Psychopathy is a personality disorder that shares behavioral overlap with the clinical diagnosis of antisocial personality disorder. However, the two terms are not synonymous. To meet criteria for psychopathy, an individual must exhibit evidence of emotional dysfunction, in particular reduced guilt and empathy, features unnecessary for a diagnosis of antisocial personality disorder. As such, only around 20%–50% of patients with antisocial personality disorder also meet criteria for psychopathy (1). Moreover, psychopathy should not be considered a more severe form of antisocial personality disorder. Patients with antisocial personality disorder often present with comorbid mood and anxiety disorders. However, psychopathy “protects” the individual from the development of such disorders (2). Instead, antisocial personality disorder should be viewed as covering a more heterogeneous population, in which some individuals exhibit pathophysiology that puts them at risk of a mood or anxiety condition, while others exhibit the emotional deficits seen in psychopathy (3).

Probably because of the reduced heterogeneity among individuals meeting criteria for psychopathy, considerable progress is being made in our understanding of the neurobiology of this disorder, with some remarkable convergence in core results. As the first study to examine cortical thickness throughout the cortex in this population using a relatively large sample, the article by Ly et al. (4) in this issue provides clarity with respect to previous results as well as a provocative new lead. The finding of reduced thickness in the temporal cortex (the temporal pole and superior temporal cortex) clearly adds to findings from previous studies indicating some degree of dysfunction in the structural integrity of this region. The findings of a thinner cortex in the left insula and dorsal anterior cingulate cortex and reduced functional connectivity between these two regions reinforce suggestions that greater attention should be given to these areas in models of psychopathy.

There are two important methodological strengths of the Ly et al. article. First, the sample size is notably larger than that of many clinical studies, allowing for greater confidence in the results. Second, the authors examined cortical thickness rather than gray matter volume. Gray matter volume is a function of both cortical thickness and cortical surface area, which is problematic because these indices are genetically uncorrelated (i.e., either index alone provides a more precise indication of potential pathophysiology than their combination) (5).

Given the methodological progressions in the previous literature, it is exciting that this study adds to the striking consistency in the reports of structural deficiencies in the temporal cortex in individuals with psychopathy. Notably, these observed structural deficiencies are mirrored in consistent reports of reduced activity within this region in functional imaging studies. Despite the robustness of these findings, it remains an open question as to how we should interpret them. They may reflect a developmental consequence of functional deficits in the amygdala, a region in which dysfunction is consistently implicated in psychopathy (6), as Ly et al. also imply. Alternatively, the results may relate to the well-documented impairment in stimulus-reinforcement learning (6) (i.e., the capacity to learn some stimuli is associated with positive outcomes and others with negative outcomes). Stimulus-reinforcement learning involves the integrated functioning of the amygdala and temporal cortex; as such, the function and structure of both these highly interconnected regions may be inevitably compromised in individuals with psychopathy. Finally, it is also possible that there may be specific computational processes, as yet unidentified, that are reliant on the temporal cortex and that are compromised in individuals with this disorder. With respect to the latter point, it should be noted that patients with autism also exhibit reduced cortical thinning within these regions of the temporal cortex (5). Autism is another disorder of social cognition, albeit one marked by computational impairments that are notably different from those in psychopathy. For example, stimulus-reinforcement learning appears to be relatively intact in autism but is severely compromised in psychopathy, while theory of mind (the capacity to include the mental states of others—their beliefs, intentions, and knowledge—in one's own internal representation of their identity) is impaired in autism but intact in psychopathy (6). It is possible that there are unidentified social cognitive functions reliant on the superior temporal cortex and temporal pole that are impaired in both disorders.

Of course difficulties in interpretation are a constant problem with studies focusing on the structural integrity of brain regions in psychiatric populations. Indeed, this issue is notable when considering the study's most provocative findings: the thinner cortex in the left insula and dorsal anterior cingulate cortex and reduced functional connectivity between these two regions in individuals with psychopathy. While both regions have been implicated in an important neurobiological theory of the disorder (7), there has been no clear specification regarding what functional role, mediated by these regions, might be disrupted. Ly et al. make reference to theories suggesting that these regions play a role in the flexible control of goal-directed behavior via signaling for top-down control (8). They note that studies have demonstrated abnormalities in the flexibility of goal-directed attention in psychopathy (9). Importantly, however, impaired performance was not among these abnormalities. Indeed, abnormalities reported during performance on the Stroop task, a task reliant on the flexible control of goal-directed behavior, have been identified as superiorities in performance (9). It is unclear why regions showing cortical thinning and reduced connectivity would allow for superior performance.

But this is not to deny the importance of the findings of Ly et al. Their data strongly reinforce the idea that the anterior insula and dorsal anterior cingulate cortex are importantly involved in psychopathy. Both regions have been implicated in previous studies and included as components in a major neurological account of the disorder (7), even though they have been regrettably ignored in more computational accounts (3). Perhaps most exciting, the existing data suggest functional specificity of impairment. As noted, these regions are implicated in the flexible control of goal-directed behavior, yet neuropsychological data suggest that this capacity is intact or even superior in individuals with psychopathy. Moreover, functional MRI (fMRI) studies involving behavioral control have revealed intact recruitment of these regions in response to error information or during sustained attention in adolescent samples (10, 11). However, these regions have also been critically implicated in decision making. Specifically, it has been argued that these regions are particularly important for the representation of negative expected values (i.e., representation of the aversive consequences of particular choices) (12). Indeed, studies have shown that this anterior insula activation in response to anticipated negative outcomes serves to guide healthy participants away from the choices eliciting these outcomes (12). Given other data, at least in studies of antisocial youths, on the notable difficulties in the representation of expected values in other regions, particularly the ventromedial frontal cortex (3), it is plausible that this functional role of the insula and dorsal anterior cingulate cortex may be disrupted in psychopathy. This possibility should be investigated in future research.

The present data have two clear clinical implications. First, they strongly reinforce the suggestion that psychopathy is a neurobiological condition. While DSM criteria were not used to provide psychiatric diagnoses in this study, it is known that individuals with psychopathy meet criteria for antisocial personality disorder, even though not all individuals with antisocial personality disorder meet criteria for psychopathy (1). While we cannot draw conclusions from these data regarding the specificity of the findings in patients with antisocial personality disorder, we can stress the fact that at least some patients meeting criteria for this diagnosis have a clear neurobiological condition. It will be important in future work to determine whether these data apply to all or most patients with antisocial personality disorder or whether, as is likely given the heterogeneity within the disorder, they are specific to those individuals with antisocial personality disorder who also meet criteria for psychopathy. Second, and provocatively, these data hold the promise of far greater diagnostic precision. Patient interview requires considerable corroboration of historical evidence and is extremely time consuming and always difficult with a population that is prone to lying. Functional imaging data are critical for understanding computational impairment but may be less useful with respect to diagnosis, not least because a typical fMRI paradigm takes considerably longer than a structural scan. In the near future, it may be possible to provide a relatively disorder-specific classification continuum for psychopathy that is based on the extent of neurobiological impairment.