TY - JOUR T1 - Testosterone modulates altered prefrontal control of emotional actions in psychopathic offenders JF - eneuro JO - eneuro DO - 10.1523/ENEURO.0107-15.2016 SP - ENEURO.0107-15.2016 AU - Inge Volman AU - Anna Katinka Louise von Borries AU - Berend Hendrik Bulten AU - Robbert Jan Verkes AU - Ivan Toni AU - Karin Roelofs Y1 - 2016/01/15 UR - http://www.eneuro.org/content/early/2016/01/15/ENEURO.0107-15.2016.abstract N2 - Psychopathic individuals are notorious for their controlled goal-directed aggressive behavior. Yet, during social challenges, they often show uncontrolled emotional behavior. Healthy individuals can control their social emotional behavior through anterior prefrontal cortex (aPFC) down-regulation of neural activity in the amygdala, with testosterone modulating aPFC-amygdala coupling. This study tests whether individual differences in this neuro-endocrine system relate to the paradoxical lack of emotional control observed in human psychopathic offenders. Emotional control was operationalized with an fMRI-adapted approach-avoidance (AA) task requiring rule-driven control over rapid emotional responses. Fifteen psychopathic offenders and 19 matched healthy controls made approaching and avoiding movements in response to emotional faces. Control of social emotional behavior was required during affect-incongruent trials, when participants had to override affect-congruent, automatic action tendencies and select the opposite response. Psychopathic offenders showed less control-related aPFC activity and aPFC-amygdala coupling during trials requiring control of emotional actions, when compared to healthy controls. This pattern was particularly pronounced in psychopathic individuals with high endogenous testosterone levels. These findings suggest that reduced prefrontal coordination underlies reduced behavioral control in psychopathic offenders during emotionally provoking situations. Even though the modest sample size warrants replication, the modulatory role of endogenous testosterone on the aPFC-amygdala circuit suggests a neurobiological substrate of individual differences, relevant for advancement of treatment and reduction of recidivism.Significance Statement: Psychopathic criminals are commonly seen as instrumentally abusive and emotionally callous, yet social challenges often trigger uncontrolled emotional behavior in those individuals. This study shows how this paradoxical aspect of psychopathy relates to altered neuro-endocrine interactions between testosterone and the cerebral circuit coordinating emotional action tendencies. The anterior prefrontal cortex, a region necessary for controlling emotional behavior, showed blunted responses and reduced connectivity with the amygdala in psychopathic criminals engaged in controlling their emotional action tendencies. This cerebral pattern was strongest in psychopathic individuals with high endogenous testosterone. This neuroendocrine signature of altered emotional control highlights the relevance of considering testosterone level of individual psychopathic patients during treatment of their impulsive behavior. ER -