly identify and re spond to task-relevant targets (Polich, 1996). Numerous studies have also f ound that the P3 amplitudes elicited by target and distracter stimuli decrease with age (Andere r et al., 1996; Fabiani & Friedman, 1995; Kok, 2000), which are believed to reflec t alterations in the degree to which attentional resources are allocated to stimuli (Fjell & Walhovd, 2001). Older adults show a posterior-t o-anterior shift in target-related P3 responses with age, which leads to a more evenly distributed sc alp topography for this component (Friedman, Kazmerski, & Fabiani, 1997). Fabiani, Frie dman, and Cheng (1998) found that older adults exhibited individual differences in the distribution of target P3 responses in an auditory oddball task. While younger adults showed a posterior-max imal scalp topography for the target stimuli, some older adults had a frontal-maximal P3 scalp distribution for the targets. These older adults who showed frontal P3 scalp distributions fo r targets performed more poorly on tests of

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22 executive functioning such as the Wisconsin Card Sorting Test and Verb al Fluency relative to older adults who showed posterior-maximal s calp topographies. These findings suggest that changes in P3 scalp topography may be reflec tive of underlying frontal lobe dysfunction in healthy aging. More specifically, it has been s uggested that older adults have more difficulty creating categorical templates of their attentional targets in working memory, which contributes to these ERP differences in target-related P3 potentials (Fabiani & Friedman, 1995; Friedman, Kazmerski, & Cycowicz, 1998). The shift to a more frontally oriented topogra phy has also been seen for distracter-related P3 responses, which also appears to be associated with an age-re lated increase in the false-alarm rate, suggesting a decline in fr ontal lobe activity with increas ing age (Friedman et al., 1993). Fjell and Walhovd (2004) recently conducted a visual three-stimulus oddball study to further explore the effects of age on P3 potentials. They found that the distracter-related P3 amplitudes were more susceptible to agerelated declines than target-r elated P3. The most pronounced impairments in distracter-related P3 potentials were seen in central and po sterior electrode sites, with less pronounced changes seen in frontal sites. Furthermore, they found that the age-related changes in P3 to distracters were linear in na ture, suggesting a gradual and steady decline across the adult lifespan. Interestingl y, Czigler and Balazs (2005) also found age-related reductions in N2 amplitudes to novel events, while P2 novelty enha ncements were still present in old adults. Taken together, these findings sugg est that the attentional orienting reflex toward novel stimuli declines with age, while earlier stages of feature discrimination remain intact. Recently, a new line of research has called into question some of the conclusions that were previously given to account for age-related change s in P3 to target and distracter stimuli. Daffner and colleagues (2005) have argued that previous research in this area has not properly

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23 controlled for differences in the level of cogni tive status between age groups. When testing cognitively high-performing ol d, middle-aged, and young adults, they found no age-related differences in P3 latency or amplitude but inst ead observed a larger, more frontally distributed P3 in old adults. When compared to younger ad ults, the older adults in this study exhibited larger P3 amplitudes for novel, target, and standa rd stimuli. These findings suggest that higher functioning older adults may empl oy increased resources and more effortful frontal activity in order to enhance their attentional processing. However, this phenomenon was non-specific in this study, and does not appear to be associated with changes in the attentional processing that were specific to target s or novel events. Importantly, these e ffects need to be qualified with the fact that the oddball task used in this study is systematically different than most other oddball paradigms in the literature, as participants make responses to all stimuli and thereby have different task demands placed on them. Nonethele ss, these initial findings have been replicated (Daffner et al., 2006), and suggest that old adu lts who are cognitively high functioning exhibit preserved (and possibly even increased) preferential processi ng for novel events. ERP Studies of Novelty in Parkinsons Disease ERP studies in Parkinsons disease have f ound that PD patients with dementia show prolonged P3 latencies, while PD patients without dementia show P3 latencies within the normal range (Ebmeier et al., 1992; Goodin & Amino ff, 1987; Graham, Yianni kas, Gordon, Coyle, & Morris, 1990). However, prolonged P3 latencies ha ve also been reported in PD patients without dementia, and these latencies are correlated with patient age and stage of the disease (Stanzione et al., 1998), along with age of symptom onset (Wang, Kuroiw a, & Kamitani, 1999). Although most studies employing the oddball paradigm have found normal P3 responses in non-demented PD patients, target-related P3 latency has been reported to be correlated with general cognitive functioning in PD patients (Bodis-Wollner et al., 1995; O'Donnell, Squires, Martz, Chen, &

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24 Phay, 1987). Target-related P3 latency and amplit ude have both been shown to correlate with multiple neuropsychological measures, including tests of attention, visu oconstructional skills, verbal fluency, memory, and executive function (Chen, Lin, Liu, Tai, & Lai, 2006). Targetrelated P3 amplitude has also been shown to correlate w ith severity of gait disturbance (Wang et al., 1999). In auditory three-stim ulus oddball tasks, deficits in bot h distractera nd target-related P3 responses have been observed in PD patients (Lagopoulos et al., 1998), leading the authors to conclude that PD is associated with impairm ents in both automatic orienting and controlled attentional processing. Only one study has examined the ERP reflecti ons of novel distracter processing in PD. Using a three-stimulus auditory oddball task, Tsuchiya, Yamaguchi, and Kobayashi (2000) found that PD patients exhibited impaired P3 res ponses to both targets and novel distracters. Distracter-related P3 amplitude was diminished over frontal scalp sites and correlated with poorer performance on a modified version of th e Wisconsin Card Sorting Test. This finding suggests that novelty processing de ficits in PD may be related to executive functioning deficits that are typically elevated in this populati on (Dubois & Pillon, 1997). Importantly, executive dysfunction in PD has been associated with em otional symptoms, including depression (Costa, Peppe, Carlesimo, Pasqualetti, & Caltagirone, 20 06) and apathy (Isella et al., 2002). Tsuchiya and colleagues (2000) did not measure emotional symptoms in their sample of PD patients, which is problematic since depression, anxiety, a nd apathy are often elevated in this group (Isella et al., 2002; McDonald, Richar d, & DeLong, 2003; Walsh & Bennett, 2001). This omission is also unfortunate because apathy ha s been significantly associated with reduced P3 amplitudes to novel distracters in other neurolog ical populations, includ ing Alzheimers disease (Daffner et al., 2001), cortical stroke (Daffner, Mesulam, Scin to, Acar et al., 2000; R. T. Knight, 1984), and

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25 subcortical stroke (Yamagata, Yamaguchi, & Koba yashi, 2004). Furthermore, some researchers have found that anxiety symptoms increase in PD patients when they experience the off state of dopaminergic therapy (Menza, Sage, Marsha ll, Cody, & Duvoisin, 1990; Siemers, Shekhar, Quaid, & Dickson, 1993), while others have report ed no relationship between anxiety and motor symptoms in PD (Stein, Heuser, Juncos, & Uhde 1990). Since distracter-related P3 potentials may be mediated by dopamine (Polich & Criado, 2006), it is possible that these ERP responses may also be associated with anxiety and moto r symptoms in PD. However, the relationship between distracter-related P3 potentials, anxi ety, and motor symptoms not been previously studied in prior research in PD. Summary and Rationale for the Current Project Despite extensive research efforts over the pa st few decades, a number of issues are still unclear as to how novel events rece ive preferential processing in th e brain. At the heart of these issues is the unavoidable probl em that novel distracter proc essing is highly influenced by experiment-specific task demands. Therefore, it can be difficult to reconcile divergent findings from different researchers using different stimuli a nd/or task parameters. It can also be difficult to draw conclusions about the implications of no velty processing when relatively few researchers adequately examine relationships between ERP reflections of novelty processing and broader levels of cognitive functioning. Comparisons across the lifespan have offered many insights into the neural mechanisms of novelty processing and how these are associated with aging. Older adul ts generally exhibit declines in distracter-related processing (N2 and P3) which are s uggestive of impaired attentional orienting. Additionally, the categorization of task -relevant information is also altered in older adults, such that target-related P3 responses beco me more frontally-distributed in a way that is consistent with frontal lobe decline requiring greater compensatory activations. However,

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26 individual differences appear to affect thes e general findings, such that cognitively high functioning older adults may show different pa tterns of distractera nd target-processing. Importantly, no studies to date have explicitly ex amined the role of dist racter novelty on these aging effects. As a result, it is not clear if age -related deficits in attent ional orienting and targetrelated processing in teract with stimulus novelty, which ma y have important implications for the way in which these deficits are understood. Studies of Parkinsons disease patients also have much to offer to our understanding of novelty processing. PD patients have been shown to be impaired in both a ttentional orienting to distracters and task-relevant processing of target s. Importantly, novel distracters fail to receive preferential processing in PD pa tients relative to age-matched controls, and these deficits are correlated with executive functioning symptoms However, the nature of novelty processing deficits in PD has not been studied extensivel y, and no relationships w ith emotional symptoms have been explored in this group. With these considerations in mind, this disser tation research will address three different aims and test the following hypotheses: 1) Specific Aim 1: Examine the effects of nove lty on distracter processing and examine the neural timecourse of preferential engagement with novel events. Hypothesis 1: Distracters will be associated with preferential engagement that is greater and begins earlier in the visual processing str eam when distracters are novel and highly salient. 2) Specific Aim 2: Examine the impact that h ealthy aging and Parkin sons disease have on novelty processing. Hypothesis 2: Healthy agi ng will be associated with intact early preferential processing of novelty (i.e., SN and P2) but im pairments in attentional orienting (i.e,. N2 and P3). Hypothesis 3: Relative to age-matched c ontrols, Parkinsons di sease patients will show reductions in the preferential proces sing of novel distracters (i.e., N2 and P3).

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27 3) Specific Aim 3: Explore the relationships between novelty processing and other domains of function. Hypothesis 4: Participants from all groups will show relationships between measures of executive functioning and dist racter-related processing. In addition, patterns of novelty processing in PD patie nts will be associated with motor and emotional symptoms. General Methods ERP Stimuli and Task Stimuli and procedures for the three-stimulus oddball task were modified from Polich and Comerchero (2003). A total of 600 stimuli were randomly presented against a black background, 70% of which were standard stimuli, 15% of which were targets, and 15% of which were distracters. Participants receiv ed four blocks of 150 trials with three breaks in between. Standard stimuli, to which the participants were told not to respond, consisted of small grey circles measuring 2 inches in diameter. Targ et stimuli were medium-sized grey circles, measuring 3 inches, and participants were inst ructed to press a button when they saw these stimuli. Distracter stimuli, to which the partic ipants were told not to respond, were large squares measuring 4.5 inches in diameter A moderate difference between the targets and standards and the large difference between the targets and dist racters was chosen to maximize the P3 response (see Comerchero & Polich, 1998) while also maximizing task accuracy. Each stimulus was presented for 75 milliseconds (ms), with a 2 sec ond inter-stimulus interval. A practice task consisting of 10 stimuli was presented in adva nce to ascertain that all participants can discriminate targets from standa rds. This practice task was repeated until all participants achieved 80% correct responses. Distracter novelty was manipulated by stimul us features contained within the large squares. Half of the distracter s were grey, like the targets and standards, and were identical in appearance throughout the experiment. The other di stracters contained colo rful fractal designs

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28 that were unique and only occurred once over the course of the experiment (see Figure 1-2 for an example). These novel distracter designs were generated by Tiera-Zon software (http://www.ktaza.com/fractal/ ). Both types of distracters were the same size, and were presented in different trial blocks to allow the opportunity to exam ine block-related effects of the distracters on the other stimuli. Half of the participants comple ted the novel distracter blocks first and third, while the other pa rticipants completed novel distract er blocks second and fourth. Presentation order of novel and non-novel distra cter blocks was counterbalanced across participants. Neuropsychological Measures Participants completed a short battery of neuropsychological te sts to assess cognitive and emotional functioning. The Mini-Mental State Exam (MMSE; M. F. Folstein, Folstein, & McHugh, 1975) was used to screen for dementia and other global cognitive problems. Additionally, participants were administered the Trail Making Test A and B (Trails; Reitan & Wolfson, 1995), Digit Symbol and Digit Span subtests from the Wechsler Adult Intelligence Scale-Third Edition (WAIS-III; Wechsler, 1997), Stroop Color and Word Test (Golden, 1978), Controlled Oral Word Association Test (B enton & Hamsher, 1989), Boston Naming TestSecond Edition-Short Form (Kaplan, Goodgla ss, & Weintraub, 2001), and Wisconsin Card Sorting Test (Heaton, Chelune, Talley, Kay, & Cu rtiss, 1993). Of the executive functioning measures, Trails B provides an assessment of di vided attention and cogni tive flexibility, Digit Symbol measures psychomotor speed and comp lex sustained attention, the Stroop Color and Word Test measures inhibition, selective atte ntion, and response confli ct, and the Wisconsin Card Sorting Test measures abstract probl em-solving and set-shifting (Lezak, Howieson, & Loring, 2004).

