ORIGINAL ARTICLE

Localization of Deformations Within the Amygdala

in Individuals With Psychopathy
Yaling Yang, PhD; Adrian Raine, DPhil; Katherine L. Narr, PhD; Patrick Colletti, MD; Arthur W. Toga, PhD

Context: Despite the repeated findings of impaired fear Main Outcome Measures: Amygdala volumes were
conditioning and affective recognition in psychopathic examined using traditional volumetric analyses and sur-
individuals, there has been a paucity of brain imaging re- face-based mesh modeling methods were used to local-
search on the amygdala and no evidence suggesting which ize regional surface deformations.
regions within the amygdala may be structurally com-
promised in individuals with psychopathy. Results: Individuals with psychopathy showed signifi-
cant bilateral volume reductions in the amygdala com-
Objective: To detect global and regional anatomical pared with controls (left, 17.1%; right, 18.9%). Surface
abnormalities in the amygdala in individuals with deformations were localized in regions in the approxi-
psychopathy. mate vicinity of the basolateral, lateral, cortical, and cen-
tral nuclei of the amygdala. Significant correlations were
found between reduced amygdala volumes and in-
Design: Cross-sectional design using structural mag-
creased total and facet psychopathy scores, with corre-
netic resonance imaging.
lations strongest for the affective and interpersonal fac-
ets of psychopathy.
Setting: Participants were recruited from high-risk com-
munities (temporary employment agencies) in the Los Conclusions: Results provide the first evidence, to our
Angeles, California, area and underwent imaging at a hos- knowledge, of focal amygdala abnormalities in psycho-
pital research facility at the University of Southern pathic individuals and corroborate findings from previ-
California. ous lesion studies. Findings support prior hypotheses of
amygdala deficits in individuals with psychopathy and
Participants: Twenty-seven psychopathic individuals indicate that amygdala abnormalities contribute to emo-
as defined by the Hare Psychopathy Checklist–Revised tional and behavioral symptoms of psychopathy.
and 32 normal controls matched on age, sex, and
ethnicity. Arch Gen Psychiatry. 2009;66(9):986-994

P
SYCHOPATHY IS A CLINICAL bust findings in individuals with psychopa-
condition conceptualized by thy is the abnormal psychophysiological
a combination of core psy- responsivity during the viewing of emo-
chopathic personalities (eg, tional stimuli and aversive conditioning
shallow affect, conning and learning,5-10 suggesting possible deficits in
manipulative) and antisocial behavioral the neurobiological system that governs
outcomes (eg, parasitic lifestyle, poor be- emotional response, particularly nega-
havioral control).1-3 Psychopathic indi- tive emotions, such as fear and anger.11-13
Author Affiliations: Laboratory viduals are particularly viewed as having The amygdala has long been known as
of Neuro Imaging, Department
a specific emotional and interpersonal style one of the most important components in
of Neurology, David Geffen
School of Medicine, University that is characterized by the inability to rec- the neural circuit underlying emotional
of California, Los Angeles ognize and experience the emotional sig- processing.14-18 An intact amygdala is found
(Drs Yang, Narr, and Toga) and nificance of social events.4 It was sug- to be necessary for fear conditioning19;
Department of Radiology, gested that as a result of their emotional thus, impairments in this structure have
School of Medicine, University impairments, individuals with psychopa- been hypothesized to contribute to the
of Southern California thy use a detached, predatory style of an- well-replicated observations of poor fear
(Dr Colletti), Los Angeles; and
Department of Criminology,
tisocial behavior as a strategy to meet their conditioning in individuals with psychopa-
Psychiatry, and Psychology, immediate needs without regard for the thy.9,20 In addition, the amygdala is an im-
University of Pennsylvania, consequences.4 Consistent with the symp- portant component of the neural systems
Philadelphia (Dr Raine). toms of psychopathy, one of the most ro- subserving reward learning, social inter-

