Intranasal Oxytocin Selectively Modulates Large-Scale Brain Networks in Humans

A growing body of evidence indicates that the neuropeptide oxytocin (OT) alters the neural correlates of socioemotional and salience processing. Yet the effects of OT over important large-scale networks involved in these processes, such as the default mode (DM), ventral attention (VA), and cingulo-opercular (CO) networks, remain unknown. Therefore, we conducted a placebo-controlled crossover study with intranasal 24 IU OT in 38 healthy male subjects using a resting-state functional magnetic resonance imaging paradigm to investigate its impact over these three networks candidates. To understand the underlying mechanisms of the neuropeptide, we compared the intranetwork connectivity for each network candidate and also the internetwork connectivity across all networks between both treatment conditions. Based on the relevance of interindividual factors for OT effects, we correlated individual network changes with behavioral performance in a decision-making task and with impulsivity scores. Our results show that OT mainly alters connectivity in the VA, on one side reducing the coupling to regions that typically form the nodes of DM, an introspective and self-referential network, and on the other side increasing the coupling to the edges of the CO, which is involved in salience processing. The results of the internetwork analyses confirmed the specificity of the OT effects. Indeed, we observed significant correlations with the erroneous performance during decision-making but not with the obtained impulsivity scores. Overall, our data support that the modulation of functional connectivity within the VA is a basic mechanism by which OT directs attentional resources from internal to external cues, preparing the brain for context-dependent salience processing.