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A neuroimaging investigation of affective, cognitive, and language functions in psychopathy Kiehl, Kent Anthony 2000

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A N E U R O I M A G I N G I N V E S T I G A T I O N O F A F F E C T I V E , C O G N I T I V E , A N D L A N G U A G E F U N C T I O N S I N P S Y C H O P A T H Y B y K E N T A N T H O N Y K I E H L B . S c , Un ive r s i t y o f Ca l i fo rn i a , D a v i s , 1993 M . A . , Un ive r s i t y o f B r i t i s h C o l u m b i a , 1996 A T H E S I S S U B M I T T E D I N P A R T I A L F U L F I L M E N T O F T H E R E Q U I R E M E N T S F O R T H E D E G R E E O F D O C T O R O F P H I L O S O P H Y in T H E F A C U L T Y O F G R A D U A T E S T U D I E S Department o f P sycho logy W e accept this thesis as confo rming to the rqquired standard T H E U N I V E R S I T Y O F B R I T I S H C O L U M B I A February, 2000 © K e n t A n t h o n y K i e h l , 2000 In presenting this thesis in partial fulfilment of the requirements for an advanced degree at the University of British Columbia, I agree that the Library shall make it freely available for reference and study. I further agree that permission for extensive copying of this thesis for scholarly purposes may be granted by the head of my department or by his or her representatives. It is understood that copying or publication of this thesis for financial gain shall not be allowed without my written permission. Department of $ (~~K.cl The University of British Columbia Vancouver, Canada Date f t W c A , j &<XS^> DE-6 (2/88) Abstract Psychopathy is a complex personality disorder denned by a constellation of affective and behavioral characteristics. There is accumulating behavioral evidence suggesting that the condition is associated with impairments in affective, cognitive, and language functions. However, relatively little is known regarding the neural systems underlying these abnormalities. The present thesis is comprised of five experiments designed to elucidate and characterize the abnormal functional architecture underlying these abnormalities in psychopathic criminals. In Experiments 1 and 2, functional magnetic resonance imaging (fMRI) was used to elucidate the neural systems underling abnormal semantic and affective processes in these individuals. In Experiments 3, 4 and 5, event-related potentials (ERPs) were used to characterize the temporal features of cognitive and language functions in psychopaths. The results from Experiment 1 revealed that compared to control participants, psychopaths performed more poorly and failed to showed the appropriate neural differentiation between abstract and concrete stimuli during a lexical decision task. These deficits were located in the right anterior superior temporal gyrus. The results from Experiment 2 indicated that psychopaths, relative to control participants, showed less activation for processing affective stimuli than for neutral stimuli in several neural regions, including the right amygdala/hippocampal formation, left parahippocampal gyrus, ventral striatum, and in the anterior and posterior cingulate. Psychopaths did show greater activation for processing affective than for neutral stimuli in regions located outside the limbic system, including bilateral inferior frontal gyrus. These latter data suggesting that psychopaths used different neural systems than d i d controls for performing the task. The results f rom Exper iments 3 and 4 indicated that psychopathy is associated wi th abnormalities in the P 3 E R P component el ici ted by target st imuli dur ing visual and auditory oddbal l tasks. In addit ion, the psychopaths ' E R P s to visual and auditory target s t imuli were characterized by large fronto-central negativities in the 350-600 mi l l i second time w i n d o w . These fronto-central E R P negativities are similar to those observed for patients w i th temporal lobe damage. In Exper iment 5, using a standard sentence processing paradigm, no group differences were observed between psychopaths and nonpsychopaths i n the amplitude o f the N 4 0 0 potential el ici ted by terminal words o f sentences that were either congruent o r incongruent w i th the previous sentence context. These results indicate that the abnormal fronto-central E R P negativities observed in previous studies o f language function in psychopaths are not related to processes involved in the generation o f the N 4 0 0 . T a k e n together, these data suggest that one o f the cardinal abnormalities in psychopathy is abnormal semantic processing o f conceptually abstract information and affective information and that these abnormalities are related to the function o f neural circuits in the anterior temporal lobes and lateral frontal cortex. Table of Contents Abstract i i Table o f Contents iv L i s t o f Tables ix L i s t o f Figures x Acknowledgment s x i i Dedica t ion x i v 1. Introduct ion .1 1.1 Genera l Introduction 1 1.2 Event-related Potentials 5 1.3 Funct iona l Magne t ic Resonance Imaging 6 1.4 Cogni t ive and Language Abnormal i t ies in Psychopathy 7 1.5 R o l e o f the Right Hemisphere in Language Process ing 10 1.6 Funct iona l Significance o f Fronto-centra l E R P negativities in Psychopaths '. 11 1.7 Event-related Potential Studies o f Psychopathy 14 1.8 Summary 16 1.9 Rationale and Hypotheses for Exper iment 1 17 1.10 Rat ionale and Hypotheses for Exper iment 2 18 1.11 Rat ionale and Hypotheses for Experiments 3, 4 and 5 19 2. Exper iment 1 - Me thods 22 2.1 Participants .22 2.2 Mater ia ls 23 iv 2.3 Procedure . . . . . 2 3 2.4 Image A c q u i s i t i o n 25 2.5 Image Processing 25 2.6 Results - Behav iora l D a t a 28 2.7 Results - Imaging D a t a 28 2.8 Summary and Discuss ion for Experiment 1 39 3. Exper iment 2 - M e t h o d s 41 3.1 Participants 41 3.2 S t imul i 41 3.3 Task and Procedure 42 3.4 Behav io ra l D a t a Analyses 42 3.5 Image Acqu i s i t i on 43 3.6 Image Processing 43 3.7 Results - Behaviora l D a t a 44 3.8 Results - Imaging D a t a 45 3.9 Summary and Discuss ion for Exper iment 2 .48 4. Exper iment 3 - M e t h o d s 50 4.1 Participants 50 4.2 S t imul i 51 4.3 Event-related Potential Record ing 51 4.4 Procedure 52 4.5 D a t a Analyses 53 4.6 Results - Behav iora l D a t a 54 4.7 Results - Event-related Potentials 54 4.7.1 P 3 0 0 Peak Ampl i tude 54 4.7.2 P 3 0 0 Peak La tency 60 4.7.3 N 5 5 0 M e a n Ampl i tude 60 4.8 Summary and Discuss ion for Exper iment 3 62 5. Exper iment 4 65 5.1 Participants 65 5.2 S t imul i 66 5.3 Event-related Potent ia l Record ing 67 5.4 Results - Behav iora l Da ta 69 5.4.1 Sample 1 69 5.4.2 Sample 2 69 5.5 Event-related Potent ial D a t a 69 5.5.1 N 2 Peak Ampl i tude Analyses Sample 1 79 5.5.2 N 2 Peak Ampl i tude Analyses Sample 2 79 5.5.3 P 3 Peak Ampl i tude Analyses Sample 1 80 5.5.4 P 3 Peak Ampl i tude Analyses Sample 2 81 5.5.5 N 4 7 5 Peak Ampl i tude Analyses Sample 1 82 5.5.6 N 4 7 5 Peak Ampl i tude Analyses Sample 2 82 5.6 Corre la t ion Analyses 83 5.7 Summary and Discuss ion for Exper iment 4 85 6. Exper iment 5 - Me thods 91 6.1 Participants 91 6.2 S t imul i 92 6.3 Event-related Potent ia l R e c o r d i n g 92 6.4 Results - Behav io ra l D a t a 95 6.5 Results - Event-related Potent ia l D a t a 95 6.5.1. N 4 0 0 Peak Ampl i tude Analyses - Difference W a v e Analyses 95 6.5.2. N 4 0 0 Peak Ampl i tude Analyses - T w o C o n d i t i o n Analyses . . 99 6.5.3 P 6 0 0 Peak Ampl i tude Analyses - Difference W a v e Analyses . 99 6.5.4 P 6 0 0 Peak Ampl i tude Analyses - T w o C o n d i t i o n Ana lyses . . . 100 6.6 Summary and Discuss ion for Exper iment 5 100 7.0 Genera l Discuss ion 103 7.1 Summary o f results. 103 7.2 Ev idence for abnormalities in processing abstract material in psychopaths 105 7.3 Ev idence for abnormalities in processing affective material in psychopaths 106 7.4 The relationship between psychopathy and the temporal lobes 108 7.5 Relat ionship between semantic processing abnormalities and other theories o f psychopathy 109 7.5.1 L o w fearhypothesis I l l 7.5.2 Response modula t ion hypothesis 112 7.5.3 A c q u i r e d psychopathy 113 7.5.2 Left hemisphere dysfunction 114 7.6 Lirnitations of the present studies 114 7.7 Implications for treatment of psychopathy 116 7.8 Suggestions for future research 116 7.9 Conclusion 118 8.0 References , 119 List of Tables Table 1. C l eck l ey ' s 16 Characteristics o f Psychopathy 2 Table 2. Items o n the Hare Psychopath Check l i s t -Rev i sed ( P C L - R ) 3 Table 3. Demographic data for the cr iminal psychopaths and cont ro l participants for Exper iment 1 29 Table 4. Behav iora l data for the lexical decision task for Exper iment 1 29 Table 5. Summary o f the significant areas o f activation for the compar ison o f the concrete st imuli versus the baseline condi t ion for Exper iment 1 34 Table 6. Summary o f the significant areas o f activation for the compar ison o f the abstract st imuli versus baseline condi t ion for Exper iment 1 35 Table 7. Behav iora l data for the visual oddbal l task in Exper iment 3 56 Table 8. Event-related potential amplitude measurements for target and nontarget s t imuli for Exper iment 3 57 Table 9. Correlat ions between psychopathy P C L - R total scores and event-related potential amplitude measurements for Exper iment 3 61 Table 10. Correlat ions between psychopathy P C L - R total scores and event-related potential amplitude measurements for Exper iment 4 84 List of Figures Figure 1. Co r t i c a l surface rendering o f the areas o f activation for the con t ro l participants for concrete st imuli versus baseline compar ison for Exper iment 1 . 3 0 F igure 2. Co r t i c a l surface rendering o f the areas o f activation for the con t ro l participants for abstract s t imuli versus baseline compar i son for Exper iment 1 31 F igure 3. Co r t i c a l surface rendering o f the areas o f activation for the psychopathic participants for concrete stimuli versus baseline comparison for Exper iment 1 32 Figure 4. Co r t i c a l surface rendering o f the areas o f activation for the psychopathic participants for abstract s t imuli versus baseline comparison for Exper iment 1 33 Figure 5. C o r t i c a l surface rendering o f the areas in wh ich cont ro l participants show significantly greater differentiation between abstract than concrete s t imuli than do psychopathic individuals for Exper iment 1 38 Figure 6. Il lustration o f the results o f the emotional memory task (Experiment 2) rendered onto four transverse brain slices 47 Figure 7. Grand-mean E R P s to visual oddbal l st imuli f rom Exper iment 3 58 Figure 8. Grand-mean E R P s to visual nontarget st imuli f rom Exper iment 3 59 Figure 9. G r a n d mean E R P s (both samples) for target s t imuli for psychopaths and nonpsychopaths for Exper iment 4 70 F igure 10. G r a n d mean E R P s (both samples) for nove l st imuli for psychopaths and nonpsychopaths for Exper iment 4 71 Figure 11. G r a n d mean E R P s (both samples) for nontarget s t imuli for psychopaths and nonpsychopaths for Exper iment 4 72 Figure 12. G r a n d mean E R P s (sample 1) for target st imuli for psychopaths and nonpsychopaths for Exper iment 4 73 Figure 13. G r a n d mean E R P s (sample 1) for novel s t imuli for psychopaths and nonpsychopaths for Exper iment 4 74 Figure 14. G r a n d mean E R P s (sample 1) for nontarget st imuli for psychopaths and nonpsychopaths for Exper iment 4 75 Figure 15. G r a n d mean E R P s sample 2) for target stimuli for psychopaths and nonpsychopaths for Exper iment 4 76 Figure 16. G r a n d mean E R P s (sample 2) for novel st imuli for psychopaths and nonpsychopaths for Exper iment 4 77 Figure 17. G r a n d mean E R P s (sample 2) for nontarget st imuli for psychopaths and nonpsychopaths for Exper iment 4 78 Figure 18. G r a n d mean E R P s for congruent terminal words o f sentences for psychopaths and nonpsychopaths for Exper iment 5 96 Figure 19. G r a n d mean E R P s for incongruent terminal words o f sentences for psychopaths and nonpsychopaths for Exper iment 5 97 Figure 20. G r a n d mean E R P s difference waves for incongruent minus congruent terminal words o f sentences for psychopaths and nonpsychopaths for Exper iment 5 98 xi Acknowledgments There are many friends and colleagues who have contributed to final product presented in this thesis. I would like to start by acknowledging my U C Davis family. M y deepest gratitude goes out to Carolyn Aldwin and Rick Levenson for adopting me into their family and for comforting me during my deepest personal losses. I would also like to thank them for training me how to think critically about neuroscience data. To Debra Long, for always being willing to take the time to answer the questions of a persistent, if not overbearing, undergraduate student. To Michael Szymanski, for the seminal lecture on event-related potentials that changed my life. To Ron Mangun, for taking a chance on an.unknown undergraduate student and for teaching me the intricacies of event-related potential and positron emission tomography data collection and analyses. To Joe Hopfinger and Todd Handy, for your friendship and collaboration that is only in its infancy. At the University of British Columbia, I would first like to acknowledge Bob Hare, for taking a chance on an enthusiastic undergraduate student. Your dedication and enthusiasm for your work has, and continues to, inspired me. To my committee members, Janet Werker, John Pinel, and Don Wilkie, for their patience and assistance with having to read yet another dissertation. To Dirnitri Papageorgis, who I know is looking down upon me, thanks for showing me how to be an instructor. To the hard working undergraduates -Sara Johnston, Derek Mitchell and Erin Fennell - who spent many difficult days with me at the prison. To Andra Smith, it seems like that bike ride in Stanley Park was only a few days ago - who would have guessed the course the next six years would take? We have to proclaim victory though - we got them scanned! I would like to thank Tony Gray, Arthur Jones and Scott Morrison for coding elegant and flexible programs. To John McDonald, for your friendship and collaboration. I owe a lot to the members of the Radiology and Physics departments. I would like to thank Drs. Alex McKay and Ken Whittall for helping us get the fMRI program started. To Dr. Forster, for supporting our imaging work throughout the years - we could not have done this anywhere else in the world. To the MRI technicians, Karen Smith, Trudy Shaw and Sylvia Renneberg, for putting up with our 'difficult' patients. I would like to acknowledge the staff and guards at the Regional Health Centre. To Johann Brink, for helping me get started. To David Kolton for his clinical acumen. Big thanks goes out the Correctional Services of Canada Regional Escort Team for transporting our subjects. To the inmates, for their participation and cooperation and for keeping the last 6 years from being anything but boring. To my extended family, for understanding why I have been so close these last six years, yet so far away. I am sorry that I have not called more often, but they only give you one phone call in prison. I have lost touch wi th t w o friends o f mine over the last few years w h o contr ibuted much to making me the person I a m today. T o B r o c k and Jake - where ever you are, I w i sh y o u the best. I w o u l d l ike to thank m y fellow students in D r . L i d d l e ' s lab - to K r i s t i n ' S c u l l y ' Laurens , your dedication to research is inspiring. T o A l a n Bates, for helping to col lect so much o f the data - you have a great future ahead o f you . T o the rest o f the lab, Adr ianna , A d r i e n , C a r o l , L i s a and Steph, thanks for your understanding and support - n o w get back to w o r k . I do not k n o w i f I can put into words the appreciation I feel for m y supervisor, Peter L i d d l e . I am often left in awe o f his enthusiasm and undying dedication to his w o r k . Ffis w o r k ethic is nothing short o f amazing. H e has tried, repeatedly, to cultivate m y thinking, wr i t ing , and understanding as a scientist. M o r e o v e r , he has shown me how to be a better person. Peter, please accept my deepest gratitude for all that you have done over the years. Th is w o r k w o u l d not have been completed without funding f rom the M e d i c a l Research C o u n c i l o f Canada, N o r m a Calder Foundat ion, John W a c k e r Foundat ion , B C M e d i c a l Services Foundat ion , and B C Heal th . I have been fortunate to be generously supported over the last four years by the M i c h a e l Smi th Scholarship, M e d i c a l Research C o u n c i l o f Canada. M u c h o f the w o r k presented in this thesis was done in col laborat ion wi th others. H o w e v e r , any faults in its presentation o r logic are mine and mine alone. Dedication This thesis is dedicated to the memory o f m y father, Jeff K i e h l . Wi thou t his enduring patience, guidance, forgiveness and uncondit ional love, I never w o u l d have been able to even begin, much less complete, such an accomplishment. D a d , I w i sh y o u cou ld be here to share this wi th me. xiv 1. Introduction 1.1 Genera l Introduct ion Psychopathy is a complex personality disorder o f unknown et iology. The modern concept o f psychopathy can be traced back to the psychiatrist P ine l (1792), who labeled the condi t ion 'madness without de l i r ium' . Th is term was used to denote the lack o f moral i ty and behavioral con t ro l in these individuals that occurred despite the absence o f any psychotic symptoms or defects in intellectual function. In the 200 years that fo l lowed, the condi t ion has been through an evolu t ion in terminology but many o f the defining characteristics have remained unchanged. These characteristics were most clearly delineated, and the current diagnostic cri teria established, by the writ ings o f the psychiatrist H e r v e y C l e c k l e y (Cleckley , 1976). In his 4 0 years o f c l in ical w o r k C leck l ey came to narrow the syndrome he cal led psychopathy to 16 characteristics (see Table 1). In subsequent years, Hare and colleagues operationalized and transformed these characteristics into items on the Hare Psychopathy Checkl is t (Hare, 1980), and its successor, the Hare Psychopathy Check l i s t -Rev ised ( P C L - R ; Hare , 1991; see Table 2). T h e P C L - R is n o w the most wide ly accepted diagnostic instrument for psychopathy. There is a substantial literature attesting to the reliability and validi ty o f the P C L - R as a measure o f psychopathy in offenders and forensic patients (Fulero, 1996; Hare , 1980; 1996; Hare & Har t , 1993; Hare , Har t , & Harpur , 1991a; 1991b; Harpur , Haks t ian , & Hare , 1988; 1989; H a r t & Hare , 1989; 1996). Fac tor analyses o f the P C L - R have revealed two correlated dimensions or factors (Harpur et a l . , 1988; 1989). 1 Table 1. C l e c k l e y ' s (1976) 16 characteristics o f psychopathy 1) Superficial charm and g o o d intelligence 2) Absence o f delusions and other signs o f irrat ional thinking 3) Absence o f nervousness or psychoneurotic manifestations 4) Unrel iabi l i ty 5) Untruthfulness and insincerity 6) L a c k o f remorse or shame 7) Inadequately motivated antisocial behavior 8) P o o r judgment and failure to learn f rom experience 9) Pathologic egocentricity and incapacity for love 10) Genera l poverty in major affective reactions 11) Specific loss o f insight 12) Unresponsiveness i n general interpersonal relations 13) Fantastic and uninviting behavior w i th drink and sometimes without 14) Suic ide rarely carried out 15) Sex life impersonal, tr ivial , and poo r ly integrated 16) Fai lure to fo l low any life plan 2 Table 2. Items on the Hare Psychopathy Check l i s t -Rev i sed ( P C L - R ; Hare , 1991). 1) Glibness and superficial cha rm 2) Grandiose senses o f self-worth 3) N e e d for stimulation/proneness to bo redom 4) Pathological lying 5) Conn ing / manipulative 6) L a c k o f remorse o r guilt 7) Sha l low affect 8) Cal lous / lack o f empathy 9) Parasitic lifestyle 10) P o o r behavioral controls 11) Promiscuous sexual behavior 12) E a r l y behavioral problems 13) L a c k o f realistic, long term goals 14) Impulsivi ty 15) Irresponsibility 16) Fai lure to accept responsibili ty for o w n actions 17) M a n y short-l ived mari tal relationships 18) Juvenile delinquency 19) Revoca t ion o f condi t ional release 20) Cr imina l versatility 3 Factor 1 includes items related to emotional and interpersonal relationships (e.g., superficial charm, egocentricity, grandiosity, deceitfulness and manipulativeness, and absence o f remorse, guilt, or empathy). Fac tor 2 items reflect impulsive and antisocial behaviors (e.g., impulsivi ty, poor behavioral controls , proneness to boredom, poo r life planning, and irresponsibili ty). Th is latter factor is most c lose ly related to the Diagnos t i c and Statistical M a n u a l o f M e n t a l Illness ( D S M I V ) classification o f An t i soc ia l Personal i ty Disorder ( A P D ; A m e r i c a n Psychiatr ic Assoc ia t ion , 1994). It is important to note that al though A P D was intended to capture the essential components o f psychopathy, it has been cr i t ic ized for over ly relying on antisocial behaviors, while excluding the affective and interpersonal characteristics considered to be central to the construct o f psychopathy (Hare, 1996; Ha re et a l . , 1991b; Har t & Hare , 1996; W i d i g e r et al . , 1996). In the fo l lowing experiments, a l l inmates were assessed wi th the Hare Psychopathy Checkl i s t -Revised . U t i l i z i n g these modern assessment techniques, researchers have found that psychopathy is associated wi th abnormalities in a number o f cogni t ive and language domains, including affective and semantic processes. T h e present thesis is compr i sed o f a series o f experiments that seek to elucidate and characterize the neural architecture underlying these cognit ive and language abnormalities in cr iminal psychopaths. Before beginning a detailed review o f the relevant research it may be helpful to briefly describe the experimental methods used in this background research and employed in the experiments to f o l l o w . 4 1.2 Event-related potentials Event-related potentials ( E R P s ) have been used successfully for over 30 years to characterize the time course and scalp topography o f the neural act ivi ty associated wi th information processing in health and disease. E R P s are s t imulus- locked segments o f the ongoing electroencephalogram ( E E G ) . E R P s are typical ly averaged over many comparable stimulus events (e.g., abstract words) in order to remove 'noise ' resulting f r o m ongoing brain activity not relevant to the processing o f the stimulus o f interest. T h e resulting series o f peaks and troughs, often labeled 'components ' , are plotted as function o f time versus amplitude. These components can be referred to in regards to their functional significance (e.g., mismatch negativity) or, more commonly , they can be labeled according to their polar i ty (e.g., negative wave [N] ; positive wave [P]) and by their ordinal posi t ion after stimulus onset. E R P components can also be referred to by their polari ty and latency in mil l iseconds f rom stimulus onset. A P I for example, w o u l d be the first positive component fo l lowing the stimulus. The N 4 0 0 , on the other hand, w o u l d be a negative component o f the E R P peaking approximately 400 milliseconds after stimulus onset. E R P s provide precise characterization, o n the order o f mil l iseconds, o f the temporal structure o f information processing. H o w e v e r , characterizing the spatial distr ibution o f the neural generators underlying these components is difficult, as there is no unique solut ion to the 'inverse p rob lem' . The inverse p rob lem refers to determining the unique dipole distribution believed to have generated the scalp potentials. Addi t iona l ly , i f one was seeking to determine a description i n terms o f a s u m o f dipoles, one w o u l d also need to determine the relative strength o f the dipoles. 