Oxytocin Affects the Connectivity of the Precuneus and the Amygdala: A Randomized, Double-Blinded, Placebo-Controlled Neuroimaging Trial

Background: Although oxytocin is one of the most widely studied neuropeptides in recent times, the mechanistic process by which it modulates social-affective behavior in the brain is not yet clearly understood. Thus, to understand the neurophysiological basis of oxytocin effects, we used resting-state functional MRI to examine the effects of intranasal oxytocin on brain connectivity in healthy males. Methods: Using a randomized, double-blinded, placebo-controlled, crossover design, 15 healthy male volunteers received 24 IU intranasal oxytocin or placebo prior to resting-state functional MRI acquisition at 3T. Results: We found that oxytocin significantly reduced the degree centrality of the right precuneus (P<.05). Oxytocin also reduced connectivity between the bilateral amygdalae and between the right precuneus and the right and left amygdala (P<.05). Although there were no significant changes in regional homogeneity at the whole brain level, posthoc results showed a reduction involving the right precuneus (P<.05). Conclusions: These results show that oxytocin affects one of the key centers in the brain for social cognition and introspective processing, the precuneus, and enhances our understanding of how oxytocin can modulate brain networks at rest. An improved understanding of the neurophysiological effects of oxytocin can be important in terms of evaluating the mechanisms that are likely to underlie the clinical responses observed upon long-term oxytocin administration.