Linking psychopathy to a specific brain abnormality could have significant clinical, legal, and scientific implications. Theories on the neurobiological basis of the disorder typically propose dysfunction in a circuit involving ventromedial prefrontal cortex (vmPFC). However, to date there is limited brain imaging data to directly test whether psychopathy may indeed be associated with any structural or functional abnormality within this brain area. In this study, we employ two complementary imaging techniques to assess the structural and functional connectivity of vmPFC in psychopathic and non-psychopathic criminals. Using diffusion tensor imaging, we show that psychopathy is associated with reduced structural integrity in the right uncinate fasciculus, the primary white matter connection between vmPFC and anterior temporal lobe. Using functional magnetic resonance imaging, we show that psychopathy is associated with reduced functional connectivity between vmPFC and amygdala as well as between vmPFC and medial parietal cortex. Together, these data converge to implicate diminished vmPFC connectivity as a characteristic neurobiological feature of psychopathy.

Background Dysfunction in ventromedial prefrontal cortex (vmPFC) is believed to play a pivotal role in the pathogenesis of mood and anxiety disorders. Leading neurocircuitry models of these disorders propose that hypoactivity in vmPFC engenders disinhibited amygdala activity, and consequently, pathologically elevated levels of negative affect. This model predicts that a selective loss or diminution of vmPFC function would result in heightened amygdala activity. While this prediction has been borne out in rodent lesion and electrophysiological studies using fear conditioning and extinction paradigms, there has not yet been a definitive test of this prediction in humans. Methods In this study, we tested this prediction through a novel use of fMRI in n=4 neurosurgical patients with focal, bilateral vmPFC damage. Results Relative to neurologically healthy comparison subjects, the vmPFC lesion patients exhibited potentiated amygdala responses to aversive images as well as elevated rest-state amygdala functional connectivity. We observed no comparable group differences for activity in other brain regions. Conclusions These results provide unique evidence for the critical role of vmPFC in regulating amygdala activity in humans, and help elucidate the causal neural interactions that underlie mental illness.

Objective Psychopathy is a personality disorder associated with severely antisocial behavior and a host of cognitive and affective deficits. The neuropathological basis of the disorder has not been clearly established. Cortical thickness is a sensitive measure of brain structure that has been used to identify neurobiological abnormalities in a number of psychiatric disorders. The purpose of this study is to evaluate cortical thickness and corresponding functional connectivity in criminal psychopaths. Method Using T1 MRI data, we computed cortical thickness maps in a sample of adult male prison inmates selected based on psychopathy diagnosis (n=21 psychopathic inmates, n=31 non-psychopathic inmates). Using rest-fMRI data from a subset of these inmates (n=20 psychopathic inmates, n=20 non-psychopathic inmates), we then computed functional connectivity within networks exhibiting significant thinning among psychopaths. Results Relative to non-psychopaths, psychopaths exhibited significantly thinner cortex in a number of regions, including left insula and dorsal anterior cingulate cortex, bilateral precentral gyrus, bilateral anterior temporal cortex, and right inferior frontal gyrus. These neurostructural differences were not due to differences in age, IQ, or substance abuse. Psychopaths also exhibited a corresponding reduction in functional connectivity between left insula and left dorsal anterior cingulate cortex. Conclusions Psychopathy is associated with a distinct pattern of cortical thinning and reduced functional connectivity.

Psychopathy is a personality disorder characterized by callous antisocial behavior and criminal recidivism. Here we examine whether psychopathy is associated with alterations in functional connectivity in three large-scale cortical networks. Using fMRI in 142 adult male prison inmates, we computed resting-state functional connectivity using seeds from the default mode network, frontoparietal network, and cingulo-opercular network. To determine the specificity of our findings to these cortical networks, we also calculated functional connectivity using seeds from two comparison primary sensory networks: visual and auditory networks. Regression analyses related network connectivity to overall psychopathy scores and to subscores for the "factors" and "facets" of psychopathy: Factor 1, interpersonal/affective traits; Factor 2, lifestyle/antisocial traits; Facet 1, interpersonal; Facet 2, affective; Facet 3, lifestyle; Facet 4, antisocial. Overall psychopathy severity was associated with reduced functional connectivity between lateral parietal cortex and dorsal anterior cingulate cortex. The two factor scores exhibited contrasting relationships with functional connectivity: Factor 1 scores were associated with reduced functional connectivity in the three cortical networks, whereas Factor 2 scores were associated with heightened connectivity in the same networks. This dissociation was evident particularly in the functional connectivity between anterior insula and dorsal anterior cingulate cortex. The facet scores also demonstrated distinct patterns of connectivity. We found no associations between psychopathy scores and functional connectivity within visual or auditory networks. These findings provide novel evidence on the neural correlates of psychopathy and suggest that connectivity between cortical association hubs, such as the dorsal anterior cingulate cortex, may be a neurobiological marker of the disorder.

The ventromedial prefrontal cortex is known to play a crucial role in regulating human social and emotional behaviour, yet the precise mechanisms by which it subserves this broad function remain unclear. Whereas previous neuropsychological studies have largely focused on the role of the ventromedial prefrontal cortex in higher-order deliberative processes related to valuation and decision-making, here we test whether ventromedial prefrontal cortex may also be critical for more basic aspects of orienting attention to socially and emotionally meaningful stimuli. Using eye tracking during a test of facial emotion recognition in a sample of lesion patients, we show that bilateral ventromedial prefrontal cortex damage impairs visual attention to the eye regions of faces, particularly for fearful faces. This finding demonstrates a heretofore unrecognized function of the ventromedial prefrontal cortex-the basic attentional process of controlling eye movements to faces expressing emotion.