5 1.3 Funct iona l magnetic resonance imaging Funct ional magnetic resonance imaging ( f M R I ) takes advantage o f the fact that as neurons are engaged in a cogni t ive operation a commensurate increase in loca l b l o o d f low occurs. This enhanced b lood f low supplies the metabohcally active neurons wi th an increased supply o f oxygenated b lood . Importantly, the increase in b l o o d f low exceeds the amount needed to meet the additional demand for oxygen, leading to an increase in the concentration o f oxygenated hemoglobin, and a corresponding di lut ion o f deoxyhemoglobin . Deoxygenated hemoglobin is a paramagnetic compound that causes spin packets in the magnetic field to dephase rapidly ( T 2 * relaxation) wh ich results in a loss o f M R signal. A loca l increase in the ratio o f oxygenated/deoxygenated hemoglobin concentration then produces a decrease in spin dephasing, wh ich results in a net increase in M R signal. This effect was termed the b l o o d oxygen level dependent ( B O L D ) contrast by K w o n g and colleagues ( K w o n g et al . , 1992). The resulting signal f rom each region in the brain can then be plot ted and analyzed as a function o f intensity versus time. Current ly, the temporal and spatial resolut ion o f f M R I is o n the order o f seconds and millimeters, respectively. Funct ional M R I has been used in the past 9 years to characterize the neural correlates o f many domains o f cogni t ive function and is readily being applied to the study o f psychopathology ( D ' E s p o s i t o , Zarahn, & Agu i r r e , 1999). 6 1.4 Cogni t ive and language abnormalities in psychopaths E a r l y empir ical research sought to elucidate cognit ive impairments in psychopathy by examining the relationship between psychopathy and hemispheric lateralization for language function (Day & W o n g , 1996; Hare , 1979; Hare & Jutai, 1988; Ha re & M c P h e r s o n , 1984; Jutai, Hare , & Conno l ly , 1987; Raine, O 'Br i en , Smiley, Scerbo, & Chan , 1990). The impetus for explor ing this relationship arose f rom cl in ica l observations o f psychopathic individuals. Numerous clinicians noted that the actual behavior o f psychopathic individuals is often str ikingly inconsistent wi th their verbalized reports (Cleckley , 1976; M c C o r d & M c C o r d , 1964), leading some to speculate that psychopathy was associated wi th language abnormalities (F lor -Henry , 1972). Subsequent research found that abnormalities in language processes are most prevalent when psychopathic individuals were required to perform tasks invo lv ing semantic processing (Hare, 1979; Hare & For th , 1985; Hare & M c P h e r s o n , 1984). F o r example, in a task that placed no explici t demands on affective processing, Hare and Jutai (1988) observed that psychopathic individuals made more errors than d id control participants in an abstract semantic categorizat ion task. H o w e v e r , psychopathic individuals performed no worse than cont ro l participants for a simple recognit ion task or categorical judgment task, suggesting that the observed cognit ive abnormalities were present only when processing abstract semantic information (see also Hare , 1979). M o r e recently, K i e h l , Hare , M c D o n a l d and B r i n k (1999) observed that psychopathic individuals performed more poor ly than cont ro l participants dur ing 'a task (Task 2 in their study) that required classifying w o r d stimuli as either concrete (e.g., table) o r abstract (e.g., 7 justice). Previous studies have demonstrated that healthy subjects respond more qu ick ly and accurately to concrete words than to abstract words i n lexical decis ion and concrete/abstract discrimination tasks (Day, 1977; H o l c o m b , K o u n i o s , Ander son , & Wes t , 1999; James, 1975; K o u n i o s & H o l c o m b , 1994; K r o l l & Merves , 1986). These data led to theories that the cognitive operations, and by inference, the neural systems, invo lved i n processing concrete and abstract words are disassociated ( H o l c o m b et al . , 1999; K i e h l et a l . , 1999b; Pa iv io , 1986; Pa iv io , 1991; Schwanenflugel , Harnishfeger, & S towe , 1988; Schwanenflugel & S towe , 1989). Consistent wi th the hypothesis that psychopathic individuals have difficulty processing abstract words , K i e h l et a l . , (1999a) found that psychopathic individuals made more errors than d id nonpsychopaths when having to classify w o r d st imuli as abstract. T h e y also recorded event-related potential ( E R P ) data during their procedure and observed that psychopathic individuals failed to show the normal E R P differentiation between concrete and abstract words (Tasks 1 and 2). In n o n c r i m i n a l and in cr iminal nonpsychopathic individuals concrete words elicit greater E R P negativity in the 300-800 mil l i second w i n d o w than do abstract words (Kounios & H o l c o m b , 1994; Paller, Kutas , Shimamura, & Squire, 1987). Th i s latter effect is strongest at fronto-temporal electrode sites suggesting frontal-temporal generators are involved in the differentiation o f concrete and abstract words . G i v e n that the differentiation between concrete and abstract words appears to be most robust 300-500 ms post-stimulus, it has been argued that this differentiation is due to modulations o f semantic generators also believed to contribute to the N 4 0 0 potential typical ly observed in w o r d and sentence processing tasks (Kutas & Hi l l ya rd , 1980b; 1983; 1984). Recent evidence suggests that the amplitude o f the N 4 0 0 may reflect processes related to the integration o f a words meaning wi thin ongoing cognit ive context (Ho lcomb , 1993). U s i n g this interpretation, it w o u l d appear 8 that psychopaths differ f rom others in the degree and extent o f cognit ive processes required to perform language tasks. Abnormal i t ies in semantic processing also have been observed in psychopathic individuals to emotional s t imuli . D a y and W o n g (1996) found that psychopathic individuals d id not show the same hemispheric laterality in behavioral performance as d i d cont ro l participants for processing negatively valenced w o r d st imuli . These results were interpreted as support for the hypothesis that psychopathic individuals do not make use o f the connotat ive-emotional processes based in the right hemisphere (Day & W o n g , 1996). Wi l l i amson , Harpur and Hare (1991) found that psychopathic individuals d i d not show the normal behavioral facili tation and E R P differentiation between emotional and neutral words during a lexica l decision task (see also K i e h l et al, 1999a, Task 3). Evidence for abnormalities in language processing also comes f rom analyses o f the speech o f psychopathic individuals. G i l l s t r o m and Hare (1988) found that psychopathic individuals use more 'beats', defined as language-related hand gestures incongruent wi th the semantic content o f their speech, than do cont ro l participants. Th is finding was interpreted as evidence that psychopathic individuals compartmentalize their speech into smaller, more discrete units than do others. Psychopathic individuals also do not differentiate, in voice analyses, between affective and neutral words (Lou th , Wi l l i amson , Alper t , Pouget , & Hare , 1998). Br ink ley , Berns te in & N e w m a n (1999) found that psychopathic individuals performed more poor ly at resolving action in spoken narratives than d id cont ro l participants. Interestingly, the performance o f the psychopathic individuals d id improve however , when they were provided wi th more concrete, tangible story guides. 9 Recent evidence f rom neuroimaging studies o f affective processing in psychopathic individuals has also revealed abnormalities in semantic processing. U s i n g Single Pho ton E m i s s i o n C o m p u t e d T o m o g r a p h y ( S P E C T ) , Intrator et al . (1997) found that psychopathic individuals show greater activation for affective than for neutral st imuli bilaterally in temporo-frontal cortex. These latter data have been interpreted as supporting the not ion that psychopaths require more cogni t ive resources to process and evaluate affective st imuli than do compar ison subjects. Thus , o n balance, accumulating evidence suggests that psychopathy is associated wi th abnormalities in semantic processing. In particular, these abnormalities appear to be strongest when accessing right hemisphere resources for processing conceptual ly abstract information o f both emotional ly valenced stimuli and affectively neutral s t imuli . 1.5 R o l e o f right hemisphere i n language processing Since the classic w o r k o f B r o c a and Wern icke , language functions have generally been assumed to reside in left hemisphere neural systems. H o w e v e r , more recent evidence f rom language studies suggests that the right hemisphere may play an important role in language processing. F o r example, patients wi th right hemisphere brain damage show deficits in verbal reasoning ability (Caramazza, G o r d o n , Zurif , & D e L u c a , 1976), in interpretation o f verbal humor (Browne l l , M i c h e l , Powe l son , & Gardner, 1983), in understanding prosody o f speech (Ross, 1981) and in comprehension and product ion o f the connotative meanings o f words and figures o f speech (Gardner & Denes, 1973; Winner & Gardner , 1977). 10 Recent evidence f rom neuroimaging studies have further implicated the right hemisphere in language functions. Beauregard et al . (1997), using P E T , observed that passive v iewing o f abstract words relative to baseline produced neuronal activation in the right inferior frontal gyrus (Beauregard et a l . , 1997). Th is right hemisphere activation was found for abstract w o r d processing but not for concrete words minus baseline comparisons or for emotional words minus baseline comparisons (Beauregard et al . , 1997). D ' E s p o s i t o et al. (1997) also found activation o f the right superior frontal gyrus during passive v iewing o f abstract words , when compared wi th active processing o f concrete words . Similar ly , several areas in the right hemisphere, including prefrontal cortex and middle temporal gyrus, have been found to be activated during comprehension o f metaphors (Bot t in i et a l . , 1994). K i e h l et a l . (1999b) found that a region in the right anterior superior temporal gyrus extending into the inferior frontal gyrus was more strongly activated for processing abstract s t imuli than for concrete s t imuli dur ing a lexical decision task, suggesting that there is a right hemisphere neural pathway or system involved in processing abstract w o r d st imuli . Thus , on balance, these data suggest that the right hemisphere may play a special role in interpreting the abstract representations o f language and also affective connotations o f language. 1.6 T h e functional significance o f the fronto-central E R P negativities in psychopaths Several studies have reported that long-latency E R P s (later than 300 ms) are different in psychopaths than in nonpsychopaths, especially during visual language tasks. Psychopaths consistently show a large frontally distributed negative wave wi th a latency o f approximately 500 mill iseconds to w o r d stimuli . W i l l i a m s o n et al. (1991) reported that psychopaths 11 exhibited a larger fronto-central N 5 0 0 to w o r d st imuli during a lexica l decis ion task than d id nonpsychopaths. T h e task employed by Wi l l i amson et al . required a G o / N o - g o decision, raising the possibil i ty that the prominent N 5 0 0 o f the psychopaths was related to poor response inhibit ion. There is accumulating evidence that psychopathy is associated wi th deficits in response inhibi t ion (K ieh l , Smi th , Hare , & L i d d l e , 1999c; Lapier re , B r a u n , & Hodg ins , 1995; Smi th et a l , 1999). H o w e v e r , K i e h l et al . (1999a) reported that psychopaths exhibited a large centro-frontal negative wave wi th latency about 350 mil l iseconds dur ing three different language tasks, a l l o f which employed a G o / G o design. M o r e o v e r , K i e h l et al. (1999c) observed fronto-central E R P negativities in psychopaths to G o trials but not during N o G o trials dur ing a G o / N o G o response inhibi t ion study. It is unl ikely therefore, that the abnormal late centro-frontal negative waves exhibited by psychopaths can be attributed entirely to difficulties in response inhibit ion. W h i l e both W i l l i a m s o n et a l . (1991) and K i e h l et al. (1999a) employed tasks that demanded linguistic processing, the late negative wave in both studies was el ici ted for al l w o r d types (i.e., posit ive, negative, and neutral words in W i l l i a m s o n et a l . , 1991; concrete and abstract words (Tasks 1 and 2) and posit ive and negative words (Task 3) in K i e h l et al . , 1999a), raising the possibi l i ty that it is independent o f stimulus content. Based o n the similar topography o f the psychopathic individuals ' N 3 5 0 ( K i e h l et a l . , 1999a) and N 5 0 0 (Wi l l i amson et al . , 1991) K i e h l et al . (1999a) suggested that there were at least two possible explanations for the functional significance o f these components . The tasks employed by Wi l l i amson et al. and K i e h l et al. (1999a) (see also K i e h l et a l . , 1999c) involved both lexico-semantic processing and required a concurrent behavioral response. Thus , i n the 300-600 mill iseconds after a w o r d stimulus is presented both semantic and decision-making 12 processes are engaged and w i l l elicit overlapping E R P components o f opposite polarity. In general, presentation o f a w o r d stimulus in the absence o f any online task demands w i l l elicit a large E R P negativity in the 300-500 ms time w i n d o w ( N 4 or N 4 0 0 ) . There is extensive evidence that links the N 4 0 0 component to processes related to integrating w o r d meanings wi th in ongoing context (Kutas , 1997; Kutas & V a n Petten, 1994). Thus , one interpretation o f the psychopaths ' fronto-central E R P negativities offered by K i e h l et al . (1999a) and W i l l i a m s o n et al. (1991) was that they may be related to an abnormally large N 4 0 0 . T o the extent that the amplitude o f the N 4 0 0 reflects cognit ive operations invo lved i n processing the semantic meanings o f words , these data are consistent w i th the hypothesis that psychopathy is associated wi th abnormal semantic processing. This latter interpretation is strengthened by the fact that abnormally large N 4 0 0 s have been reported in other psychopathological condit ions wi th conceptual and empir ica l l inks to psychopathy ( B l a c k w o o d , Whal ley , Christ ie , & B lackburn , 1987; F o r d , et al . , 1994; M c C a r l e y , Faux , Shenton, & Nestor , 1991). H o w e v e r , there are no studies to date that have examined the relationship between psychopathy and the semantic processing related to the generation o f the N 4 0 0 . The other interpretation offered by K i e h l et al . (1999a) for the functional significance o f the psychopaths ' N 3 5 0 was that it was related to an abnormally small P 3 potential. The P 3 as used here, refers to a family o f posit ive E R P potentials occurr ing at a latency o f 300 mill iseconds or more. In general, any task that requires a binary decis ion ( G o / N o G o ; G o / G o tasks) w i l l elicit a large posit ive component in the E R P . Since the d iscovery o f the P 3 more than 30 years ago (Sutton, Tuet ing , Zub in , & John, 1967), there has been considerable effort to delineate the functional significance o f this component(s) . In general, these studies suggest that the P3 is sensitive to changes i n the al locat ion o f attentional resources and 13 processes invo lved in contextual updating and decision making (Alexander et a l . , 1995a; Pri tchard, 1981). Since defective al locat ion o f attentional resources and abnormal decision making processes are postulated features o f psychopathy (Harpur & Hare , 1990; K o s s o n , 1996; K o s s o n & N e w m a n , 1986; N e w m a n , 1998) it may be possible that the large fronto-central negativities seen in psychopaths might results f rom a lack o f attenuation f rom a typical ly large posit ive potential. A l t h o u g h P 3 responses have been w e l l characterized in a number o f c l in ica l condit ions, relatively little is k n o w n about them in psychopathy. These studies are summarized below. 1.7 E R P studies o f psychopathy There have been six E R P studies on psychopathy defined according, to P C L (an early version o f the P C L - R , Hare , 1980) or P C L - R scores (Forth & Hare , 1989; Jutai & Hare , 1983; Jutai et al . , 1987; K i e h l et a l . , 1999a; Raine & Venables , 1988; W i l l i a m s o n et al . , 1991). F ive reported information concerning P3s , though only two studies employed paradigms in which the salience o f st imuli was manipulated i n a manner expected to elicit a P 3 response. These were the study by Jutai et al . (1987), wh ich employed an auditory phoneme discrimination task, and the study by Raine and Venables (1988), w h i c h employed a visual continuous performance task. Jutai et al . (1987) found no significant difference between psychopaths and nonpsychopaths in the amplitude or latency o f the P 3 , though they d id observe a late positive wave (at 600 mill iseconds) in psychopaths ' waveforms for target s t imuli (phonemes) during a dual task procedure (playing video games and making phonemic discriminations). V i s u a l 14 inspection o f the waveforms in their study indicated that the P 3 amplitude was smaller in the psychopaths than in nonpsychopaths. It should noted that Jutai et al . d i d not record f rom parietal electrodes, usually the opt imal site for detection o f P 3 . In contrast, Raine and Venables (1988) reported that the amplitude o f parietal P 3 to target s t imuli i n the visual modali ty was greater in psychopaths than in nonpsychopaths. In the remaining three studies that reported information about P 3 , there was no evidence indicating that P3 amplitude was abnormal in psychopaths. H o w e v e r , these studies d id not employ paradigms that manipulated the salience o f the st imuli . Overa l l , the findings provide equivocal information about the nature o f P 3 in psychopathy. T h e on ly study (Raine &Venab le s , 1988) that reported significant P3 differences found larger P3s in psychopaths than in nonpsychopaths. Th is finding was contrary to the expectation that psychopaths w o u l d have abnormally l o w P 3 amplitude to oddbal l s t imuli , as is observed in other patient groups wi th impaired ability to allocate attentional resources ( B l a c k w o o d et a l , 1987; Pfefferbaum, R o t h , & F o r d , 1995). It should be noted that Raine and Venables (1988) used visual st imuli , whereas many o f the studies in other disorders employed auditory st imuli . T h e unexpected result obtained by Raine and Venables (1988) justifies further explora t ion o f the P 3 el ici ted by visual st imuli . W i t h regard to the P 3 elicited by non-salient st imuli , al l the studies that have reported relevant data (Jutai, Hare , & Conno l ly , 1987; Fo r th & Hare , 1989; Raine & Venables , 1988) have found that psychopaths do not differ f rom nonpsychopaths. Th i s effect is consistent wi th the observation that psychopaths have a normal , o r enhanced, ability to ignore irrelevant material (Jutai, 1989; Jutai & Hare , 1983). 15 Overa l l , the results o f studies o f E R P components wi th a latency o f 300 milliseconds or longer in psychopaths raise two major questions. Firs t , does the visual P3 el ici ted by oddbal l s t imuli have abnormally l o w amplitude and long latency in psychopaths, as w o u l d be expected f rom the evidence that impaired al location o f attentional resources is a characteristic o f the condi t ion? Secondly, can the late fronto-central negative waves reported by W i l l i a m s o n et al . (1991) and K i e h l et al . (1999a) be elicited by visual st imuli that do not involve linguistic processing? 1.8 Summary Accumula t ing evidence suggests that psychopathy is associated wi th abnormalities in semantic processing for stimuli o f affective connotations and for non-affective conceptually abstract st imuli . A l t h o u g h several o f the studies investigating semantic processes in psychopaths have used E R P s to assess the temporal features o f the psychopaths ' information processing abnormalities, little is k n o w n regarding the neural sources underlying these processes. E R P studies o f cognit ive and language function in psychopathy have also observed large late fronto-central E R P negativities in the psychopaths ' waveforms to language and task-relevant st imuli . The functional significance o f these component(s) is unclear and may be related to abnormalities in attentional processes, decis ion making processes (e.g., P3 ) and/or semantic processes (e.g., N 4 ) . 16 1.9 Rationale and Hypotheses for Exper iment 1 The purpose o f the Exper iment 1 was to use functional magnetic resonance imaging to elucidate the neural architecture underlying lexico-semantic processing i n c r imina l psychopathic individuals during performance o f a concrete/abstract lex ica l decision task ( K i e h l et al . , 1999a; 1999b). Previously , using a similar task, we observed that psychopathic individuals failed to show the normal E R P differentiation between concrete and abstract words ( K i e h l et a l . , 1999a). M o r e o v e r , we observed that for the psychopathic individuals, a l l w o r d stimuli el icited a large fronto-central negativity (N350) suggesting aberrant semantic processing (see also W i l l i a m s o n et al . , 1991). P r io r f M R I research f rom our laboratory has shown that lexica l decisions to concrete and abstract stimuli are associated wi th activation o f bilateral fusiform gyrus, anterior cingulate, left middle temporal gyrus, right posterior superior temporal gyrus and left and right inferior frontal gyrus ( K i e h l et a l . , 1999b). A direct comparison between the abstract and concrete stimuli epochs yielded a significant area o f activation in right anterior temporal cortex suggesting that this right hemisphere site is implicated in differentiating abstract f rom concrete words . K i e h l et al. (1999b) interpreted this effect as support for the not ion that there is a right hemisphere pathway involved in processing abstract words . G i v e n that psychopathic individuals have difficulty processing abstract information (Hare & Jutai, 1988; K i e h l et al . , 1999a), in particular information that draws on right hemisphere resources, we hypothesized that we w o u l d observe reduced neural differentiation between abstract and concrete s t imuli in the right hemisphere for psychopathic individuals relative to cont ro l participants. W e specifically hypothesized that this effect w o u l d be present 17 in the right anterior superior temporal gyrus. W e also expected psychopathic individuals to be slower and less accurate than cont ro l individuals when processing abstract words (Hare & Jutai, 1988; K i e h l et a l . , 1999a). 