Social communication through touch and mutual grooming can convey highly salient socio-emotional signals and has been shown to involve the neuropeptide oxytocin (OXT) in several species. Less is known about the modulatory influence of OXT on the neural and emotional responses to human interpersonal touch. The present randomized placebo (PLC)-controlled within-subject pharmacofunctional magnetic resonance imaging (fMRI) study was designed to test the hypothesis that a single intranasal dose of synthetic OXT (24 IU) would facilitate both neural and emotional responses to interpersonal touch in a context-(female vs male touch) and trait-(autistic trait load) specific manner. Specifically, the experimental rationale was to manipulate the reward value of interpersonal touch independent of the intensity and type of actual cutaneous stimulation administered. Thus, 40 heterosexual males believed that they were touched by either a man or a woman, although in fact an identical pattern of touch was always given by the same female experimenter blind to condition type. Our results show that OXT increased the perceived pleasantness of female, but not male touch, and associated neural responses in insula, precuneus, orbitofrontal, and pregenual anterior cingulate cortex. Moreover, the behavioral and neural effects of OXT were negatively correlated with autistic-like traits. Taken together, this is the first study to show that the perceived hedonic value of human heterosexual interpersonal touch is facilitated by OXT in men, but that its behavioral and neural effects in this context are blunted in individuals with autistic traits.

Current perspectives on the evolutionary roots of human morality suggest it arose to incentivize social cooperation by promoting feelings of disgust toward selfish behavior, although the underlying neural mechanisms remain unclear. To investigate whether the ancient mammalian neuropeptide oxytocin (OXT) influences self-referential processing in the domains of emotion evaluation and moral decision making, we conducted a pharmaco-functional magnetic resonance imaging (fMRI) and a behavioral experiment involving 157 healthy women and men who were treated with either OXT (24 IU) or placebo (PLC) intranasally. Our results show that OXT facilitated cortical midline responses during self-processing of disgust and selectively promoted self-interest moral judgments in men. In contrast, in women OXT increased the reaction time difference between accepted and rejected moral dilemmas and led them to suppress their self-interest and respond more altruistically for the benefit of others. Taken together, these findings suggest an OXT-related sexual dimorphism in human moral behavior which evolved adaptively to optimize both protection and nurturing of offspring by promoting selfish behavior in men and altruistic behavior in women.

An emerging theme in the neuroscience of emotion is the question of how acute stress shapes, and distorts, social-emotional behavior. The prevailing neurocircuitry models of social-emotional behavior emphasize the central role of the amygdala. Acute stress leads to increased central levels of norepinephrine (NE) and cortisol (CORT), and evidence suggests that these endogenous neuromodulators synergistically influence amygdala responses to social-emotional stimuli. We therefore hypothesized that amygdala responses to emotional facial expressions would be susceptible to pharmacologically induced increases in central NE and CORT levels. To specifically test this hypothesis, we measured amygdala activation to emotional faces using functional magnetic resonance imaging in 62 healthy subjects under four pharmacological conditions: (1) single oral dose of placebo, (2) 4 mg of the selective NE-reuptake inhibitor reboxetine (RBX), (3) 30 mg of hydrocortisone, or (4) both drugs in combination. We found that a decrease in amygdala activation to positive facial emotion was coupled with an increase in amygdala activation to negative facial emotion in the RBX-CORT combined challenge condition. In conclusion, a pharmacologically induced elevation of central NE and CORT levels in healthy subjects created a negative response bias in the amygdala that did not exist at baseline. Our results implicate a causative role of NE-CORT interactions in the emergence of a negative bias of cognitive and emotional functions which is germane in stress-related affective spectrum disorders.