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 action, and moral emotion and reasoning,21-26 where the Psychopathy ratings made by 2 different laboratory assistants
ability to recognize the emotions signaled by facial ex- during separate phases of testing. A cutoff of 23 (high) and 15
pressions is crucial for making advantageous decisions (low) on the total PCL-R score was used to define psychopa-
in a complex social environment.19 Therefore, it has also thy, resulting in a total of 27 individuals with psychopathy
(PCL-R score range, 23-40) and 32 controls (PCL-R score range,
been hypothesized that disturbances in amygdala struc-
5-14). This cutoff was chosen to be consistent with our prior
ture or function may contribute to the social dysfunc- research on this sample36,41-43 and is similar to the optimal cut-
tion and impaired moral decision making in individuals off suggested by taxometric analyses of the PCL-R.44 The gen-
with psychopathy.27 eral term of individuals with psychopathy is used in this article
Studies have revealed that the amygdala is not a ho- to refer to community individuals with a PCL-R score higher
mogeneous structure and can be differentiated into ap- than 23. Demographic, cognitive, and diagnostic characteris-
proximately 13 nuclei. Although the functional specific- tic information were collected as follows: (1) age, sex, and eth-
ity of the nuclei in the human amygdala remains unclear, nicity; (2) socioeconomic status45; (3) full-scale IQ as assessed
considerable evidence from animal studies suggests that by the Wechsler Adult Intelligence Scale–Revised46; (4) hand-
several nuclei of the amygdala are involved in the pro- edness as assessed by the abbreviated Oldfield Inventory47; (5)
lifetime diagnosis of drug/alcohol dependence as assessed by
cessing of emotion.28,29 For example, the basolateral and
the Structural Clinical Interview for Axis I DSM-IV Disor-
lateral nuclei have been linked to the encoding of sensory- ders39; and (6) the number of alcohol drinks used in the past
specific features, whereas the central nucleus has been month as assessed by the alcohol use questionnaire.36 Written
associated with encoding the motivational or affective as- informed consent was obtained from all subjects and the study
pects.30 The importance of the amygdala and its subdi- was approved by the University of Southern California insti-
visions in emotional processing and social functioning tutional review board.
has led to several predictions that global and regional defi-
cits of the amygdala may contribute to features of psy-
chopathy31-34; however, to our knowledge, no study to MAGNETIC RESONANCE IMAGE ANALYSIS
date has examined the structural integrity of the amyg-
dala in psychopathic individuals. Structural magnetic resonance images were collected on a
Using a community sample, we examined the struc- 1.5-T Philips (Shelton, Connecticut) S15/ACS scanner (rep-
etition time = 34 milliseconds, echo time = 12.4 milliseconds,
ture of the amygdala in psychopathic and control groups. voxel size=0.9⫻0.9⫻1.7 mm).36 Before the delineation pro-
It was hypothesized that psychopathic individuals would cess, each image volume was first corrected for magnetic
show a global volume reduction in the amygdala and re- field inhomogeneities48 and head tilt and alignment by using
gional morphological alterations in the approximate lo- 6-parameter rigid-body registrations.44 During the registra-
cations of basolateral, lateral, and central nuclei. Fur- tion procedure, the image volumes were placed in a com-
thermore, we examined correlations between the amygdala mon coordinate space.49
and degree of psychopathy using the 4-facet concept of The delineation of the amygdala was conducted by 2
psychopathy, which includes interpersonal (eg, super- independent technicians (premedical neuroscience trainees)
ficial charm, manipulative), affective (eg, shallow affect, who received extensive training on the delineation protocols
lack of remorse), lifestyle (eg, impulsivity, irresponsibil- under the supervision of one of us (Y.Y.). These 2 techni-
cians, blind to group membership, traced the amygdala fol-
ity), and antisocial (eg, poor behavioral control, crimi- lowing a delineation protocol adopted from previously vali-
nal versatility) facets.35 It was predicted that reduced amyg- dated methods50-52 and based on the atlas of the amygdala
dala volume would correlate more prominently with the anatomy by Mai et al.53 The images were first resampled to
core features of psychopathy (ie, interpersonal and af- 1-mm thickness to improve the visibility of anatomical
fective facets) than the secondary features of antisocial details for identifying the structure. The amygdala was
behavior (ie, lifestyle and antisocial facets), which are more traced in coronal brain slices from posterior to anterior
common in nonpsychopathic offenders and not as spe- while using the digitized surface contours simultaneously
cific to the syndrome of psychopathy. displayed in both sagittal and transverse planes to facilitate a
more accurate identification of the boundaries that separate
the amygdala from surrounding structures (Figure 1). The
METHODS amygdala was traced on magnified images (⫻4) to allow bet-
ter precision in identifying the anatomical boundaries.
PARTICIPANTS Amygdala tracing in each hemisphere began when the struc-
ture appeared as a pebble of gray matter superior to the tem-
Eighty-six subjects were recruited from 5 temporary employ- poral horn of the lateral ventricle and inferior to the white
ment agencies in Los Angeles, California.35 Samples from this matter of the parietal lobe. As the lateral ventricle moved to
community have been found to show relatively higher rates of a more lateral position as the brain volumes moved anterior,
psychopathy/antisocial personality.36 Psychopathy was as- the alveus appeared and was used as the inferior boundary
sessed using the Hare Psychopathy Checklist–Revised (PCL-R)3,35 that separates the amygdala from the hippocampus. The
and supplemented by 5 sources of collateral data that in- inferior boundary shifted to the temporal lobe white matter
cluded (1) the Interpersonal Measure of Psychopathy37 rat- when the alveus was no longer visible. The tracing of the
ings; (2) self-reported crime and violence assessed using an adult amygdala was continued anteriorly until the lateral ventricle
extension36 of the National Youth Survey self-report delin- completely separated the temporal lobe from the rest of the
quency measure38; (3) criminal history transcripts obtained from cerebrum. For each subject, right and left amygdala volumes
the Department of Justice; (4) data derived from, and behav- were extracted using these tracings. To assess interrater reli-
ioral observations made during, the Structured Clinical Inter- ability, 10 different randomly selected cases were traced and
view for Axis I DSM-IV Disorders and Axis II Personality Dis- the interrater intraclass correlation coefficients for amygdala
orders39,40; and (5) independent Interpersonal Measure of volumes ranged between 0.91 and 0.95. Whole-brain vol-