1.10 Rationale and Hypotheses for Exper iment 2. Psychopathy has long been associated wi th deficits or abnormalities in affective processing (Christ ianson et a l . , 1996; D a y & W o n g , 1996; Hare , 1993; K i e h l et a l . , 1999a; Patr ick, 1994; Pa t r ick , Brad ley , & L a n g , 1993; Patr ick, Cuthbert , & L a n g , 1994; Wi l l i amson et al . , 1991). H o w e v e r , relatively little is k n o w n regarding the neural architecture underlying these abnormalities. M o s t empir ical research on the affective processes o f psychopaths has used behavioral methods or peripheral measures o f neural activity (Patr ick, 1994). One o f the most consistent findings f rom these studies is that psychopaths fail to experience o r appreciate the emotional significance o f stimuli in the way that nonpsychopaths do (Christ ianson et a l . , 1996; Pat r ick et al . , 1993; 1994; Wi l l i amson et a l , 1991). F o r example, Wi l l i amson et al. found that psychopaths fail to show normal behavioral facilitation and event-related potential ( E R P ) differentiation between emotional and neutral words (Wi l l i amson et a l . , 1991). Subsequent research has confirmed the presence o f affective abnormalities in psychopaths ( K i e h l et al . , 1999a). These anomalies appear to be most prominent in response to negatively valenced emotional st imuli (Patr ick et a l . , 1993; 1994). A l though E R P s have provided valuable information regarding the temporal features o f these abnormalities, their l imited spatial resolut ion has left the neural sources poor ly characterized. 18 Here we investigate the neural systems underlying affective processing in psychopaths and controls using functional magnetic resonance imaging during an affective memory task. P r io r research wi th this affective memory task in cont ro l participants revealed that affective stimuli elicit greater activation than do neutral st imuli in both l imbic and cor t ica l brain regions, including the amygdala, h ippocampal formation, and temporal and frontal cor tex ( K i e h l et al . , 1998b). O u r pr imary hypothesis was that psychopaths, relative to cont ro l participants, w o u l d show less activation in these l imbic and cor t ica l structures during processing o f the affective stimuli . W e also expected the psychopaths to show less behavioral differentiation between affective and neutral st imuli than w o u l d cont ro l participants. 1.11 Rat ionale and Hypotheses for Experiments 3, 4 and 5. Several studies have reported that long-latency E R P s (e.g., 300-600 ms post-stimulus) are different in psychopaths than in nonpsychopaths, especially during visual language tasks. The most consistent feature is the appearance in psychopaths o f a large frontally distributed negative wave wi th a latency o f approximately 450 mill iseconds. There are (at least) two possible explanations for the functional significance o f these components. Firs t , the fronto-central E R P negativities may be related to aberrant semantic processes that w o u l d lead to an abnormally large E R P component structure in the 300-600 mi l l i second post-stimulus time w i n d o w (e.g., N 4 0 0 ) . Second, the large fronto-central E R P negativities in psychopaths may be related to defective attentional, contextual updating and decision making processes. These abnormal processes may lead to small posit ive potentials in similar time w i n d o w s (e.g., P3) , the result o f wh ich might be augmented late E R P negativity seen in psychopaths. 19 In Exper iment 3 we required participants to respond to nonlinguist ic task-relevant visual st imuli (visual oddbal l task). Th is paradigm engages processes related to attentional cont ro l and decision making, but no explici t demands are placed on semantic processing. The visual oddball task is w e l l characterized and is k n o w to elicit a robust P 3 in healthy participants (Alexander et al . , 1995). W e expected that the P 3 el ici ted by the salient (oddball) st imuli w o u l d be smaller and w o u l d have longer latencies in psychopaths than in nonpsychopaths. W e also hypothesized that the psychopaths, but not nonpsychopaths, w o u l d exhibit a late centro-frontal negative wave even though the st imuli do not require linguistic processing. Las t ly , we expected that the amplitude and latency o f the P 3 el ici ted by the non-salient st imuli (e.g., nontargets) w o u l d be the same in psychopaths as in nonpsychopaths, consistent wi th the observation that psychopaths have a normal , or enhanced, ability to ignore irrelevant material (Jutai, 1989; Jutai & Hare , 1983). In Experiment 4, we examined the neural response to auditory oddbal l st imuli . E R P s elicited by task-relevant auditory stimuli have been shown to be abnormal in a number o f psychopathological condit ions ( B l a c k w o o d et al . , 1987; F o r d , 1998; M c C a r l e y , Hs i ao , Freedman, Pfefferbaum, & D o n c h i n , 1996). A l s o , the cogni t ive processes generating the P 3 are believed to be modal i ty nonspecific. Thus , any abnormalities observed in psychopaths during the visual oddbal l task should also be observed in the auditory oddbal l task. Therefore, the predictions for Exper iment 4 were the same as Exper iment 3. In Exper iment 5 E R P s were recorded while participants were engaged in a standard sentence processing task that required semantic processing but no concurrent decision making processes. The primary a im o f this experiment was to examine the integrity o f the neural systems underlying semantic processes in the absence o f concurrent task demands to attempt 20 to isolate and characterize the conditions in wh ich large fronto-central negativities are elicited. The specific hypothesis was that psychopaths, relative to nonpsychopaths, w o u l d show a larger N 4 0 0 to the terminal words o f sentences that were either congruent o r incongruent wi th the previous sentence context. Th is latter effect w o u l d be consistent w i th the hypothesis that psychopathy is associated wi th abnormal semantic activation. In summary, the a im o f experiments 3-5 is to determine i f the fronto-central E R P negativities previously observed in psychopaths during language tasks ( K i e h l et a l . , 1999a; Wi l l i amson et a l , 1991) are due to abnormalities in semantic processes (i.e., N 4 ) and/or in combinat ion wi th abnormalities in attentional/contextual updating processes (i.e., P3 ) . 21 2.0 Experiment 1 Methods 2.1 Participants. Criminal psychopathic individuals (n=8; all male) were inmates from a maximum-security prison located in Abbotsford, British Columbia, Canada. Psychopathic inmates were transported the University of British Columbia Hospital's MRI unit by the Correctional Services of Canada Regional Escort Team. Noncriminal control participants (n=8; all male) were recruited from the general population. The noncriminal control group was matched with the psychopathic group on gender, age, parental socioeconomic status (assessed with the Hollingshead criteria for parental social position), education level, and IQ, measured with the National Adult Reading Test (NART; Sharpe & O'Carroll, 1991) and Quick Tests (Amnions & Ammons, 1962; 1979a; 1979b). These data are summarized in Table 3. There were no group differences on any of these measures (all p/s > .50). Al l participants were free from any history of head injury or psychotic illness (in self and first-degree relatives), were right-handed (Annett, 1970), and spoke English as their first language. Al l participants had normal or corrected to normal vision. No participants met the criteria for substance abuse according to the D S M I V criteria within the last 6 months. Two clinicians used the Hare Psychopathy Checklist-Revised (PCL-R) to assess psychopathy (Hare, 1991). The PCL-R is a reliable and valid measure of psychopathy (Fulero, 1996; Hare, 1980; 1991; Hare et al., 1990a; 1990b; 1991b; Harpur et al., 1988; 1989; Harpur & Hare, 1994; Hart & Hare, 1989; Hart, Hare, & Harpur, 1992). Each of the 20 items on the PCL-R is scored on a 3-point scale (0-2) according to the extent to which it applies to the inmate. Al l inmates had a PCL-R score above 28 (which range from 0 - 40) on the PCL-22 R (mean 32.8, S D 2.9), wh ich is above the mean score on the P C L - R (23.6, S D 7.9) listed i n the test manual for normative data o f 1192 prison inmates (Hare, 1991). N o n e o f the cont ro l participants had a cr iminal history. 2.2 Mater ia ls . St imulus words (3 to 8 letters in length) were selected f rom the w o r d norms o f T o g l i a and Ba t t ig (1978) and were either concrete or abstract. W o r d s rated as more than .75 standard deviations above or be low the mean concreteness rating contained in the w o r d norms were defined as concrete and abstract, respectively. The w o r d lists for each task d id not differ in w o r d frequency o r length (Francis & Kuce ra , 1982). Fur thermore, on ly affectively neutral words (at or wi th in one standard deviation o f the mean pleasantness rating given in T o g l i a and Bat t ig , 1978) were selected in order to eliminate any confound o f emotionali ty. W e developed sets o f pronounceable pseudowords by selectively altering one letter o f each o f the concrete and abstract words . 2.3 Procedure. S t imul i were presented to the participant by a computer cont ro l led projection system that delivered a visual stimulus to a rear-projection screen located at the entrance to the magnet bore. The participant v i ewed this screen through a mi r ro r system attached to the top o f the head c o i l . T h e scanning r o o m and magnet bore were darkened to a l low easy visualizat ion o f the experimental st imuli . T w o stimulus runs were presented, each consisting o f a series o f four thirty second lexical decision b locks alternating wi th a baseline session. E a c h run was prefaced by a ten second rest session that was col lected to a l low for Ti effects to stabilize. These images were not included in any subsequent analyses. D u r i n g the lexical decis ion b locks 15 letter st imuli 23 (350 ms durat ion; 1650 ms inter-stimulus interval) were randomly presented. A l l st imuli were presented in capital letters. D u r i n g the baseline session, the characters " * * * * * ' ' were cont inuously displayed for 29.5 seconds (500 ms inter-stimulus interval). St imulus runs were balanced such that equal proport ions o f w o r d and pseudoword s t imul i were presented. L e x i c a l decision blocks consisted o f either concrete words and associated pseudowords or abstract words and associated pseudowords. The w o r d and its associated pseudoword d id not appear during the same run. Concre te and abstract lexica l decis ion b locks were presented in a r andom order. T h e participant was not informed o f the concrete/ abstract manipulation. Participants were instructed to respond wi th one hand each time the letter s t imuli presented formed a real Eng l i sh speaking w o r d and to respond wi th their other hand i f the letter stimuli d id not fo rm an Eng l i sh speaking w o r d . T h e hand used to make the response was counter-balanced across participants. Reac t ion time and accuracy were equal ly stressed. A commercia l ly available M R I compatible fiber-optic response device (L igh twave M e d i c a l , Vancouver , B . C . ) was used to acquire behavioral responses. A cus tom visual (and auditory) presentation package ( V A P P ; http:/ /www.psychiatry.ubc.ca/sz/nilab/software/vapp/) was used to precisely con t ro l the t iming o f the experimental st imuli and record ing o f a l l behavioral data. P r io r to entry into the scanning r oo m, each participant performed a practice b lock o f lexical decisions, repeated twice, to ensure he understood the instructions. N o n e o f the stimuli used in the practice b locks were used in the f M R I session. Reac t ion times were computed on trials for wh ich the participant responded correctly wi th in 1500 ms post-stimulus. E r ro r s included incorrect responses wi th in 1500 ms post-stimulus o r any response wi th a latency o f greater than 1500 ms fo l l owing the onset o f the target stimulus. W e performed 2 G r o u p (Psychopath, Cont ro l ) X 2 W o r d (concrete, abstract) 24 X 2 L e x i c a l (real w o r d , pseudoword) repeated-measures analyses o f variance ( A N O V A s ) o n the reaction time and accuracy data. Planned comparisons were then performed to test our hypothesis that psychopathic individuals w o u l d respond s lower and be less accurate for the lexical decisions for abstract words than w o u l d cont ro l participants. 2.4 Image acquisi t ion. Funct iona l data was col lected using a c l in ical G E 1.5 T whole body system fitted wi th a H o r i z o n echo-speed upgrade. The participant 's head was firmly secured using a cus tom head holder and external references were used to pos i t ion the anterior commissure - posterior commissure ( A C - P C ) line at right angles to the slice-select gradient. Convent iona l spin echo T i weighted sagittal localizers were acquired to conf i rm external land-marking. Funct ional image volumes were col lected wi th a gradient-echo sequence ( T R / T E 2500/50 ms, flip angle 9 0 ° , F O V 24 x 24 c m , 64 x 64 matrix, 62.5 k H z bandwidth , 3.75 by 3.75 m m in plane resolution, 4 m m slice thickness, 23 slices) effectively cover ing the entire brain (except for the ventral cerebellum). 2.5 Image processing. Funct iona l images were reconstructed offline and the t w o runs were separately realigned using the procedure by Fr i s ton et al . (1996) as implemented i n Statistical Parametric M a p p i n g ( S P M 9 6 , We l l come Department o f Cogni t ive N e u r o l o g y ; Fr i s ton et al . , 1995b). The realignment procedure is used to cont ro l for head movement dur ing the scanning per iod and involves minimiz ing the sum o f the squares o f the differences between the first image and subsequent images using an iterative algori thm. The translation ( in x, y and z directions) and rotat ion (about the or ig in (centered at the anterior commisure) i n x , y, and z degrees) corrections d id not exceed 2.5 m m and 2.5 degrees, respectively, for any o f the 25 participants. A mean functional image volume was constructed for each participant for each run f rom the realigned image volumes. Th i s mean image volume was then used to determine parameters for spatial normal izat ion into the modif ied Tala i rach space employed in S P M 9 6 using both affine and nonlinear components (Friston et a l , 1995a). In this space, coordinates are expressed relative to a rectangular coordinate frame wi th the or ig in at the midpoint o f the anterior commissure and the y-axis passing through the posterior and anterior commisures. Because each brain differs in size and shape, spatial normal izat ion procedures are commonly used in functional imaging studies to a l low voxel-based comparisons to be made wi thin and across groups o f participants. Addi t iona l ly , transforming all individual brains into a standard space (e.g., Tala i rach space) facilitates comparisons wi th other studies that have employed similar spatial normalizat ion procedures. The normalizat ion parameters detennined for the mean functional volume were then applied to the corresponding functional image volumes for each participant. Adjusted mean functional images were then created for the lexica l decis ion b locks and rest session by col lapsing across the time points in each o f the three condi t ions. In the computat ion o f these adjusted mean images a temporal delay o f 6 seconds was incorporated to account for the relatively s low onset o f the hemodynamic response and the data were high pass filtered (.1 H z ) to remove noise associated wi th l o w frequency confounds (e.g., respiratory artifact; see Ho lmes , Josephs, B u c h e l , & Fr i s ton , i n press). These adjusted mean images (concrete st imuli , abstract st imuli , and rest) were then smoothed wi th a l O x l O x l O m m Gaussian kernel . The smoothed adjusted mean images were then entered into a t w o stage analyses. B o t h stages o f analyses employed univariate tests at each voxe l in the adjusted mean images using the Genera l L inea r M o d e l ( G L M ; Fr is ton et 26 al . , 1995b). The application o f the G L M to each voxe l generates values for a statistical parameter such as the F statistic o r the t statistic for each v o x e l . These statistics are employed to construct statistical parametric maps ( S P M s ) in wh ich the value in each v o x e l represents the value o f the statistic o f interest. A map in wh ich v o x e l values represent values o f F is k n o w n as an S P M { F } while a map in wh ich voxe l values are values o f t is k n o w n as an S P M { t } (Fris ton et al . , 1995b). The S P M { t } can then be transformed into a S P M { Z } u s i n g a probabil i ty integral transformation. These S P M { Z } s can then be displayed (usually by color iz ing) or rendered onto structural M R I s in Tala i rach space for i l lustration. Because mult iple voxels were examined, a correct ion for multiple comparisons based o n the theory o f Gaussian fields was employed (Wors ley , 1994; Wors l ey & Fr i s ton , 1995). Repor ted statistical levels are significant at the voxe l level (Wors ley & Fr is ton, 1995) and were a l l greater than p < .05 corrected for multiple comparisons unless otherwise noted. In the first stage, we performed a confirmatory analysis in the con t ro l participants by compar ing the concrete and abstract st imuli versus the rest condi t ion . These latter analyses were performed to determine whether we cou ld replicate the results o f our previous study ( K i e h l et a l . , 1999b) in this new sample o f healthy participants. W e also performed an identical analysis in the psychopathic group. In the second stage we compared the differences between the abstract and concrete stimuli between groups. Here w e tested our hypothesis that con t ro l participants w o u l d show greater activation for processing o f abstract st imuli than for concrete s t imuli than w o u l d psychopathic individuals (i.e., G r o u p x Cond i t i on interaction). 27 Results 2.6 Behaviora l data. Consistent wi th our hypothesis, psychopathic individuals were significantly s lower to respond to abstract words than were con t ro l participants [planned comparison, F (1, 14) = 4.40, p < .05]. H o w e v e r , con t ro l participants were, in general, faster to respond than were the psychopathic individuals [main effect o f G r o u p , F (1,14) = 9.17, p < .009]. Post hoc tests also revealed that psychopaths were s lower to respond to concrete words than were cont ro l participants. There were no group differences in accuracy for real w o r d stimuli. H o w e v e r , psychopathic individuals were less accurate than were cont ro l participants for responding to the pseudoword stimuli [Group x L e x i c a l interaction, F (1,14) = 8.99, p < .0096]. Summary statistics o f the behavioral data are presented i n Table 4. Overa l l , real w o r d stimuli were responded to faster than were pseudoword st imuli [main effect o f L e x i c a l , F (1,14) = 32.62, p < .0001]. Concre te words were responded to more qu ick ly than were abstract words [Lex ica l x W o r d interaction, F (1,14) = 10.59, p < .0058]. Concrete stimuli (words and pseudowords) were classified more accurately than were abstract st imuli [main effect o f W o r d , F (1,14) = 7.94, p < .0137]. 2.7 Imaging data. Illustrations o f the areas o f activation for the concrete s t imuli versus baseline and abstract st imuli versus baseline comparisons for the con t ro l participants and psychopathic individuals are illustrated in Figures 1 and 2, and 3 and 4, respectively. The psychopathic individuals showed a very similar pattern o f act ivat ion as was observed for the cont ro l participants for the two comparisons o f the w o r d st imuli versus baseline (see Tables 5 and 6). F o r the psychopathic individuals , act ivat ion for both 28 Table 3. Demographic data for the cr iminal psychopaths and con t ro l participants for Exper iment 1. G r o u p A g e M e a n ( S D ) Years o f formal education M e a n ( S D ) N A R T score M e a n ( S D ) Q u i c k test M e a n ( S D ) Hol l ingshead parental social posi t ion index M e a n ( S D ) Contro ls 27.9 (5.0) 12.4 (.74) 111.82 (7.0) 104.75 (5.4) 4.25 (3.4) Psychopaths 33.9 (7.6) 11.13 (1.46) 111 .19(7 .5) 102.75 (9.9) 4.25 (1.4) Table 4. Behav iora l data for the cr iminal psychopaths and con t ro l participants for the concrete/abstract lexical decision task in Exper iment 1. React ion times (milliseconds) C o n t r o l Participants M e a n ( S D ) Psychopaths M e a n ( S D ) Concrete words 608.5 (65.7) 678.6 (52.0) Abstract words 640.6 (80.2) 714.5 (59.2) Pseudoconcrete stimuli 709.2 (81.2) 845.6 (113.9) Pseudoabstract st imuli 700.5 (86.3) 833.9 (93.1) Percentage correct Concrete words 94.3 (3.5) 96.2 (3.4) Abstract words 89.5 (3.6) 88.5 (11.9) Pseudoconcrete st imuli 95.0 (3.3) 91.3 (5.7) Pseudoabstract st imuli 93.6 (3.7) 85.0 (9.9) 29 Figure 1. Co r t i c a l surface rendering o f the areas o f activation for the con t ro l participants for the concrete st imuli versus baseline comparison. These renderings depict 4 views: top left, right hemisphere; top right, left hemisphere; bot tom left, left hemisphere mid-sagit tal slice; bo t tom right, right hemisphere mid-sagittal slice. The areas o f act ivat ion are thresholded at a z-score o f 4 .0 o r greater. 30 Figure 2. C o r t i c a l surface rendering o f the areas o f activation for the cont ro l participants for the abstract s t imuli versus baseline comparison. These renderings depict 4 v iews: top left, right hemisphere; top right, left hemisphere; bo t tom left, left hemisphere mid-sagittal slice; bo t t om right, right hemisphere mid-sagittal slice. The areas o f act ivat ion are thresholded at a z-score o f 4.0 or greater. 31 Figure 3. Co r t i c a l surface rendering o f the areas o f act ivat ion for the psychopathic participants for the concrete stimuli versus baseline compar ison. These renderings depict 4 views: top left, right hemisphere; top right, left hemisphere; bo t t om left, left hemisphere mid-sagittal slice; bo t tom right, right hemisphere mid-sagittal slice. The areas o f activation are thresholded at a z-score o f 4 .0 or greater. Figure 4. Cor t i ca l surface rendering o f the areas o f activation for the psychopathic participants for the abstract st imuli versus baseline comparison. These renderings depict 4 views: top left, right hemisphere; top right, left hemisphere; bo t tom left, left hemisphere mid-sagittal slice; bo t tom right, right hemisphere mid-sagittal slice. 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However, no significant activation was observed in the right anterior superior temporal gyrus for the psychopathic individuals for the abstract versus baseline comparison (see Tables 5 and 6).. In the control participants, the pattern of activation for the concrete stimuli versus baseline and abstract stimuli versus baseline comparisons largely confirmed previous results using this task (Kiehl et a l , 1999b). In both studies, processing of concrete stimuli and abstract stimuli (relative to the baseline condition) elicited activation in the bilateral superior parietal lobules, anterior cingulate, inferior frontal gyrus, insula, precuneus, bilateral fusiform gyrus, left middle temporal gyrus and right posterior superior temporal gyrus (see Tables 5 and 6). In addition, significant activation was found in bilateral premotor cortex consistent with the fact that the lexical decision was indicated with a button press using either the right or left hand. In the control participants, we observed significant activation bilaterally in the thalamus for processing abstract words. In our previous study, activation of the thalamus only reached trend levels (see Tables 5 and 6). Comparison of the abstract stimuli versus baseline revealed a very similar pattern of activation to the concrete stimuli versus baseline comparison. As in our previous study, activation in the right anterior superior temporal gyrus was observed for the abstract stimuli versus baseline comparison that was not observed for the concrete stimuli versus baseline comparison. In the second stage analyses, as predicted, control participants produced greater activation for processing of abstract, compared to concrete, stimuli than did the psychopathic individuals in the right anterior superior temporal gyrus (Talairach coordinates, 52, 15, -10; 37 z-score 3.35, p < .001; see Figure 5). There was also a trend for greater activation during the processing of abstract stimuli relative to that for concrete stimuli for control participants than psychopathic individuals in the right lateral frontal cortex (Talairach coordinates, 34, 11, 32, p < .0001, uncorrected for multiple comparisons). Figure 5. Cortical surface rendering of the areas in which control participants show significantly greater activation for processing of abstract stimuli than for concrete stimuli than did psychopathic individuals. The region was located in the right anterior superior temporal gyrus (Talairach coordinates, x= 52, y = 15, z = -10). The displayed area of activation is thresholded at a z-score of 3.0 or greater. 