Neural Correlates of Interpersonal Space Permeability and Flexibility in Autism Spectrum Disorder.

Previous research indicates that the size of interpersonal space at which the other is perceived as intrusive (permeability) and the ability to adapt interpersonal distance based on contextual factors (flexibility) are altered in Autism Spectrum Disorder (ASD). However, the neurophysiological basis of these alterations remains poorly understood. To fill this gap, we used fMRI and assessed interpersonal space preferences of individuals with ASD before and after engaging in cooperative and non-cooperative social interactions. Compared to matched controls, ASDs showed lower comfort in response to an approaching confederate, indicating preference for larger interpersonal space in autism (altered permeability). This preference was accompanied by reduced activity in bilateral dorsal intraparietal sulcus (dIPS) and left fusiform face area (FFA), regions previously shown to be involved in interpersonal space regulation. Furthermore, we observed differences in effective connectivity among dIPS, FFA, and amygdala in ASDs compared to controls, depending on the level of experienced comfort. No differences between groups were observed in interpersonal space regulation after an experienced social interaction (flexibility). Taken together, the present findings suggest that a dysregulation of the activity and connectivity of brain areas involved in interpersonal space processing may contribute to avoidance of physical proximity and social impairments in ASD.

Fairness norm violations in anti-social psychopathic offenders in a repeated trust game.

Psychopathic offenders have a high propensity to violate social norms, as indicated for instance by their widespread lying and cheating behaviour. The reasons for their norm violations are not well understood, though, as they are able to recognise norms in a given situation and also punish norm violators. In this study, we investigated whether psychopathic offenders would violate fairness norms during a repeated trust game because of increased profit-maximising concerns. We measured back-transfer decisions in the repeated trust game, and affective arousal by means of skin conductance responses (SCR) in violent offenders with varying degrees of psychopathy, and non-offenders with low-trait psychopathy. Psychopathy in offenders was measured with the Psychopathy Checklist-Revised (PCL-R). In the task, a participant and an interaction partner entrusted each other money for multiple rounds with the goal to earn as much money as possible. Fairness norm violations were positively associated with Factor 2 scores (the lifestyle/anti-social psychopathy subscale) of the PCL-R, but this was not accompanied by clear profit-maximising behaviour. In addition, anticipatory arousal to self-advantageous decisions was higher in all offenders, independent of their degree of psychopathy, compared with non-offenders. The results of our study widen our understanding of social decision-making in psychopathy. They also suggest treatment possibilities in offenders scoring high on Factor 2, targeting empathic concern and related prosocial intentions to overcome norm-violating behaviour.

The Human Basolateral Amygdala Is Indispensable for Social Experiential Learning.

Trust and betrayal are central to our social world, and adaptive responses to generous and selfish behavior are crucial to our economic and social well-being [1]. We learn about others' trustworthiness through trial and error during repeated interactions [2]. By reinforcing and suppressing behavior during positive and negative interactions with conspecifics, rodent research has established a crucial role for the basolateral amygdala (BLA) in social experiential learning [3, 4]. The human BLA has undergone a reorganization with massive expansion relative to other amygdala nuclei [5], and there is no translational research on its role in experiential learning. The human amygdala is traditionally researched as a single structure [6], neglecting the sub-nuclei's structural und functional differences [7], which might explain inconsistent findings in research on social interactions [8, 9]. Here, we study whether the human BLA is necessary for social and non-social experiential learning by testing a group of five humans with selective bilateral damage to the BLA. We compared their learning behavior in a repeated trust game, and a non-social control task, to healthy, matched controls. Crucially, BLA-damaged subjects, unlike control subjects, completely failed to adapt their investments when interacting with a trustworthy and an untrustworthy partner. In the non-social task, BLA-damaged subjects learned from positive outcomes but differed from the controls by not learning from negative outcomes. Our data extend findings in rodent research by showing that the human BLA is essential for social experiential learning and provide confirmatory evidence of divergent mechanisms for differentially valenced outcomes in non-social learning.