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 umes, obtained as previously described,54 were retained for obtained at each spatially equivalent amygdala surface point
use as covariates to control for individual differences in were then compared between groups to reveal local surface de-
brain size in analyses of amygdala morphology. formations/expansions and the results were displayed on the
group averaged left or right amygdala.
SURFACE-BASED MESH AVERAGING
STATISTICAL ANALYSES
Surface meshes were constructed for the amygdala using surface-
based anatomical modeling, and skeletonizing methods were Analyses of the amygdala volumes were conducted using SPSS
used to identify regional morphological changes of the amyg- (SPSS Inc, Chicago, Illinois). The general linear model was used
dala.55 The surface contours representing each individual’s left to assess the amygdala volume differences between the psy-
or right amygdala were made spatially uniform within and across chopathy and control groups, while covarying for total brain
subjects, where each surface was made to represent 15 000 sur- volume. Socioeconomic status and substance dependence, for
face points or nodes. Radial distances from the central core (me- which groups differed significantly, were also included in the
dial axis) of each amygdala to the spatially normalized surface statistical analyses as covariates. Partial correlations were con-
points were then computed within subjects. These distances ducted on the entire sample of 59 to assess the association be-
tween amygdala volume and total and facet psychopathy scores,
while controlling for total brain volume. All tests of signifi-
A B C cance were 2-tailed with an ␣ level of .05.
The same statistical models described earlier were imple-
mented using the statistical program R (www.r-project.org) to
identify regional changes in amygdala surface anatomy be-
tween groups and assess relationships between amygdala sur-
Lateral Alveus
face deformations and psychopathy scores. Uncorrected 2-tailed
ventricle probability values obtained from these analyses conducted for
each amygdala surface point were color coded and displayed
D E on the averaged surface of the entire group to allow initial vi-
sualization of localized group differences in amygdala surface
structure. Structural variation of the human amygdala and in-
dividual differences in the relative position of amygdala nuclei
across the surface do not allow the locations of amygdala nu-
Hippocampus clei to be determined with a high degree of accuracy in imaging
data. Thus, the boundaries of the different subnuclei (Figure 2)
are approximations as they are based on an extrapolation of the
Figure 1. The amygdala was traced in high-resolution T1-weighted images relative nuclei positions in 1 atlas.53 Permutation tests with a
using the software MultiTracer (http://air.bmap.ucla.edu/MultiTracer). Trac- threshold of P⬍.05 were applied to control for multiple spa-
ing was performed in contiguous coronal slices (A-C showing posterior to tially correlated comparisons (statistical tests performed at 15 000
anterior) while referencing orthogonal sagittal (D) and transverse (E) planes
to confirm the correct identification of anatomical boundaries. Even though amygdala surface locations) to ensure that the overall pattern
only the tracings of the right amygdala are illustrated, the left amygdala was of effects in the surface-based maps could not have been ob-
traced following the same protocol. served by chance alone.56-58

