Neuroimaging of Psychopathy and Antisocial Behavior:
A Targeted Review
R. J. R. Blair
Published online: 29 January 2010
# US Government 2010
Abstract The goal of this article is to provide a selective
and targeted review of the neuroimaging literature on
psychopathic tendencies and antisocial behavior and to
explore the extent to which this literature supports recent
cognitive neuroscientific models of psychopathy and
antisocial behavior. The literature reveals that individuals
who present with an increased risk for reactive, but
not instrumental, aggression show increased amygdala
responses to emotionally evocative stimuli. This is consis-
tent with suggestions that such individuals are primed to
respond strongly to an inappropriate extent to threatening or
frustrating events. In contrast, individuals with psychopath-
ic tendencies show decreased amygdala and orbitofrontal
cortex responses to emotionally provocative stimuli or
during emotional learning paradigms. This is consistent
with suggestions that such individuals face difficulties with
basic forms of emotional learning and decision making.
The disorder of psychopathy characterizes an individual
who shows pronounced problems in emotional processing
(reduced guilt, empathy, and attachment to significant
others; callous and unemotional [CU] traits) and who is at
increased risk for displaying antisocial behavior [1, 2]. It is
a developmental disorder. Recent work has confirmed the
stability of CU traits in particular and the disorder more
generally from childhood into adulthood .
The goalofthisarticle istoprovide a selective and targeted
review of the neuroimaging literature on psychopathy and
antisocial behavior. My goal is to explore the extent to which
the current literature supports the cognitive neuroscientific
models of psychopathy and antisocial behavior that I have
been developing during the past 10 years [4, 5••].
It should be noted, however, that functional MRI (fMRI)
studies of psychopathic traits have used a variety of assessment
tools and populations. There have been studies of healthy
undergraduates and unemployed individuals distinguished by
their scores on self-report measures [6–8] as well as studies on
clinical/forensic populations and youth with disruptive behav-
ior disorders distinguished by their scores on the Psychopathy
Checklist-Revised and Psychopathy Checklist-Youth Version,
respectively [9–11]. The current review concentrates on these
studies. However, it also considers fMRI studies of conduct
disorder (CD) [12, 13] and recent work on reactively
aggressive populations [14••, 15, 16]. This review does not,
however, consider the early imaging studies on antisocial
populations that, although critical in laying the foundation of
this literature, lacked contemporary techniques for anatomic
precision and thus are difficult to interpret.
The Models to Be Evaluated
The models described subsequently have been presented in
considerably greater detail elsewhere [5••]. They make a
fundamental distinction between instrumental and reactive
aggression. Reactive aggression is triggered by a frustrating
or threatening event and involves unplanned, enraged
attacks on the object perceived to be the source of the
R. J. R. Blair (*)
Mood and Anxiety Program, National Institute of Mental Health,
Room 206, 15K North Drive, MSC 2670,
Bethesda, MD 20892, USA
Curr Psychiatry Rep (2010) 12:76–82
threat/frustration. In contrast, instrumental aggression is
purposeful and goal directed (eg, to obtain the victim’s
possessions). This distinction between instrumental and
reactive aggression has been made for some time .
Moreover, considerable data suggest the existence of two
relatively separable populations of aggressive individuals:
individuals who present with mostly reactive aggression
and those who present with high levels of proactive and
reactive aggression . Patients with intermittent explo-
sive disorder and anxiety disorders such as post-traumatic
stress disorder are at increased risk for reactive aggression.
In contrast, individuals with psychopathy show increased
levels of proactive and reactive aggression .
With respect to reactive aggression, animal work
indicates a gradated response to threat: distant threats
induce freezing, then, as they draw closer, flight and finally
reactive aggression when they are very close and escape is
impossible . Animal work further indicates that this
progressive response to threat is mediated by a basic threat
system that runs from medial amygdaloidal areas down-
ward, largely via the stria terminalis to the medial
hypothalamus, and from there to the dorsal half of the
periaqueductal gray (PAG) . This neural system—
amygdala-hypothalamus-PAG—is thought to mediate
reactive aggression, including frustration-induced reactive
aggression, in humans as well [5••, 20]. It is proposed that
this system is regulated by medial, orbital, and inferior
frontal cortices. Frontal regulatory activity can involve 1)
attentional priming of nonemotional stimuli (and conse-
quent reduced representation of emotional stimuli) either
automatically  or in a controlled fashion  or 2) the
suppression of amygdala activity by medial orbitofrontal
cortex (OFC)  and/or more anterior and slightly lateral
regions of the OFC .
