Social functioning predicts individual changes in EEG microstates following intranasal oxytocin administration: A double‐blind, cross‐over randomized clinical trial

Abstract Oxytocin (OXT) modulates social behaviors. However, the administration of exogenous OXT in humans produces inconsistent behavioral changes, affecting future consideration of OXT as a treatment for autism and other disorders with social symptoms. Inter‐individual variability in social functioning traits might play a key role in how OXT changes brain activity and, therefore, behavior. Here, we investigated if inter‐individual variability might dictate how single‐dose intranasal OXT administration (IN‐OXT) changes spontaneous neural activity during the eyes‐open resting state. We used a double‐blinded, randomized, placebo‐controlled, cross‐over design on 30 typically developing young adult men to investigate the dynamics of EEG microstates corresponding to activity in defined neural networks. We confirmed previous reports that, at the group level, IN‐OXT increases the representation of the attention and salience microstates. Furthermore, we identified a decreased representation of microstates associated with the default mode network. Using multivariate partial least square statistical analysis, we found that social functioning traits associated with IN‐OXT‐induced changes in microstate dynamics in specific spectral bands. Correlation analysis further revealed that the higher the social functioning, the more IN‐OXT increased the appearance of the visual network‐associated microstate, and suppressed the appearance of a default mode network‐related microstate. The lower the social functioning, the more IN‐OXT increases the appearance of the salience microstate. The effects we report on the salience microstate support the hypothesis that OXT regulates behavior by enhancing social salience. Moreover, our findings indicate that social functioning traits modulate responses to IN‐OXT and could partially explain the inconsistent reports on IN‐OXT effects.