Mapping social reward and punishment processing in the human brain: A voxel-based meta-analysis of neuroimaging findings using the social incentive delay task.

Social rewards or punishments motivate human learning and behaviour, and alterations in the brain circuits involved in the processing of these stimuli have been linked with several neuropsychiatric disorders. However, questions still remain about the exact neural substrates implicated in social reward and punishment processing. Here, we conducted four Anisotropic Effect Size Signed Differential Mapping voxel-based meta-analyses of fMRI studies investigating the neural correlates of the anticipation and receipt of social rewards and punishments using the Social Incentive Delay task. We found that the anticipation of both social rewards and social punishment avoidance recruits a wide network of areas including the basal ganglia, the midbrain, the dorsal anterior cingulate cortex, the supplementary motor area, the anterior insula, the occipital gyrus and other frontal, temporal, parietal and cerebellar regions not captured in previous coordinate-based meta-analysis. We identified decreases in the BOLD signal during the anticipation of both social reward and punishment avoidance in regions of the default-mode network that were missed in individual studies likely due to a lack of power. Receipt of social rewards engaged a robust network of brain regions including the ventromedial frontal and orbitofrontal cortices, the anterior cingulate cortex, the amygdala, the hippocampus, the occipital cortex and the brainstem, but not the basal ganglia. Receipt of social punishments increased the BOLD signal in the orbitofrontal cortex, superior and inferior frontal gyri, lateral occipital cortex and the insula. In contrast to the receipt of social rewards, we also observed a decrease in the BOLD signal in the basal ganglia in response to the receipt of social punishments. Our results provide a better understanding of the brain circuitry involved in the processing of social rewards and punishment. Furthermore, they can inform hypotheses regarding brain areas where disruption in activity may be associated with dysfunctional social incentive processing during disease.

Effects of route of administration on oxytocin-induced changes in regional cerebral blood flow in humans.

Could nose-to-brain pathways mediate the effects of peptides such as oxytocin (OT) on brain physiology when delivered intranasally? We address this question by contrasting two methods of intranasal administration (a standard nasal spray, and a nebulizer expected to improve OT deposition in nasal areas putatively involved in direct nose-to-brain transport) to intravenous administration in terms of effects on regional cerebral blood flow during two hours post-dosing. We demonstrate that OT-induced decreases in amygdala perfusion, a key hub of the OT central circuitry, are explained entirely by OT increases in systemic circulation following both intranasal and intravenous OT administration. Yet we also provide robust evidence confirming the validity of the intranasal route to target specific brain regions. Our work has important translational implications and demonstrates the need to carefully consider the method of administration in our efforts to engage specific central oxytocinergic targets for the treatment of neuropsychiatric disorders.

Effects of Intranasal Oxytocin on the Interpretation and Expression of Emotions in Anorexia Nervosa.

Altered social-emotional functioning is considered to play an important role in the development and maintenance of anorexia nervosa (AN). Recently, there has been increasing interest in investigating the role of intranasal oxytocin in social-emotional processing. The present study aimed to investigate the effects of intranasal oxytocin on the interpretation and expression of emotions among people with AN. Thirty women with AN and 29 age-matched healthy women took part in the present study, which used a double-blind, placebo-controlled, cross-over design. The participants received a single dose of 40 IU of intranasal oxytocin in one session and a placebo spray in the other. Fifteen minutes after administration, the participants completed the Reading the Mind in the Eyes Test to assess the interpretation of complex emotions and mental states followed by a video task, which assessed expressions of facial affect when they were viewing humorous and sad film clips. The intranasal oxytocin did not significantly influence the expression or interpretation of emotions in the AN or healthy comparison groups. The AN group expressed significantly less positive emotion, spent more time looking away and reported experiencing a significantly more negative affect in response to the film clips. The finding that intranasal oxytocin had little to no effect on the interpretation or expression of emotions in either group supports the notion that the effects of oxytocin on social-emotional processing are not straightforward and may depend on individual and environmental differences, as well as the emotion being processed. Replication of these findings is necessary to explore the effect of timing on the effects of oxytocin before firm conclusions can be drawn. Nonetheless, these findings add to the steady accumulation of evidence that people with AN have reduced emotional expression and avoidance of emotionally provoking stimuli.

The Analgesic Effect of Oxytocin in Humans: A Double-Blind, Placebo-Controlled Cross-Over Study Using Laser-Evoked Potentials.

Oxytocin is a neuropeptide regulating social-affiliative and reproductive behaviour in mammals. Despite robust preclinical evidence for the antinociceptive effects and mechanisms of action of exogenous oxytocin, human studies have produced mixed results regarding the analgesic role of oxytocin and are yet to show a specific modulation of neural processes involved in pain perception. In the present study, we investigated the analgesic effects of 40 IU of intranasal oxytocin in 13 healthy male volunteers using a double-blind, placebo-controlled, cross-over design and brief radiant heat pulses generated by an infrared laser that selectively activate Aδ- and C-fibre nerve endings in the epidermis, at the same time as recording the ensuing laser-evoked potentials (LEPs). We predicted that oxytocin would reduce subjective pain ratings and attenuate the amplitude of the N1, N2 and P2 components. We observed that oxytocin attenuated perceived pain intensity and the local peak amplitude of the N1 and N2 (but not of P2) LEPs, and increased the latency of the N2 component. Importantly, for the first time, the present study reports an association between the analgesic effect of oxytocin (reduction in subjective pain ratings) and the oxytocin-induced modulation of cortical activity after noxious stimulation (attenuation of the N2 LEP). These effects indicate that oxytocin modulates neural processes contributing to pain perception. The present study reports preliminary evidence that is consistent with electrophysiological studies in rodents showing that oxytocin specifically modulates Aδ/C-fibre nociceptive afferent signalling at the spinal level and provides further specificity to evidence obtained in humans indicating that oxytocin may be modulating pain experience by modulating activity in the cortical areas involved in pain processing.