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29 Emotional Measures Participants also completed a short set of self-report questionnaires to assess emotional functioning. The State-Trait Anxi ety Inventory (STAI; Speilber ger, Gorusch, Lushene, Vagg, & Jacobs, 1983) was used to provide information regarding the participan ts general levels of anxiety as manifest in temporary states of distress and more l ong-term personality traits. The Beck Depression Inventory-Second Edition (BDI-II; Beck, 1996) was used to assess for elevated levels of depression symptoms. Unfortunatel y, the BDI-II was not normed on older adults, and contains items assessing somatic symptoms of depres sion that may lead to inflated scores in the elderly. Therefore, the Geriatric Depression Sc ale (GDS; Yesavage et al., 1983) was used in addition to the BDI-II to assess depression symptoms. Unlike the BDI-II, the GDS was normed on an elderly population and was designed to avoi d somatic symptoms that complicate diagnosis in the presence of comorbid, age-related medical conditions (Blazer, 2002). Finally a modified Apathy Evaluation Scale (AES; Star kstein et al., 1992) was used to assess self-re ported apathy symptoms. EEG Acquisition and Reduction EEG was recorded from 64 scalp sites us ing a 64-channel geodesic sensor net and amplified at 20K using an Electrical Geodesics Incorporated (EGI; Eugene, Oregon) amplifier system (nominal bandpass .10 100Hz). Electrode placements enabled r ecording vertical and horizontal eye movements reflected in electrooculographic (EOG) activity. EEG was initially referenced to Cz and digitized continuously at 250 Hz with a 16bit analog-to-digital converter. A right posterior electrode se rved as common ground. Impedan ce of electrodes was generally maintained below 50 k consistent with procedures suggested by the manufacturer. Following the recording session, EEG was then re -referenced into a virtual montage using Brain Electrical Source Analysis software (BES A version 5.2; Scherg, 1990). This montage

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30 used a combined ears reference and calculated EEG data from electrode sites based on the International 10-10 system, several of which were interpolated from the original 64 channels on the EGI net (see Figure 1-4). The electrodes used in statistical analyses consisted of midline sites Fz, Cz, Pz, and Oz. Of note, the Fpz electr ode was interpolated from a mixture of channels 6 and 11, Fz was interpolated from channels 3 an d 8, and Oz was interpolated from channels 37, 38, and 40. Cz and Pz activity corresponded with th e recordings taken from the vertex reference and channel 34, respectively. EEG data were then adjusted for movement, electromyographic muscle artifact, electro-ocular ey e movement, and blink artifacts using computer algorithms in BESA. EEG activity was excluded from the re maining data using th reshold criteria that maximized the number of trials accepted from each individual. The average voltage threshold that was used for excluding trials was 109.2 V ( SD : 2.5, range: 100-150) V. Point-to-point transitions were not allowed to exceed 75 V. Individual-subject event-related potentials (ERPs) were extracted and averaged together from the ongoing EEG recording in discrete temporal windows that coincide with the onset of each stimulus. ERP averages from each partic ipant were then calculated separately for standards, targets, and distracters. Stimulus-l ocked epochs were extrac ted with a duration of 200 ms prior to stimulus presentation and 800 ms post-stimulus presentation. All averaged ERP epochs were baseline-corrected using a 200 ms window prior to stimulus onset and digitally filtered at 30 Hz low-pass and a .1 Hz high-pa ss. All ERP components were scored on peak amplitude and peak latencies during a specified time window. Time windows used for scoring the different ERP components were as follo ws: occipital SN: 100200 ms, central P2: 120-240 ms, frontal N2: 175-350 ms, a nd midline P3: 300-650 ms.

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31 Data Analysis Independent and paired samples t-tests were performed to examine between-group and within-group differences on neuropsychological and oddball task behavioral data. Detection accuracy data that were not normally distri buted underwent arcsine transformation (Neter, Wasserman, & Kutner, 1985), which can correct for skewedness caused by low probability of error rates on the task. For analyses involving RT, median RTs were employed for correct responses (Ratcliff, 1993). ERP peak amplitude s and latencies were examined with 2-Group (young, older) x 3-Stimulus (standard, target, dist racter) x 3-Electrode Site (Fz, Cz, Pz) x 2Distracter (novel, non-novel) repe ated measures analyses of vari ance (ANOVAs). In line with a priori hypotheses, planned contra sts were used to decompose interaction effects. When applicable, these contrasts utilized orthogonal po lynomial comparisons across different stimulus conditions and electrode sites. To assist in interpreta tion of these contrasts, factors were always entered into ANOVAs in the same order. Electr ode site was always ordered in an anterior-toposterior fashion (Fz, Cz, Pz). Stimulus type was always ordered in a manner consistent with increasing novelty (standard, target distracter). Orthogonal contrast vector rules specified linear contrasts over electrode site and stimulus type separately, using weights of -1, 0, +1. Quadratic contrasts were then defined applied to electrode site and stimulus type, using weights of +1, -2, +1. Visual examples of orthogona l contrasts used in ERP data an alysis can be seen in Figure 13. Linear trends observed over electrode site in dicated that the ERP amplitude was greatest in either frontal (Fz) or posterior (Pz) channels. Quadratic trends over electrode site reflected equal amplitude in frontal (Fz) and poste rior (Pz) channels but a different amplitude at the central site (Cz). Linear trends were observed over stimulus type indicated that ERP amplitude was greatest for either distracters or standard stimuli. Qu adratic trends over stimul us type reflected equal amplitudes elicited by standard and distracter stim uli but different amplitude evoked by targets.

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32 In addition to planned contrasts, follow-up posthoc comparisons were made using Bonferroni corrections for multiple comparisons. The H uynh-Feldt epsilon adjustment (Huynh & Feldt, 1976) was used for all repeated measures ANOVAs with greater than 1 degree of freedom; uncorrected degrees of freedom and corrected p -values are reported. For analyses that yielded significant interactio ns with electrode site, ERP amplitudes from the three stimulus conditions were normalized and then re-analyzed. Component amplitudes were zscore transformed across the three stimulus condi tions to eliminate the main effect of electrode site, which placed the stimulus-rel ated amplitudes on the same metric scale (see Kounios & Holcomb, 1994) and equated the sensitivity to detect differences across conditions at the different recording sites. Along with analyses of peak amplitude a nd latency data, some ERP components were subjected to difference wave calculations. Diffe rence waves for each participant were computed by subtracting the individual par ticipants average waveforms from two conditions of interest. These computations allowed for a comparison of the effects of a particular stimulus condition after controlling for the effects of another. These difference wa ves were visually inspected for topographic differences over the scalp, and anal yzed by calculating the mean amplitude over a time window where the condition-related differences were maximal. These calculations were made at the scalp site where the original ERP component had a maximal distribution. Pearson correlation coefficients were then used to m easure the relationships between difference wave amplitudes and neuropsychological data of interest Hierarchical regre ssion models were also used to assess the individual contributions of certain neuropsychological predictor variables on ERP difference wave responses.

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33 Figure 1-1. Schematic illustra tion of different paradigms th at elicit the P300. (A) A P300 deflection is elicited target stimuli that require a response. (B) 2-stimulus oddball tasks generate a larger P300 to an infreque nt target stimulus, re lative to a frequent non-target (standard). (C) In 3-stimulus oddball tasks, P3 a potentials are elicited by infrequent distracter stimuli, while P3b potentials are evoked by infrequent target stimuli. Note: T = target, S = standard, a nd D = distracter. Adapted from Polich and Criado (2006).

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34 Figure 1-2. Sample fractal design used as a novel distracter in the oddball task.

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35 0 1 2 3 4 5 6 7 8 9 10 FzCzPz Electrode SiteMean Amplitude (V) Condition 1 Condition 2 0 1 2 3 4 5 6 7 8 9 10 StandardTargetDistracter StimulusMean Amplitude (V) Condition 1 Condition 2 Figure 1-3. Examples of planned comparisons used in ERP data analysis. (A) Orthogonal contrasts reveal a linear trend over electro de site for Condition 1, with greatest amplitude over the posterior site (Pz). Condition 2 shows a quadratic trend over electrode site, with greater amplitudes over fr ontal and posterior site s (Fz, Pz) relative to central (Cz). (B) Orthogonal contrasts re veal a linear trend over stimulus type for Condition 1, with greatest amplitude elic ited by distracters. Condition 2 shows a quadratic trend over stimuli, with gr eater amplitudes evoked by standards and distracters relative to targets. A B

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36 Figure 1-4. Montage used for the EEG anal yses, showing interna tional 10 positions interpolated from the 64-channel geodesic sensor net (EGI; Eugene, Oregon). Primary sites of interest were midline sites Fz, Cz, Pz, and Oz.

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37 CHAPTER 2 EXPERIMENT 1: THE IMPACT OF HE ALTHY AGING ON PREFERENTIAL NOVELTY PROCESSING Overview and Predictions Experiment 1 was conducted to examine th e effects of distracter novelty on ERP reflections of attentional orien ting and determine if healthy aging impacts these effects. The inclusion of both young and older age groups also allowed for the examination of interacting effects of age and novelty on atte ntional orienting. In additio n, it was anticipated that the colorful properties of the novel distracters would differentially engage earl y visual attention with greater SN and P2 amplitudes rela tive to non-novel distracters. It was also predicted that young participants would show selective attentional orienting effects to distracters in the form of increased N2 and distracter P3 amplitudes relative to targets and standard s timuli. In line with previous P3 findings on novel versus non-novel distracters (Polich & Comerchero, 2003), novel distracters were not expected to differ from non-novel distracter s on overall P3 characteristics. However, novel distracters were expected to re ceive greater preferenti al processing than nonnovel distracters, as reflected in N2 amplitudes that have been shown to be more sensitive to unfamiliar stimuli (Daffner, Mesulam, Scinto, Calvo et al., 2000). With regard to predicted effect s of age, older participants we re expected to show decreased attentional orienting toward distracters, meani ng that distracter-related P3 and N2 amplitudes would be attenuated relative to the young group. Contrary to predictions for the young group, a novelty enhancement effect of N2 was not expected in older participants, due to their overall impairments in attentional orienting. However, novelty-related P2 and SN enhancements were expected to be intact in the older participants, si nce the neural processes that give rise to these components are rooted in sensory discrimination, which should be preserved into old age. All participants were expected to show correlati ons between distracter-s tandard difference waves

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38 and measures of executive functi oning, particularly those that assess working memory (Digit Span) and inhibition (Stroop Interference). Methods Participants Twenty-two young participants (ages 18-35) and twenty older particip ants (ages 49-77) were recruited for this study. The two groups were matched for gender ( 2 = .22, p > .70) and handedness ( 2 = .001, p > .90), although older participants ha d a higher mean level of education compared to those in the young group, t (35) = -3.5, p = .001. Of the young participants, 22 completed all the cognitive measures while 11 completed only a limited battery of the MMSE, Trails A and B, Digit Symbol, Stroop, and WCST. All of the older participants completed all measures. All participants were screened for the presence of psychiatric illness, learning disability, neurological disease, or history of other major medi cal problems affecting cognition. Table 2-1 provides demographi c and neuropsychological da ta for the participants. Procedures After informed consent was obtained, particip ants began an experimental session which lasted approximately 3 hours. Two participants (one in each group) needed to divide their session over two days due to scheduling difficulties but all other individu als completed all tasks in the same experimental session. Participants received either financial compensation ($10 per hour) or course credit for their participation. Results Behavioral Data Oddball task performance Behavioral data from the oddball task ar e presented in Table 2-2. A 2-Group x 2Distracter ANOVA was perf ormed on reaction time to targets, which revealed no significant

