Oxytocin Differentially Modulates Amygdala Responses during Top‐Down and Bottom‐Up Aversive Anticipation

Abstract The ability to successfully regulate negative emotions such as fear and anxiety is vital for mental health. Intranasal administration of the neuropeptide oxytocin (OXT) has been shown to reduce amygdala activity but to increase amygdala–prefrontal cortex connectivity during exposure to threatening stimuli suggesting that it may act as an important modulator of emotion regulation. The present randomized, between‐subject, placebo‐controlled pharmacological study combines the intranasal administration of OXT with functional magnetic resonance imaging (fMRI) during an explicit emotion regulation paradigm in 65 healthy male participants to investigate the modulatory effects of OXT on both bottom‐up and top‐down emotion regulation. OXT attenuates the activation in the posterior insular cortex and amygdala during anticipation of top‐down regulation of predictable threat stimuli in participants with high trait anxiety. In contrast, OXT enhances amygdala activity during the bottom‐up anticipation of unpredictable threat stimuli in participants with low trait anxiety. OXT may facilitate top‐down goal‐directed attention by attenuating amygdala activity in high anxiety individuals, while promoting bottom‐up attention/vigilance to unexpected threats by enhancing amygdala activity in low anxiety individuals. OXT may thus have the potential to promote an adaptive balance between bottom‐up and top‐down attention systems depending on an individual's trait anxiety level.