38 2.8 Summary and Discussion of Experiment 1 / This study was designed to elucidate the abnormal functional neural architecture underlying lexico-semantic processing in psychopathy. Consistent with previous research, psychopathic individuals performed more poorly, manifest as slower reaction times, than did control participants for processing of abstract word stimuli (Hare & Jutai, 1988; Kiehl et al., 1999a). Psychopaths also responded less accurately than control participants for classifying pseudoword stimuli. Some have argued that the cognitive operations associated with processing of pseudoword stimuli are similar to those for processing real word stimuli (see Kounios & Holcomb, 1994). One could also argue that pseudoword stimuli are more similar to abstract word stimuli than to concrete word stimuli. This suggests that the poor behavioral performance of the psychopathic individuals for processing pseudoword stimuli may be related to difficulties in lexico-semantic processing of abstract representations of linguistic stimuli. In general, the pattern of neural activation associated with processing concrete and abstract stimuli was similar in the psychopathic individuals and control participants. However, psychopathic individuals showed clear deficits in activating the right anterior superior temporal gyrus and surrounding cortex for processing abstract stimuli and they failed to show the appropriate neural differentiation in this region for abstract and concrete stimuli relative to control participants. The anterior superior temporal gyrus is a multimodal association cortex with rich connections with frontal and parietal cortex (Mendola et a l , 1999). In general, the anterior temporal lobe is believed to be involved in a circuit that integrates the outcome of sensory 39 analyses wi th previously stored semantic information ( M e n d o l a et a l . , 1999). R e m o v a l o f the nondominant hemisphere, for treatment o f intractable epilepsy, results i n impairment i n the recal l and recogni t ion o f visual and auditory patterns that are difficult to code verbally. One might argue that these stimuli are more abstract than concrete and effective processing o f these stimuli may rely on the function o f this region o f cortex ( D o y o n & M i l n e r , 1991; K i m u r a , 1963; M e i e r & French, 1965; M i l l e r & M i l n e r , 1985; Shankwei ler , 1966; Smi th & M i l n e r , 1988; Warr ing ton & James, 1967). It is important to note that the right hemisphere abnormalities observed in the psychopathic individuals do not appear to be due to any gross structural brain pathology. High-resolut ion structural M R I scans were col lected in a l l participants and none had any overt brain pathology. It may be possible that more detailed analyses o f the structural M R I data may reveal subtle structural brain abnormalities in the psychopathic offenders, but at this time there is no evidence to support the view that the cognit ive abnormalities observed in the present study are due to structural brain damage. In other words , it appears that the abnormalities observed in the psychopathic individuals in the present study are functional, rather than structural, in nature. In summary, these data suggest that psychopathy is associated w i t h abnormalities in semantic processing o f conceptual ly abstract information. These abnormalities appear to be local ized to the right anterior superior temporal gyrus and surrounding cor tex. These data are consistent wi th the hypothesis that psychopathy is related to right hemisphere abnormalities, particularly in the temporal lobe. 40 3. Exper iment 2 Methods 3.1 Participants. C r imina l psychopaths (n=8; al l male) were inmates f rom a maximum-securi ty pr ison located in Abbots ford , Br i t i sh Co lumbia , Canada. M a t c h e d noncr iminal con t ro l participants (n=8; al l male) were recruited from the general populat ion. T h e two groups o f participants were matched for gender (all male), age [Psychopaths 33.9 ( S D 7.6); Cont ro l s 31.9 ( S D 8.4)], parental socioeconomic status [Psychopaths 4.25 ( S D 1.4); Cont ro l s 3.1 ( S D 1.55)], and I Q (measured wi th the Na t iona l A d u l t Read ing Test [Psychopaths 111.2 ( S D 7.5); Cont ro ls 108.9 ( S D 11.5)] and Q u i c k Tests [Psychopaths 102.7 ( S D 9.9); Cont ro l s 109.6 ( S D 17.5)]). There were no group differences on any o f these measures (all p.'s > .35). A l l participants were free f rom any history o f head injury or psychotic illness (in self and first-degree relatives), were right-handed (Annett , 1970), and spoke Eng l i sh as their first language. N o participant met the criteria for substance abuse according to the D S M I V criteria wi th in the last 6 months. T h e Hare Psychopathy Checkl i s t -Revised ( P C L - R ) was used to assess psychopathy (Hare, 1991). A l l inmates scored above the mean psychopathy score [23.6, S D 7.9] for the 1192 pr ison inmates presented in the P C L - R manual. T h e range o f P C L - R scores in our sample was 28-36 (mean 32.8, S D 2.9). The Psychopathy Checkl i s t : Screening V e r s i o n ( P C L : S V ) was used to assess psychopathy i n the noncriminals. The P C L : S V is an abbreviated version o f the P C L - R used in nonforensic populations. N o n e o f the noncriminals met the P C L : S V criteria for psychopathy. 41 3.2 St imul i . St imulus words were either neutral o r negative in connotat ion, and were selected f rom the 7-point pleasantness ratings given in T o g l i a and Ba t t ig (1978). W o r d s rated as more that 1.3 standard deviations above the mean pleasantness rating were defined as negative (e.g., hate). W o r d s wi th in 1.3 standard deviations o f the mean pleasantness rat ing were defined as neutral in affect. The w o r d lists d id not differ significantly in length (3-8 letters), imagery o r concreteness (Tog l i a & Bat t ig , 1978), or frequency (Francis & K u c e r a , 1982). 3.3 Task and Procedure. T h e experimental procedure consisted o f three phases. In the first phase (encoding), participants were asked to memorize a list o f twelve words presented serially, one at a time (500 ms duration, 2000 ms ISI) . D u r i n g the second phase (rehearsal), participants were instructed to mentally rehearse the list o f words presented in the first phase. The third phase (recognition) consisted o f a recognit ion test, in wh ich twelve words were presented and participants were instructed to indicate (yes or no) , using the index and middle fingers o f their right hand, whether they recognized the w o r d as being f rom the list presented during the first phase. H a l f o f the w o r d st imuli presented during the th i rd phase were presented in the first phase. A c c u r a c y was stressed. A t the comple t ion o f the last phase, a brief rest per iod ensued. E a c h phase and rest per iod lasted 25 seconds. E igh t total repetitions o f the three phases (plus rest period) were presented in two stimulus runs. U n k n o w n to the participants, half o f the phases contained w o r d st imuli (i.e., al l s t imuli f rom phase 1 and phase 3) that were either negative or neutral in affect. A M R I compatible fiber-optic response device (Lightwave M e d i c a l , Vancouver , B . C . ) was used to acquire behavioral responses. A l l st imuli were presented (white on black background) in an outline o f a rectangular box ( 6 x 4 42 visual degrees). Word stimuli were all presented in lower case letters and were approximately 5 x 3 visual degrees in size. Prior to entry into the scanning room, each participant performed two practice runs consisting of two repetitions of the three phases to ensure understanding of the instructions. Al l of the word stimuli presented in the practice runs were neutral in affect and none were used in the fMRI session. Stimuli were presented to the participants in the same manner as Experiment 1. 3.4 Behavioral data analyses. We performed repeated-measures Group (psychopath, control) X Condition (negative, neutral) analyses of variance (ANOVAs) on the accuracy data. Planned comparisons were used to determine if both groups showed the expected greater accuracy recognition of emotional stimuli than for neutral stimuli. 3.5 Image acquisition. Image acquisition was performed in the same manner as for Experiment 1. 3.6 Image processing. As in Experiment 1, functional images were reconstructed offline and the two runs were separately realigned using the procedure by Friston et al. (1996) as implemented in Statistical Parametric Mapping (SPM97, Wellcome Department of Cognitive Neurology). Translation and rotation corrections for this Experiment did not exceed 3 mm and 3 degrees, respectively, for any of the participants. A mean functional image volume was constructed for each participant for each run from the realigned image volumes. This mean image volume was then used to determine parameters for spatial normalization into the modified Talairach space employed in SPM97 using both affine and nonlinear components 43 (Fris ton et a l . , 1995a). The normalizat ion parameters determined for the mean functional volume were then applied to the corresponding functional image volumes for each participant. Adjusted mean functional images were then created for the affective and neutral phases for each participant by col lapsing across al l three phases for each condi t ion. In the computat ion o f these adjusted mean images, variations in global intensity were removed using propor t ional scaling and a temporal delay o f 6 seconds was incorporated to account for the relatively s low onset o f the hemodynamic response. These adjusted mean images were analyzed by compar ing the differences between affective and neutral st imuli between the two groups. W e were primari ly interested in the areas in wh ich greater activation was observed for processing o f affective stimuli than for neutral st imuli and where these differences were significantly different between psychopaths and controls. Results 3.7 Behav io ra l data. Consistent wi th previous research, negative words were recalled more accurately than were neutral words (main effect o f W o r d , F (1 , 14) = 19.42, p < .0006). This effect was most pronounced in the cont ro l participants (planned comparison: F (1, 14) = 16.93, p < .001), who correct ly classified 82 .12% ( S D 8.3) and 90.63 ( S D 7.7) o f the neutral and negative words , respectively, during the recognit ion condi t ion. Psychopaths also showed a statistical trend for more accurate recall o f affective st imuli than for neutral st imuli (planned comparison: F (1 , 14) = 4.49, p < .06), correct ly classifying 84 .25% ( S D 4.4) and 88.63 ( S D 6.06) o f the neutral and negative words , respectively. Importantly, there were no overal l 44 group differences in accuracy, suggesting that both groups were actively engaged in performance o f the task. 3.8 Imaging data. Analyses o f the imaging data revealed that con t ro l participants showed significantly greater activation for processing o f affective than for neutral s t imuli than d id the psychopathic individuals in the fo l lowing regions: anterior and poster ior cingulate, left posterior fusiform gyrus, left posterior h ippocampal gyrus, right anterior parahippocampal gyrus, extending into the amygdala and the ventral striatum (see F igure 6). Other areas where psychopathic individuals showed little differentiation between negative and neutral st imuli included the left inferior frontal gyrus and right superior parietal lobule. H o w e v e r , these latter areas d i d not reach statistical significance after the stringent correct ion for mult iple comparisons employed in S P M 96 (p < .0001 uncorrected). Interestingly, psychopaths d id show greater activation for processing o f affective than for neutral s t imuli in a number o f brain regions located outside the l imbic system. These areas included the left anterior superior temporal gyrus/inferior frontal gyrus, right inferior frontal gyrus, left precentral gyrus, left and right parietal lobe, and middle temporal gyrus (Figure 6). 45 Figure 6 legend. G r o u p statistical parametric maps ( S P M { Z } s ) rendered onto four transverse slices o f a standard reference brain in Talairach space. T h e z-levels depicted for the four slices are -18, -8, 22 , 28 m m below and above the anterior commisure/posterior comrnisure line, respectively. Lef t hemisphere is on the left side o f each slice. Areas depicted in blue indicate areas in wh ich controls show significantly greater emotional than neutral differentiation than do psychopaths. These areas include: slice 1: right hippocampus/amygdala (34, -11 , -20; z-score 4 .74) ; left parahippocampal gyrus (-38, -22, -16; z-score 4.93); left fusiform gyrus (-49, -38, -12; z -score 5.05); slice 2: right putamen/ventral striatum (15, 11, -8 ; z-score 4 .75) ; slice 3 and 4: left anterior cingulate (-15, 26, 28; z-score 5.20); left posterior cingulate ( -8 , -38 , 16; z-score 5.36). Dep ic t ed in red are areas in which psychopaths show greater emot ional than neutral differentiation than do controls. These areas include: slice 1: left anterior superior temporal gyrus (-45, 22, -24; z-score 5.31) extending into the inferior frontal gyrus (-38, 26, -20; z -score 4.89); slice 2: right inferior frontal gyrus (64, 22, 16; z-score 4.71); slice 3: right posterior superior temporal gyrus (34, -52, 24; z-score 4.70); left middle temporal gyrus (-64, 8, 28 ; z-score 5.13); and the left postcentral gyrus (-49, -19, 24; z-score 5.08). Th is latter effect was also observed in the right precuneas (19, -34, 44; z-score 4 .84; data not depicted). C o l o r bars o n the bo t tom right corner indicate the range o f z-score units for the t w o comparisons. A z-scores o f 4.50 is equivalent to a probabil i ty level o f p = .05, corrected for multiple comparisons. See next page for Figure 6 46 Figure 6. See previous page for legend. 3.9 Summary and Discuss ion for Experiment 2 This study was designed to elucidate and characterize the abnormal functional architecture underlying affective processing in psychopathic offenders. Psychopathic offenders showed reduced affective-neutral differentiation than d i d con t ro l participants in the hippocampal/amygdala formation, ventral striatum, and in the anterior and posterior cingulate. In general, the observed regions o f activation i n the anterior and posterior cingulate and posterior fusiform gyrus have been associated wi th attentional mechanisms (Heinze et a l . , 1994; M a d d o c k & B u o n o c o r e , 1997; Posner & Rothbart , 1998). T h e amydgala, ventral striatum, and hippocampal formation typical ly are associated wi th processes related to emotion and memory (Adolphs , Tranel , & Damasio , 1998; Bechara , Damas io , Damas io , & L e e , 1999; I rwin et a l , 1996). Taken together, these findings suggest that the neural systems associated wi th attentional processing o f affective st imuli and that impart affect at both the l imbic and neocort ical level are abnormal in psychopaths . The finding that the areas observed to differentiate affective f rom neutral s t imuli in psychopaths included regions generally associated wi th semantic and decis ion-making processes are consistent w i th the hypothesis that psychopaths employ non- l imbic cognit ive strategies to process affective material (Wil l iamson et a l . , 1991). T h e observation that psychopathic individuals showed greater activation for affective than neutral s t imuli in bilateral anterior superior temporal gyrus/inferior frontal gyrus is consistent w i th the findings o f a recent brain imaging study that required participants to make lexica l decisions about affective and neutral stimuli. Psychopaths, but not nonpsychopaths, p roduced greater activation for processing o f affective than neutral st imuli in bilateral fronto-temporal cort ices (Intrator et a l . , 48 1997). These latter data have been interpreted as supporting the not ion that psychopaths require more cogni t ive resources to process affective information than do normal individuals. Presumably, in the absence o f appropriate l imbic and cor t ica l input regarding the affective characteristics o f st imuli forces psychopaths to use alternative cogni t ive operations and/or strategies to process affective material. These alternative strategies may recruit different neural structures than those used by most individuals, and perhaps addit ional cogni t ive resources, to aid in the processing o f the affective st imuli . A t the present time the e t io logy o f these abnormalities is unknown . H o w e v e r , an extensive body o f c l in ica l data suggests that abnormalities in emot ional processing are present at an early age in this populat ion (Fr ick , 1998). In summary, this experiment has shown that processing o f affective s t imuli is associated wi th less l imbic activation in psychopaths than in con t ro l participants. Th i s experiment has also shown that psychopaths appear to use alternative neural systems to process affect. These findings provide the first visualization o f the neural processes that may underlie affective anomalies that clinicians have described in psychopaths. 49 4.0 Experiment 3 Method 4.1 Participants. The participants were 21 male inmates from a federal forensic psychiatric facility near Vancouver, British Columbia. They were participants in a violent offender or sex-offender treatment program. Volunteers were selected for the study if they were between 18 and 55 years of age, had normal, or corrected-to-normal vision, were free from any reported serious head injury or neurological impairment, had no DSM-IV Axis I diagnosis (American Psychiatric Association, 1994), and were right handed (Annett, 1970). Volunteers participated in two sessions: a videotaped semi-structured interview and the experimental recording session. Information from the interview and an extensive review of institutional files were used by two clinicians to independently complete the PCL-R on each inmate. Each of the 20 items on the PCL-R is scored on a 3-point scale (0-2) according to the extent to which it applies to the inmate. The mean and standard deviation of PCL-R total scores (which can range from 0 to 40) for the entire sample were 25.9 and 9.1, respectively. Because of the continuing debate as to whether psychopathy is discrete condition or a dimension of personality (Cooke, 1998; Cooke & Michie, 1997), we performed both categorical and correlational analyses. For the purposes of categorical analyses, an approximate median split was used to create two groups. Inmates with a PCL-R score of 29 or above (n = 11) were defined as Psychopaths (mean = 33.2, standard deviation = 2.2), and those with a PCL-R score of 27 or below (n = 10) were defined as Nonpsychopaths (mean = 17.9, standard deviation = 6.8). Using this procedure all but one of the Psychopaths had a PCL-R score above 30 (the suggested cutoff point for psychopathy given by Hare, 1991). Three of the 5 0 Nonpsychopaths had scores above the recommended cutoff of 20 on the PCL-R (Hare, 1991). The liberal cutoff point on the PCL-R for inclusion into the Nonpsychopathic group would, if anything, lend to a conservative bias to our experimental hypotheses. The kappa coefficient for two independent raters for classification into Psychopathic and Nonpsychopathic groups by PCL-R scores was 1.00. The inter-rater reliability for two raters for total PCL-R scores was 0.86. Mean age and years of formal education were 27 and 33, and 10.5 and 10.8 years for Psychopaths and Nonpsychopaths, respectively. The two groups did not differ significantly on either of these measures (p > .20). Participants were rated as average to above average intelligence by a psychiatric screening interview completed for participation in the treatment programs. We paid each inmate $5.00 for the PCL-R interview and $10.00 for the experiment. The total of $15.00 was equivalent to 2 days prison wage. As an additional incentive, we told the participants that the participant who had the best reaction time and accuracy would receive an extra $10.00. The study was conducted in accordance with Institutional and University ethical standards. 4.2 Stimuli. Each stimulus, displayed on a computer monitor, consisted of a white square on a black background. The target stimulus was a four-by-four centimeter square and the nontarget stimulus was a six-by-six centimeter square. The larger stimuli subtended a visual angle of 8.5 by 8.5 degrees, and the smaller stimuli subtended an angle of 3.8 by 3.8 degrees. 4.3 Event-related Potential Recording. Scalp potentials were recorded from tin electrodes (ElectroCap International) placed over prefrontal (F7, Fpz, F8), frontal (F3, Fz, F4), temporal 51 (T3, T4), central (C3, Cz, C4), and parietal (P3, Pz, P4) sites according to the International 10-20 System of electrode placement. Vertical eye movements were monitored from an electrode on the supra orbital ridge of the right eye. Al l electrodes were referenced to an electrode located at the right mastoid process. One additional channel, left mastoid to right mastoid, was recorded for the purposes of allowing digital re-referencing to an average of left and right mastoids (Nunez, 1981; Nunez, 1990). Electrical impedance was checked before and after the experiment. In all cases, the electrode impedances were below 5 Kohms. The E E G channels (Grass Model 8-18C) were amplified with a bandpass of .1 to 70 Hz, digitized on-line at a rate of 256 samples per second, and recorded on computer hard disk. The sampling epoch was 1300 milliseconds, beginning with a 100 millisecond pre-stimulus baseline period. Artifact rejection was performed before averaging to evaluate trials contaminated by blinks (greater than 50 microvolts) or amplifier blocking. These rejected trials did not exceed 5% of trials in any condition and there were no group differences in the number of trials averaged in any condition. The ERPs were then digitally filtered with a zero-phase shift 20 Hz low pass filter to reduce electromyographic noise. 