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39 effect of distracter type or group x distracter interaction. Wh en the two groups were analyzed separately with paired samples t -tests, however, reaction time to ta rgets was found to be affected by distracter type fo r older participants, t (14) = 2.6, p < .05, with faster responses during trial blocks that presented novel distra cters. In order to correct fo r high levels of skewedness caused by the low probability of errors on the task, error rates were subjected to arcsine transformation and then analyzed using a 2-Group x 3-Stimul us x 2-Distracter Type ANOVA. There was a main effect of stimulus type on accuracy, F (2,34) = 34.3, p < .001, 2 = .50, such that false alarms to distracters were more common than in correct target responses, which were in turn more common than false alarms to standards ( ps < .05). Distracter type also exerted a main effect on accuracy, F (2,34) = 70.2, p < .001, 2 = .67, and significantly in teracted with stimulus type, F (2,34) = 48.8, p < .001, 2 = .59, such that false alarms to distracters were elevated during trial blocks that presented novel distracters. Cognitive and emotional functioning The participant groups performed compar ably on the MMSE, Boston Naming Test, Controlled Word Association Test, Semantic Fluency, Digit Span, and the Wisconsin Card Sorting Test, while endorsing similar levels of emotional symptoms. Young participants outperformed older participants on Trails A and B, Digit Symbol Coding, and Stroop Color Word Naming ( ps < .01). Although no individuals met diagnostic criteria for any psychiatric disorder, two members of each group obtained a score on the AES that was above the conventional clinical cutoff for apathy (14). Event-Related Potential Data Standard stimuli waveforms contained an average (+ SD ) of 167.8 + 22.6 trials (range: 113-204), while target wave forms contained 35.5 + 5.2 trials (range: 24-46) and distracter waveforms contained 34.7 + 5.1 (range: 20-44). A 2-Group x 3-Stimulus x 2-Distracter

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40 ANOVA confirmed that there were no groupor distracter-related differences in the number of trials comprising the waveforms. Stimulus-loc ked ERP waveforms from the oddball task can be seen in Figures 2-1 and 2-2. Mean ERP amplitude and latency data are pr esented in Tables 2-3 through 2-6. SN component A 2-Group x 3-Stimulus x 2-Distracter ANOVA of SN amplitude revealed a significant main effect of group, F (1,35) = 7.2, p = .01, 2 = .17, with older participants exhibiting greater negative amplitudes compared to young participants. There was also a main effect of stimulus type, F (2,70) = 34.8, p < .001, 2 = .50, with maximal amplitude to distracters ( ps < .001). A main effect of distracter type was also significant, F (1,35) = 21.9, p < .001, 2 = .39, which was qualified by a significant stimul us x distracter interaction, F (1,35) = 23.4, p < .001, 2 = .40. SN amplitude was dramatically larger for novel distracters relative to non-novel ( p < .001), as shown in Figure 4-3. A 2-Group x 3-Stimulus x 2-Dist racter ANOVA of SN peak la tency revealed significant main effects of stimulus, F (2,70) = 5.0, p = .01, 2 = .13 and distracter, F (1,35) = 4.5, p < .05, 2 = .11. Additionally, distracter t ype interacted significantly wi th a linear trend over stimulus, F (1,35) = 6.5, p < .05, 2 = .16, such that SN latencies were faster for novel distracters than nonnovel ( p < .01), as shown in fig 2-3. SN latencies did not differ across group. P2 component A 2-Group x 3-Stimulus x 2-Distracter ANOV A of central P2 amplitude revealed significant main effects of group, F (1,35) = 12.3, p = .001, 2 = .26, stimulus, F (2,70) = 20.8, p < .001, 2 = .37, and distracter, F (1,35) = 4.5, p < .05, 2 = .11. A significant linear trend over stimulus interacted with distracter, F (1,35) = 4.5, p < .05, 2 = .11, such that distracter-related P2 amplitudes were larger during when the distra cters were novel. When examining the group x

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41 stimulus x distracter interaction for a similar polynomial trend, a significant quadratic trend over stimulus type was found to inte ract with group and distracter, F (1,35) = 4.5, p < .05, 2 = .11. Older participants exhibited larger distracter-related P2 amplitude s in the novel distracter block, while young participants did not show this novelty enhancement (Figure 2-4). A 2-Group x 3-Stimulus x 2-Dist racter ANOVA of P2 latency re vealed a significant effect of stimulus, F (2,70) = 7.4, p = .001, 2 = .17, and a stimulus x distracter interaction, F (2,70) = 4.0, p < .05, 2 = .10. Distracter-related P2 latency wa s shorter for both participant groups when the distracters were novel. P2 latency did not vary across group. N2 component A 2-Group x 3-Stimulus x 2-Distracter ANOV A of frontal N2 amplitude revealed significant main effects of group, F (1,35) = 36.5, p < .001, 2 = .51 and stimulus, F (2,70) = 4.7, p < .05, 2 = .12, the latter of which was qualified by a significant stimulus x distracter interaction, F (2,35) = 4.6, p < .05, 2 = .12. Novel distracters elicited larger N2 components than targets and standard stimuli ( ps < .01) but this effect was not seen for non-novel distracters. To assess for group differences in this novelty ef fect, data were subjected to polynomial trend contrasts of stimulus type across distracter and group. A significant in teraction of group x quadratic trend over stimul us x distracter emerged, F (1,35) = 4.1, p < .05, 2 = .11, revealing that distracter-related N2 amplitudes were enhan ced by novelty in young participants only (see Figure 2-5). A 2-Group x 3-Stimulus x 2-Distracter ANOV A of frontal N2 latency detected a significant group x dist racter interaction, F (1,35) = 16.9, p < .001, 2 = .33, in which older participants had longer N2 late ncies to stimuli as a whole than young when the trial block presented novel distracters.

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42 P3 component A 2-Group x 3-Stimulus x 3-Site x 2-Distract er ANOVA of P3 amplitude revealed main effects group, stimulus, and electrode site, as seen in Table 2-7. Peak P3 amplitudes were larger for young participants compared to older pa rticipants. Follow-up comparisons across participants revealed that distra cter-related P3 amplitudes were la rger than those from targets ( p < .001), which were in turn larger than those evoked by standards ( p < .001). As expected, a group x stimulus interaction was significant, with young participants exhibiting larger P3 amplitudes from target and distracter stimuli rela tive to older adults, as shown in Figure 2-6. Importantly, there was also a significant group x quadratic trend over st imulus x distracter interaction, with older participants exhibiting smaller am plitudes for targets during the novel distracter block relative to young pa rticipants. There were also si gnificant group x site, stimulus x site, and group x stimulus x site interactions in the data. The stimulus x site interaction remained si gnificant following amplitude normalization. Standard P3 amplitudes were equal across site, wh ile target P3 amplitudes maintained a maximal posterior distribution, larger for the parietal site than the frontal ( p < .001). Conversely, distracter P3 amplitudes displayed a maximal anteri or distribution, larger for the frontal site than the parietal ( p < .001). The group x stimulus x site in teraction was also significant in the normalized data, with young participants demonstr ating a more posteriorly distributed targetrelated P3 response and ol der participants showing anteriorly di stributed P3 to targets, as shown in Figure 2-7. Both groups showed a central maximu m for their distracter-related P3 responses. A 2-Group x 3-Stimulus x 3-Site x 2-Dist racter ANOVA of P3 latency was also performed, with significant result s shown in table 2-8. A significant group x stimulus x site interaction found that older par ticipants exhibited prolonged P3 latency for targets over the parietal site. Additionally, a gr oup x stimulus x distract er interaction reveal ed that relative to

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43 older participants, young particip ants target-re lated P3 latencies were shorter when non-novel distracters were presented ( p < .001) and distracter-related P3 latencies were shorter for novel distracters ( p < .01). Difference waves In order to isolate the en dogenous components that were more specific to processing distracters, difference waves were calculated by subtracting the st andard stimulus ERP waveforms from those elicited by distracters. Si milarly, target difference waves were calculated by subtracting the standard stimulus ERP waveform s from those elicited by targets. Distracter and target difference waves were calculated for each age group, and these difference waves showed maximal positive amplitudes with a latenc y of approximately 400 ms, seen in Figures 28 and 2-9. This corresponds approximately with P3 latencies of the peak amplitude seen in the original distracter and target waveforms. Mean amplitudes of these difference waves were calculated using a time window from 380-420 ms in order to quantify these condition-specific effects. For distracter difference waves, a 2-Group x 3-Site x 2-Distracter ANOVA revealed main effects of group, F (1,35) = 4.3, p < .05, 2 = .11, electrode site, F (2,70) = 17.7, p < .001, 2 = .34, and a group x site interaction, F (2,70) = 11.6, p < .001, 2 = .25. Young participants exhibited difference waves that had larger posit ive amplitudes over central and parietal sites relative to older participants ( ps < .05). For target difference waves, a 2-Group x 3-Site x 2Distracter ANOVA revealed ma in effects of distracter, F (2,70) = 4.9, p < .05, 2 = .12 and electrode site, F (2,70) = 8.6, p < .001, 2 = .20, along with a group x site interaction, F (2,70) = 17.3, p < .001, 2 = .33, and a group x di stracter interaction, F (2,70) = 4.1, p = .05, 2 = .11. Relative to young participants, members of th e older group had smaller positive amplitudes for

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44 the target difference wave over the parietal site ( p < .01), and their overall responses were reduced during trial blocks presenting novel distracters ( p < .05). Relationship with neuropsychological performance Several demographic and neurops ychological variables correlated with distracter and target difference wave amplitudes, as shown in Table 2-9. Age correlated with target-standard amplitudes for novel distracter blocks only, while digit span backwards correlated with novel and non-novel distracter-standard amplitudes. Digit Sy mbol performance correlated with target and distracter difference wave amplitudes regardle ss of distracter novelty. Phonemic fluency performance correlated with non-no vel distracter amplitudes. Surprisingly, education level was negatively correlated with novel and non-novel dist racter-related P3 responses, suggesting perhaps that lengthy doctoral prog rams (and/or never-ending dissert ation projects) may lead to blunted attentional orienting. The most interesting of these correlations is the finding that age was significantly correlated with target responses only when targ ets were presented in the context of novel distracters. In order to furt her examine these age-target rela tionships, hierarchical regression models were used to predict target difference wave amplitudes for novel and non-novel distracter blocks separately. Both models entered Digit Sy mbol score in step 1 (since this performance on this measure was consistently correlated with target difference waves during both distracter blocks) and age in step 2. As shown in Ta ble 2-10, the initial m odel with Digit Symbol performance as the lone predicto r explained 12% of the variance in target amplitude from novel distracter trials. The additi on of age significantly added to the model, accounting for an additional 10% of the variance and causing Digit Sy mbol to lose its signif icance as a predictor of target amplitude. Table 2-11 shows the effects wh en taking this same regression approach with target amplitudes from the non-novel distracter block, Digit Symbol score explained a similar

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45 amount of initial variance (11%) as the lone predictor. Howeve r, the addition of age did not significantly add to this model, and Digit Symbol remained a significant predictor of target amplitude even after accounting for its shared variance with age. Taken together, these regression results illustrate that the effect of age on target processing was unique to novel distracter trials only. Discussion In this experiment, distracter s of differing levels of novelty were presented in the context of a three-stimulus oddball task. The novel distracters were designe d to be deviant in both shortterm context (i.e., infrequent, une xpected, task-irrelevant) and stim ulus features (i.e., colorful, complex patterns) such as to maximize preferential processing that begins in early stages of visual processing. The non-novel di stracters were designed to elic it attentional orienting without the same degree of early preferential processi ng as the novel stimuli. The first goal was to observe the effects of distracter novelty on ERP reflections of a ttentional orienting. The second goal was to observe the effects of healthy aging on these patterns of preferential engagement of novel stimuli. As hypothesized, novel distracters differentially engaged the vi sual attention system in ways that non-novel distracters did not. Novel distracters elicited robust SN responses with larger amplitudes and shorter latencies than nonnovel distracters. Similarly, P2 responses to novel distracters were larger and faster than those for non-novel dist racters. These results were driven by the salient color patterns contained within the novel distra cters that made them distinct from the other grey stimuli in the task. Thes e early stages of atten tional processing are not specific to a novelty response, per se, but none theless provide a manipulation check which assures that these stimuli were receiving the maximal level of engagement from the start.