Reactive aggression need not be maladaptive—it may be
an appropriate response to the level of threat/frustration.
However, it can become maladaptive because of prior
priming of the basic amygdala-hypothalamus-PAG threat
system (due to prior threat exposure of an endogenous
condition) and/or impaired frontal regulation. Under these
circumstances, the response of the basic threat system to a
threatening/frustrating provocation will be disproportion-
ately strong (ie, much more likely to involve extreme
reactive aggression). This predicts that patients at height-
ened risk of showing reactive (although not instrumental)
aggression should show heightened amygdala responses
to emotionally provocative stimuli and reduced frontal
emotional regulatory activity.
With respect to instrumental aggression/antisocial be-
havior, it is argued that this form of goal-directed motor
response is no different than any other form of motor
response [5••]. As such, it is mediated by motor cortex and
caudate. However, the interesting thing about instrumental
aggression/antisocial behavior is that this type of behavior
was chosen to achieve the goal rather than a more prosocial
choices, and the costs and benefits are represented as being
associated with these choices. For most individuals, the
benefits of antisocial goal solutions are not sufficiently great
(relative to prosocial alternatives) and/or the costs of these
antisocial goal solutions are too great (eg, the harm to the
victim, the risk of loss of liberty) to make these solutions
desirable. However, for individuals with psychopathy, the
instrumental antisocial behavior can be maladaptive (ie, it is
initiated because of dysfunctional representation of the costs
of the behavior). It is argued that this relates to amygdala and
OFC dysfunction [5••]. The amygdala is critical for stimulus
reinforcement learning and feeding reinforcement expectancy
information forward to the OFC to allow good decision
making to occur. It is argued that both these critical processes
are disrupted in individuals such that they have difficulty
socializing (due to dysfunction in stimulus reinforcement
learning) and make poor decisions (relating to the OFC
dysfunction) [5••]. In short, this predicts that individuals with
psychopathic traits will show reduced amygdala and OFC
Testing the Models
Maladaptive Reactive Aggression
Relatively few studies have considered populations that
show a marked increase for reactive, but not instrumental,
aggression. Two recent studies investigated a population of
spouse abusers who, they demonstrated, show an increased
risk for reactive, but not instrumental, aggression [14••, 24].
Work also has been done to investigate patients with
intermittent explosive disorder . Such patients are
characterized by recurrent acts of impulsive, affectively
driven aggression that are disproportionate to any actual
provocation. Paradigms used included viewing of emotional
images , viewing of emotional expressions , and an
emotional Stroop test [14••]. The greatest amount of work
has been done with patients with borderline personality
disorder (BPD), another patient group characterized by
impulsive, affectively driven aggression .
The model briefly outlined above hypothesizes that
patients with a selectively increased risk for reactive
aggression will show increased responsiveness of the basic
amygdala-hypothalamus-PAG threat system and/or reduced
frontal regulatory activity. In line with this hypothesis, all
three patient groups showed increased amygdala respon-
siveness to threatening stimuli relative to comparison
individuals [14••, 15, 16, 25–28]. It should be noted that
Curr Psychiatry Rep (2010) 12:76–8277
one of these studies did not note increased amygdala
responsiveness to emotional images in the spouse abusers
. However, the investigators did observe increased
fusiform and occipital cortex activity. The amygdala is
intimately connected with the fusiform and occipital cortex
and serves to prime emotional representations within these
regions. Thus, it is possible that this increased cortical
activity reflects increased amygdala activity that was
obscured by the difficulty of scanning the amygdala due
to susceptibility artifacts. None of the three studies reported
increased responsiveness of the hypothalamus and PAG.
However, neither region is typically investigated in current
With respect to reduced frontal regulatory activity, there
has been one report of reduced activations in the spouse
abusers proximal to the right anterior cingulate cortex
(ACC) and left middle frontal gyrus during the emotional
Stroop test [14••]. Strikingly, reduced middle frontal cortex
activation across facial expressions has been reported in the
patients with intermittent explosive disorder, as has been a
notably reduced OFC response in these patients selectively
to angry expressions . However, it should be noted that
these indications of hypofrontality were not seen in the
second study on spouse abusers . The other study on
spouse abusers did report reduced activity in the middle
frontal cortex, but the region involved white rather than
gray matter; thus, these data must be considered with
caution [14••]. Data on patients with BPD have been
mixed. Two studies reported reduced cingulate cortex
activity during aggression provocation  and expression
processing . However, this has not been observed in
other studies examining expression processing [25, 28] or
emotionally provocative images . Moreover, there have
been reports of increased activity in patients with BPD
within the lateral OFC during aggression provocation 
and inferior frontal cortex in response to expressions .