4.4 Procedure. The experiment was conducted in a dimly-lit room in a quiet part of the institution. After attachment of the electrodes the inmate sat in a comfortable chair approximately 60 cm from the computer monitor. He previewed the stimuli and was told to respond as quickly and accurately as possible, by pressing a designated button on a computer keyboard whenever a small square (the target) appeared, but not to respond when a large square (nontarget) appeared. The hand used to respond was counterbalanced across participants. The stimulus duration was 50 milliseconds, with a random 750 - 1250 inter-52 stimulus interval. Two hundred trials were presented in 2 blocks of 100. Within each block 25 % of the trials were the target stimuli and 75% of the trials were nontarget stimuli. The participant performed a block of 10 practice trials, repeated twice, to insure he understood the instructions before beginning the experiment. 4.5 Data analysis. We performed separate t-tests on the reaction time, percentage of correct hits and errors of commission. A N O V A s were performed on the ERP data; one for lateral sites and one for midline sites. These analyses included factors of Group (psychopath vs. nonpsychopath) x Condition (target vs. nontarget) x Site (prefrontal, frontal, central, parietal, and temporal for lateral analyses; prefrontal, frontal, central, and parietal for midline analyses). For lateral sites, there also was a factor for Hemisphere (left and right). Two ERP components were measured (relative to the 100 ms prestimulus baseline); the P300 and the N550. For the P300 we performed both peak amplitude and latency measurements. In order to reduce the effect of latency jitter on the P300 peak amplitude measurement, we also quantified the P300 as the mean amplitude in the 325 - 425 millisecond window. Analysis of the mean amplitude measurement of the P300 largely confirmed the peak amplitude analysis. The amplitude of the N550 was quantified as the mean value in the 550-650 window. Following the A N O V A , planned comparisons were performed on the predicted effects. Type I error rate was maintained below .05 by using the Dunn-Bonferroni correction. Other effects of interest were tested using simple effects analyses or Tukey's multiple comparisons. The Geisser-Greenhouse correction was used for any repeated measures that contained more than one degree of freedom in the numerator (Geisser & Greenhouse, 1958). A l l probability levels are reported using epsilon-adjusted degrees of freedom. The McCarthy and Wood (1985) 53 correction was applied to any Group x Site or Group x Hemisphere interaction. In all cases, this correction did not decrease the probability level below significance. We also performed correlation analyses comparing the P300 amplitude and the amplitude of the N550 with PCL-R total scores. A l l participants were included in these analyses. Results 4.6 Behavioral data. Participants had no difficulty correctly responding to or correctly classifying the two stimuli. There were no group differences in any of the three behavioral measures (all p's > .05). The behavioral results are presented in Table 7. 4.7 Event-related Potentials. Grand mean ERPs for the Psychopaths and Nonpsychopaths are presented in Figures 7 and 8 for the target and nontarget stimuli, respectively. 4.7.1 P300 peak amplitude. Analyses of the lateral sites yielded a main effect of Group [F (1, 19) = 5.75, p < .03] and a Group x Condition interaction [F (1,19) = 4.82, p < .05]. This pattern of results indicated four things: 1) the P300 to target stimuli was larger for nonpsychopaths than for psychopaths; 2) the P300 was larger for targets than for nontargets for nonpsychopaths; but 3) this latter effect was not significant for psychopaths; and 4) there were no ERP differences between psychopaths and nonpsychopaths for the nontarget stimuli. P300 amplitude measurements for Psychopaths and Nonpsychopaths are summarized in Table 8. 54 There was a significant Group x Hemisphere interaction [F (1, 19) = 4.54, p < .05]. This effect indicated that the P300 was more lateralized (right hemisphere) in Nonpsychopaths than in Psychopaths. At midline sites there was a significant Group x Condition interaction [F (1, 19) = 5.66, p < .03] and a Group x Site interaction [F (3, 57) = 4.76, p < .006, 8 = .55], and a Group x Condition x Site interaction [midline, F (3, 57) = 5.55, p < .002, 8 = .55]. As with the lateral analyses, 1) Nonpsychopaths had a larger P300 for the target stimuli than did Psychopaths; and 2) Nonpsychopaths, relative to Psychopaths, showed greater central and posterior P300 differentiation between target and nontarget stimuli. There was no P300 difference between conditions for Nonpsychopaths at frontal sites. There was a trend for Psychopaths to show a slightly larger P300 to target than to nontarget stimuli at the anterior site (Fpz). In general, the P300 was larger for target than for nontarget stimuli [main effect of Condition: lateral, F (1, 19) = 18.70, p < .00001; midline, F (1, 19) = 5.66, p < .004] with this effect being greater at right than left hemisphere central and parietal sites [Condition x Site x Hemisphere interaction: lateral, F (4, 76) = 5.73, p < .002, e= .68; Condition x Site interaction: midline, F (3, 57) = 4.75, p < .006, 8 = .55]. Across stimulus types the P300 was larger at central and parietal sites than at anterior or temporal sites [main effect of Site: lateral, F (4, 76) = 23.36, p < .001, e = .40; midline, F (3, 57) = 11.13, p < .001, 8 = .54]. The results of the correlational analyses between PCL-R scores and the peak amplitude of the P300 to target stimuli are summarized in Table 9. Significant negative correlations were found at central and parietal sites, indicating that the smaller P300 to target stimuli was characteristic of psychopathy. 55 Table 7. Behavioral Experiment 3. data for Psychopaths and Nonpsychopaths for the visual oddball task in Reaction times (ms) Percentage of Correct Hits Errors of Commission Psychopaths Nonpsychopaths Mean (Std) 416 (45.9) 403 (30.5) Mean (Std) 96.2 (1.1) 94.0 (5.1) Mean (Std) 0.54 (0.7) 1.80 (1.9) 56 oo cd O O vo VO CO CO ON VO O CN t-» co co H oo CN O T t VO 00 CN CN r-d oo d ON vo d ~ H Tt OH O P r-: o CO CO T t in O r-i - J CN OO VO d d OH T t CN co m' vd vq T t d co' co co co P H CN T t VO ON CO O Tt in CN co d CN vo in d d T t U co vd vo >—i in vd ^ co 9 Tt T t r-CN CN T t © ON r-vd vd CN CN CO CO co r-CN CN co U ON CO T t ON in in w-i wo ^ Tt 9 co ON »-< < CN 2 o o VO ON VO VO T t T t <N m r7l CN ^ H CN CN CN CO ON in r-' CN ON iri T t co co oo CN CO PL, 00 vo in x t co H oo d 00 o oo PH co ON T t w-i co co o d vo CN O CN CN CN in vq vd in CO CN CN CN d CN ON CN r-i r-PH O 00 in in in r~; CN I-H 00 in d CO o U OH CD T3 -a 1' cd ^ cd CD D i O o CO OH JS ;=> 3 cd 08 oo D , D oo CM -C O • S o 2 tt oo cd CD O •JS > O syc 00 -c a. 60 JS D J CD 00 & Psyc Non ontar Psyc Non H CD -o 3 I cd O m mi a 3 oo J3 o 00 •*—» cd DH O o & oo JS —^» cd CD S3 H 00 OH DH a o 00 JS 3 2 C _ .5 - c o *3 "tt - C cd00 Qi JS ~ _ D O § OH Z Figure 7. Grand-averaged ERPs to target stimuli for Experiment 3. By convention, negative amplitude is plotted up. TARGET STIMULI EOG NONPSYCHOPATHS PSYCHOPATHS 58 Figure 8. Grand-averaged ERPs to nontarget stimuli for Experiment 3. By convention, negative amplitude is plotted up. NONTARGET STIMULI E O G N O N P S Y C H O P A T H S P S Y C H O P A T H S 59 4.7.2 P300 peak latency. The P300 was earlier at prefrontal sites than at any other scalp site [main effect of Site: midline, F (3, 57) = 5.70, p < .01; lateral, F (4, 76 = 10.67, p < .001], an effect found only for the target condition and not the nontarget condition [Condition x Site interactions: midline, F (3, 57) = 13.64, p < .0001; lateral, F (4, 76) = 9.46, p < .001]. Latency measurements also were faster over left hemisphere sites than at right hemisphere sites [main effect of Hemisphere: F (1, 19) = 8.68, p < .008]. There were no P300 peak latency differences between Psychopaths and Nonpsychopaths. 4.7.3 N550 mean amplitude. Analyses of this time window confirmed that Psychopaths had a larger N550 than did Nonpsychopaths [main effect of Group: lateral, F (1,19) = 9.43, p < .007; midline, F (1, 19) = 14.04, p < .002] an effect found for the target stimuli but not for the nontarget stimuli [Group x Condition interactions: lateral, F (1, 19) = 7.20, p < .02; midline, F (1, 19) = 10.01, p < .008]. The N550 was more anterior than posterior [main effect of Site: lateral, F (4, 76) = 5.46, p < .006, 8 = .60; midline, F (3, 57) = 7.26, p < .004, e = .56; Condition x Site interactions: lateral, F (4, 76) = 7.19, p < .002, e = .56; midline, F (3, 57) = 10.51, p < .002, e = .58] and more prominent over the left hemisphere than the right hemisphere [main effect of Hemisphere: F (1,19) = 20.53, p < .0001; and Condition x Hemisphere interaction: F (1, 19) = 11.10, p < .005]. N550 amplitude measurements for Psychopaths and Nonpsychopaths are summarized in Table 8. As for the P300 results, significant negative correlations were found between PCL-R scores and the N550 amplitude measurements at frontal and central sites (see Table 9). 60 0\ CD a o g oj oo 00 03 o O u Ji c3 i-< o Ji o T? H en H (3 •a a aID l_i o &• -8 a C3 H ° 3 O 2 £ C M § P-. TT U N u cn U 2 o o oo Oi I U CU >, -a c3 O EX -| 2 N C <D 0) •5 co JO O0 c3 e ~ o .2 -4-> — cd oo tl o SI CO, U S T4 -.45 .05 -.24 .29 T3 -.40 .08 -.48 .03 P4 ° CN Tf ^ vn o cn ^ L, 1 1 Pz »n g q i* i* P3 -.47 .03 -.43 .05 C4 -.54 .02 -.47 .03 Cz -.58 .007 -.61 .003 C3 CN (N) *T) ^ "O o © 1 1 F4 O oo T — 1 CN m H <n o 1 1 Fz -.29 .20 -.56 .008 F3 CN ^ i—< (-o ^ cn "} © F8 O r-, « H. -1 VO CN CN 1 1 Fpz CN O ^ Tt i—l VO Tt <—, r F7 2 ^ £; o """J vo ^ »—i 1 • 1° PCL-R P300 peak amplitude R p value N550 mean amplitude R p value 4.8 Summary and Discussion for Experiment 3 This study was designed to assess the topographic variation in the P300 response while psychopaths and nonpsychopaths performed a visual oddball task. We predicted that the P300 response to target stimuli would be smaller in psychopaths than in nonpsychopaths consistent with the hypothesis that psychopathy is associated with an impaired ability to allocate attentional resources. The ERP results clearly supported this prediction. As Figure 7 illustrates, the P300 response to the target stimuli was significantly smaller for psychopaths than for nonpsychopaths. This effect was present despite the fact that there were no behavioral differences between groups. This finding may be due to the simplicity of the behavioral task (e.g., ceiling effects) or, more likely, representative of the greater sensitivity of ERP measures to group differences in information processing. This latter conclusion is consistent with a number of other ERP studies on psychopathy (Jutai et al., 1987; Raine & Venables, 1988; Kiehl et al., 1999a) which found ERP differentiation occurred with little or no behavioral differences between experimental conditions. The reduced P300 amplitude for target stimuli in psychopaths apparently contradicts the finding by Raine and Venables (1988) of an enhanced P300 to visual target stimuli, making it necessary to examine the methodology of both studies. First, with regard to paradigm, Raine and Venables (1988) employed a visual continuous performance task (CPT), whereas in this study we employed a visual oddball task. In the CPT the participant must discriminate between multiple different nontarget stimuli, whereas in the oddball paradigm all nontargets are identical. With regard to participant classification, both studies distinguished psychopaths from nonpsychopaths by performing a median split on scores on the P C L (Raine & Venables, 62 1988) or its revision, the P C L - R (present study) i n a pr ison sample. Ra ine and Venables (1988) d id not report the median score in their sample. H o w e v e r , i f that sample was representative o f the larger Br i t i sh pr ison popula t ion from w h i c h it was d rawn ( P C L - R mean score 17.8, standard deviation 8.6, as reported i n Hare , 1991), the median score was probably substantially lower than the median score o f 29 i n the present experiment. H o w e v e r , the results o f the correlational analysis suggest that differences between studies i n the median values should not affect the findings. The psychopaths ' P 3 0 0 deficit to target st imuli supports the longstanding idea that psychopathy is characterized by an inabil i ty o r deficiency in sustaining attention o r appropriately allocating attentional resources to task (Cleckley , 1976; Hare , 1993; K o s s o n , 1996; K o s s o n & N e w m a n , 1986). Because this performance "defici t" was present only for the target condi t ion and not the nontarget condi t ion, it appears to indicate that it is a specific, rather than a global deficit in psychopathy. It might be that psychopaths are abnormal in their ability to mobi l ize and rapidly focus attention to st imuli to wh ich they are required to respond. Once focused, it may be extremely difficult for them to re-mobi l ize and swi tch attentional resources (cf. Jutai & Hare , 1983) W e have provided further confirmation that psychopaths exhibit an abnormal late centro-frontal negativity in a task that requires a decision and response. H o w e v e r , i n contrast to W i l l i a m s o n et al . (1991) and K i e h l et al . (1999a), we observed this negativity for a task that places no explici t demands on linguistic processing. Th is raises the quest ion o f what aspect o f processing is responsible for the negativity? W i l l i a m s o n et al. employed a G o / N o - g o paradigm, indicating that the late negativity might be due at least in part to response inhibit ion. O u r observation that the late negativity only occurred in response to the target st imuli 63 indicates that it is unl ikely to be due to response inhibit ion, confi rming the conc lus ion o f K i e h l et al. It remains to be determined what other processes these negative waves represent. It should be noted that the larger N 5 5 0 in psychopaths than in nonpsychopaths may have been due, at least in part, to the psychopaths ' reduced P300 . Alternat ively, the smal l P 3 0 0 o f the Psychopaths may be related to the presence o f the large N 5 5 0 . One additional interesting effect found in this study was that the peak amplitude o f the P 3 0 0 was greater over the right than over the left hemisphere electrode sites in nonpsychopaths but not in psychopaths. There is a relatively large body o f evidence that suggests psychopathy is associated wi th weak ly or unusually lateralized cerebral hemispheres ( D a y & W o n g , 1996; Hare & Jutai, 1988; H a r e & M c P h e r s o n , 1984). T h i s hemispheric asymmetry in nonpsychopaths is very similar that found in healthy participants during a visual discrimination task (Alexander et al . , 1995b). Indeed, the morphology and scalp distribution o f the P 3 0 0 for the nonpsychopaths in our study very closely resembles that o f healthy participants in Alexander et al 's study. Interestingly, Alexander et al. interpreted the right frontal-central asymmetry o f the P 3 0 0 to be reflective o f processes i nvo lved in the sustained engagement o f attentional focus. These findings suggest that future research examining the relationships among psychopathy, cerebral asymmetry, and attentional processes w i l l be fruitful. In summary, this experiment attempted to clarify the relationships between psychopathy and the P 3 0 0 response el ici ted by target stimuli dur ing a v isual oddbal l task. The present results are consistent wi th the c l in ica l literature o n psychopathy and support the hypothesis that psychopathy is associated wi th difficulties in the effective modula t ion and al location o f attentional resources. 64 5.0 Exper iment 4 Me thods 5.1 Participants. The participants were 80 male inmates f rom a federal maximum-securi ty pr ison facility near Vancouve r , Br i t i sh Co lumbia . Volunteers were selected for the study i f they were between 18 and 55 years o f age, were free f rom any reported serious head injury or neurological impairment and had no D S M - I V A x i s I diagnosis (Amer i can Psychiatr ic Assoc ia t ion , 1994). Volunteers participated in t w o sessions: a videotaped semi-structured interview and the experimental recording session. Information f rom the interview and an extensive review o f institutional files were used complete the P C L - R on each inmate. E a c h o f the 20 items on the P C L - R is scored on a 3-point scale (0-2) according to the extent to wh ich it applies to the inmate. Inter-rater reliabili ty for two raters for a subset o f the inmates (n=30) was .83. The total populat ion o f 80 inmates was broken into two samples. W i t h i n each sample, inmates wi th a P C L - R score o f 30 or above were defined as Psychopaths and those wi th a P C L - R score be low 30 were defined as Nonpsychopaths . Sample 1 was comprised o f 23 Psychopaths [mean P C L - R score 32.5 ( S D 1.7)] and 21 Nonpsychopaths [mean P C L - R score 20.85 ( S D 5.99)] col lected by the present author. Sample 2 was a replication sample col lected by a research assistant and was comprised o f 18 Psychopaths [mean P C L - R score 33.94 ( S D 2.48)] and 18 Nonpsychopaths [mean P C L - R score 20.35 ( S D 6.39)]. Statist ical analyses were performed separately for each sample. F o r Sample 1, the mean age and years o f formal education were 33.9 and 35.8, and 11.0 and 11.4 years for Psychopaths and Nonpsychopaths, respectively. F o r Sample 2, mean 65 age and years o f formal education were 32.5 and 31.4, and 10.4 and 11.2 years for Psychopaths and Nonpsychopaths , respectively. T h e Na t iona l A d u l t Read ing Test ( N A R T ) and Q u i c k tests were used to assess I Q . N A R T and Q u i c k scores were unavailable for 4 inmates. F o r Sample 1 the N A R T and Q u i c k scores for Psychopaths were 108.9 ( S D 9.6) and 103.2 ( S D 11.85) and for Nonpsychopaths they were 107.6 ( S D 10.3) and 103.5 ( S D 8.5), respectively. F o r Sample 2 the N A R T and Q u i c k scores for Psychopaths were 112.3 ( S D 7.3) and 105.45 ( S D 10.8) and for Nonpsychopaths they were 110.9 ( S D 9.36) and 105.8 ( S D 9.21), respectively. F o r both samples, there were no group differences in age, years o f formal education, N A R T or Q u i c k scores (all p ' s > .50). W e pa id each inmate $5.00 for the P C L - R interview and $10.00 for the experiment. T h e total o f $15.00 was equivalent to 2 days prison wage. The study was conducted in accordance wi th Institutional and Univers i ty ethical standards. 5.2 S t imul i . The target (1500 hz tones), novel (e.g., ramped tones, r a n d o m sounds) and nontarget (1000 hz tones) stimuli were presented with a probabil i ty level o f .125, .125 and .75, respectively. A l l s t imuli were 200 milliseconds in durat ion wi th a r andom 1000 -1500 ms inter-stimulus interval. T h e only constraint on the order o f stimulus presentation was that two l o w probabili ty st imuli cou ld not occur after each other, otherwise the presentation o f stimuli was random. S i x runs o f 64 stimuli were col lected. Participants were instructed to respond as qu ick ly and accurately as possible to the target s t imuli and to ignore the nontarget and novel st imuli . The hand used to respond to the target stimuli was counterbalanced across participants. T w o runs o f 20 st imuli were g iven as practice. 66 5.3 Event-related Potent ia l Record ing . Scalp potentials were recorded f rom tin electrodes (E lec t roCap International) placed over 29 electrode sites according to standard placement guidelines o f the International 10-20 System. Ver t i ca l and hor izonta l e lect roocularogram ( E O G ) were moni tored from a bipolar electrode pair located o n the lateral and supra orbital ridges o f the right eye. A l l E E G electrodes were referenced to the nose. T w o addit ional channels, left and right mastoids were recorded. E lec t r i ca l impedances were maintained be low 10 kohms throughout the experiment. The E E G channels ( S A instruments) were amplified (20,000 gain) wi th a bandpass o f .01 to 100 H z , digi t ized on-line at a rate o f 256 samples per second, and recorded on computer hard disk. The length o f the recording epoch was 1200 mill iseconds wi th a 100 mi l l i second pre-stimulus baseline. Single-trials wi th voltages greater than (+ or -) 75 microvol t s at any electrode site or E O G artifact were excluded. F o u r participants (all nonpsychopaths f rom Sample 2) were excluded because o f excessive artifacts (greater than 4 0 % o f target trials). After exclusion o f these participants, there were no significant group differences in the number o f trials averaged in any condi t ion. The E R P s were digitally filtered wi th a zero-phase shift 30 H z l o w pass filter to reduce electromyographic contamination and ambient electrical noise. Three components were analyzed by measuring the peak amplitude, relative to a 100 mil l isecond prestimulus baseline, in the fo l lowing latency w indows 175-265 ms (N2) , 275-425 ms (P3), and 425-625 ms (N475) . These windows were centered upon the peak latency o f each o f the components in the grand average waveforms. Separate A N O V A s were performed on midline, medial and lateral sites. These A N O V A s included factors o f G r o u p [Psychopath and Nonpsychopath] , Cond i t i on [nontarget, target and novel] , and Site [frontal (F7, F 3 , F z , 67 F 4 , F 8 ) , fronto-central (Fc7 , F c 3 , F e z , F c 4 , F c 8 ) , central ( T 3 , C 3 , C z , C 4 , T 4 ) , temporo-parietal (Tp7 , P 3 , P z , P 4 , T p 8 ) , and temporo-occipi ta l (T5 , 0 1 , O z , 0 2 , T 6 ) ] . F o r medial and lateral A N O V A s there was an addit ional factor o f Hemisphere [right and left]. M i d l i n e (Fpz) and medial ( F p l , Fp2) A N O V A s also included an addit ional level o f Site [prefrontal]. F o l l o w i n g the A N O V A , planned comparisons were performed on the predicted effects. Type I error rate was maintained be low .05 by using the Dunn-Bonfe r ron i correct ion. Other effects o f interest were tested using simple effects analyses or T u k e y ' s mult iple comparisons. The Geisser-Greenhouse correct ion was used for any repeated measures containing more than one degree o f freedom i n the numerator (Geisser & Greenhouse, 1958). The M c C a r t h y and W o o d (1985) correct ion was applied to any G r o u p x Site or G r o u p x Hemisphere interaction and is only reported in condit ions in wh ich the observed effect became nonsignificant. In addition to the A N O V A s we also performed a correlat ion analyses between the peak amplitude o f the E R P components and P C L - R total scores using the entire sample (n=76). Cor re la t ion analyses were not performed separately for P C L - R factor 1 and factor 2 scores as the correlat ion between these factors was extremely high (r = .86), making any inferences regarding the relationship between factor structure difficult. 68 5.4 Behav io ra l data-Results 5.4.1 Sample 1. There were no significant group differences in the percentage o f correct hits [Psychopaths 97.28 ( S D 6.07); Nonpsychopaths 98.0 ( S D 3.6)], react ion times [Psychopaths 486 .90 ms ( S D 92.8); Nonpsychopaths 459 ms ( S D 62.9)] , or numbers o f false alarms to nove l [Psychopaths 0.82 ( S D 1.6); Nonpsychopaths 1.0 ( S D 1.5)] o r nontarget s t imuli [Psychopaths 9.1 ( S D 5.7); Nonpsychopaths 8.52 ( S D 4.4)]; a l l p ' s > .25). 5.4.2 Sample 2. A s in Sample 1, there were no significant group differences in the percentage o f correct hits [Psychopaths 93.6 ( S D 12.4); Nonpsychopaths 98.8 ( S D 2.3)] , react ion times [Psychopaths 424 ms ( S D 79.3) ; Nonpsychopaths 404 ms ( S D 88.8)] , o r numbers o f false alarms to nove l [Psychopaths 1.7 ( S D 1.4); Nonpsychopaths 2.5 ( S D 3.0)] o r nontarget s t imuli [Psychopaths 12.7 ( S D 7.6); Nonpsychopaths 15.6 ( S D 7.6)]; al l p ' s > .13). 5.5 Event-related potentials. G r a n d mean group (across both samples) E R P s for target, novel , and nontarget s t imuli are presented i n Figures 9, 10, and 11, respectively. G r a n d mean E R P s for target, nove l and nontarget s t imuli for Sample 1 are presented i n Figures 12, 13, and 14, respectively. T h e repl icat ion g roup (Sample 2) , grand mean E R P s for target, nove l and nontarget s t imuli are presented in Figures 15, 16, and 17, respectively. 