Oxytocin modulates neural circuitry for social cognition and fear in humans

Abstract

In non-human mammals, the neuropeptide oxytocin is a key mediator of complex emotional and social behaviors, including attachment, social recognition, and aggression. Oxytocin reduces anxiety and impacts on fear conditioning and extinction. Recently, oxytocin administration in humans was shown to increase trust, suggesting involvement of the amygdala, a central component of the neurocircuitry of fear and social cognition that has been linked to trust and highly expresses oxytocin receptors in many mammals. However, no human data on the effects of this peptide on brain function were available. Here, we show that human amygdala function is strongly modulated by oxytocin. We used functional magnetic resonance imaging to image amygdala activation by fear-inducing visual stimuli in 15 healthy males after double-blind crossover intranasal application of placebo or oxytocin. Compared with placebo, oxytocin potently reduced activation of the amygdala and reduced coupling of the amygdala to brainstem regions implicated in autonomic and behavioral manifestations of fear. Our results indicate a neural mechanism for the effects of oxytocin in social cognition in the human brain and provide a methodology and rationale for exploring therapeutic strategies in disorders in which abnormal amygdala function has been implicated, such as social phobia or autism.

Figures

Figure 1.

Oxytocin effects on amygdala activation. A, Rendering on normal coronal MRI at the level of the anterior commissure (in neurological orientation: the brain left is on the viewer's left). The response to face stimuli is on the left, and the response to scene stimuli is on the right. Top, Placebo; bottom, oxytocin. See Table 2 for statistical information. B, Significantly higher activation under placebo than oxytocin (main effect of drug condition). See Table 2 for statistical information. C, Plot of BOLD in the amygdala ROI (ANOVA; significant main effect of drug condition: F(1,56) = 4.2, p = 0.045; main effect of task and drug-by-task interaction were not significant).

Figure 2.

Significant decrease in coupling of the amygdala to the midbrain under oxytocin. A, Maps of significant difference in connectivity from the amygdala to the midbrain, in neurological orientation. See Table 2 for statistical information. B, Plot of oxytocin effect on correlation with the amygdala (Pearson's r) at the midbrain location showing maximum linkage to the amygdala during the placebo condition (coordinates: -6, -24, -15), highly significant decrease under oxytocin (p < 0.004; t test).