In short, no definitive support currently exists for the
hypothesis of reduced regulatory activity, at least not using
affective provocative paradigms in reactively aggressive
individuals. There have been consistent findings examining
the impact of serotonergic challenges (d,l fenfluramine and
meta-chloropiperazine) on patients with BPD reporting
reduced serotonergic uptake within the medial OFC [29,
30]. However, although this does indicate serotonergic
abnormalities in BPD, particularly within the OFC, it
cannot be taken as direct evidence of reduced emotional
regulation by the OFC. Importantly, though, the affective
provocation paradigms used up to now would not neces-
sarily have revealed frontal regulatory activity (which has
proven difficult to replicably demonstrate in paradigms that
do not implicate the lateral frontal cortex in emotional
reappraisal). As such, the hypothesis remains relatively
Maladaptive Instrumental Aggression
A growing body of literature has examined a population at
marked increased risk for instrumental aggression: youth
and adults with psychopathic traits. This work has involved
structural and functional imaging. The model briefly
outlined above hypothesizes that individuals with psycho-
pathic traits should show impairment in the role of the
amygdala in stimulus reinforcement learning and in the role
of the OFC in reinforcement expectancy-based decision
With respect to the structural imaging studies, most
findings have been isolated and not yet replicated. There
have been reports of reduced amygdala volume ,
asymmetric  and reduced hippocampus volume ,
increased colossal white matter volume and length, and
reduction in callosal thickness  in adults with psycho-
pathic traits. There has also been a report of increased
striatum size in adults with psychopathic traits , a
region of interest because of its role in emotional learning
. It should be noted, however, that these structural
imaging studies used manual tracing or semiautomated
region-of-interest-guided measurement of brain structures,
thereby potentially introducing an observer bias [37••].
However, four recent studies used voxel-based morphom-
etry, a fully automated and unbiased technique for
characterizing regional brain volume and tissue concentra-
tion . The results of these studies have been more
consistent [37••, 39–41]. All four studies reported structural
abnormalities within the superior temporal cortex, and three
of the four reported structural abnormalities within the OFC
and insula [39, 40]. However, it should be noted that
whereas the studies with adult samples reported reduced
gray matter volume within these regions, the study with
youth with psychopathic tendencies reported increased gray
matter volume [37••]. De Brito et al. [37••] interestingly
proposed that this inconsistency may reflect a potential
delay in cortical maturation, but clearly more work is
With respect to the functional imaging studies, the
findings have been relatively consistent. The paradigms
investigated have all involved stimulus reinforcement-based
decision making (emotional expressions, particularly of fear,
sadness, and happiness, serve to initiate reinforcement-based
decision making) [5••] or other amygdala-dependent forms
of emotional learning. These paradigms include expression
processing [6, 11, 42–44], blocked presentation of emotional
and neutral images , aversive conditioning , emo-
tional memory , moral reasoning , prisoner’s dilemma
, and reversal learning . In line with the model
outlined previously, in almost all of these studies, the
individuals with psychopathic traits showed reduced amyg-
dala and OFC responses.
78Curr Psychiatry Rep (2010) 12:76–82
There are four exceptions to this generalization. First, in
line with findings that the OFC is only infrequently seen
responding to emotional expressions , studies of
expression processing only identified reduced amygdala,
and not OFC, responding in individuals with psychopathy
[6, 11, 42, 43], although one study  observed reduced
amygdala-OFC functional connectivity during expression
processing. Second, in line with findings that the amygdala
is not necessary for reversal learning , no reduced
amygdala responding was seen in the youth with psycho-
pathic tendencies during reversal learning . Thus, the
first two of these exceptions would be expected on the basis
of our understanding of the functional roles of the
amygdala and OFC. Indeed, these exceptions are theoret-
ically critical. They demonstrate that the amygdala and
OFC dysfunction cannot be attributed to dysfunction in
only one of these systems that is propagated, because of
their intimate connections  to the other system. This is
because atypical activity is seen in both regions on tasks in
which the other region has no or limited involvement.