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46 Attentional orienting to novel events is hypothesi zed to take place in two different sets of processes that are reflected in di fferent ERP components. In line with predictions, the first stage of attentional orienting was selectively engaged by novel distracters in this experiment, resulting in larger N2 amplitudes. Nonnovel distracters elicited N2 am plitudes that were no different from targets. This finding offers a dramatic c ontrast to what was seen for the second stage of attentional orienting which gave ri se to the P3 response. Distr acter stimuli as a whole elicited larger P3 amplitudes than targets, regardless of their degree of novelty. However, no additional preferential processing occurred due to increased novelty in the colorful distracters. These results provide support for the dist inction between N2 and P3 as reflecting different stages of attentional orienting. As expected, older adults in this experiment showed similar patterns to young for the early preferential processing reflected in SN and P2. In fact, older pa rticipants exhibited larger SN amplitudes and enhanced P2 responses for novel distracters relative to young participants. Although it is consistent with previous research for older adults to show P2 novelty enhancements that are equal to that of young adults (Czigler & Balazs, 2005), it was not expected for older participants in this study to exhibit greater P2 amplitudes. This finding has not been reported in any othe r known studies examining novelty pr ocessing in aging; however, these results may be explained in terms of an increased susceptibility to involuntary capture of attention in the older adults. Andres, Parmentier and Excera (2006) found that older adults showed a larger distraction effect for task irre levant sounds and attributed this to a greater capture of attention due to defic its in frontal lobe filtering of i rrelevant information. Consistent with this explanation, th e older adults in this experiment ma y have exhibited larger SN and P2 amplitudes because of an impaired ability to inhib it attentional capture to the novel distracters. It

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47 is noteworthy that this attentional capture wa s limited only to these early components, and did not lead to a subsequent enhancem ent of attentional orienting in N2 or P3 responses in the older adults. In line with predictions, older participants showed deficits in attentional orienting. In contrast to young participants, older adults fail ed to show an enhanced N2 response to novel distracters. Older adults also showed less preferentia l processing reflected in P3 responses for infrequent stimuli as a whole (targets and distract ers). These effects are striking given the nature of their enhanced processing of novel distracters, reflected in the SN and P2 components that occur earlier in the visual processing stream. Th is finding is important si nce attentional orienting relies in part on a healthy frontal lobe, while early visual processi ng is more dependent on posterior cortical areas. Of a dditional note is the way that olde r participants pr ocessed targets during the oddball task. P3 respons e to targets had a fr ontally maximal distri bution in the older adults, relative to a parietally maximal distri bution for young adults. Th is finding replicates a host of prior studies (e.g,. Friedman et al., 1997), and provides evidence that the older participants needed to activate greater frontal ly-mediated processing resources in order to successfully respond to the targets. Overall, these findings suggest that the older adults in this study had alterations in frontal l obe contributions to at tentional processing wh ile exhibiting intact posterior visual processing. In the face of these expected age-related findi ngs, it is interesting to note how the older participants target-related processing was in fluenced by the type of distracter that was presented. During blocks involvi ng novel distracters, older adu lts demonstrated reduced P3 processing of targets relative to young adults. In other words, older participants were more distracted by the novel distract ers than young, and this impact caused selective impairments on

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48 target-related P3 processing. Pa radoxically, their reaction times to targets during these blocks actually decreased a replicati on of a surprising finding first re ported by Fabiani and Friedman (1995). It is possible that this occurred because the older adults in this study recruited greater frontal resources as they processed the targets, and these additional resources enabled them to respond to them more quickly. Regardless, the hier archical regression results illustrate that age was a significant predictor of target processi ng when novel distracters were presented and accounted for more variance than performance on a complex attention task (Digit Symbol). In contrast, age was not a significant predictor of targ et processing for trials in which the distracters were not novel. Taken together, these results suggest that olde r participants in this experiment processed target trials differently from young participants when novel distracters were present. Increased frontal involvement in older adults was likely ne eded to offset a reduced ability to maintain memory templates for the target stimuli, as suggested by pr evious studies (e.g., Fabiani & Friedman, 1995; Friedman et al., 1998). What ma kes the findings of this experiment unique is that the novelty of the distracters played a role in how easily targets we re processed (i.e., how easily their memory templates were maintained). This is the first study of its kind that has detected a link between the degree of distracter novelty and the ease with which targets are categorized.

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49 Table 2-1. Mean and standard deviation ( SD ) demographic and neuropsychological data for young and older participants. Young Older Mean ( SD ) Mean ( SD ) p Demographics Age (years) 21.6 (3.2) 65.0 (9.5) < .001 Education (years) 14.7 (.9) 17.4 (3.3) .001 Female (%) 55 -47 -ns Right-Handed (%) 86 -87 -ns Cognitive Functioning MMSE 29.0 (1.1) 28.5 (1.5) ns Boston Naming Test 55.8 (3.7) 57.1 (3.8) ns COWA (FAS) 37.3 (10.4) 44.6 (12.0) ns Semantic Fluency (Animals) 22.8 (3.0) 22.1 (5.3) ns Digit Span Forward 7.2 (1.0) 7.1 (1.3) ns Digit Span Backward 5.1 (1.3) 5.5 (1.4) ns Trails A (sec) 20.7 (4.7) 28.0 (10.3) < .01 Trails B (sec) 48.6 (17.2) 65.0 (28.0) < .05 Digit Symbol 89.2 (12.9) 75.6 (13.3) < .01 Stroop Word Reading 101.9 (14.1) 99.3 (13.0) ns Stroop Color Naming 79.7 (13.6) 73.5 (15.3) ns Stroop Color Word Naming 47.1 (12.4) 38.6 (11.5) < .05 WCST Categories Completed 5.8 (.9) 5.7 (1.0) ns WCST Total Errors 18.2 (17.0) 18.7 (15.0) ns WCST Perseverative Errors 8.8 (5.2) 10.5 (9.1) ns WCST Set Failure .1 (.4) .3 (.6) ns Emotional Functioning BDI-II 2.1 (2.8) 2.8 (3.3) ns GDS 1.6 (2.1) .9 (1.3) ns AES 8.1 (4.1) 7.9 (4.9) ns STAI State 26.9 (5.4) 27.5 (7.5) ns STAI Trait 30.5 (5.8) 27.7 (5.7) ns

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50 Table 2-2. Mean reaction time and accuracy data from the oddball task Young Older Mean ( SD ) Mean ( SD ) p Non-Novel Distracter Reaction time to targets (ms) 468 (80) 478 (69) ns Target response errors (%) 2.3 (3.9) 1.6 (2.2) ns False alarm to distracters (%) .5 (1.6) .5 (.9) ns False alarm to standards (%) .1 (.2) .1 (.3) ns Novel Distracter Reaction time to targets (ms) 466 (75) 462 (73) ns Target response errors (%) 1.4 (2.1) 1.5 (3.1) ns False alarm to distracters (%) 4.7 (.7) 4.6 (.6) ns False alarm to standards (%) .1 (.3) .3 (.5) ns Table 2-3. Peak amplitudes (V) from young part icipants for each stimulus type across novel and non-novel distra cter blocks. Standard Target Distracter Electrode Site Mean ( SD ) Mean ( SD ) Mean ( SD ) Oz SN Novel -1.0 (2.0) -.80 (2.8) -7.1 (6.1) Non-Novel -.7 (2.0) -1.2 (3.0) -1.0 (3.4) Cz P2 Novel 2.0 (1.9) 3.1 (3.6) 4.0 (3.4) Non-Novel 1.8 (1.8) 1.9 (2.2) 3.2 (2.9) Fz N2 Novel -2.9 (1.6) -2.7 (2.2) -5.1 (2.7) Non-Novel -2.8 (1.5) -3.7 (2.5) -3.5 (2.9) Fz P3 (Frontal) Novel 4.5 (3.1) 8.2 (3.8) 10.1 (6.1) Non-Novel 4.7 (3.1) 6.6 (3.5) 9.6 (5.6) Cz P3 (Central) Novel 8.2 (4.4) 13.9 (5.1) 17.5 (8.5) Non-Novel 8.6 (4.2) 12.2 (4.5) 17.3 (8.0) Pz P3 (Parietal) Novel 8.3 (3.9) 16.2 (4.9) 16.5 (6.2) Non-Novel 8.1 (3.3) 14.3 (4.1) 16.0 (7.1)

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51 Table 2-4. Peak latencies (ms) from young partic ipants for each stimulus type across novel and non-novel distracter blocks. Standard Target Distracter Electrode Site Mean ( SD ) Mean ( SD ) Mean ( SD ) Oz SN Novel 154.7 (34.5)151.8 (35.4) 134.9 (20.3) Non-Novel 154.0 (37.1)157.1 (28.2) 156.2 (32.7) Cz P2 Novel 209.8 (37.2)183.8 (39.4) 160.0 (30.0) Non-Novel 208.2 (39.6)190.4 (46.3) 188.9 (43.1) Fz N2 Novel 216.2 (43.2)221.4 (49.1) 236.2 (34.0) Non-Novel 234.2 (52.0)232.5 (47.3) 234.0 (42.3) Fz P3 (Frontal) Novel 394.7 (48.9)411.6 (84.8) 377.8 (35.0) Non-Novel 406.9 (71.5)376.4 (48.8) 405.1 (57.1) Cz P3 (Central) Novel 390.5 (58.2)451.4 (105.8) 380.4 (49.7) Non-Novel 415.3 (83.6)366.4 (30.3) 400.9 (68.3) Pz P3 (Parietal) Novel 375.4 (81.8)444.9 (86.9) 376.9 (30.3) Non-Novel 418.9 (86.5)350.7 (46.3) 388.5 (91.9)

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52 Table 2-5. Peak amplitudes (V) from older par ticipants for each stimulus type across novel and non-novel distracter blocks. Standard Target Distracter Electrode Site Mean ( SD ) Mean ( SD ) Mean ( SD ) Oz SN Novel -1.9 (1.9) -3.0 (2.6) -8.7 (5.2) Non-Novel -2.4 (1.3) -2.9 (2.2) -4.8 (3.5) Cz P2 Novel 4.1 (2.3) 4.5 (2.5) 7.4 (3.6) Non-Novel 4.3 (2.0) 5.0 (2.0) 5.7 (3.4) Fz N2 Novel -.09 (1.5) -.21 (1.8) -.67 (3.2) Non-Novel .00 (1.4) .04 (1.5) -.10 (2.1) Fz P3 (Frontal) Novel 5.3 (2.2) 8.9 (3.8) 10.4 (3.8) Non-Novel 5.4 (2.1) 9.5 (4.3) 10.3 (3.5) Cz P3 (Central) Novel 8.5 (3.3) 10.4 (6.2) 14.9 (5.9) Non-Novel 8.9 (3.4) 10.6 (6.5) 14.2 (5.4) Pz P3 (Parietal) Novel 7.7 (3.4) 10.9 (6.4) 12.9 (4.9) Non-Novel 8.0 (3.0) 10.6 (6.6) 11.4 (5.3)