69 Figure 9. Grand mean ERPs (both samples) for target stimuli for psychopaths (dashed) and nonpsychopaths (solid). By convention, negative amplitude is plotted up. Tick marks are in units of 100 milliseconds. F p l [ i n I i i i I i |-0 400 800 Fpz Fp2 E0G H I--r- * N . i M r w i — Nonpsychopath -- Psychopath 70 Figure 10. G r a n d mean E R P s (both samples) for nove l s t imuli for psychopaths (dashed) and nonpsychopaths (solid). B y convention, negative amplitude is plot ted up. T i c k marks are in units o f 100 mil l iseconds. F p l Fpz Fp2 EOG - Nonpsychopath - Psychopath Figure 11. G r a n d mean E R P s (both samples) for nontarget st imuli for psychopaths (dashed) and nonpsychopaths (solid). B y convention, negative amplitude is p lot ted up. T i c k marks are in units o f 100 mill iseconds. F " 5 . 0 j t Y . " p i F J\\ 1 II 1 1 1 1 u p z F J\ X M I I II Ir p2 Ml A U 1 1 1 1 1 1 1 1 1 1 1 1 1 1 r 0 400 800 F7 F L._Al 1 1 1 1 1 1 1 L. 1 V / V \ J 1 1 1 r _ p- - _ 3 F Mi * u 1 1 1 1 1 . '1 V v i J I 1 1 H z F / | \ | *. u 1 1 1 1 I 4 /III A LL 1 II 1 Ft7 F L i J i V 1 1 1 1 1 1 1 L. c3 F Jill 1 1 1 1 1 1 1 Ln c z F Jill A L4 1 1 1 1 Inl c4 Jill 1 1 1 l l l l T3 C L _ / \ | 1 1 1 1 1 1 1 L 3 C / V 1 1 1 1 1 1 1 L-. z C Jill L 1 1 1 1 1 1 1" 4 /ill 1 1 1 1 1 1 1 Tp7 P L - iV\ l 1 1 1 II 1 1 L 3 p L A | 1 1 1 1 1 [ 1 L— Z P A\ 1 1 II 1 1 1 4 A l 1 II 1 1 1 1 r n V J I N 1 L J r M 1 1 i u r n v i l L U J J h E0G Ft8 T4 Tp8 f + T5 01 Oz 03 T6 • - ^ J J J J J ^-Kj^cUUJ h ^ L l l i J h^LLLUJ h^ iM i i J N o n p s y c h o p a t h P s y c h o p a t h 72 Figure 12. Grand mean ERPs (Sample 1) for target stimuli for psychopaths (dashed) and nonpsychopaths (solid). By convention, negative amplitude is plotted up. Tick marks are in units of 100 milliseconds. 5 . 0 pX . , 1 ' i T | i i i 1 i y 0 400 800 F7 Fpl /s Fpz f\ Fp2 r N EOG • ^ y t > t \ j i - $ ^ y ^/V^TW'VJ M ^ O f H ^ Nonpsychopath Psychopath 73 Figure 13. G r a n d mean E R P s (Sample 1) for novel st imuli for psychopaths (dashed) and nonpsychopaths (solid). B y convention, negative amplitude is p lot ted up. T i c k marks are units o f 100 mill iseconds. F p l Fpz Fp2 EOG - Nonpsychopath - Psychopath Figure 14. G r a n d mean E R P s (Sample 1) for nontarget st imuli for psychopaths (dashed) and nonpsychopaths (solid). B y convention, negative amplitude is plot ted up. T i c k marks are in units o f 100 mill iseconds. F p l F p z F p 2 EOG i n | i i i | i (-0 4 0 0 8 0 0 A A K I M ] h % H ^ M J h / W ^ M J •folium F8 Tp7 P3 Pz P4 Tp8 T5 01 Oz 03 T6 v^UiJJJ H ^ ^ U I U J H t^^ iLUJ H ^ H ± y H^mjiJ Nonpsychopath Psychopath 75 Figure 15. G r a n d mean E R P s (Sample 2) for target s t imuli for psychopaths (dashed) and nonpsychopaths (solid). B y convention, negative amplitude is plot ted up. T i c k marks are in units o f 100 mill iseconds. F p l Fpz Fp2 EOG-5.0 M V , , I i n j i i i | i h 0 400 800 ' • ^ n ^ M r - A C ^ i ^ l h ^ l ^ M Nonpsychopath Psychopath 76 Figure 16. G r a n d mean E R P s (Sample 2) for novel st imuli for psychopaths (dashed) and nonpsychopaths (solid). B y convention, negative amplitude is plot ted up. T i c k marks are units o f 100 mill iseconds. F p l Fpz Fp2 EOG .0 , , • n | i i i | i h 0 400 800 F7 F3 Nonpsychopath Psychopath Figure 17. G r a n d mean E R P s (Sample 2) for nontarget s t imuli for psychopaths (dashed) and nonpsychopaths (solid). B y convention, negative amplitude is plot ted up. T i c k marks are in units o f 100 mill iseconds. F "5.0 MY , ," p i F A l 1 1 1 II 1 1 IT-pz F A i i u 1111 v-P 2 A l 1 LI 1 1 II H—|—1—rH—|—M—i—(—1 0 400 800 F7 F L,_Al 1 1 1 1 1 1 1 L. 3 F /ill 1 LI 1 1 1 1 Lr z F /ill i i i i i i i t -4 /l\l 1 LJ 1 1 1 1 MNULW-LJJJ r Ft? F 1 r, / \ 1 1 1 1 1 1 1 1 Ir-c3 F /111 1 1 1 1 1 1 1 In cz F /111 1 LI 1 1 1 1 U c4 / i i i i i i I I I I EOG F8 Ft8 T3 C3 Cz C4 T4 Tp7 P3 Pz P4 TpB •H&tuy ^  ^ \^^ uuu ^ -ptgm T5 01 Oz 03 T6 ^*H$m# h4^i jJ iy Nonpsychopath Psychopath 78 N 2 peak amplitude analyses. 5.5.1 Sample 1. The N 2 peak amplitude for target s t imuli was larger for Psychopaths than for Nonpsychopaths . Th is effect was greatest at fronto-central sites. T h e N 2 el ici ted by novel stimuli was larger for Psychopaths than for Nonpsychopaths at centro-parietal sites [main effect o f G r o u p , midline, F (1, 42) = 4 .01 , p < .05; medial , F (1 , 42) = 4.57, p < .038; lateral F (1, 42) = 5.62, p < .022; G r o u p x Cond i t ion X Site trend, midline, F (10, 420) = 2.28, p < .063; medial F (10, 420) = 2.13, p < .083; G r o u p x Cond i t i on trend, medial , F (2, 84) = 2.4, p < .10; G r o u p x Cond i t i on x Site trend, lateral, F (8, 336) = 2.188, p < .096]. A c r o s s al l participants the N 2 was larger for target and nove l s t imuli than for nontarget s t imuli [main effect o f Cond i t ion , midline, F (2, 84) = 65 .33 , p < .001 ; medial , F (2, 84) = 68.68, p < .001; lateral, F (2, 84) = 54.14, p < .001]. F o r target s t imuli , the N 2 had a fronto-central distr ibution, asymetrically larger o n the left hemisphere than the right hemisphere [Condi t ion X Site interaction, midline, F (10, 420) = 35.94, p < .001, medial , F (10, 420) = 33 .01 , p < .000, lateral, F (8, 336) = 12.74, p < .001; Si te x Hemisphere interaction, medial , F (5, 210) = 6.26, p < .001; Cond i t i on x Site x H e m i interaction, medial , F (10, 420) = 4.08, p < .001, lateral F (8, 336) = 2.57, p < .039; main effect o f Site, midline, F (5, 210) = 11.06, p < .001, medial , F (5, 210) = 10.91, p < .001, lateral, F (4, 168) = 7.45, p < .005]. 5.5.2 Sample 2. The N 2 el ici ted by target and nove l s t imuli was larger for Psychopaths than for Nonpsychopaths at midline sites [Psychopathy x Cond i t i on interaction, F (2, 60) = 3.40, p < .05]. 79 There were no significant group effects at medial o r lateral sites and no group differences i n the N 2 elicited by nontarget st imuli . A s in the Sample 1 above, across al l participants, the N 2 was larger for target and novel st imuli than for nontarget st imuli [main effect o f Cond i t i on , midl ine, F (2, 60) = 52.62, p < .001, medial , F (2, 60) = 54.00, p < .001, lateral, F (2, 60) = 57.76, p < .001]. The target N 2 was maximal at fronto-central sites, while the novel N 2 had a more posterior distribution [Condi t ion x Site interaction, midline, F (10, 300) = 29.85, p < .001, medial , F (10, 300) = 32.28, p < .001, lateral, F (8, 240) = 12.98, p < .001; main effect o f Site, midl ine, F (5, 150) = 14.83, p < .001, medial , F (5, 150) = 18.00, p < .001, lateral, F (4, 120) = 11.11, p < .001]. P 3 peak amplitude analyses. 5.5.3 Sample 1. There were no overal l group differences in the amplitude o f the P 3 . A t temporal sites the P 3 was slightly larger on the left (Ft3 , T 3 , T 5 ) than the right hemisphere (Ft4, T 4 , T 6 ) for Psychopaths, this effect was reversed for Nonpsychopaths [Group x Site x Hemisphere interaction, lateral, F (4, 168) = 2.53, p < .04; nonsignificant after application o f the M c C a r t h y and W o o d (1985) correct ion] . A c r o s s al l participants, the P 3 was larger for target and nove l s t imuli than for nontarget st imuli [main effect o f Cond i t ion , midline, F (2, 84) = 58.85, p < .001, medial , F (2, 84) = 48.59, p < .001, lateral, F (2, 84) = 23.10, p < .001]. T h e target P3 had a posterior distribution, while the P3 elicited by novel st imuli had a fronto-central distr ibution [Condi t ion x Site interaction, midline, F (10, 420) = 32 .41 , p < .001, medial , F (10, 420) = 23.61, p < .001, lateral, F (8, 336) = 11.29, p < .001]. Interestingly, as Alexander et a l . , (1996) 80 observed, the target P 3 in the present sample was slightly larger over the right hemisphere than the left hemisphere at fronto-central electrodes and this hemispheric asymmetry switched at parietal electrodes [Condi t ion x Site x Hemisphere interaction, lateral, F (8, 336) = 2.56, p < .029; main effect o f Site, midline, F (5, 210) = 31.18, p < .001, medial , F (5, 210) = 28.51, p < .001],.lateral, F (4, 168) = 39.70, p < .001]. 5.5.4 Sample 2. The P 3 for target s t imuli and nove l st imuli was slightly smaller for Psychopaths than for Nonpsychopaths at medial sites. This latter effect was l imited to the P 3 for novel stimuli at lateral sites [ G r o u p x Cond i t i on interaction, midl ine, F (2, 60) = 2.43, p < .10, medial, F (2, 60) = 3.08, p < .05, lateral, F (2, 60) = 4.23, p < .019; main effect o f G r o u p , midline, F (1, 30) = 3.26, p < .081, medial , F (1 , 30) = 4 .01 , p < .05, lateral, F (1 , 30) = 3.78, p < .061]. W e note however , that the Psychopaths ' small P3 for target s t imuli may have been due to the large fronto-central negativity in the 350-600 mil l isecond w i n d o w (see below) . A s in sample 1, the P 3 was larger for target and nove l s t imuli than for nontarget stimuli [main effect o f Cond i t ion , midline, F (2, 60) = 33.23, p < .001, medial , F (2, 60) = 28.41, p < .001, lateral, F (2, 60) = 12.53, p < .001]. The P 3 for target s t imuli was maximal at parietal sites, while the P 3 to novel s t imuli had a more fronto-central distr ibution [Condi t ion x Site interaction, midline, F (10, 300) = 20.56, p < .001, medial , F (10, 300) = 13.56, p < .OOUateral , F (8, 240) = 6.02, p < .002; main effect o f Site, midline, F 5(, 150) = 12.78, p < .001; medial , F (5, 150) = 12.72, p < .001, lateral, F (4, 120) = 30.55, p < .001]. There were no hemispheric asymmetries for the P 3 in this sample. 81 N 4 7 5 peak amplitude analyses 5.5.5 Sample 1. A s predicted, the N 4 7 5 elicited by target st imuli was significantly larger for Psychopaths than for Nonpsychopaths [Group x Cond i t i on interaction, midline, F (2, 84) = 3.44, p < .05, medial , F (2, 84) = 3.92, p < .038, lateral, F (4, 168) = 6.23, p < .008; main effect o f G r o u p , midline, F (1, 42) = 4.39, p < .042, medial , F (1, 42) = 4 .57, p < .038, lateral, F 1, 42) = 3.67, p < .062]. Th is effect was largest at fronto-central electrode sites [Group x Cond i t i on x Site interaction, midline, F (10, 420) = 2.076, p < .025, medial , F (10, 420) = 2.02, p < .030, lateral, F (8, 336) = 2.32, p < .020; G r o u p x Site interaction, midline, F (5, 210) = 5.57, p < .007, medial , F (5, 210) = 6.04, p < .006]. A t many sites, the N 4 7 5 elicited by target st imuli was more than twice the amplitude in Psychopaths as it was in Nonpsychopaths . A c r o s s participants, the N 4 7 5 was larger for target s t imuli than for nove l o r nontarget stimuli [main effect o f Cond i t i on , midline, F (2, 84) = 17.53, p < .001, medial , F (2, 84) = 13.33, p < .001, lateral, F (2, 84) = 7.85, p < .002], this effect having a fronto-central distribution, [main effect o f Site, midline, F (5, 210) = 86.36, p < .001, medial , F (5, 210) = 94 .91 , p < .001, F (4, 168) = 105.23, p < .001; Cond i t i on x Site interaction, midl ine, F (10, 420) = 28.444, p < .001, medial , F (10, 420) = 25.68, p < .001, lateral, F (8, 336) = 28.393, p < .001; Site x Hemisphere interaction, medial , F (5, 210) = 3.78, p < .015; C o n d i t i o n x Site x Hemisphere interaction, medial , F (10, 420) = 2.74, p < .027]. 5.5.6 Sample 2. A s in Sample 1, N 4 7 5 elicited by target st imuli was significantly larger for Psychopaths than for Nonpsychopaths . This effect was greatest at fronto-central sites [Group 82 x C o n d i t i o n x Site interaction, midline, F (10, 300) = 1.78, p < .06; G r o u p x Cond i t i on interaction, midline, F (2, 60) = 7.23, p < .002, medial , F (2, 60) = 7.20, p < .002, lateral, F (2, 60) = 6.15, p < .004; main effect o f G r o u p , midline, F (1 , 30) = 6.29, p < .018, medial , F (1, 30) = 6.95, p < .013, F (1 , 30) = 8.52, p < .007]. A c r o s s al l participants, the N 4 7 5 was larger for target than for nove l or nontarget s t imuli , an effect greatest at fronto-central electrodes [Condi t ion x Site interaction, midline, F (10, 300) = 12.70, p < .001, medial , F (10, 300) = 13.36, p < .001, lateral, F (8, 240) = 10.95, p < .001; main effect o f Cond i t ion , midline, F (2, 60) = 18.38, p < .001, medial , F (2, 60) = 15.25, p < .001, lateral, F (2, 60) = 7.16, p < .001; main effect o f Site, midl ine, F (5, 150) = 19.84, p < .001, medial , F (5, 150) = 17.36, p < .001, lateral, F (4, 120) = 27.17, p < .001]. 5.6 Corre la t ion analyses. Correlat ions between P C L - R total scores and the amplitude o f the N 2 , P 3 , and N 4 7 5 E R P components are presented in Table 10. These analyses revealed that psychopathy scores were negatively related to the N 2 for target and nove l s t imuli at centro-parietal electrodes. There were no significant correlations between psychopathy scores and the peak amplitude o f the P3 for target or novel st imuli . U s i n g mean amplitude measurements o f the P 3 (to cont ro l for latency jitter) we observed that there were significant correlations between psychopathy scores and the target P3 at frontal sites. There was a s trong negative relationship between psychopathy scores and the peak amplitude o f the N 4 7 5 . Consistent wi th the A N O V A results, these correlations were strongest at fronto-central sites. 83 Table 10. Correlations between psychopathy PCL-R total scores and the amplitude of the N2, P3, and N475 ERP components for target and novel stimuli. Correlations are based upon the entire sample of participants (n=76). Note: p.a. = peak amplitude; m.a. = mean amplitude; ***p < .01; **p < .05; *p < .10 Electrode N2 p.a. N2 p.a. P3 p.a. P3 p.a. P3 m.a. P3 m.a. N475 p.a. N475 p.a. Site target novel target novel target novel target novel FP1 -.229** -.102 -.068 -.025 -.143 -.006 -.223** -.142 FPZ -.226** -.102 -.070 .020 -.150* .013 -.257** -.122 FP2 -.202* -.093 -.077 .003 -.161* -.001 -.250** -.106 F7 -.199* -.139 -.137 -.090 199** -.066 -.237** -.141 F3 -.192* -.188* -.047 -.011 -.137 -.035 - 272*** -.139 FZ -.193* -.207* -.028 .008 -.125 -.030 -.296*** -.158* F4 -.184 -.181 -.058 -.018 -.161* -.058 -.310*** -.193** F8 -.156 -.121 -.170* -.120 -.227** -.139 - 273*** -.226** FT7 -.136 -.125 -.095 -.093 -.162* -.068 -.212** -.102 FC3 -.184 -.212* -.069 -.037 -.149* -.061 270*** -.153* FCZ -.184 -.228** -.048 -.013 -.144* -.052 - 291*** -.189** FC4 -.177 -.214* -.110 -.056 -.191** -.089 320*** -.219** FT8 -.152 -.189* -.155* -.140 -.174* -.121 -.232** -.197* T3 -.103 -.208* -.079 -.128 -.109 -.130 -.169* -.112 C3 -.168 -.250** -.105 -.078 -.174* -.097 -.249** -.135 CZ -.209* -.286** -.097 -.067 -.177* -.096 - 270*** -.202** C4 -.185* -.237** -.138 -.057 -.187** -.079 - 293*** -.196** T4 -.212* -.151 -.176* -.102 -.178* -.044 -.263** -.150* TP7 -.189* -.233** -.116 -.105 -.146* -.105 -.154* -.096 CPZ -.213* -.301*** -.103 -.039 -.158* -.070 -.239** -.120 TP8 -.241** -.201* -.182* -.049 -.177* -.019 -.262*** -.103 P3 -.238** -.280** -.116 -.021 -.152* -.053 -.205** -.023 PZ -.229** -.315*** -.091 -.011 -.128 -.044 -.200** -.051 P4 -.229** -.282** -.125 -.003 -.144* -.031 -.215** -.061 T5 -.224** -.206* -.138 -.045 -.149* -.039 -.165* -.082 T6 -.222** -.276** -.129 -.024 -.130 -.033 -.166* -.036 O l -.243** -.285** -.122 -.013 -.134 -.037 -.114 -.018 OZ -.188* -.219* -.060 .026 -.077 -.008 -.026 -.062 02 -.236** -.272** -.136 .004 -.137 -.017 -.156* -.027 84 5.7 Summary and Discuss ion for Experiment 4 This experiment was designed to examine the modal i ty specificity o f the late fronto-central negative waves that have been observed in the event-related potentials o f psychopaths for tasks that employ visual st imuli ( K i e h l et al . , 1999a; Wi l l i amson et a l , 1991). Consistent wi th these studies, a large fronto-central negativity (N475) was observed in the psychopaths ' E R P s to task relevant st imuli . Th is effect was robust in both samples o f psychopaths. There was some evidence o f a smaller P 3 to target and novel stimuli for psychopaths compared to nonpsychopaths; however , this reduction in P 3 amplitude may have been due to the overlapping N 4 7 5 in the psychopaths ' waveforms. W e also observed that the N 2 for both target and novel stimuli was larger for psychopaths than for nonpsychopaths. In general, there appeared to be a negative shift in the psychopaths' E R P s to target st imuli that began as early as 100 mill iseconds and proceeded until about 800 mill iseconds post-stimulus. The finding that the P3 was not reliably reduced is somewhat at odds wi th the findings from Exper iment 3, in wh ich we observed that the P3 to visual oddbal l s t imuli was reduced in psychopaths relative to nonpsychopaths. H o w e v e r , as noted in Exper iment 3, the small P3 o f the psychopaths to target st imuli may have been due to the large over lapping fronto-central negativity (N550) . H o w e v e r , in the present study the mean amplitude o f the P 3 to target st imuli was negatively correlated with P C L - R scores at frontal sites. Studies have n o w shown that large fronto-central negativities are present in psychopaths ' E R P s to visual w o r d stimuli , visual oddbal l s t imuli , v isual target st imuli in a G o / N o go task, and auditory oddball st imuli . G i v e n the ubiquity i n wh ich these odd waveforms seem to be found, what might be their functional significance? 85 A l t h o u g h the tasks in which fronto-central E R P negativities have been observed for psychopaths are quite different, they do due share a number o f methodologica l similarities. Firs t , each o f the tasks required a speeded behavioral response raising the possibi l i ty that the some o f the observed effects may be due to processes related to mo to r preparation and execution. T o explore this possibili ty, we investigated the response- locked potentials for target s t imuli in the present study. There were no group differences i n these potentials, nor was there any evidence o f any fronto-central E R P negativities. Addi t iona l ly , research from our laboratory has shown that these fronto-central negativities are present in psychopaths ' E R P s for task relevant st imuli that do not require a manual response. In t w o studies, one employing visual st imuli and one employing auditory st imuli , we have observed that fronto-central E R P negativities are observed when psychopaths are required to silently count, rather than manually respond, to l o w probabi l i ty target stimuli (K ieh l , 1999). Thus , o n balance, these data suggest that the observed fronto-central E R P negativities do not appear to be due to processes related to mo to r cont ro l . Ano the r similarity c o m m o n to each o f the aforementioned tasks is that they required processes required to attentional cont ro l . A s we discussed in the summary for Exper iment 3, there is g rowing evidence for abnormalities in attentional processes in psychopathy. H o w e v e r , the N 2 potential has also been associated wi th attentional processes and this component was larger for psychopaths than for nonpsychopaths. Th is latter effect suggests greater al location o f attentional processes for processing target st imuli for psychopaths than for nonpsychopaths. Some have argued that psychopaths tend to 'overfocus ' on stimuli o f immediate relevance, ignor ing otherwise potentially important cues (Jutai, 1989; Jutai & Hare , 1983). In the present study, such an 'overfocusing ' should have led to behavioral differences 86 between groups. I f psychopaths were processing the st imuli faster than were nonpsychopaths because o f this greater al location o f attentional resources, then w e should have observed superior response speeds for psychopaths than for nonpsychopaths for processing target stimuli . N o such effect was observed. W e note however, that the absence o f group differences in performance in the present study may have been due to cei l ing effects. Addi t iona l ly , i f psychopaths were 'overfocusing ' on the task relevant s t imuli , we might also have observed a greater number o f false alarms to nontarget and/or nove l s t imuli for psychopaths compared to nonpsychopaths. A g a i n , no such effects were observed. Thus , we are sti l l left wi th no definitive explanation for the presence o f these fronto-central negativities in the psychopaths ' E R P s to task relevant/Stimuli. In Exper iments 1 and 2, functional abnormalities were observed in psychopaths in frontal, temporal , and l imbic structures. Th is raises the possibi l i ty that the fronto-central E R P negativities i n psychopaths may be related to abnormalities in frontal, temporal or l imbic structures. Ev idence f rom studies o f the intracranial electrode recordings (Halgren, 1980; Ha lg ren et a l . , 1995a; 1995b; Halgren , M a r i n k o v i c , & Chauve l , 1998), event-related f M R I studies o f healthy participants ( K i e h l , Laurens, Du ty , Forster , & L i d d l e , 1998a; M c C a r t h y , L u b y , G o r e , & G o l d m a n - R a k i c , 1997; M e n o n , F o r d , L i m , G l o v e r , & Pfefferbaum, 1997; Op i t z , M e c k l i n g e r , V o n Cramon , & K r u g g e l , 1999) and psychopathological populations ( K i e h l & L i d d l e , 1999), and f rom patients wi th brain damage (Knight , 1984; 1996; Knight , Grabowecky , & Scabini , 1995; Kn igh t & Nakada , 1998; Knigh t , Scabini , W o o d s , & Claywor th , 1989) indicate that frontal, temporal , and l imbic structures are implicated in auditory and visual oddbal l tasks. Thus , an examination o f auditory and visual E R P studies o f patients w i th damage to frontal, temporal and/or l imbic structures may reveal similar late fronto-central E R P negativities. Th is search ' 87 revealed that fronto-central E R P negativities to oddbal l s t imuli have been found in patients who have undergone anterior temporal lobe resection for treatment o f intractable epilepsy (Johnson, 1988; 1989; Johnson & Fed io , 1987; R u g g , P ickles , Potter , & Rober ts , 1991; Scheffers, Johnson, & R u c h k i n , 1991). Addi t iona l ly , fronto-central E R P negativities to target s t imuli are observed for patients wi th temporal lobe damage due to cerebral infarction (Yamaguch i & Kn igh t , 1993; 1995). Pal ler and colleagues have shown that fronto-central E R P negativities are el ici ted by target s t imuli i n monkeys wi th induced temporal lobe lesions (Paller, Z o l a - M o r g a n , Squire, & Hi l lya rd , 1988). T o our knowledge , fronto-central E R P negativities to oddbal l stimuli have not been observed in frontal or parietal lobe damaged patients (Yamaguch i & Knigh t , 1993; 1995). These data suggest that the most plausible interpretation o f the fronto-central E R P negativities for psychopaths is that they are related to the presence o f temporal lobe abnormalities. This latter interpretation is supported by the fact that the N 2 component elicited by target stimuli is larger for patients wi th temporal lobe damage than for con t ro l participants (Johnson, 1989; Y a m a g u c h i & K n i g h t , 1993). M o r e o v e r , the P3 component in these latter patients appears to be on ly slightly abnormal at frontal sites. Thus , the similarities between psychopaths and patients w i th temporal lobe damage are present for the N 2 , P 3 and N 4 7 5 components o f the E R P el ic i ted by target stimuli . A d d i t i o n a l similarities between psychopaths and patients w i th temporal lobe abnormalities are discussed in the General Discuss ion . If the fronto-central E R P s in psychopaths are related to abnormal function o f the temporal lobe and removal o f the temporal lobe also causes these potentials, then where might these potentials be generated? Studies o f the intracranial sources o f the P 3 suggest that the polari ty inversions (e.g., electrical negativities in the 300-600 mi l l i second post-stimulus time 88 window) are found in the amygdala, anterior cingulate cortex, and inferior lateral frontal cortex (Halgren, 1999; Ha lg ren et a l . , 1995a; 1995b). G i v e n that fronto-central E R P negativities are present for patients in wh ich the amygdali are removed, this suggests that the most l ikely candidate for the neural generator(s) o f the fronto-central negativities is the anterior cingulate and/or inferior lateral frontal cortex. Consistent w i t h this not ion, preliminary source local izat ion analyses, performed wi th B r a i n E lec t r i ca l Source Analyses ( B E S A ) software, have revealed that a single dipole in the anterior cingulate appears to be a plausible solut ion to the inverse p rob lem for the psychopaths ' N 4 7 5 . U s i n g a two-d ipole model , we have observed that the best solut ion for the additional dipole is in the right inferior lateral frontal cortex. It is important to note that these latter analyses were prel iminary and that some have argued that source model ing o f E R P components later than 300 ms may be an i l l -posed question given the number o f possible generators and the mathematical uncertainty o f determining a unique solution to account for all these putative sources (Halgren et al . , 1998). The interpretation that psychopathy is associated wi th aberrant activity in the anterior cingulate is consistent wi th a number o f other lines o f research. In Exper iment 2 w e observed that compared wi th cont ro l participants, psychopaths failed to show greater neural activation for affective st imuli than for neutral st imuli in the anterior cingulate. Addi t iona l ly , we have observed that psychopathy is associated wi th a reduced error-related negativity ( E R N ) for error trials during a G o / N o go task (Gehr ing, 1993; Gehr ing , Co les , M e y e r , & D o n c h i n , 1990; Gehr ing , Goss , Coles , & M e y e r , 1993). T h e E R N is believed to be generated in the anterior cingulate (K ieh l , L i d d l e , & Hopf inger , in press; Scheffers, Coles , Bernstein, & Gehr ing , 1996; Tucke r , 1998). Thus , the small E R N for psychopaths is consistent w i th the hypothesis that psychopathy is associated wi th anterior cingulate abnormalities. 