The third exception is also theoretically important.
Previous fMRI work with reversal learning and other
paradigms demonstrated that prediction errors (punish-
ments, or the absence of reward when reward is expected)
induce reductions in OFC activity . In the study on
reversal learning , healthy youth and youth with
attention-deficit/hyperactivity disorder (ADHD) showed
this reduction in OFC activity following an unexpected
punishment. In contrast, youth with psychopathic traits did
not and in this condition actually showed increased OFC
activity. These data are important in that they indicate that
OFC activity, at least when engaged by reinforcement
expectancy-based information, is neither upregulated by
expectations of reinforcement-based information [7, 46, 47]
nor downregulated by reinforcement prediction errors .
The fourth exception concerns the two specific studies
[44, 45]. The first involved a small number of adults with
psychopathic traits and comparison adults (n=6 in each
group) performing gender judgements on fearful, happy,
and neutral expressions . In contrast to other work
[6, 11, 42, 43], this study reported no reduced amygdala
responses in the individuals with psychopathy. However, it
should be noted that this study did observe reduced
fusiform activity and, as noted previously, amygdala
responses are typically highly correlated with those of
fusiform cortex when processing emotional expressions
. Thus, it is perhaps likely, particularly given the other
literature and the study’s small size, that this result reflects a
type II error. This cannot be the explanation for the data
obtained by the second study . This study involved
passive viewing of emotional images, and although the
sample size was again very small (n=6 in each group), it
reported that adults with psychopathic traits showed
increased amygdala responses relative to the comparison
individuals. There is no easy explanation for the inconsis-
tency of this finding with the rest of the literature. However,
it is possible that there were problems with classification. It
is notable that the results of this study were very similar to
those obtained with the reactively aggressive spouse
abusers and patients with intermittent explosive disorder
[14••, 15, 24].
It should be noted that an alternative theory has
suggested that the insula, anterior and posterior cingulate
cortex, parahippocampal gyrus, and anterior superior
temporal gyrus may also be dysfunctional in psychopathy
. All—or at least part of all—these regions show
structural connectivity with the amygdala , and most
show considerable connectivity with the OFC . How-
ever, the evidence of reduced activity in individuals with
psychopathy is currently mixed. It is best for reduced
superior temporal cortex. This has been reported in several
fMRI studies [9, 10, 42, 43], although it is not always seen
[46, 47]. Notably, this region was also consistently
implicated in the structural MRI studies described previ-
ously. It has also been reported for the posterior cingulate
cortex [7, 9, 10, 42, 46, 47]. The evidence is poorer for the
parahippocampus, for which two studies have reported
reduced activity in individuals with psychopathic traits [9,
42] and five have not [7, 10, 43, 46, 47]. It is also poor for
the ACC, for which again two studies have reported
reduced activity [9, 46] and five have not [7, 10, 42, 43,
47]. Finally, the evidence is particularly poor for the insula,
for which only one study has found reduced activity 
and most have not [7, 9, 10, 42, 43, 47]. Indeed, it is worth
pointing out that both the dorsal ACC and the anterior
insula have been found to show appropriate responses to
punished reversal errors, indicating intact sensitivity to at
least some of their functional triggers in youth with
psychopathic traits .
Of course, the extent to which the paradigms used are
typically associated with neural activity in these addi-
tional regions can be debated. However, should stronger
data emerge, it will be necessary to determine whether
aberrant neural activity indicates functional impairment
in the region identified or a secondary effect of the
functional impairment within the amygdala and OFC
that is propagated via the connections between these
regions and the identified region. Certainly, although
considerable neuropsychological data support amygdala
and OFC dysfunction [5••], no neuropsychological data
support dysfunction within the insula, anterior and
posterior cingulate cortex, parahippocampal gyrus, or
anterior superior temporal gyrus. Indeed, intact perfor-
mance on episodic memory  and Stroop tasks 
suggests that at least memory functions of the hippocam-
pus and response conflict/competition functions of the
Curr Psychiatry Rep (2010) 12:76–8279
dorsal ACC are not dysfunctional in individuals with
Neuroimaging of Conduct Disorder Samples
Undifferentiated by Level of Psychopathic Traits
A body of literature has examined youth with CD using
both structural and fMRI techniques. Of course, there are
complexities involved with interpreting studies of patients
with CD. This is because the diagnosis of CD does not
consider the presence of psychopathic traits. Thus, patient
groups are likely to include individuals who show relatively
selectively increased levels of reactive aggression (and
heightened amygdala responsiveness) as well as those who
show psychopathic traits/reactive and instrumental aggres-
sion (and reduced amygdala and OFC responsiveness).
