Oxytocin Enhancement of Emotional Empathy: Generalization Across Cultures and Effects on Amygdala Activity

Accumulating evidence suggests that the neuropeptide oxytocin (OXT) can enhance empathy although it is unclear which specific behavioral and neural aspects are influenced, and whether the effects are modulated by culture, sex, and trait autism. Based on previous findings in Caucasian men, we hypothesized that a single intranasal dose of OXT would specifically enhance emotional empathy (EE) via modulatory effects on the amygdala in an Asian (Chinese) population and explored the modulatory role of sex and trait autism on the effects. We first conducted a double-blind, randomized between-subject design experiment using a modified version of the multifaceted empathy task to determine whether OXT's facilitation of EE can be replicated in Chinese men (n = 60). To further explore neural mechanisms behind and potential sex differences, functional MRI and skin conductance measures were acquired in an independent experiment incorporating men and women (n = 72). OXT enhanced EE across experiments and sex, an effect that was accompanied by reduced amygdala activity and increased skin conductance responses. On the network level OXT enhanced functional coupling of the right amygdala with the insula and posterior cingulate cortex for positive valence stimuli but attenuated coupling for negative valence stimuli. The effect of OXT on amygdala functional connectivity with the insula was modulated by trait autism. Overall, our findings provide further support for the role of OXT in facilitating EE and demonstrate that effects are independent of culture and sex and involve modulatory effects on the amygdala and its interactions with other key empathy regions.