A Anterior Anterior Anterior Anterior

Superior view AB
Inferior view
PACI
AAA
PirT
AI ACo
La La PHA
PHA
BL Medial Medial Medial Medial
PCo BL
PCo
Ce BM MeA
MeA
Ce

Left amygdala Right amygdala Left amygdala Right amygdala

B

P value
.01 .05 .10

Figure 2. The amygdala nuclei and significant regional amygdala surface deformations. A, Schematic representation of the amygdala nuclei is mapped onto the
3-dimensional left and right amygdala surfaces. Structural variation of the human amygdala and individual differences in the relative position of the amygdala
nuclei across the surface do not allow the locations of the amygdala nuclei to be determined with a high degree of accuracy in imaging data. Thus, the boundaries
of the different subnuclei are approximations based on an extrapolation of the relative nuclei positions derived from the atlas of Mai et al.53 AAA indicates anterior
amygdaloid area; AB, accessory basal nucleus; ACo, anterior cortical nucleus; AI, amygdaloid island; BL, basolateral nucleus; BM, basomedial nucleus; Ce, central
nucleus; La, lateral nucleus; MeA, medial amygdaloid nucleus; PACl, preamygdalar claustrum; PCo, posterior cortical nucleus; PHA, parahippocampal-amygdaloid
transition area; PirT, piriform cortex. B, Statistical maps showing significant regional amygdala surface deformations in individuals with psychopathy (n =27)
compared with healthy controls (n=32) as encoded by the color bar (uncorrected P value). No surface expansion in the amygdala in individuals with psychopathy
was observed.

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 Table 1. Demographic, Cognitive, and Diagnostic Measures for Psychopathy and Control Groups

Mean (SD) [Range]

Psychopathy Control
(n= 27) (n = 32) Statistics
Age, y 32.22 (6.57) 30.84 (7.14) F1,57 = 1.60; P=.21
Socioeconomic status 30.30 (7.73) 36.77 (10.81) F1,57 = 6.71; P=.01
Ethnicity ␹1,57
2
= 0.82; P=.44
White 12 18
Other 15 14
Sex ␹1,57
2
= 1.61; P=.27
M 25 26
F 2 6
Full-scale IQ 98.11 (14.13) 103.84 (17.36) F1,57 = 1.86; P=.18
Handedness ␹1,57
2
= 1.07; P=.49
Right 23 25
Left 3 7
Psychopathy
Total PCL-R3,35 score 27.96 (4.93) [23-40] 10.56 (2.83) [5-14] F1,57 = 192.6; P⬍ .001
Facet 1 (interpersonal) 5.41 (1.50) [3-8] 1.78 (1.43) [0-5] F1,57 = 224.5; P⬍ .001
Facet 2 (affective) 5.26 (1.68) [2-8] 1.34 (1.15) [0-4] F1,57 = 209.1; P⬍ .001
Facet 3 (lifestyle) 7.19 (2.00) [3-10] 3.41 (1.88) [0-7] F1,57 = 348.0; P⬍ .001
Facet 4 (antisocial) 7.00 (2.06) [4-10] 2.13 (1.66) [0-6] F1,57 = 287.6; P⬍ .001
Substance/alcohol dependence ␹1,57
2
= 17.26; P⬍ .001
Present 19 6
Absent 7 26
No. of alcohol drinks/mo 6.56 (7.32) 4.29 (6.50) F1,57 = 1.56; P=.22