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53 Table 2-6. Peak latencies (ms) from older part icipants for each stimulus type across novel and non-novel distracter blocks. Standard Target Distracter Electrode Site Mean ( SD ) Mean ( SD ) Mean ( SD ) Oz SN Novel 160.0 (21.8)155.7 (21.9) 147.7 (13.6) Non-Novel 161.6 (23.5)156.0 (20.8) 152.0 (18.5) Cz P2 Novel 195.7 (45.4)185.3 (37.1) 173.9 (30.0) Non-Novel 197.3 (42.5)171.2 (40.5) 189.6 (43.1) Fz N2 Novel 216.3 (50.9)243.2 (49.7) 240.5 (37.9) Non-Novel 202.4 (28.9)218.1 (43.2) 212.8 (38.3) Fz P3 (Frontal) Novel 409.9 (43.0)437.9 (58.6) 418.7 (48.9) Non-Novel 392.5 (47.8)417.6 (49.9) 430.9 (50.3) Cz P3 (Central) Novel 391.7 (47.5)472.3 (85.3) 424.8 (48.1) Non-Novel 381.9 (36.4)438.1 (66.0) 421.6 (34.5) Pz P3 (Parietal) Novel 388.3 (61.3)482.4 (91.5) 425.9 (72.2) Non-Novel 383.5 (59.4)487.5 (94.4) 410.7 (69.1) Table 2-7. Summary of the 2-Group x 3-Stimul us x 3-Site x 2-Distr acter ANOVAs performed on P3 peak amplitude data. Amplitude Normalized Amplitude F p 2 F p 2 Groupa Stimulusb 51.7 <.001 .60 Siteb 68.4 <.001 .66 Distractera G x Stima 4.3 <.05 .11 G x Siteb 12.4 <.001 .26 G x Da S x Sc 14.0 <.001 .29 5.1 .004 .13 Stim x Db Site x Db G x S x Sc 8.4 <.001 .19 4.3 .009 .11 G x Stim x Db G x Site x Db S x S x Dc G x S x S x Dc adf = 1,35, bdf = 2,70, cdf = 4,140

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54 Table 2-8. Summary of the 2-Group x 3-Stimul us x 3-Site x 2-Block ANOVAs performed on P3 peak latency data. Latency F p 2 Groupa 4.1 .05 .11 Stimulusb 8.7 <.001 .20 Siteb Blocka 6.5 <.05 .16 G x Stimb 8.6 <.001 .20 G x Siteb G x Ba Stim x Sitec 4.7 .001 .12 Stim x Bb 9.1 <.001 .21 Site x Bb G x Stim x Sitec 2.7 <.05 .07 G x Stim x Bb 6.1 <.01 .15 G x Site x Bb Stim x Site x Ba 5.5 <.05 .14 G x Stim x Site x Ba 4.7 <.05 .12 adf = 1,35, bdf = 2,70, cdf = 4,140 Table 2-9. Significant correlations between P3 difference waves and neuropsychological measures for young and older groups combined. Distracter Standard Target Standard Novel Non-Novel Novel Non-Novel Age -.45** -.19 Education -.47** -.38* Digit Span Backwards -.39* -.37* Digit Symbol .38* .45** .34* .37* COWA -.10 -.36* p < .05, ** p < .01

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55 Table 2-10. Summary of hi erarchical regression analysis for variables predicting the amplitude of the target-standard difference wave from novel distracter trials. B SE B Step 1 Constant -8.58 5.01 Digit Symbol .127 .06 .34* Step 2 Constant 1.29 6.71 Digit Symbol .05 .07 .14 Age -.09 .04 -.38* Note R2 = .12 for Step 1 ( p < .05); R2 = .10 for Step 2 ( p < .05). p < .05. Table 2-11. Summary of hi erarchical regression analysis for variables predicting the amplitude of the target-standard difference wa ve from non-novel distracter trials. B SE B Step 1 Constant -9.38 4.56 Digit Symbol .13 .05 .34* Step 2 Constant -9.79 6.50 Digit Symbol .13 .07 .38* Age <.01 .04 .02 Note R2 = .11 for Step 1 ( p < .05); R2 < .01 for Step 2 (p > .90). p = .05.

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56 Figure 2-1. Grand-averaged standa rd, target, and distracter ERPs from the midline electrodes for young adults. Microvolts on the y -axis, milliseconds on the x -axis.

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57 Figure 2-2. Grand-averaged standa rd, target, and distracter ERPs from the midline electrodes for older adults. Microvolts on the y -axis, milliseconds on the x -axis.

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58 -9 -8 -7 -6 -5 -4 -3 -2 -1 0 1 StandardTargetDistracter StimulusMean Amplitude (V) Novel Non-Novel 130 140 150 160 170 180 StandardTargetDistracter StimulusMean Latency (ms) Novel Non-Novel Figure 2-3. Mean amplitudes and latencies for the SN component as a function of stimulus condition and distracter type. Note: error bars reflect standard error of the mean. 0 1 2 3 4 5 6 7 8StandardTargetDistracterStandardTargetDistracterMean Amplitude (V) Novel Non-Novel YoungOlder Figure 2-4. Mean amplitudes and latencies for the P2 component as a function of stimulus condition and distracter type for the two pa rticipant groups. Note: error bars reflect standard error of the mean.

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59 -7 -6 -5 -4 -3 -2 -1 0 1StandardTargetDistracterStandardTargetDistracterMean Amplitude (V) Novel Non-Novel Young Older Figure 2-5. Mean amplitudes for the N2 compon ent as a function of stimulus condition and distracter type for the two pa rticipant groups. Note: error bars reflect standard error of the mean. 6 7 8 9 10 11 12 13 14 15 16 StandardTargetDistracter StimulusMean Amplitude (V) Young Older Figure 2-6. Mean amplitudes for the P3 compone nt as a function of stimulus condition for young and older participants. Note: error bars reflect st andard error of the mean.

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60 -1.5 -1 -0.5 0 0.5 1 1.5FzCzPzFzCzPzNormalized (z-score) Amplitude Distracter Target StandardYoungOlder Figure 2-7. Normalized (z-score) ERP amplitudes for the P3 as a function of electrode site and stimulus condition for young and older particip ants. Note: error bars reflect standard error of the mean.

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61 Figure 2-8. Spherical sp line voltage maps for the difference waves of distracter standard stimulus across participant groups, taken at 400 ms.

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62 Figure 2-9. Spherical splin e voltage maps for the difference wave s of target standard stimulus across participant groups taken at 400 ms.

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63 CHAPTER 3 EXPERIMENT 2: THE IMPACT OF PA RKINSONS DISEASE ON PREFERENTIAL NOVELTY PROCESSING Overview and Predictions Experiment 2 was conducted to examine th e effects of Parkin sons disease on ERP reflections of attentional orienting. In line wi th previous findings, it was predicted that PD patients would show decreased attentional orientin g (reflected in N2 and P3 amplitudes) toward novel distracters relative to contro ls. Given the fact that older a dults from Experiment 2 showed reduced effects of distracter novelty on their N2 and P3 responses, it was not expected that these ERP components would differ as a function of distracter novelty fo r PD patients. However, it was anticipated that target-related processing woul d be impacted in PD patients in a way similar to that of the older adults from Experiment 1. Assuming that age-relate d frontal lobe changes give rise to impaired target proc essing, then it would seem likely that fronto-striatal disruptions in PD would lead to even more alterations in target P3 pro cessing when novel distracters are present. Despite these expect ed changes in the PD group, early sensory processing was still expected to elicit greater SN and P2 amp litudes relative to non-novel distracters. Along with differences in N2 and P3 responses PD patients were also expected to show correlations between novel dist racter processing and measur es of apathy and executive functioning, while controls were expected to show relationships only between distracter processing and executive functioning. More spec ifically, distracter amplitudes in PD patients were expected to correlate with self-reported sy mptoms of apathy (AES), while participants as a whole were expected to show correlations between distracter amplitudes and performance on the Stroop test, Digit Symbol, Trails B, and the Wisconsin Card Sorting Test.

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64 Methods Participants Participants for this study were sixteen pati ents with idiopathic Parkinsons disease and fifteen healthy age-matched controls. Exclusionary criteria for the control participants were the presence of psychiatric illness, learning disabili ty, or history of neurol ogical disease or head injury. To be included in the PD group, patients n eeded to meet diagnostic criteria for PD and be free of dementia or any other medical illness that would potentially suppress their cognitive performance. The clinic al criteria for diagnosis of idiopathic PD included at le ast two of four cardinal motor signs (akinesia, bradykinesia, resting tremor, rigidity ; Hughes, Ben-Shlomo, Daniel, & Lees, 1992) and a history of dem onstrated therapeutic response to dopamine replacement therapy, as indicat ed by a marked improvement in motor signs measured by the United Parkinson Disease Rating Scale-Third Ed ition (UPDRS; Fahn & Elton, 1987). In this study, all PD patients obtained a score of 25 or hi gher on the MMSE (M. F. Fo lstein et al., 1975). Additional dementia screening was done with the Dementia Rating Scale (Mattis, 1988), on which patients generally did very well (mean + SD = 136.6 + 6.5). Control participants were recruited from the community. Parkinsons disease patients were recruited through the Movement Disorders Center of the Univ ersity of Florida. Patients received standard measures for staging their motor symptoms and disease course, including the motor subscale of the UPDRS and a modified Hoehn-Yahr scale (Hoehn & Yahr, 1967). Whenever possible, patients were evaluated with the UPDRS on and off medication. Of the sixteen PD patients, seven received Hoehn-Yahr scores of 2, two were given the score of 2.5, two were scored as 3, and one was a 4. Dem ographic and neuropsychological data for the participants can be seen in Table 3-1.

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65 Procedures All participants provided informed consent pr ior to the experimental session. For members of the healthy control group, the experiment took place in one session that lasted approximately 3 hours (except for two participants who needed to divide their session over two days due to scheduling difficulties). In contra st, most PD patients participated in the study over the course of two days which helped to prevent fatigue from adversely affecting their results. Patients were not given a full motor assessment at the time of te sting for this experiment; however, data from UPDRS and modified Hoehn-Yahr scales were collected during a prior visit to the Movement Disorders Center that took place w ithin one calendar year of the e xperimental session. Controls received financial compensation at the rate of $10 per hour for their participation. PD patients were not paid, but willingly volunt eered to participate in conjunc tion with their visits to the Movement Disorders Center. Results Behavioral Data Oddball task performance Behavioral data from the oddball task ar e presented in Table 3-2. A 2-Group x 2Distracter ANOVA was perf ormed on reaction time to targets, which revealed no significant effect of distracter type or group x distracter interaction. Wh en the two groups were analyzed separately with paired samples t-tests, however, reaction time to targets was found to be affected by distracter type for controls, t (14) = 2.6, p < .05, with faster responses during trial blocks that presented novel distracters. In order to correct for high levels of skewedness caused by the low probability of errors on the task, error rates were subjected to arcsine transformation and then analyzed using a 2-Group x 3-Stimulus x 2-Di stracter ANOVA. Response accuracy showed a group x distracter interaction, F (2,29) = 5.8, p < .05, 2 = .17, such that controls showed a

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66 decline in overall stimulus accuracy when novel distracters were presented, while PD patients showed the opposite pattern. Distra cter type also signi ficantly interacted with stimulus type, F (2,58) = 15.2, p < .001, 2 = .34. Follow-up comparisons rev ealed that false alarms to distracters were greater than both false alarms to standards and target misses, but only when distracters were novel ( ps < .001). Cognitive and emotional functioning The participant groups performed compar ably on the MMSE, Boston Naming Test, Controlled Word Association Test, Semantic Fluency, and Digit Span, while PD patients exhibited decreased performance on Trails A and B, Digit Symbol, Stroop Word reading, and the Wisconsin Card Sorting Test ( ps < .01). PD patients also exhibited more symptoms of depression (BDI and GDS) and anxiety (state and trait) than controls ( ps < .01). PD patients reported elevated levels of apathy symptoms re lative to controls, but this difference was not statistically significant. Four PD patients and two controls obta ined a score on the AES that was above the conventional clinical cutoff for apathy (14). Event-Related Potential Data Standard stimuli waveforms contained an average (+ SD ) of 167.8 + 25.3 trials (range: 97204), while target waveforms contained 33.7 + 7.4 trials (range: 18-46) and distracter waveforms contained 35.4 + 6.0 (range: 20-44). A 2-Group x 3-Stimul us x 2-Distracter ANOVA confirmed that there were no groupor distracter-related differences in the number of trials comprising the waveforms. Stimulus-locked ERP waveforms from the oddball task can be seen in Figures 3-1 and 3-2. Mean ERP amplitude and latency data are presented in Tables 3-3 through 3-6. SN component A 2-Group x 3-Stimulus x 2-Distracter ANOVA of SN amplitude revealed a significant main effect of group, F (1,29) = 4.8, p < .05, 2 = .14, with controls exhibiting greater SN

