Testosterone Modulates Altered Prefrontal Control of Emotional Actions in Psychopathic Offenders(1,2,3)

Abstract

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) downregulation of neural activity in the amygdala, with testosterone modulating aPFC-amygdala coupling. This study tests whether individual differences in this neuroendocrine system relate to the paradoxical lack of emotional control observed in human psychopathic offenders. Emotional control was operationalized with an fMRI-adapted approach-avoidance task requiring rule-driven control over rapid emotional responses. Fifteen psychopathic offenders and 19 matched healthy control subjects 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 with healthy control subjects. 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 that is relevant for the advancement of treatment and the reduction of recidivism.

Keywords: amygdala; connectivity; emotion; fMRI; prefrontal; psychopathy.

Figure 1.

The emotional control AA task. The AA task involved the presentation of happy and angry faces, and the performance of approach and avoidance responses. During the AA task, the participants had to select their response according to the perceived emotion of the face. At the beginning of each block of 12 trials, the participants received instructions on whether to pull the joystick toward themselves (approach) or push it away (avoid) when seeing a face with a particular emotion. When viewing happy or angry faces, automatic stimulus–response tendencies trigger corresponding approach or avoidance actions. These tendencies could be followed during the affect-congruent condition (approach–happy, avoid–angry). In contrast, when task instructions required participants to avoid happy faces or to approach angry faces, automatic tendencies needed to be controlled and overridden with the instructed response (affect-incongruent condition). Participants saw the faces and moved the joystick while lying in a MR scanner (top left corner of the table). Figure adapted from Volman et al. (2011a, 2013).

Figure 2.

Behavioral results. Mean RTs (±SEM) for the affect-congruent and affect-incongruent conditions of the AA task for the healthy control subjects and psychopathic offenders. The groups were significantly slower to provide affect-incongruent responses (approach–angry; avoid–happy) than affect-congruent responses (approach–happy; avoid–angry), with no significant group differences.

Figure 3.

Testosterone modulations of the cerebral congruency effect in psychopathic offenders and healthy control subjects. A, D, Brain image showing testosterone-modulated congruency effects (affect-incongruent−affect-congruent) in the psychopathic offenders in the bilateral aPFC (A) and right supramarginal gyrus (D). B, E, Bar graphs showing the mean activation (±SEM) of the active voxels within the yellow circles per group. *p_FWE < 0.05. ns, Not significant. C, F, Scatterplots showing the correlation of the mean activation of active voxels within the yellow circles with testosterone (log-transformed and standardized) for the healthy control group and the psychopathy group. The ROI activations are presented at p < 0.05, uncorrected for visualization purposes. There are no outliers [Mahalanobis distances D ²_i < 4.2 (cutoff at p < 0.05; D = 7.74); Barnett and Lewis, 1978; Stevens, 1996]. Healthy control subjects show an increased aPFC activity for the congruency effect and no modulation by testosterone, while in psychopathic offenders endogenous testosterone levels modulate the activity of the aPFC and right supramarginal gyrus.

Figure 4.

Group difference on congruency-related aPFC–amygdala connectivity. A, Brain images illustrating the congruency-related modulation of connectivity between the right aPFC (yellow circle, axial slice) and the right amygdala (coronal slice) for the congruency contrast. The activations are presented at p < 0.05, uncorrected for visualization purposes. B, Bar graph visualizing the strength of the congruency-specific change (±SEM) in aPFC–amygdala connectivity for the healthy control subjects and psychopathic offenders. There is a significant negative aPFC–amygdala coupling in the healthy control subjects, which is not present in the psychopathic offenders.