Abbreviation: PCL-R, Hare Psychopathy Checklist–Revised.

RESULTS volumetric findings (left, permutation-corrected P=.047;

right, P=.002) (Figure 2). The results remained signifi-
cant after controlling for whole-brain volume, socioeco-
PSYCHOPATHIC INDIVIDUALS VS CONTROLS nomic status, and substance/alcohol dependence (left, per-
mutation-corrected P =.049; right, P=.006). In terms of
Subject Characteristics localization, little evidence could be found for deforma-
tions in the vicinity of accessory basal nuclei, basome-
Groups differed significantly on socioeconomic status and dial nuclei, medial amygdaloid nuclei, and piriform cor-
history of substance/alcohol dependence (Table 1). To tex (Figure 2). Regarding the remaining 9 nuclei, the
rule out these potential confounds, they were included as strongest evidence was found for deformations in the ap-
covariates in the general linear models used for the volu- proximate locations of anterior and posterior cortical and
metric analyses as well as the surface-based analyses. central nuclei (superior view) and basolateral and lat-
eral nuclei (superior and inferior view) of the amygdala.
Traditional Volumetric Analyses

Psychopathic individuals showed a significant volume re- CORRELATION ANALYSES

duction in the amygdala compared with controls
(F2,55 =3.85; P= .03), with whole-brain volume as a co- Traditional Volumetric Analyses
variate. As illustrated in Figure 3, individuals with psy-
chopathy showed a 17.14% volume reduction in the left To determine whether the amygdala volume deficit was
amygdala and an 18.93% volume reduction in the right associated with a particular facet of psychopathy, corre-
amygdala compared with controls. While the right amyg- lational analyses on the entire sample of 59 subjects were
dala showed a tendency toward greater volumetric re- conducted. Findings revealed significant negative cor-
duction than the left, no significant laterality effect was relations between amygdala volumes and the psychopa-
observed (F1,56 =0.61; P=.44). Group differences for both thy total and facet scores, with the correlations stron-
left and right amygdala volumes remained significant af- gest for the affective and interpersonal facets (Table 2).
ter correcting for the whole-brain volume, socioeco- All findings remained significant after controlling for
nomic status, and substance/alcohol dependence (P=.02 whole-brain volume, socioeconomic status, and substance/
and P=.02, respectively). alcohol dependence (all P ⬍.01).

Surface-Based Mesh Modeling Methods Surface-Based Mesh Modeling Methods

Surface-based modeling analysis revealed bilateral shape As demonstrated in Figure 4, surface-based analyses
differences of the amygdala that were consistent with the revealed similar negative correlations between the

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 P =.03 Table 2. Correlations Between Amygdala Volumes
2750 Individuals with psychopathy
Normal controls
and the Total and 4 Facet Scores of Psychopathy in the
Mean (SD) = 2482.3 (101.5) Entire Sample of 59, Controlling for Whole-Brain Volume
2500
P =.02
Left Amygdala Right Amygdala
Mean (SD) =
2087.2 (110.5)
2250 P P
Mean (SD) = 2130.8 (82.7)
Score Correlation Value Correlation Value
Volume, mm3