89 In summary, the N 2 , P 3 , and N 4 7 5 components o f the E R P were different for psychopaths than for nonpsychopaths for auditory target st imuli . The enlarged N 2 and N 4 7 5 and reduced frontal P 3 in psychopaths are similar to E R P abnormalities found in patients wi th temporal lobe damage. This suggests that the most plausible interpretation for the presence o f the late fronto-central E R P negativities in psychopaths is that they are an electrophysiological signature o f anterior temporal lobe abnormalities. « 90 6.0 Exper iment 5 Me thods 6.1 Participants. T h e participants were 50 male inmates f rom a federal maximum-securi ty prison facility near Vancouve r , Br i t i sh Co lumbia . Volunteers were selected for the study i f they were between 18 and 55 years o f age, were free from any reported serious head injury or neurologica l impairment and had no D S M - I V A x i s I diagnosis (Amer ican Psychiatr ic Assoc ia t ion , 1994). Forty-eight inmates were right hand dominant and two were left hand dominate (Annett , 1970). Volunteers participated in t w o sessions: a videotaped semi-structured interview and the experimental recording session. Information f rom the interview and an extensive review o f insti tutional files were used complete the P C L - R on each inmate. E a c h o f the 20 items on the P C L - R is scored on a 3-point scale (0-2) according to the extent to which it applies to the inmate. Inmates wi th a P C L - R score o f 30 or above (n = 25) were defined as Psychopaths (mean = 33.5, S D = 2.), and those wi th a P C L - R score be low 30 (n = 25) were defined as Nonpsychopaths (mean = 20.1 , S D = 6.6). The mean age and years o f formal education were 32.5 and 32 .1 , and 10.1 and 10.9 years for Psychopaths and Nonpsychopaths , respectively. T h e N A R T and Q u i c k I Q measures were 107.8 ( S D 10.0) and 102.7 ( S D 12.6), and 106.8 (11.4) and 103.3 (11.76) for Psychopaths and Nonpsychopaths , respectively. There were no differences between the Psychopaths and Nonpsychopaths on any o f these measures (p's > .50). 91 W e paid each inmate $5.00 for the P C L - R interview and $10.00 for the experiment. The total o f $15.00 was equivalent to 2 days pr ison wage. T h e study was conducted in accordance wi th Institutional and Univers i ty ethical standards. 6.2 S t imul i . One hundred sentences (eight to ten words in length) were presented one w o r d at a time (500 ms stimulus duration and ISI) o n a computer monitor . E q u a l proport ions o f the sentences ended wi th a w o r d that was either semantically congruent (e.g.. The man went to the store to buy a loaf o f bread.) or semantically incongruent (e.g., The man went to the store to buy a loa f o f mi lk . ) wi th the previous sentence context. The sentences were the same as those used by N i z n i k i e w i c z et al. (1997). T h e order o f sentence presentation was random. Let ter s t imuli were approximately 2 x 1 visual degrees. A l l s t imuli were presented white o n black background i n a cont inuously displayed rectangular box . A prompt (asterisk) was presented 1000 ms after the offset o f the last w o r d to indicate that the participant should make the sense/no sense discrimination. T h e hand used to make judgment was counterbalanced across participants. E R P s were analyzed only for correct ly classified terminal words . A s an additional measure to attempt to further reduce the possibil i ty that motor responses might confound the results, accuracy was stressed and response time was de-emphasized. 6.3 Event-related Potent ia l Record ing Scalp potentials were recorded f rom tin electrodes (E lec t roCap International) placed over 29 electrode sites according to standard placement guidelines o f the International 10-20 Sys tem (see F igure 1). V e r t i c a l and hor izonta l e lectroocularogram ( E O G ) were moni tored from a bipolar electrode pair located o n the lateral and supra orbi tal ridges o f the right eye. A l l E E G electrodes were referenced to the nose. T w o addit ional channels, left and right mastoids were recorded. E lec t r i ca l impedances were maintained be low 5 kohms throughout the experiment. The E E G channels ( S A instruments) were amplified (20,000 gain) w i th a bandpass o f .01 to 100 H z , digi t ized on-line at a rate o f 256 samples per second, and recorded o n computer hard disk. The length o f the recording epoch was 1200 ms wi th a 100 ms pre-stimulus baseline. Single-trials w i th voltages greater than (+ or -) 75 microvol t s at any electrode site or E O G artifact were excluded. F o u r participants (three nonpsychopaths and one psychopath) were excluded because o f excessive artifacts (greater than 4 0 % o f trials). After exclusion o f these participants, there were no significant group differences in the number o f trials averaged in any condi t ion. The E R P s were digi tal ly filtered wi th a zero-phase shift 30 H z l o w pass filter to reduce electromyographic contaminat ion and ambient electrical noise. The analyses proceeded in two stages. T w o components were analyzed, the N 4 0 0 and P600 . T h e N 4 0 0 is typical ly measured as the peak amplitude i n the 300-500 ms post-stimulus time w i n d o w in the difference wave o f incongruent minus congruent stimuli . H o w e v e r , several studies o f the N 4 0 0 in psychopathological populations have shown that relying solely on the difference wave measurements can lead to misleading results. F o r example, in the literature o n the N 4 0 0 and schizophrenia for example, early studies reported that the N 4 0 0 (measure in difference waves) was smaller for schizophrenic patients than for controls (Adams et a l . , 1993; G r i l l o n , A m e l i , & Glazer , 1991). H o w e v e r , subsequent research has shown that the N 4 0 0 is larger for schizophrenic patients than for cont ro l participants for both congruent and incongruent sentence 93 endings (Nestor et al . , 1997; N i z n i k i e w i c z et al . , 1997). Th is indicates that the baseline measurement is important for determining group differences. F o r these reasons, separate analyses were performed on both the peak amplitude o f the N 4 0 0 and P 6 0 0 measured in the difference wave and f rom incongruent and congruent condit ions. In the first set o f A N O V A s , the N 4 0 0 and P 6 0 0 were measured i n the difference wave only. In the second set o f A N O V A s , the N 4 0 0 and P 6 0 0 were measured for both congruent and incongruent sentence endings. The N 4 0 0 and P 6 0 0 were quantified as the peak amplitude (relative to the 100 ms prestimulus baseline) in the 300-500 ms and 500-800 mil l isecond time windows , respectively. These windows were centered upon the peak latency o f each o f the components in the grand average waveforms. Separate A N O V A s were performed on midline, medial and lateral sites. The first set o f A N O V A s included factors o f G r o u p [Psychopath and Nonpsychopath] , and Site [frontal (F7, F 3 , F z , F 4 , F 8 ) , fronto-central (Fc7 , F c 3 , F e z , F c 4 , F c 8 ) , central (T3 , C 3 , C z , C 4 , T 4 ) , temporo-parietal (Tp7 , P 3 , P z , P 4 , T p 8 ) , and temporo-occipi tal (T5 , O l , O z , 0 2 , T 6 ) ] . F o r medial and lateral A N O V A s there was an additional factor o f Hemisphere [right and left]. M i d l i n e (Fpz) and medial ( F p l , F p 2 ) A N O V A s also included an additional level o f Site [prefrontal]. F o r the second set o f A N O V A s there was an addit ional factor o f C o n d i t i o n [Incongruent and Congruent] . T h e Geisser-Greenhouse correct ion was used for any repeated measures containing more than one degree o f freedom in the numerator (Geisser & Greenhouse, 1958). F o l l o w i n g the A N O V A , planned comparisons were performed on the predicted effects. T y p e I error rate was maintained be low .05 by using the Dunn-Bonfe r ron i correct ion. Other effects o f interest were tested using simple effects analyses or T u k e y ' s multiple comparisons. 94 Results 6.4 Behaviora l data. A c r o s s al l participants performance was more accurate for classifying congruent words than for classifying incongruent words [main effect o f C o n d i t i o n , F (1, 44) = 5.41, p < .025]. There were no significant group differences i n the number o f errors commit ted [Psychopaths, congruent st imuli , 2.45 ( S D 2.79); incongruent s t imuli , 3.86 ( S D = 4.25); Nonpsychopaths , congruent st imuli , 1.58 ( S D 1.24); incongruent s t imuli , 2.91 ( S D 2.73)]. 6.5 Event-related potentials. G r a n d mean group E R P s for congruent terminal words , incongruent terminal words and for the incongruent-congruent difference waves are presented in Figures 18, 19, and 20, respectively. N 4 0 0 peak amplitude analyses. 6.5 1. Difference wave analyses. There were no significant group differences in the amplitude o f the N 4 0 0 at midline, medial or lateral sites. A c r o s s al l participants, the N 4 0 0 was largest at centro-parieto-temporal sites [main effect o f Site, midline, F (5, 220) = 11.31, p < .001, medial , F (5, 220) = 11.02, p < .001]. Consistent wi th previous research, this effect was slightly larger over the right than the left hemisphere [Site x Hemisphere interaction, lateral, F (5, 220) = 3.13, p < .017; main effect o f Hemisphere, lateral, F (1, 44) = 4 .80, p < .034]. 95 Figure 18. G r a n d mean E R P s for congruent terminal words o f sentences for psychopaths (dashed) and for nonpsychopaths (solid). B y convention, negative amplitude is plotted up. T i c k marks are in units o f 100 mill iseconds. F p l Fpz Fp2 EOG - Nonpsychopath - Psychopath Figure 19. G r a n d mean E R P s for incongruent terminal words o f sentences for psychopaths (dashed) and for nonpsychopaths (solid). B y convention, negative amplitude is plot ted up. T i c k marks are in units o f 100 mill iseconds. Figure 20. Grand mean ERP difference waves for incongruent minus congruent terminal words of sentences for psychopaths (dashed) and for nonpsychopaths (solid). By convention, negative amplitude is plotted up. Tick marks are in units of 100 milliseconds. F p l Fpz Fp2 EOG - Nonpsychopath - Psychopath 98 6.5.2 T w o condi t ion analyses. A s in the difference wave analyses, there were no significant group differences in the N 4 0 0 elicited by congruent o r incongruent terminal words . Ac ros s all participants, N 4 0 0 was larger for incongruent than for congruent sentence endings [main effect o f condi t ion, midline, F (1, 44) = 18.62, p < .001, medial , F (1 , 44) = 18.68, p < .001, lateral, F (1, 44) = 10.82, p < .002] this effect was largest at centro-temporo-parietal sites [Condi t ion x Site interaction, midline, F (5, 220) = 7.56, p < .001, medial , F (5, 220) = 7.14, p < .001]. The N 4 0 0 for incongruent stimuli was slightly larger over left hemisphere temporo-parietal and occipi ta l sites than the analogous right hemisphere sites [Condi t ion x Site x Hemisphere, medial , F (5, 220) = 3.08, p < .018, Cond i t i on x Site x Hemisphere interaction,, lateral, F (4, 176) = 2.73, p < .049; Cond i t ion x Hemisphere interaction, medial , F (1, 44) = 7.53, p < .009, lateral, F (1, 44) = 8.99, p < .004; Site x Hemisphere interaction, medial , F (5, 220) = 4.68, p < .029, lateral, F (4, 176) = 4 .31 , p < .010; M a i n effect o f Site, midline, F (5, 220) = 6.04, p < .001, medial , F (5, 220) = 5.49, p < .011]. There we no hemispheric asymmetries for the N 4 0 0 el ici ted by congruent terminal words . P 6 0 0 peak amplitude analyses 6.5 3 Difference wave analyses. There were no significant group differences in the amplitude o f the P600 . The P 6 0 0 difference wave was largest centro-parietal sites [main effect o f Site, rnidline, F (5, 220) = 11.45, p < .001, medial , F (5, 220) = 10.18, p < .001, lateral, F (4, 176) = 15.61, p < .001], an effect slightly larger on the right than the left hemisphere [Site x Hemisphere interaction, medial , F (5, 220) = 3.02, p < .019; Site x Hemisphere, lateral, F (4, 176) = 2.97, p < .033]. 99 6.5.4 Two condition analyses. As in the difference wave analyses, there were no significant group differences in the amplitude of the P600. Across all participants, the P600 was larger for incongruent stimuli than for congruent stimuli [main effect of condition, midline, F (1, 44) = 9.42, p < .004, medial, F (1, 44) = 6.48, p < .01]. This latter effect was stongest at cento-parietal sites [Condition x Site interaction, midline, F (5, 220) = 8.83, p < .001, medial, F (5, 220) = 7.98, p < .001], lateral, F (4, 176) = 13.01, p < .001; Main effect of Site, midline, F (5, 220) = 20.64, p < .001; medial, F (5, 220) = 10.16, p < .001, lateral, F (4, 176) = 8.12, p < .001; Site x Hemisphere interaction, medial, F (5, 220) = 3.03, p < .019]. 6.6 Summary and Discussion for Experiment 5 This study was designed to examine the relationship between psychopathy and semantic processes related to the generation of the scalp recorded N400 ERP. In general, sentence processing studies of the N400 elicited by terminal word stimuli suggest that this component is related to processes involved with accessing and integrating word meanings within ongoing context. Previous studies of language functioning in psychopathy have consistently observed the presence of large fronto-central ERP negativities in psychopaths' waveforms elicited by linguistic stimuli. One interpretation offered for the functional significance of these components was that they were related to abnormal semantic activation akin to that believed to generate N400 potentials. However, the data from the present experiment do not support this interpretation. In the present study, there were no group 100 differences in the amplitude of the N400 elicited by either congruent or incongruent word stimuli assessed at 29 scalp electrodes. Indeed, across all participants, the N400 was similar in amplitude and topography as is that found in studies of noncriminals (Niznikiewicz et al., 1997). Source localization studies of the N400 have suggested that there are generators located in the anterior temporal lobe. Specifically, these studies have found that regions just anterior to the amygdala generate negative field potentials in the 300-500 millisecond post-stimulus time window (Guillem, N'Kaoua, Rougier, & Claverie, 1995; McCarthy, Nobre, Bentin, & Spencer, 1995; Nobre & McCarthy, 1995). These studies have also implicated the fusiform gyrus in the generation of the N400. Recent event-related fMRI data from our lab has confirmed that the anterior temporal lobes are activated during processing of congruent and incongruent terminal words of sentences. We have observed that greater activation is found for processing of incongruent terminal words than for congruent words bilaterally in the medial anterior temporal lobe and in left lateral frontal cortex (Kiehl, Laurens, & Liddle, 1999). The results of Experiments 1 and 2, and the interpretation offered for the results from Experiments 3 and 4, strongly suggest that psychopathy is associated with functional abnormalities in the anterior temporal lobe. In Experiment 1 we found that psychopathy was associated with abnormalities in the right anterior superior temporal gyrus (Talairach coordinates, x = 56, y = 15, z = -10) during performance of a concrete/abstract lexical decision task. The right hemisphere (x = 38, y = 22, z = -28) region we observed to differentiate incongruent from congruent stimuli in our event-related fMRI study appears to fall approximately 30 mm medial and 25 mm inferior to the region we observed abnormalities 101 for psychopaths in Exper iment 1. In Experiment 2, we observed that psychopaths failed to show greater activation for processing affective stimuli than for neutral s t imuli in the right amydgala/ parahippocampal region (Talairach coordinates, x = 34,y = -11 , z = -20) and left parahippocampal formation (Talairach coodinates, x = -38, y = -22, z = -16). Compar i son o f these latter sites wi th those found to be greater activated for processing o f incongruent than for congruent st imuli suggest these sites were approximately 30 m m distance f rom each other (x = -34, y = 22, z = -25; left hemisphere site f rom K i e h l , Laurens, and L i d d l e , 1999) Thus , to the extent that the scalp recorded N 4 0 0 is generated in the anterior temporal lobe, it w o u l d appear to be located distal to those sites in wh ich we have observed abnormalities in psychopathy. T o summarize, there were no group differences between psychopaths and nonpsychopaths in the amplitude o f the N 4 0 0 or P 6 0 0 for either congruent o r incongruent terminal words o f sentences. The present data do not support the hypothesis that psychopathy is associated wi th abnormalities in processes related to the generation o f the N 4 0 0 E R P . 102 7.0 Genera l Discuss ion 7.1 Summary o f results This thesis is comprised o f five experiments that were designed to elucidate the functional neural architecture and characterize the temporal features o f information processing abnormalities in affective, cognit ive and language functions in c r imina l psychopaths. Exper iments 1 and 2 sought to elucidate the neural systems underlying semantic and affective processes in psychopathy using f M R I . Experiments 3, 4 and 5 examined the temporal features o f cognit ive and language function in psychopaths using E R P s . In Exper iment 1 we observed that psychopaths performed more poor ly and showed significantly less neural differentiation between abstract and concrete s t imuli than d id cont ro l participants. These deficits were located in the right anterior superior temporal gyrus. In Exper iment 2 we observed that psychopaths, relative to con t ro l participants, showed reduced neural differentiation between affective and neutral s t imuli in several neural regions, including the right amygdala/hippocampal junct ion, left parahippocampal formation, ventral striatum, and in the anterior and posterior cingulate. Psychopaths d i d show greater activation for affective than for neutral s t imuli in regions located outside the l imbic system, suggesting that they used alternative neural systems for performing the task (see also Intrator et al . , 1997). In Exper iment 3 we observed that psychopathy was associated wi th abnormalities o f the P 3 component o f the E R P elici ted by visual oddbal l st imuli . In Exper iment 4 we observed that psychopathy was associated wi th abnormalities o f the N 2 and P 3 components o f the E R P elici ted by auditory oddbal l st imuli . These data are consistent wi th the g rowing literature 103 showing that psychopaths differ f rom others in the modula t ion and al locat ion o f attentional resources (Harpur & Hare , 1990). The most prominent difference between psychopaths and cont ro l participants was that the psychopaths ' E R P s to visual and auditory target st imuli were characterized by a large fronto-central negativity in the 350-600 mi l l i second time w i n d o w . These fronto-central E R P negativities are also observed in patients wi th temporal lobe damage, suggesting, as do the results f rom Experiments 1 and 2, that psychopathy is associated wi th functional abnormalities in the temporal lobe(s). Exper iment 5 examined the neural systems underlying semantic processes related to the generation o f the N 4 0 0 E R P . In sentence processing studies, this component o f the E R P is believed to be related to semantic processes associated wi th integrating w o r d meanings within the ongoing discourse (Kutas & H i l l y a r d , 1980a; 1980b; 1983; Ku tas & V a n Petten, 1994). In this experiment we used the classic N 4 0 0 paradigm (e.g., Ku tas & H i l l y a r d , 1980b) in which participants are required to judge whether the terminal words o f sentences were either congruent or incongruent wi th the previous sentence context. W e d i d not observe any group differences between psychopaths and nonpsychopaths in behavioral performance or in the amplitude o f the N 4 0 0 elici ted by either congruent or incongruent terminal words . Taken together wi th the results f rom Exper iments 3 and 4, these data suggest that the functional significance o f the late fronto-central E R P negativities that have been reported in previous E R P studies o f language processes in psychopathy ( K i e h l et al . , 1999a; W i l l i a m s o n et al . , 1991) are not due to abnormalities in processes related to the generation o f the N 4 0 0 . 