Indeed, it is notable that about 40% of patients with CD are
comorbid for a mood/anxiety disorder , yet the presence
of the emotional component of psychopathy protects the
individual from depressed mood and anxiety .
Three studies have examined structural abnormalities in
youth with CD [13, 58, 59]. Two reported reduced
amygdala volumes [13, 59], whereas the third reported
reduced temporal cortical volume (the amygdala was
included within the temporal cortex region of interest
examined) . There also have been reports of reduced
OFC  and insular volumes , but these have only
been seen in individual studies and have not yet been
A series of fMRI studies examined patients with CD [12,
60–62••, 63–65]. In two studies by the same group that
examined patients with CD during passive viewing, the
youth with CD showed a reduced differential response
between emotional and neutral images within the dorsal
ACC [60, 61]. Both studies took a region-of-interest
approach to the data, examining group differences only
for the ACC, OFC, amygdala, and hippocampus  or
only for the ACC . Sterzer et al.  found that youth
with CD showed a reduced differential response between
emotional and neutral images within the amygdala that was
moderated by anxiety level; the less anxious youths with
CD showed the least amygdala responses. In line with this,
anxiety level is usually inversely correlated with the
emotion dysfunction component of psychopathy .
Rubia and colleagues [12, 62••, 63] conducted a series of
fMRI studies examining patients with pure CD (not
comorbid for ADHD) and patients with pure ADHD (not
comorbid for CD). These studies focused primarily on
paradigms such as the Simon , continuous performance
[62••], and stop tasks . Interestingly, impairment on
these tasks is often found in patients with ADHD but not in
patients with CD (at least not those without comorbid
ADHD) . As such, these studies form an interesting
complement to two studies examining youth with psycho-
pathic traits and patients with ADHD [10, 42]. These
studies examined reversal learning and the response to
fearful expressions, respectively—capacities impaired in
individuals with psychopathic traits, but not patients with
ADHD. In all three studies by Rubia and colleagues [12,
62••, 63], the patients with ADHD, but not those with CD,
showed reduced activity within the inferior frontal cortex, a
consistent finding in studies of ADHD. There were findings
of reduced activation in the patients with CD in several
regions, but none of these replicated across the three tasks.
However, interestingly, in the one study that examined
responses to rewarded outcomes, patients with CD, but not
ADHD, showed reduced responses to these rewarded trials
[62••]. This is particularly interesting, as it complements
previous findings in which only youth with psychopathic
traits, not youth with pure ADHD, failed to demonstrate the
reduction in the OFC following the prediction error of
unexpected punishment .
Two recent fMRI studies of youth with CD examined
viewing of emotional stimuli  and individuals in pain
. In both studies, amygdala responsiveness was in-
creased in the youth with CD relative to control youth. This
is notably different from most of the literature on
individuals with psychopathic traits. However, such results
may be expected if these youth were predominantly
reactively aggressive [14••, 15, 24].
In summary, the available data strongly support the
suggestion that individuals who are predominantly reac-
tively aggressive (at least spouse abusers and patients with
intermittent explosive disorder) show atypically increased
amygdala responses to emotional stimuli. This would be
consistent with suggestions that the risk for reactive
aggression is increased if the basic responsiveness of the
threat system is increased; the individual is more likely to
show reactive aggression rather than flight/freezing in
response to a threatening/frustrating stimulus. Currently,
however, the suggestion that reactively aggressive individ-
uals show reduced frontal regulatory activity remains
without strong support.
The data also strongly support the suggestion that
amygdala and OFC functioning is disrupted in individuals
with psychopathic tendencies. Other systems may also be
affected, but this has not been clearly demonstrated.
Critically, these studies provide us with biomarkers of the
disorder. The dysfunctions observed are specific to psycho-
pathic traits and are not seen in other patient populations.
As such, they allow us indices of treatment response that
80Curr Psychiatry Rep (2010) 12:76–82
are not confounded by a patient’s truthfulness or a
clinician’s skill. It is to be hoped that this work will
provide us the information to manage and ideally cure
patients with this disorder.
No potential conflict of interest relevant to this article
Papers of particular interest, published recently, have been
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