Mean (SD) = Total psychopathy −0.39 .002 −0.40 .002

2000
1819.1 (90.0) Interpersonal facet −0.45 ⬍.001 −0.36 .005
Affective facet −0.49 ⬍.001 −0.47 ⬍.001
1750 Lifestyle facet −0.22 .10 −0.34 .009
Antisocial facet −0.24 .07 −0.27 .04

1500

1250 Findings of amygdala volume reductions in individu-

Left Amygdala Right Amygdala als with psychopathy are consistent with lesion studies show-
ing that damage to the amygdala results in emotional im-
Figure 3. Amygdala volumes in psychopathic individuals and normal pairments similar to those of psychopathy. Animals with
controls, with total brain volume as a covariate. The vertical lines represent selective lesions to the amygdala have been found to show
the standard error. The group mean (SD) volume is indicated.
substantial impairments in fear conditioning and abnor-
mal responsivity to threatening objects. For example, Hitch-
amygdala and psychopathy scores, which again were
cock and Davis59 demonstrated that lesions to the amyg-
more pronounced for the affective and interpersonal
dala impaired fear-potentiated startle response in rats. In a
facets. The permutation analyses showed that bilateral
recent study, Machado and Bachevalier60 found that rhe-
amygdala deformations were significantly correlated
sus monkeys with selective lesions to the amygdala showed
with total (left, permutation-corrected P = .004; right,
profound behavioral changes that precluded positive so-
P ⬍ .001), interpersonal (left, permutation-corrected
cial interactions (eg, decreased affiliation and popularity
P ⬍ .001; right, P = .001), and affective (left, permuta-
within the group) and decreased reactivity to threatening
tion-corrected P⬍.001; right, P⬍.001) scores. The life-
gestures. Similar findings have been reported showing that
style and antisocial facets of psychopathy showed
monkeys with bilateral amygdala lesions displayed blunted
significant associations with the left amygdala
emotional response (ie, lack of fear) and decreased defen-
(permutation-corrected P=.02 and .01, respectively) but
sive behavior to threats (ie, a fake snake).61,62 These behav-
not the right amygdala (permutation-corrected P=.12 and
ioral changes found in animals with amygdala lesions may
.16, respectively). These correlations remained signifi-
suggest, albeit indirectly, that amygdala structural abnor-
cant after controlling for whole-brain volume, socioeco-
malities may contribute to the classic findings of poor fear
nomic status, and substance/alcohol dependence (all per-
conditioning and impaired emotion recognition observed
mutation-corrected P ⬍ .03). Consistent with group
in individuals with psychopathy.7,9,63
analyses, increased psychopathy scores were associated with
In humans, selective lesions to the amygdala are rare,
increased regional atrophy approximately in the cortical,
making it difficult to draw clear conclusions regarding
central, basolateral, and lateral nuclei of the amygdala
the role such lesions play in modulating the emotion and
(Figure 4).
behavior of patients. However, evidence suggests that there
are similarities between the affective and social impair-
COMMENT ments resulting from amygdala lesions and the behav-
ioral dysfunctions characterizing individuals with psy-
To our knowledge, this study is the first to show local- chopathy. For example, Adolphs et al19 demonstrated in
ized structural abnormalities of the amygdala in indi- a case study that extensive bilateral amygdala damage (as
viduals with psychopathy. In this study, psychopathic in- a result of Urbach-Wiethe disease) led to difficulty in rec-
dividuals were found to show bilateral amygdala volume ognizing emotions in facial expressions, particularly when
reductions compared with controls. Significant regional the patient was responding to a highly arousing facial ex-
deformations were found to be most prominent in the pression such as fear, similar to the impairments ob-
vicinity of the basolateral, lateral, cortical, and central nu- served in individuals with psychopathy.64 Several sub-
clei of the amygdala in individuals with psychopathy. In sequent studies reported similar findings and show a
addition, negative correlations were found between amyg- consistent pattern of intact facial identification and im-
dala volumes and all 4 psychopathy facet scores, with cor- paired recognition of the facial expression of fear in pa-
relations being most pronounced for the affective and in- tients with amygdala lesions such as those caused by dis-
terpersonal facets of psychopathy. Results could not be ease (eg, encephalitis) and/or resection (eg, lobectomy
attributed to demographic group differences in socio- or amygdalotomy).15,65-71
economic status or substance/alcohol dependence. Find- Observations from studies of patients with temporal lobe
ings provide initial evidence indicating amygdala struc- epilepsy (TLE) may also provide evidence in support of our
tural abnormalities as 1 key element in the neurobiological findings linking altered amygdala morphology with psy-
bases of psychopathy. chopathy. Although amygdala damage in patients with TLE