104 7.2 Evidence for abnormalities in abstract processing in psychopaths. The findings f rom Exper iment 1 add to the accumulating evidence suggesting that psychopathy is associated wi th abnormalities in processing conceptual ly abstract information. Studies have shown that psychopathic individuals have difficulty processing abstract words (current data f rom Exper iment 1; K i e h l et a l . , 1999a), performing abstract categorizat ion tasks (Hare & Jutai, 1988; K i e h l et a l . , 1999a), and understanding and interpreting proverbs (Gi l l s t rom, 1994). These data suggest that psychopathy is associated wi th deficits o r impairments in semantic processing o f abstract material. E R P studies have shown that differentiating abstract words f rom concrete words ( K i e h l et a l , 1999a; K o u n i o s & H o l c o m b , 1994; Paller et al, 1987) begins to occur in the processing stream at approximately 200 mill iseconds post stimulus. Psychopaths however, do not show this same E R P differentiation between abstract words and concrete words during a concrete/abstract lexical decision task o r during a concrete/abstract d iscr iminat ion task ( K i e h l et al . , 1999a). These data suggest that abnormalities in information processing begin to occur in psychopaths as early as 200 mill iseconds after a w o r d stimulus is presented. It is also important to note that i n these latter tasks psychopaths differed f rom nonpsychopaths in their E R P s to al l w o r d st imuli . That is, beginning as early as 200 ms post st imulus psychopaths ' E R P to concrete and abstract words , as w e l l as to pseudoconcrete and pseudoabstract st imuli , were associated wi th greater fronto-central E R P negativities than were nonpsychopaths ' E R P s . In Exper iment 1, we observed that psychopaths failed to activate the right anterior superior temporal gyrus for processing abstract words relative to baseline and failed to use this region for differentiating abstract st imuli f rom concrete s t imuli i n a manner consistent wi th 105 that found in controls. The anterior superior temporal gyrus is a mul t imoda l association cor tex believed to be invo lved i n a circuit that integrates the outcome o f sensory analyses wi th previously stored semantic information ( M e n d o l a et a l . , 1999). Th is latter interpretation o f the function o f the anterior superior temporal gyrus suggests that this region w o u l d exert its influence on information processing at approximately 150-250 mi l l i second post stimulus. Th is information, combined wi th the E R P data f rom K i e h l et al. (1999a) showing that the differences between psychopaths and others for semantic processing occur at approximately 200 ms post stimulus, suggest that the anterior superior temporal gyrus may be the site at wh ich information processing difficulties begin in psychopaths. T h e fact that the right anterior superior temporal gyrus was not activated for processing abstract w o r d s t imuli (even compared to baseline) suggests a focal abnormality in the psychopaths ' information processing stream. One might speculate that i f this region is not functioning appropriately, alternative systems may be recruited for performing computations o n abstract material . 7.3 Evidence for abnormalities in affective processing in psychopaths. Studies have also shown that psychopathy is associated wi th abnormalities in processing affective information. Psychopaths have difficulty processing affectively valenced w o r d (Day & W o n g , 1996; Intrator et al . , 1997; K i e h l et al . , 1999a; W i l l i a m s o n et a l . , 1991), and speech (Lou th et al . , 1998) st imuli , making judgments regarding emot ional polari ty (Wil l iamson, Harpur , & Hare , 1990), and interpreting emotional metaphors (Hayes, 1995). Psychopaths also fail to show the normal 'nar rowing ' o f details when recal l ing affective information as do nonpsychopaths (Christ ianson et a l . , 1996). The results f rom Exper iment 2 106 indicate that psychopaths perform in a similar manner as do controls for memory for affective s t imuli ; however the neural systems engaged in these cogni t ive operations are quite different between psychopaths and controls . Psychopaths d id not show the same pattern o f activation for affective (compared to neutral) s t imuli as d i d controls i n mul t ip le l imbic sites, inc luding the amygdala, hippocampus, and anterior and posterior cingulate. U n l i k e Exper iment 1, psychopaths d i d show evidence o f using alternative neural systems for performing the task. These regions included bilateral inferior frontal gyrus. Th i s suggests that in the absence o f input f rom the l imbic system, psychopaths were forced to use a different system(s) to perform the task than were noncriminals. Evidence for abnormalities in l imbic function also comes f rom other research in psychopathy. Pa t r ick and colleagues have shown that psychopaths do not show the same pattern o f startle potentiation during v iewing o f negatively valenced stimuli as do nonpsychopaths (Patr ick, Bradley , & L a n g , 1993). There is a large body o f animal research indicating that startle potentiation to negatively valenced s t imuli is mediated by circuits in the l imbic system, in particular, circuits in the amygdala ( reviewed by Patr ick, 1994). A l t h o u g h more research is needed in this area, these data suggest that the abnormal emotional behavior o f psychopaths may be related to deficits in l imbic function. In summary, psychopathy is associated wi th abnormalities in semantic processing o f conceptual ly abstract information and also abnormalities in processing affective information. A t the present time it is unclear whether these abnormalities in semantic processing are related to that same cognit ive process o r different cognit ive processes o r some combinat ion thereof. What is clear f rom the present data is that the neural systems that underlie these abnormalities appear to include lateral frontal and anterior temporal cortex. W e note that these t w o regions are highly interconnected via the uncinate fasciculus. Th is raises the possibi l i ty that some o f 107 the observed abnormalities in psychopaths may be related to disruption of function of circuits linking frontal cortex with temporal cortex. Indeed, perhaps a more precise characterization of the observed abnormalities in psychopaths would be that there appears to be an abnormal relationship between activity in frontal and temporal cortex (including limbic system). That is, some areas in the temporal lobe (and limbic system) appear to show abnormally small changes in response to stimuli while some frontal areas appear to show abnormally large changes. In Experiment 1 psychopaths failed to activated the right anterior superior temporal gyrus for processing of abstract words. In Experiment 2 psychopaths showed reduced activity associated with affective processing in the amygdala, hippocampal formation, and anterior and posterior cingulate. However, psychopaths showed greater activation associated with processing affective stimuli than did controls bilaterally in the inferior frontal gyrus. It is also plausible to suggest that the abnormal fronto-central ERP negativities in psychopaths (Experiments 3 and 4) occur from weakened input from temporal lobe structures which may lead to excessive activation of frontal cortex. Indeed, the similarity between the observed psychopathological and neural abnormalities in psychopaths and those observed in patients with temporal lobe damage (or temporal lobectomy for treatment of epilepsy) deserves further comment. 7.4 The relationship between psychopathy and the temporal lobes. Similarities between patients with temporal lobe abnormalities and criminal psychopathic individuals exist on several levels. On the behavioral level, detailed psychological and personality assessments of the patients with temporal lobe epilepsy suggests 108 a high incidence o f psychopathic-l ike behavior. Indeed, some studies have reported that pre-ope ra t ive^ the prevalence o f psychopathic-l ike behaviors are as high as 7 0 % o f patients wi th anterior temporal lobe epilepsy ( H i l l , P o n d , M i t c h e l l , & Falconer, 1957). Interestingly, removal o f the anterior temporal lobe appears to alleviate these behavioral problems in the majority o f cases. H i l l and colleagues (1957) reported that improvements in personality functioning fo l lowing temporal lobectomy included reduced hostility, more appropriate sexual behavior (e.g., reduced use o f prostitutes and sexual fetishes), increased warmth in social relationships, and increased empathy. It is also noteworthy that little or no intellectual deficits were observed in these patients after surgery for their epilepsy (Falconer & Serafetinides, 1963; H i l l et al . , 1957). N o t e that removal o f the anterior temporal lobe reduced the psychopathic traits, implying that these traits might reflect pathological temporal lobe over-activity or disruption in circuits that involve the anterior temporal lobes. Similarit ies between patients wi th temporal lobe abnormalities and cr iminal psychopathic individuals also come f rom the E R P data f rom the present series o f experiments. D a t a f rom these studies have revealed the presence o f large fronto-central E R P negativities in the 300-800 mil l i second post-stimulus time w indow in psychopaths for a variety o f st imuli . These abnormal fronto-central E R P negativities have been elicited by w o r d st imuli ( K i e h l et al . , 1999a; Wi l l i amson et a l , 1991), simple visual st imuli (Experiment 3; (see also Braverman, 1993), and task relevant auditory stimuli (Experiment 4). A number o f interpretations o f functional significance o f these fronto-central E R P negativities have been suggested, including abnormalities in attentional, executive, and semantic processes ( K i e h l et a l . , 1999a; W i l l i a m s o n et al . , 1991). Examina t ion o f E R P data f rom similar tasks w i t h patients w i th anterior temporal lobe abnormalities indicate that these patients also show strong evidence for 109 abnormal fronto-central negativities (Johnson, 1989; Y a m a g u c h i & Kn igh t , 1993). Indeed, the similarities in waveform morphology and topography between these t w o groups are str iking. Paller and colleagues (1988) have also shown that fronto-central E R P negativities are el ici ted by auditory oddbal l st imuli in monkeys fo l lowing temporal lobe lesions (Paller, M c C a r t h y , Roessler , & A l l i s o n , 1992; Pal ler et a l , 1988). A s noted in the summary and discussion for Exper iment 1, it is important to note that these abnormalities in psychopaths occur in the absence o f any overt structural brain abnormalities. H i g h resolut ion structural M R I s have now been evaluated in 23 psychopathic offenders and none have any evidence o f overt structure brain pathology ( K i e h l , 1999). It is relevant to note that neither psychopaths nor temporal lobe damaged (or temporal lobectomy) patients show any evidence o f behavioral impairment in visual o r auditory oddbal l tasks. A s mentioned in the discussion for Experiment 4, given that fronto-central E R P negativities exist in patients who have had severe damage to the temporal lobe, were might these potentials be generated? Halgren and colleagues have reported that negative polari ty inversions in the 300-500 ms post-stimulus time w indow for auditory target st imuli are found in the anterior cingulate, amygdala and inferior lateral frontal cortex (Halgren, 1999; Halgren et al . , 1995a; 1995b). Recent event-related f M R I studies o f the hemodynamic response to visual and auditory oddbal l st imuli have confirmed that these sites are implicated in the processing o f task-relevant st imuli (see K i e h l et al. 1998a). In Exper iment 2 abnormalities in affective processing in psychopaths were observed in the left anterior cingulate, right amygdala and bilaterally in the inferior lateral frontal cortex. These latter data suggest that the abnormal fronto-central E R P negativities may also be related to abnormal function o f these 110 neural structures. H o w e v e r , it is important to reiterate that loca l iz ing the neural sources underlying E R P components is difficult. Perhaps future studies should combine the high temporal resolution o f E R P s wi th the high spatial resolut ion o f f M R I to elucidate the neural systems that underlie the fronto-central E R P negativities in psychopaths. 7.5 Relat ionship between semantic processing abnormalities and other theories o f psychopathy. 7.5.1 L o w fear hypothesis The observation that abnormalities in semantic processing o f conceptual ly abstract material and affective information are a prominent feature o f psychopathy may throw light upon several o f the existing theories o f psychopathy. F o r example, the l o w fear hypothesis o f psychopathic behavior posits that psychopathic individuals suffer from a chronic need for stimulation, compounded by a relative fearlessness o f novel and dangerous situations ( L y k k e n , 1957; 1982; 1995; Patr ick, 1994; Pat r ick et al . , 1993; 1994; see Levenson , 1990; 1992; Levenson, K i e h l , & Fi tzpatr ick, 1995, for crit icisms o f this v iew) . I f the semantic (and perhaps l imbic) systems that normal ly incorporate the meaning o f fearful s t imuli are not functioning normally, then this may lead to augmented appetitive behavior that w o u l d otherwise be inhibited. M o r e o v e r , failing to process the meaning o f contextual cues related to emotional, including learned fearful st imuli , may lead to psychopathic behaviors. Ill 7.5.2 Response modulat ion hypothesis T h e hypothesis that abnormalities in semantic processing may be a fundamental feature in psychopathy might also help explain N e w m a n and colleagues finding that psychopathic individuals are less l ikely than nonpsychopathic individuals to show interference to contextual cues (Newman, Schmitt & V o s s , 1997). Th is latter study was designed to evaluate the generality o f the response modulat ion hypothesis o f psychopathy ( N e w m a n , 1998). Br ief ly , the response modulat ion hypothesis argues that psychopaths suffer f rom an information processing deficit that impedes their ability to 'automatically ' process contextual cues that, in nonpsychopathic individuals, normally augment behavior. There is n o w large body o f literature suggesting that psychopathy is associated wi th a failure to accommodate these contextual cues to modulate behavior (see N e w m a n , 1998, for a review) . In clarifying their use o f the term 'automatic ' , N e w m a n et al . , indicated that "the term is used to indicate that psychopaths do not consider the meaning (emphasis mine) o f their words , their actions, and situational cues in a spontaneous way". Interestingly, patients wi th right hemisphere lesions show reduced interference effects for language stimuli compared to left hemisphere brain damage patients or cont ro l participants ( D o y o n & M i l n e r , 1991). Studies have also shown that w o r d meanings can be accessed automatically (e.g., in the absence o f awareness) up to 600 ms post-stimulus ( L u c k , V o g e l , & Shapiro, 1996). U s i n g E R P s we have shown that abnormalities in differentiating the semantic aspects o f w o r d st imuli occur in psychopaths as early as 200 mill iseconds post-stimulus ( K i e h l et a l , 1999a). Thus , the deficits in psychopaths for accommodat ing contextual cues, those that are possibly semantic in nature, may lead to 112 less interference, at least in part, because o f a relative deficit (or advantage) i n abstracting the meaning o f the contextual cue. 7.5.3 ' A c q u i r e d sociopathy ' mode l o f psychopathy Several previous investigators have emphasized the probable involvement o f frontal cortex in psychopathy. F o r example, Damas io and colleagues have suggested that 'acquired sociopathy ' , a condi t ion putatively related to psychopathy, is the result o f damage to the orbi tal frontal cortex (Damasio, 1994; Damas io , Tranel , & Damas io , 1990; Hare , 1993). In Exper iment 2, we observed that, compared wi th controls, psychopaths generated excessive activation in the lateral aspects o f the orbi tal cortex for processing affective st imuli . Unfortunately, due to susceptibility artifact in the frontal sinuses, w e were unable to directly examine the role o f the medial orbital cortex in these experiments. W e also observed that, relative to con t ro l participants, psychopaths showed reduced act ivation for processing affective st imuli i n the anterior cingulate. Add i t iona l evidence for anterior cingulate abnormalities in psychopathy comes f rom recent evidence demonstrating that psychopathy is associated wi th reductions in the amplitude o f the error-related negativity ( E R N ; K i e h l , Bates & L i d d l e , 1999). The E R N is associated wi th processes related to error detection and is bel ieved to be generated in the anterior cingulate cortex (K ieh l , L i d d l e & Hopf inger , in press). Thus , although there may be some similarities between 'acquired sociopathy ' and psychopathy, the present data do not appear to address this relationship directly. It is important to reiterate, however , that psychopathy does not appear to be related to gross structural lesions akin to those k n o w n to cause 'acquired sociopathy ' . 113 7.5.4 Left hemisphere dysfunction Some theorists have also argued that psychopathy is associated wi th dominant o r left hemisphere frontal abnormalities (F lor -Henry , 1972). H o w e v e r , there have been mixed results supporting this v iew (Hare, 1979; Jutai, Hare , & Conno l ly , 1987). In the present series o f experiments we have observed differences between psychopaths and others i n cognit ive and language functions located in both the left and right hemispheres. M o r e o v e r , from the available evidence, it w o u l d appear that psychopathy is associated wi th both left and right hemisphere dysfunction. 7.6 Limi ta t ions o f the present studies There are a number o f limitations in the present series o f experiments that should be addressed in future work . In Experiments 1 and 2 the sample sizes for each group were small, wh ich raises the possibil i ty that some o f the observed effects may be sample specific. A c c o r d i n g to current estimates, sample sizes o f approximately 9 participants per group are adequate for delineating group effects in posi tron emission tomography ( P E T ) studies (Holmes , 1999). Because f M R I typically has better signal-to-noise ratios than do P E T studies, the sample sizes in the present study appear to be adequate. Nevertheless, future studies should consider employing larger sample sizes. Funct iona l imaging studies, including the present studies, also commonly employ fixed-effect models for data analyses, which means that the results o f Experiments 1 and 2 must be qualified as case studies. 114 A second l imitat ion o f the Experiments 1 and 2 is that we d i d not use an incarcerated nonpsychopathic cont ro l group. This raises the issue that some o f the observed effects in the psychopathic group may be due to the effects o f incarceration or cr iminal i ty per se rather than psychopathy. In our previous E R P studies that p rov ided the basis for propos ing Experiments 1 and 2 we observed that the nonpsychopathic inmates' behavioral data and E R P s to concrete and abstract words (Task 1 and Task 2; K i e h l et al . , 1999a) and to affective words (Task 3, K i e h l et a l . , 1999a; W i l l i a m s o n et al . , 1991) were very similar to those observed for noncr iminal controls (Koun ious & H o l c o m b , 1994; Pal ler et a l . , 1987; K i e h l , 1999). In addit ion, numerous other studies have shown that the performance o f nonpsychopathic inmates parallels that o f noncriminals in various cognit ive and psychophysio logica l measures (e.g., Chris t ianson et al . , 1996; Hare , 1984; Har t , Fo r th , & Hare , 1990; Pa t r ick et al . , 1993; N e w m a n et al . , 1997; Smi th , Arnet t , & N e w m a n , 1992). M o r e o v e r , in Exper iments 3, 4, and 5, the performance and E R P data o f the incarcerated nonpsychopaths was very similar to that observed in studies o f noncriminals. Therefore, in v iew o f the major logis t ical difficulties in performing M R I studies in inmates o f a maximum-securi ty prison, w e elected to study only psychopathic offenders. It is important to note that the cont ro l groups employed in Experiments 1 and 2 were matched wi th the psychopathic groups on gender, age, education, I Q measures, socio-economic status and handedness. Nevertheless, we cannot exclude the possibil i ty that the observed differences between psychopaths and non-inmate controls might be due to factors associated wi th criminali ty or incarceration. H o w e v e r , w e consider that the taking into account the previous E R P studies using similar tasks, i n wh ich the nonpsychopathic inmate controls exhibited normal E R P s , make such an explanation unlikely. Furthermore, the available evidence indicates that incarceration itself does not impair abstract 115 thinking. F o r example, Goethals (1981) has shown that length o f incarceration is unrelated to impairments i n performance in Raven ' s progressive matrices test, a test o f abstract thinking (Goethals, 1981). Las t ly , we cannot rule out the possibil i ty that history o f substance abuse may have contributed to the findings o f Exper iments 1 and 2. A l l reasonable measures were made to reduce the possibil i ty that substance abuse may have contr ibuted to the observed effects, including recruit ing inmates who were free f rom any D S M - I V diagnosis o f substance abuse in the last six months, requir ing urine samples for drug testing at the time o f study, and examining the pr ison records for history o f failed urine tests. Nevertheless, the t w o groups d id l ike ly differ in the their history o f drug use and the interpretation o f the results must take this into account. 7.7 Implications for treatment o f psychopathy These data may have important implications for treatment and management o f psychopaths. Dif f icu l ty understanding and comprehending conceptual ly abstract and affective information may be part o f the reason why psychopathic individuals are so resistant to psychological treatment (Grann, Langs t roem, Tengstroem, & K u l l g r e n , 1999; Hare , 1998; L o s e l , 1998; R i c e , Harr i s , & Cormie r , 1992; Wal lace , V i t a l e , & N e w m a n , 1999). M a n y treatment programs used in forensic settings teach information that is not only abstract in content but also affective (e.g., role playing, empathy modules). I f psychopathy is associated wi th impairments in interpreting and understanding these types o f information, then psychopathic individuals may be at a distinct disadvantage in these programs and may require 116 alternative treatment regimes. M o r e o v e r , perhaps treatment and management o f psychopathic individuals w o u l d be particularly improved i f these programs emphasized concepts in more concrete forms. 7.8 Suggestions for future research Current ly , cognit ive and language abnormalities have only been characterized in samples o f adult psychopathic populations. Howeve r , the l imited published evidence does indicate that language abnormalities are present in adolescent psychopathic individuals (Raine et a l , 1990). Th is raises the issue o f when do these abnormalities originate? Unfortunately, very little is k n o w n about the onset and course o f psychopathy (for review see F r i ck , 1998) and even less is k n o w n about the cognit ive correlates o f the syndrome at young ages. Clear ly , anecdotal and c l in ica l evidence suggest that psychopathy is present at a very early age. Indeed, some have even l inked psychopathic- l ike behavior to attachment theory in children as early as 6 months o f age ( M a g i d & M c K e l v e y , 1988). M o d e r n psychopathy assessment techniques are currently investigating identifying these individuals as a very early age (For th & B u r k e , 1998; F r i c k , 1998). Future studies should consider employing the tasks used in the present series o f experiments to examine the possibil i ty that these abnormalities may be present at younger ages. Indeed, these tasks may prove to be useful in evaluating individuals at r isk for psychopathy. 117 7.9 Conclusion The results from studies of affective and semantic processes in psychopaths suggest that the disorder is related to difficulties in processing abstract material and also processing affective information. These abnormalities appear to involve sites in the anterior temporal lobes and inferior frontal lobes, including the limbic system (Experiments 1 and 2). 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