Testosterone abolishes implicit subordination in social anxiety.

Neuro-evolutionary theories describe social anxiety as habitual subordinate tendencies acquired through a recursive cycle of social defeat and submissive reactions. If so, the steroid hormone testosterone might be of therapeutic value, as testosterone is a main force behind implicit dominance drive in many species including humans. We combined these two theories to investigate whether the tendency to submit to the dominance of others is an implicit mechanism in social anxiety (Study-1), and whether this can be relieved through testosterone administration (Study-2). Using interactive eye-tracking we demonstrate that socially anxious humans more rapidly avert gaze from subliminal angry eye contact (Study-1). We replicate this effect of implicit subordination in social anxiety in an independent sample, which is subsequently completely abolished after a single placebo-controlled sublingual testosterone administration (Study-2). These findings provide crucial evidence for hormonal and behavioral treatment strategies that specifically target mechanisms of dominance and subordination in social anxiety.

Cortisol administration induces global down-regulation of the brain's reward circuitry.

Research in rodents and humans has shown divergent effects of the glucocorticoids corticosterone and cortisol (CRT) on reward processing. In rodents, administration of CRT increases reward drive by facilitating dopamine release in the ventral striatum. In humans, correspondingly, risky decision-making increases when CRT levels are elevated. Human stress studies contrariwise show that elevated CRT is accompanied by a decrease in reward-related brain activity. There are however no direct insights into how CRT acts on the reward system in the human brain. Accordingly, we used pharmacological functional magnetic resonance imaging (pharmaco-fMRI) to investigate the effects of CRT on the brain's reward system. In a randomized within-subject design we administered a high dose of CRT (40 mg) and placebo to twenty healthy male volunteers on separate days, and used a monetary incentive delay task to assess the effects of the hormone on the striatum and the amygdala in anticipation of potential reward. In contrast to animal studies, we show that this high dose of CRT strongly decreases activity of the striatum in both reward and non-reward conditions. Furthermore, we observed reductions in activity in the basolateral amygdala, a key regulator of the brain's reward system. Crucially, the overall down-regulation of the brain's reward circuit was verified on the subjective level as subjects reported significantly reduced reward preference after CRT. In sum, we provide here direct evidence in humans that CRT acts on brain regions involved in reward-related behavior, that is, the basolateral amygdala and the striatum. Our findings suggest that CRT in the quantity and time course presently used globally down-regulates the reward system, and thereby decreases motivational processing in general.

Acute effects of Sceletium tortuosum (Zembrin), a dual 5-HT reuptake and PDE4 inhibitor, in the human amygdala and its connection to the hypothalamus.

The South African endemic plant Sceletium tortuosum has a long history of traditional use as a masticatory and medicine by San and Khoikhoi people and subsequently by European colonial farmers as a psychotropic in tincture form. Over the past decade, the plant has attracted increasing attention for its possible applications in promoting a sense of wellbeing and relieving stress in healthy individuals and for treating clinical anxiety and depression. The pharmacological actions of a standardized extract of the plant (Zembrin) have been reported to be dual PDE4 inhibition and 5-HT reuptake inhibition, a combination that has been argued to offer potential therapeutic advantages. Here we tested the acute effects of Zembrin administration in a pharmaco-fMRI study focused on anxiety-related activity in the amygdala and its connected neurocircuitry. In a double-blind, placebo-controlled, cross-over design, 16 healthy participants were scanned during performance in a perceptual-load and an emotion-matching task. Amygdala reactivity to fearful faces under low perceptual load conditions was attenuated after a single 25 mg dose of Zembrin. Follow-up connectivity analysis on the emotion-matching task showed that amygdala-hypothalamus coupling was also reduced. These results demonstrate, for the first time, the attenuating effects of S. tortuosum on the threat circuitry of the human brain and provide supporting evidence that the dual 5-HT reuptake inhibition and PDE4 inhibition of this extract might have anxiolytic potential by attenuating subcortical threat responsivity.