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 A
Total psychopathy
Anterior Superior view Anterior Anterior Inferior view Anterior

Medial Medial Medial Medial

P value

Left amygdala Right amygdala .01 .05 .10 Left amygdala Right amygdala

B Interpersonal facet

C Affective facet

D Lifestyle facet

E Antisocial facet

Figure 4. Statistical maps showing significant negative correlations between the amygdala surface structure and total psychopathy (A) and interpersonal (B),
affective (C), lifestyle (D), and antisocial (E) facet scores across the entire sample of 59 subjects. The uncorrected P values corresponding to significant r values
are encoded by the color bar. The regional deformations were confirmed by permutations indicating an overall pattern of significant correlations between
deformations in the amygdala and the increase in the total and facet scores.

often occurs in conjunction with damage to other regions ments in emotion recognition. For example, Houghton et
of the brain, pathological findings are regionally isolated al78 reported that impairments in the ability to recognize
in some cases.72-74 Volumetric reductions indicating pa- negative emotional expressions were associated with re-
thology of the amygdala are frequently documented in pa- duced amygdala volume in patients with TLE. In addi-
tients with TLE (with reports ranging between 10%-57% tion, several studies have shown that TLE-induced amyg-
amygdala volume reductions),75 where the lateral and basal dala damage also results in impaired social judgment (ie,
nuclei appear most susceptible to seizure-induced dam- rate aversive facial appearances as more positive) because
age.72,75-77 Patients who have TLE and exhibit concomi- of the difficulty in recognizing negative facial emo-
tant amygdala damage have been found to show impair- tions,79,80 again consistent with behavioral dysfunction re-