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67 amplitudes compared to PD patients. Ther e was also a main effect of stimulus, F (2,58) = 27.6, p < .001, 2 = .49, with distracters eliciting the maxi mal SN. Additionally, a main effect of distracter was also significant, F (1,29) = 18.4, p < .001, 2 = .39, which was qualified by a significant stimulus x distracter interaction, F (1,29) = 11.7, p = .001, 2 = .29. Distracters as a whole elicited larger SN amplit udes than targets and standards ( ps < .05), but this effect was enhanced when the distracters were novel ( ps < .001), as shown in Figure 3-3. A 2-Group x 3-Stimulus x 2-Dist racter ANOVA of SN peak la tency revealed significant group x stimulus interaction, F (2,58) = 11.6, p < .001, 2 = .29, such that distracter-related SN responses in PD patients were pr olonged relative to ot her stimuli, while co ntrols did not show this pattern. There was also a stim ulus x distracter type interaction, F (2,58) = 3.9, p < .05, 2 = .12, that was qualified by a group x linear trend ov er stimulus x distract er type interaction, F (1,29) = 5.1, p < .05, 2 = .15. For controls, distracters were processed with faster SN responses than other stimuli, particularly when the distracters were novel. Although PD patients were slower with their overall SN responses to distracters relativ e to other stimu li, they still processed novel distracters more qui ckly than non-novel distracters ( p < .01). P2 component A 2-Group x 3-Stimulus x 2-Distracter ANOVA of P2 amplitude revealed a significant main effect of group, F (1,29) = 6.6, p < .05, 2 = .19, with controls exhibiting greater P2 amplitudes compared to PD patients. Ther e was also a main effect of stimulus, F (2,58) = 22.7, p < .001, 2 = .44, as P2 amplitude was greater for dist racters than any other type of stimulus ( ps < .001). As shown in Figure 3-4, a significant stim ulus x distracter inte raction also emerged, F (1,33) = 14.8, p = .001, 2 = .34, such that distracter-related P2 amplitudes were larger during when the distracters were novel. There were no group differences in this stimulus x distracter interaction.

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68 A 2-Group x 3-Stimulus x 2-Distracter ANOVA was conducted on P2 latency, but no main effects or interactions were found. N2 component A 2-Group x 3-Stimulus x 2-Distracter ANOV A of frontal N2 amplitude revealed a significant linear trend over stimulus, F (1,29) = 5.2, p < .05, 2 = .15, with maximal N2 amplitude evoked by distracters, followed by targets, and then standard stimuli. A 2-Group x 3-Stimulus x 2-Distracter ANOVA of frontal N2 latency found a generalized significant main effect of distract er, such that N2 responses from all stimuli that were presented in novel distracter blocks exhibited longer peak latency relative to non-no vel distracter blocks, F (1,29) = 12.3, p < .01, 2 = .30. P3 component A 2-Group x 3-Stimulus x 3-Site x 2-Dist racter ANOVA of P3 amplitudes revealed significant main effects of stim ulus and electrode site, as sh own in Table 3-7. Targetand distracter-related P3 amplitudes did not differ but were both larger than standard stimuli ( ps < .001). Overall amplitudes were smaller at Fz relative to central and parietal sites ( ps < .01). Significant stimulus x site and site x distracter interac tions were subjected to follow-up analyses using normalized amplitude data. The site x distracter interaction was no longer significant following amplitude normalization. However, the stimulus x site inte raction remained significant with normalized data, demonstrating a quadratic trend over stimulus that interacted with a quadratic trend over electrode site, F (1,29) = 13.5, p = .001, 2 = .32. P3 distribution was maximal for distracters at the central site, while target-related amplitude was maximal at frontal and parietal sites (see Figure 3-5).

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69 A 2-Group x 3-Stimulus x 3-Site x 2Distra cter ANOVA on P3 latenc y data revealed a main effect of stimulus and stimulus x site inte raction, as shown in table 3-8. Overall, targetrelated P3 responses were the slowest to reach peak latency ( ps < .05), and this effect was most pronounced at the parietal site ( ps < .01), as shown in Figure 3-6. Taken together with the amplitude data, these results show that PD patie nts P3 responses were generally affected by distracter novelty in the same way as healthy controls. Difference waves In order to isolate the endogenous components more specific to processing distracters and targets, difference waves were calculated by subt racting the standard stimulus ERP waveforms from those elicited by distracters and targets. Novel and non-novel distra cter type difference waves were calculated for each group, and thes e difference waves showed maximal positive amplitudes with a latency of approximately 400 ms shown in Figure 3-7. This corresponds with P3 latencies of the peak amplitude seen in the or iginal distracter and target waveforms. Mean amplitudes of these difference waves were calc ulated using a time window from 380-420 ms. For distracter difference waves, a 2-Group x 3Site x 2-Distracter ANOVA revealed a main effect of electrode site, F (2,70) = 5.7, p < .01, 2 = .16, and a site x distracter interaction, F (2,70) = 4.0, p < .05, 2 = .12. Distracters elicited a centrally-d istributed maximal difference wave, and the site that showed the largest novelty enhancem ent was the parietal site. For target difference waves, a 2-Group x 3-Site x 2-Dist racter ANOVA revealed only a main effect of electrode site, F (2,70) = 5.1, p < .05, 2 = .15, with frontal and parietal si tes showing larger amplitudes than central for both groups ( ps < .05). Relationship with neuropsychological performance Several significant correlati ons were found between neur opsychological measures and difference waves for distracters and targets, as sh own in Table 3-9. Controls showed correlations

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70 between digit span backward a nd the distracter-standard difference wave amplitude, while Digit Symbol performance was correla ted with the target-standard difference wave amplitude. Similarly to Experiment 1, education level was also negatively correlated with distracterstandard difference amplit ude in the control group. PD patients showed a large number of correla tions between distracter-standard difference wave amplitude and measures of cognition, emo tional symptoms, and motor symptom severity. It was interesting to note that several of these correlations we re stronger for novel distracters, while others were stronger for non-novel distra cters. Notably, Stroop interference score and Digit Symbol correlated had positive correlati ons with non-novel distra cter difference wave amplitudes, while apathy and trait anxiety symp toms correlated negatively with amplitudes from novel distracter difference waves. Of the emotional measures given, only state anxiety symptoms correlated with non-novel distracter di fference waves. Additionally, target-standard difference wave amplitude correlated with scores on the GDS and Wisconsin Card Sorting Test. In order to assess the unique relationshi ps between distracter processing and neuropsychological measures, hier archical regression models we re conducted. The first model included three different measures of emotional sy mptoms as predictors for the novel distracterstandard difference wave amplitude, as shown in Table 3-10. Apathy score from the AES was selected for step 1 of this model because of th e previous research showing a relationship between apathy and distracter P3 amplitudes in other neurological populations. BDI score was then added to the model in order to determine if apathy exhibited a relationship with distracter processing that was unique from that of depressi on, followed by the trait anxiety score from the STAI. The initial model with apathy score as the lone predictor explained 54% of the variance in novel distracter-standard difference wave amplitude The addition of BDI and STAI trait anxiety

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71 factors into the regression did not account fo r any additional variance in distracter-related amplitude. In order to better understand the unexpected significant correlation between anxiety and novel distracter P3 amplitude, additional hierar chical regression models were conducted to determine if motor symptoms accounted for this relationship. Trait anxi ety was included as a predictor for the novel distracter-standard differen ce wave amplitude in the first step, with motor symptoms taken from the Hoehn-Yahr Scale and UPDRS (both on meds) included in the second step. As shown in Table 3-11, the initial model with trait anxiety as the lone predictor explained 73% of the variance in novel distracter differe nce wave amplitude, yet the addition of motor symptoms did not account for any additional variance. When examining the role of state anxiety in predicting non-novel distracter difference wa ve amplitude, a similar result was found. As shown in Table 3-12, state anxiety explained 47% of the variance in non-novel distracter amplitude, and the addition of motor symptoms did not account for any additional variance. As a result, state and trait anxiety emer ged as significant predictors of distracter processing, even after controlling for effects of motor symptoms. Discussion This experiment used the same parameters as Experiment 1 to examine the ways in which novel stimuli are preferentially proc essed in Parkinsons disease. The first goal was to observe the effects of distracter novelty on ERP reflections of attentional orientin g and determine if PD patients differ in novelty processing relative to age-matched controls. The second goal was to explore the relationships betw een novelty processing and broader symptoms in PD. As predicted, novel distracters engaged the early visual attention system in ways that were not seen for non-novel distracters. PD patients showed larger SN and P2 responses to novel distracters compared to non-novel distracters, although both of these effects were smaller for PD

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72 patients compared to controls. However, no differences were found between PD patients and controls with regard to the eff ects of distracter novelty on atten tional orienting or target-related processing. N2 responses were larger for distra cters than targets, but did not differ between groups. Both groups also showed a lack of P3 enhancement from distracters and similar scalp distributions of overall P3 respons es. Distracters were associated with a maximal response over the parietal electrode, while targ et-related P3 responses showed scalp distributions that were large at both frontal and parietal sites, an eff ect that is commonly obser ved in older adults (e.g., Fabiani & Friedman, 1995). Contrary to predictions, these findings s uggest that PD patients do not experience additional deficits in attentiona l orienting or target processing beyond those associated with healthy aging. Differences did emerge, however, when examining the relationships between P3 responses and measures of neuropsychological and neurological functioning. PD patients showed correlations between distracter processi ng and a much broader range of symptoms that fell into distinct cognitive, emotional, and motor categories. In line with predictions, all of the cognitive factors that correla ted with distracter processi ng were measures of executive functioning (Stroop interference, Di git Symbol, verbal fluency, and Trails B). Of the emotional measures, apathy and trait anxiety correlated with novel distracter processing, while motor symptom severity scores corre lated with both novel and non-nove l distracter responses. The negative correlation between novel distracter P3 and apathy scores was expected, given previous reports that othe r neurological patients with dama ge to frontal or subcortical regions show this same relationship (Daffner et al., 2001; R. T. Knight 1984; Yamagata et al., 2004). Subsequent analysis with hierarchical regression found that th e relationship between apathy and novelty distracter P3 amplitude rema ined significant after accounting for the effects

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73 of depression. Furthermore, trait anxiety di d not explain any additi onal variance in novel distracter processing beyond that of apathy and depression. Howe ver, trait and state anxiety emerged as significant predictors of distracter pro cessing above and beyond that accounted for by motor symptoms. This is an interesting fi nding, since there has be en some data linking anxiety and motor fluctuations in PD, with some studies find ing increased anxiety symptoms when patients are in the off state of dopaminerg ic therapy (Menza et al ., 1990; Siemers et al., 1993). Unfortunately, since PD patients typically spread their participation across different days to prevent fatigue, the data from the STAI, moto r symptom scales, and EEG experiment were not collected at the same time. As a result, the precise temporal relations hip between distracter processing and momentary fluctuations in anxi ety or motor symptoms could not be fully assessed with the current study. Target-related P3 responses in PD patients correlated with depression symptoms endorsed on the GDS and measures of WCST performance ( categories completed, perseverative errors). Although many cognitive processes are required for success on the WCST, this task is generally understood to measure executive f unctioning (Lezak et al., 2004). Impairment on the WCST has previously been associated with distracter-related P3 processing in PD (Tsuchiya et al., 2000), so it was somewhat unexpected that WCST performance correlated with target-related P3 amplitude in this study. When examining the relationshi ps between distracter-r elated processing and neuropsychological measures, st roop interference and Digit Sym bol performance both correlated strongly with non-novel distracter processing. However, these cogni tive measures had virtually no correlation with novel distracter processing. The opposite finding was the case for apathy and trait anxiety scores, which correlated strongl y with novel distracter processing only.