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 ported in individuals with psychopathy. These human le- interpreting the results. First, the sample size is mod-
sion studies demonstrate that amygdala lesions lead to est, thus raising the risk of potential type II error.
outcomes of affective impairments that parallel to some ex- However, the sample size is comparable with those
tent the profile of individuals with psychopathy7,12,81 and used in other magnetic resonance imaging studies, and
support the findings of this study in suggesting that struc- the use of correlation analyses on the entire sample of
tural impairments in the amygdala may predispose to the 59 subjects increases the power for detecting any asso-
emotional and social dysfunction in individuals with ciation between amygdala volume and psychopathy.
psychopathy. Second, there was the lack of absolute objectivity due
The surface-based mesh modeling analyses indicate to the nature of manual tracing. However, the method
regional atrophy in amygdala structure in the vicinity of was used to test the specific hypotheses of regional
the basolateral, lateral, central, and cortical nuclei in in- morphological deformations in the amygdala in indi-
dividuals with psychopathy, echoing the complexity of viduals with psychopathy, which would not have been
the clinical descriptions of this disorder. The most ro- possible if an automated imaging analysis method,
bust evidence suggests that the lateral, basolateral, and such as voxel-based morphometry, was used. Third,
central nuclei of the amygdala are independently and in- although we controlled for socioeconomic status and
teractively involved in emotional processing, including substance dependence, a possibility remains that other
fear conditioning and autonomic reactivity to affective confounds may contribute to the amygdala structural
stimuli,28-30 while other studies have further linked these alterations observed in individuals with psychopathy,
nuclei to reward-related learning, behavioral inhibition, such as pharmacological treatments received prior to
and decision making.28 With regard to the cortical nu- the scanning. Another limitation of this study is that
clei, the very few findings are suggestive that this region even though we were able to conduct the group com-
may be involved in parenting, social interaction, and the parisons on a surface point-by-point level to elucidate
regulation of stress and anxiety.28 Therefore, the re- the approximate locations of the amygdala deforma-
gional morphological abnormalities of the amygdala ob- tions, we were unable to test the significance values
served in this study may reflect a variety of emotional and for each distinct nucleus. Therefore, while surface
behavioral features in individuals with psychopathy. Fu- maps indicate a more pronounced amygdala deforma-
ture research using higher-resolution imaging will be tion in the cortical, central, basolateral, and lateral
needed to identify the structural alterations within each nuclei, the possibility remains that the findings also
nucleus of the amygdala, but the even greater challenge reflect deformations of nuclei relatively less repre-
will be to delineate the human functional significance of sented on the surface (eg, medial amygdaloid and
such deformations based on the behavioral neurosci- basomedial nuclei). Last, the standard resolution of
ence animal literature. structural imaging data does not yet allow reliable
In addition to the significant amygdala volume reduc- localization of structural alterations within specific
tions in individuals with psychopathy, reduced vol- amygdala nuclei. The precise identification of the
umes were found to correlate with increased total psy- amygdala nuclei in humans requires a combination of
chopathy scores across the entire sample. The correlations histological/immunohistochemical methods and neu-
were found to be most pronounced for the affective and rochemical and cytoarchitectonic criteria,90 which was
interpersonal facets of psychopathy. These findings are not possible in this study using in vivo imaging with a
consistent with 1 abstract reporting a correlation be- 1.5-T scanner. As a result, it needs to be made clear
tween reduced volumes in the right amygdala and in- that the labeling of the schematic representation of the
creased affective-interpersonal scores of psychopathy in amygdala nuclei shown in this study was based on
a violent offender sample.82 Results are further sup- information obtained from a single human brain
ported by evidence from functional imaging studies show- atlas53 and has not been validated in any probabilistic
ing a higher degree of abnormal activation in the amyg- manner. Nonetheless, this approach was chosen taking
dala to be associated with an increase in the psychopathy into account the methodological and technological dif-
score during affect recognition, prisoner’s dilemma tasks, ficulties to best illustrate the approximate locations of
and moral decision making.83-85 The associations be- regional amygdala deformations in individuals with
tween reduced amygdala volume and increased psy- psychopathy and illuminate the need for future studies
chopathy total and facet scores are in line with evidence to examine the amygdala as a heterogeneous structure
indicating that, in addition to emotional processing, the and identify subtle and localized structural changes
amygdala mediates a variety of brain functions, includ- within the amygdala. Although the precise localization
ing attention, memory, social judgment, and moral de- of structural changes within specific nuclei awaits fur-
cision making, through its neural connections with the ther research, this study is the first, to our knowledge,
prefrontal cortex and other subcortical structures.79,86-89 to provide an examination of localized morphological
Therefore, our findings support the hypothesis that a alterations in the amygdala in individuals with psy-
higher degree of structural abnormalities in the amyg- chopathy. The advance in the understanding of the
dala may contribute to a greater manifestation of the af- neuropathology in psychopathy could greatly benefit
fective-interpersonal impairments and, to a lesser de- from future studies examining the mediating risk fac-
gree, an increase in antisocial behavior and lifestyle in tors (eg, autonomic fear conditioning response)
individuals with psychopathy. together with structural imaging data to translate
There are several potential limitations of the pres- amygdala structural impairments directly into func-
ent study that need to be taken into account when tional impairments in individuals with psychopathy.

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grants K02 MH01114-06 and MH50940 (Dr Raine), and 2003;985:233-250.
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Career Development Award K01 MH073990 from the Na- Curr Opin Neurobiol. 2004;14(2):148-155.
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RR13642 from the National Center for Research Re- 27. Raine A, Yang Y. Neural foundations to moral reasoning and antisocial behavior.
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