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74 The reason for these different co rrelation patterns is not clear; however, it is possible that the divergent relationships with distracter novelty were influe nced by task-related differences caused by the experimental manipula tion of distracter novelty. Anal ysis of false alarm rates to distracters revealed that PD patients committed more errors when the distracters were novel (6.0%) than when they were not (4.7%). Furthe rmore, controls were over 10 times more likely to commit a false alarm to a novel distracter than one that was non-novel. ERPs were taken only from correct trials, so distracter false alarms did not directly contribute to differences in the ERP waveforms. However, the fact that participants were more likely to generate false alarms when the distracters were novel suggests that the two distracter conditions required differing degrees of inhibition. It would be logical that the more challenging response inhibition condition (trial blocks containing novel distracter s) would require cognitive proce sses similar to that measured neuropsychological tasks like St roop, WCST, or Digit Symbol that tap inhibition and other related executive functioning abilities. Instead, the data seem to be suggesting another story. Novel distracter processing was most strongly correlated with apathy, trait anxiety, and motor symptom severity. Perhaps the relationship between novel di stracter processing and neuropsychological measures were lacking because the inhibitory pro cesses required to prevent false alarms of novel distracters are not as simple or unitary as they are for non-novel dist racters. Furthermore, it is possible that additional neural reso urces were required to successfully inhibit a false alarm to the novel distracters (due to increa sed perceptual salience), and these extra resources might be beyond the scope of the P3 to measure. Whatev er the reason behind these particular findings, these correlation patterns raise the possibility that novelty pr ocessing may interact with broader cognitive and emotional functions in ways that are more complex than first thought.

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75 Table 3-1. Mean and standard deviation ( SD ) demographic and neuropsychological data for controls and PD participants. Controls (n=15) PD Patients (n=16) Mean ( SD ) Mean ( SD ) p Demographics Age (years) 65.0 (9.5) 63.5 (8.7) ns Education (years) 17.4 (3.3) 13.7 (3.1) < .01 Female (%) 47 -25 -ns Right-Handed (%) 87 -100 -ns Cognitive Functioning MMSE 28.5 (1.5) 29.2 (1.1) ns Dementia Rating Scale --136.6 (6.5) Boston Naming Test 57.1 (3.8) 56.6 (2.3) ns COWA (FAS) 44.6 (12.0) 37.1 (14.9) ns Semantic Fluency (Animals) 22.1 (5.3) 19.3 (6.5) ns Digit Span Forward 7.1 (1.3) 7.0 (1.1) ns Digit Span Backward 5.5 (1.4) 5.6 (1.4) ns Trails A (sec) 28.0 (10.3) 47.3 (25.7) .01 Trails B (sec) 65.0 (28.0) 119 (55.6) < .01 Digit Symbol 75.6 (13.3) 49.4 (16.8) < .001 Stroop Word Reading 99.3 (13.0) 83.9 (15.5) < .001 Stroop Color Naming 73.5 (15.3) 63.3 (13.8) ns Stroop Color Word Naming 38.6 (11.5) 32.3 (11.4) ns WCST Categories Completed 5.7 (1.0) 3.7 (1.9) .001 WCST Total Errors 18.7 (15.0) 40.4 (19.3) < .01 WCST Perseverative Errors 10.5 (9.1) 22.9 (12.5) < .01 WCST Set Failure .3 (.6) 1.3 (.9) .001 Emotional Functioning BDI-II 2.8 (3.3) 11.7 (8.1) .001 GDS .9 (1.3) 8.0 (7.9) < .01 AES 7.9 (4.9) 10.4 (8.0) ns STAI State 27.5 (7.5) 39.1 (11.3) < .01 STAI Trait 27.7 (5.7) 39.1 (12.3) < .01 Disease Characteristics Duration of Symptoms (yrs) --10.4 (2.82) -UPDRS Motor On Meds --26.2 (13.2) -Hoehn-Yahr Scale On Meds --2.4 (.6) -UPDRS Motor Off Meds --34.1 (12.4) -LED --1129.0 (637.8) -Antidepressant Medications (%) --37.5 --

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76 Table 3-2. Behavioral da ta from the oddball task. Controls PD Patients Mean ( SD ) Mean ( SD ) p Non-Novel Distracter Reaction time to targets (ms) 478 (69) 476 (97) ns Target response errors (%) 1.6 (2.2) 9.1 (10.1) < .01 False alarm to distracters (%) .4 (.9) 4.7 (9.8) ns False alarm to standards (%) .1 (.3) 4.2 (8.8) ns Novel Distracter Reaction time to targets (ms) 462 (73) 483 (72) ns Target response errors (%) 1.5 (3.1) 4.8 (7.3) ns False alarm to distracters (%) 4.6 (.6) 6.0 (3.5) ns False alarm to standards (%) .3 (.5) 2.2 (4.3) ns Table 3-3. Peak amplitudes (V) from the cont rol group for each stimulus type across novel and non-novel distracter blocks. Standard Target Distracter Electrode Site Mean ( SD ) Mean ( SD ) Mean ( SD ) Oz SN Novel -1.9 (1.9)-3.0 (2.6) -8.7 (5.2) Non-Novel -2.4 (1.3)-2.9 (2.2) -4.8 (3.5) Cz P2 Novel 4.1 (2.3)4.5 (2.5) 7.4 (3.6) Non-Novel 4.3 (2.0)5.0 (2.0) 5.7 (3.4) Fz N2 Novel -.09(1.5)-.21 (1.8) -.67 (3.2) Non-Novel .00(1.4).04 (1.5) -.10 (2.1) Fz P3 (Frontal) Novel 5.3 (2.2)8.9 (3.8) 10.4 (3.8) Non-Novel 5.4 (2.1)9.5 (4.3) 10.3 (3.5) Cz P3 (Central) Novel 8.5 (3.3)10.4 (6.2) 14.9 (5.9) Non-Novel 8.9 (3.4)10.6 (6.5) 14.2 (5.4) Pz P3 (Parietal) Novel 7.7 (3.4)10.9 (6.4) 12.9 (4.9) Non-Novel 8.0 (3.0)10.6 (6.6) 11.4 (5.3)

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77 Table 3-4. Peak amplitudes (V) from PD patients for each stimulus type across novel and nonnovel distracter blocks. Standard Target Distracter Electrode Site Mean ( SD ) Mean ( SD ) Mean ( SD ) Oz SN Novel -1.0 (2.9)-2.1 (3.4) -4.3 (4.7) Non-Novel -.90 (2.4)-1.2 (3.0) -2.4 (3.7) Cz P2 Novel 2.5 (1.7)2.2 (3.0) 5.5 (3.4) Non-Novel 2.3 (1.8)3.0 (2.7) 3.0 (3.2) Fz N2 Novel -1.3 (1.8)-2.2 (3.3) -2.5 (3.7) Non-Novel -1.6 (1.7)-1.3 (3.1) -2.7 (2.7) Fz P3 (Frontal) Novel 5.6 (2.8)8.0 (5.3) 9.0 (4.6) Non-Novel 5.6 (2.6)9.6 (5.2) 9.2 (4.9) Cz P3 (Central) Novel 7.1 (3.4)8.5 (6.6) 11.1 (4.8) Non-Novel 7.1 (3.6)10.3 (7.8) 11.1 (6.1) Pz P3 (Parietal) Novel 7.0 (3.4)9.6 (6.4) 10.8 (4.5) Non-Novel 6.9 (3.5)11.2 (5.7) 10.1 (5.2)

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78 Table 3-5. Peak latencies (ms) from controls for each stimulus type across novel and non-novel distracter blocks. Standard Target Distracter Electrode Site Mean ( SD ) Mean ( SD ) Mean ( SD ) Oz SN Novel 160.0 (21.8)155.7 (21.9) 147.7 (13.6) Non-Novel 161.6 (23.5)156.0 (20.8) 152.0 (18.5) Cz P2 Novel 195.7 (45.4)185.3 (37.1) 173.9 (30.0) Non-Novel 197.3 (42.5)171.2 (40.5) 189.6 (43.1) Fz N2 Novel 216.3 (50.9)243.2 (49.7) 240.5 (37.9) Non-Novel 202.4 (28.9)218.1 (43.2) 212.8 (38.3) Fz P3 (Frontal) Novel 409.9 (43.0)437.9 (58.6) 418.7 (48.9) Non-Novel 392.5 (47.8)417.6 (49.9) 430.9 (50.3) Cz P3 (Central) Novel 391.7 (47.5)472.3 (85.3) 424.8 (48.1) Non-Novel 381.9 (36.4)438.1 (66.0) 421.6 (34.5) Pz P3 (Parietal) Novel 388.3 (61.3)482.4 (91.5) 425.9 (72.2) Non-Novel 383.5 (59.4)487.5 (94.4) 410.7 (69.1)

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79 Table 3-6. Peak latencies (ms) from PD pa tients for each stimulus type across novel and nonnovel distracter blocks. Standard Target Distracter Electrode Site Mean ( SD ) Mean ( SD ) Mean ( SD ) Oz SN Novel 150.3 (33.6)144.3 (35.0) 151.5 (19.8) Non-Novel 139.8 (34.3)144.0 (33.6) 164.5 (19.9) Cz P2 Novel 167.0 (44.4)167.0 (39.0) 171.3 (31.3) Non-Novel 177.3 (46.6)176.5 (43.7) 168.0 (50.3) Fz N2 Novel 244.3 (44.3)237.8 (40.9) 250.5 (31.6) Non-Novel 234.0 (36.8)228.3 (45.5) 232.0 (45.2) Fz P3 (Frontal) Novel 416.3 (59.9)462.0 (95.3) 453.3 (81.1) Non-Novel 415.3 (69.6)446.3 (91.7) 432.0 (76.6) Cz P3 (Central) Novel 436.5 (87.3)463.3 (121.6) 431.0 (72.7) Non-Novel 425.3 (90.7)454.5 (121.6) 422.5 (71.5) Pz P3 (Parietal) Novel 379.5 (61.7)447.8 (112.9) 393.0 (76.7) Non-Novel 397.5 (76.5)444.8 (89.8) 409.8 (78.5) Table 3-7. Summary of the 2-Group x 3-Stimul us x 3-Site x 2-Distracter ANOVAs performed on P3 peak amplitude data. Amplitude Normalized Amplitude F p 2 F p 2 Groupa Stimulusb 22.7 <.001 .44 Siteb 14.1 <.001 .33 Distractera G x Stimb G x Site G x Da Stim x Sitec 8.5 <.001 .23 3.1 < .05 .10 Stim x Db Site x Db 3.5 <.05 .11 G x S x Sc G x Stim x Da G x Site x Db S x S x Dc G x S x S x Dc adf = 1,29, bdf = 2,58, cdf = 4,116

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80 Table 3-8. Summary of the 2-Group x 3-Stimul us x 3-Site x 2-Distr acter ANOVAs performed on P3 peak latency data. Latency F p 2 Groupa Stimulusb 11.9 <.001 .29 Siteb Distractera G x Stimb G x Site G x Da Stim x Sitec 4.0 <.01 .12 Stim x Db Site x Db G x S x Sc G x Stim x Da G x Site x Db S x S x Dc G x S x S x Dc adf = 1,29, bdf = 2,58, cdf = 4,116

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81 Table 3-9. Significant correlations between di fference waves and neur opsychological measures for control and PD groups separately. Distracter Standard Target Standard Novel Non-Novel Novel Non-Novel Controls Education -.72*** -.61* Digit Span Backward -.35 -.55* Digit Symbol .62* .57* PD Patients Cognitive Stroop Interference .14 .71** Digit Symbol .11 .55* Animal Fluency .37 .51* Trails B -.55* -.27 WCST Categories -.56* -.57* WCST Persev Errors -.65* -.59* Emotional AES -.61** -.30 BDI -.41 -.10 STAI Trait -.65** -.44 STAI State -.37 -.61* GDS -.43 -.20 .57* .39 Motor UPDRS -.54* -.61* Hoehn-Yahr -.63* -.28 p < .05, ** p < .01, *** p < .001

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82 Table 3-10.Summary of hierarchical regression analysis for variables predicting the amplitude of the novel Distracter-Standard difference wave. B SE B Step 1 Constant 6.40 .98 AES -.28 .07 -.73** Step 2 Constant 6.19 1.12 AES -.33 .14 -.87* BDI .063 .14 .16 Step 3 Constant 7.02 3.00 AES -.31 .18 -.79 BDI .08 .16 .21 STAI Trait Anxiety -.04 .12 -.14 Note R2 = .54 for Step 1 ( p < .01); R2 = .007 for Step 2; R2 = .004 for Step 3 (ps >.65). p < .05, ** p < .01. Table 3-11.Summary of hierarchical regression analysis for variables predicting the amplitude of the novel Distracter-Standard difference wave. B SE B Step 1 Constant 10.72 1.74 STAI Trait Anxiety -.209 .04 -.86** Step 2 Constant 11.56 2.32 STAI Trait Anxiety -.19 .06 -.80* Hoehn-Yahr Scale (on meds) .03 .07 .10 UPDRS (on meds) -.87 1.29 -.19 Note R2 = .73 for Step 1 ( p = .001); R2 = ..02 for Step 2 ( p > .80). p < .05, ** p < .01.

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83 Table 3-12.Summary of hierarchical regression analysis for variables predicting the amplitude of the non-novel Distracter-Standard difference wave. B SE B Step 1 Constant 10.06 2.98 STAI State Anxiety -.21 .08 -.69* Step 2 Constant 8.12 3.87 STAI Trait Anxiety -.23 .09 -.75* Hoehn-Yahr Scale (on meds) -.07 .11 -.22 UPDRS (on meds) 1.81 1.86 .34 Note R2 = .47 for Step 1 ( p < .05); R2 = .06 for Step 2 ( p > .60). p < .05.

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84 Figure 3-1. Grand-averaged standa rd, target, and distracter ERPs from the midline electrodes for healthy controls. Microvolts on the y -axis, milliseconds on the x -axis.

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85 Figure 3-2. Grand-averaged standa rd, target, and distracter ERPs from the midline electrodes for PD patients. Microvolts on the y -axis, milliseconds on the x -axis.

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86 -8 -7 -6 -5 -4 -3 -2 -1 0 1 StandardTargetDistracter StimulusMean Amplitude (V) Novel Non-Novel Figure 3-3. Mean amplitudes for the SN compon ent as a function of stimulus condition and distracter type. Note: Error bars reflect standard error of the mean. 2 3 4 5 6 7 StandardTargetDistracter StimulusMean Amplitude (V) Novel Non-Novel Figure 3-4. Mean amplitudes for the P2 compone nt as a function of stimulus condition and distracter type. Note: Error bars reflect standard error of the mean.

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87 -1 0 1 FzCzPz StimulusNormalized (z-score) Amplitude Distracter Target Standard Figure 3-5. Normalized (z-score) ERP amplitudes for the P3 as a function of electrode site and stimulus condition for both groups combined. Note: Error bars re flect standard error of the mean.

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88 370 390 410 430 450 470 490 FzCzPz StimulusMean Latency (ms) Distracter Target Standard Figure 3-6. ERP latencies for the P3 as a func tion of electrode site and stimulus condition for both groups combined. Note: Error bars reflect standard error of the mean.

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89 Figure 3-7. Spherical sp line voltage maps for the difference waves of distracter standard stimulus across participant groups, taken at 400 ms.

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90 Figure 3-8. Spherical splin e voltage maps for the difference wave s of target standard stimulus across participant groups taken at 400 ms.

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91 CHAPTER 4 GENERAL DISCUSSION These two experiments examined novelty pr ocessing across young and older adults and between Parksinsons disease patients and age-ma tched controls. By manipulating distracter features, it was possible to examine the effects of novelty on attentional or ienting to unexpected events. The first aim of this project was to examine the effects of novelty on distracter processing and examine the neural timecourse of preferential engagement with novel events in healthy young adults. As predic ted, distracting novel stimuli that contained colorful designs were associated with preferenti al processing that began early in visual processing, reflected in SN and P2 component enhancements. Also in line with predictions, these novelty features did not change the preferential pr ocessing reflected in the P3 component, yet N2 was enhanced beyond the level seen for non-novel distracters. This supports the notion that the N2 reflects subprocesses of attentional orienting which serve as an index of stimulus unfamiliarity (Daffner, Mesulam, Scinto, Calvo et al., 2000). While th is N2 enhancement effect has been seen in previous studies, it has not been reported in conjunction with the early components of visual attention (SN, P2) that were also enhanced for novel distracters. Furthermore, this finding is important since N2 differences have only rarely been studied in older adults and PD patients. The second aim was to examine the impact of healthy aging and Pa rkinsons disease on novelty processing. Both healthy older adults and PD patients failed to exhibit N2 enhancements in response to novelty, even when distracters we re highly novel and preferentially engaged early visual attention (SN, P2). The reasons for thes e deficits are not entire ly clear, but are likely related to compromised frontal l obe structures that are part of the network that mediates attentional orienting. Indeed, front al shifts in target-related scal p distribution were seen for the older adults and PD patients, suggesting that th ey required additional frontal lobe resources to

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92 perform the task. Even so, older participants target P3 responses were selectively altered by the presence of novel distracters, s uggesting that the increase in task-irrelevant novelty processing disrupted their ability to maintain memory templates of task-relevant stimuli. Contrary to expectations, PD patients and healthy agematched controls did not significantly differ in their ERP re flections of attentional orienting (N2, P3). P3 amplitudes were slightly smaller in the PD group co mpared to controls, but this di fference did not reach statistical significance. Although impairments in novelty P3 amplitudes have previously been reported in this clinical population (Tsuchiy a et al., 2000), the results of th e current study are not supportive of a definitive impairment in a ttentional orienting in PD that goes beyond the general effects of aging. However, PD patients did exhibit differe nces from controls in the manner with which their attentional orie nting measures (P3 amplitude) were asso ciated with other forms of cognitive and emotional processing. The third aim of this project was to explore the relationshi ps between novelty processing and other domains of psychological function. In Experiment 1, young and older adults showed similar relationships between measures of executive function and distracter-related P3 processing. In Experiment 2, PD patients genera ted P3 responses to novel distracters that were negatively correlated with apathy scores (even while accounting for symptoms of depression), such that patients who were more apathetic de monstrated smaller P3 amplitudes in response to the novel distracters. This finding was predicted, given previous reports that other neurological disorders are characterized by this same relati onship (Daffner, Mesulam, Scinto, Acar et al., 2000; Daffner et al., 2001; R. T. Knight, 1984; Yamagata et al., 2004). Another interesting finding was that anxiety was negatively associated with distracter-related P3 amplitudes, even while controlling for motor symptoms. Finally, it was notable that some neuropsychological

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93 measures only correlated with novel distracter P3 amplitudes in PD patients, while others correlated only with responses evoked from non -novel distracters. Unfortunately, the current project was not statistica lly powered for an in-depth analysis of these relationships. However, these dissociations could reflect meaningful differences in th e way that novelty processing interacts with broader psychological functioning and should be explored further in future research. Although novelty processing is often conceptuali zed as an automatic reflex that orients attention toward unexpected events, a recent st udy found that novelty effects are vulnerable to top-down modulation. Using a three-stimulus oddba ll task similar to the one involved in this project, Chong and colleagues (2008) included an interesting condition in which participants were instructed to visually explore the novel s timuli as task-relevant invitations for further processing, rather than ignoring them as task ir relevant distracters. This condition led to enhanced novelty processing, as reflected in larger P3 amplitudes, and provided dramatic evidence that changes in context both expe rimentally and personall y derived can have dramatic changes on how novel information is pro cessed. The results of the current study clearly support this notion that indivi dual differences in psychologi cal functioning are strongly associated with ERP reflections of novelty pr ocessing, as apathy and anxiety were found to explain large portions of the variance in distracter P3 amplitudes. This project possessed several weaknesses that need be take n into account when generalizing conclusions. First of all, the mean age of the older particip ants was 65, yet this age varied considerably within the group (range: 49-77). It would have been desirable to limit the sample to a more homogenous age range so that the findings could be better generalized and compared to other aging studies that had more restrictive age ra nges. Similarly, the PD patient

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94 group also suffered from limitations in that the sample size was rela tively small in relation to the heterogeneity of symptoms presented. Furthe rmore, all PD patients were recruited from clinical/research settings affiliated with an academic medical center. Many of these patients were participating in other resear ch/clinical evaluations in conjunc tion with their participation in this project. Therefore, cer tain levels of symptoms (e.g., apathy, cognitive dysfunction) may have been subject to a selection bias. As a result, the PD-relate d findings may not generalize to all PD patients. However, both of these lim itations should have actually worked against the hypotheses and made it more difficult to obtain signi ficant ageand PD-relate d effects; therefore, participant characteristic s of the older and PD groups do not appear to be a major obstacle in interpreting the results of this study. On the contrary, they speak to the robustness of the ageand PD-related findings that were obtained. Another limitation is that no estimates of IQ were obtained from par ticipants during this study, which may have been helpful for interpreting re sults in light of global cognitive abilities. This became an important weakness as the st udy reached its completion, since young and older age groups could not be balanced in terms of ove rall education level. While education is not believed to have been a major confound in the curre nt project, it is possible that it influenced some of the group-related differenc es, particularly with regard to the relationships between P3 responses and other cognitive variables. A measur e of IQ could have provided a way to ensure that global cognitive abilities were similar acro ss groups. As a screening tool, the MMSE was not likely sensitive enough to provide this level of information. Nevertheless, other studies similar to this have also suffered from group differences in educati on, which appears to be somewhat inevitable when investigati ng aging (e.g., Daffner et al., 2005).

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95 This project also contained numerous methodological strengths First, the concept of novelty was operationalized successfu lly by using two sets of task -irrelevant distracters that differed in their degree of novelty features. The experimental manipulation of distracter novelty allowed for concrete conclusions to be draw n about the effects of novelty on attentional processing across the three participant groups. Th e novel stimuli were designed in such as a way as to maximize their likelihood of receiving preferential proce ssing in all stages of visual processing. This high degree of pe rceptual salience led to measurab le differences in early visual processing that could then be used for compar ison with the subsequent attentional orienting processes. These stimuli genera ted dramatic effects on early visu al processing in all participant groups, verifying that the impairments of attent ional orienting in select groups could not be explained in terms of a gene ralized attentional deficit. Another clear strength was the use of ERPs to characterize the rapid changes in neural processing that occurred during the oddball task. ERPs were used as a way as to probe the processing resources devoted to different stages of attentiona l processing and offered insights into the underlying neural mechanisms in ways that behavior al data alone could not achieve. Importantly, a large number of neuropsychologica l tests were also administered, providing the opportunity for maximal convergence of res earch findings across different methods. Overall, the overarching goal of this dissert ation was to better understand how novelty is processed in the brain and examine how healt hy aging and Parkinsons disease impact novelty processing. The results of these two experime nts have provided strong evidence that novel events receive preferenti al neural processing in ways that ar e governed by both the features that characterize the event, as well as the feat ures that characterize the individual. Neurophysiological changes in older adults and PD patients give rise to novelty processing

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96 deficits in these two groups, wh ich can be precisely measured w ith ERPs. Future research is needed to continue characterizing the nature of these deficits and the relationships they have with broader psychological functioning.

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105 BIOGRAPHICAL SKETCH David Andrew Stigge Kaufman completed a Bachelor of Arts degree in biology and psychology from Bethel College in North Newton Kansas, in 1998. After teaching high school science for five years, he began his doctoral tr aining in the Department of Clinical and Health Psychology at the University of Florida. In 2005, he earned a Master of Science degree in psychology. In 2009, he earned a Ph.D. in clinical psychology, with specia lization in clinical neuropsychology, following a one-year clinical internship at the University of California, Los Angeles in Los Angeles, California.