Effects of four-week intranasal oxytocin administration on large-scale brain networks in older adults.

Oxytocin (OT) is a crucial modulator of social cognition and behavior. Previous work primarily examined effects of acute intranasal oxytocin administration (IN-OT) in younger males on isolated brain regions. Not well understood are (i) chronic IN-OT effects, (ii) in older adults, (iii) on large-scale brain networks, representative of OT's wider-ranging brain mechanisms. To address these research gaps, 60 generally healthy older adults (mean age = 70.12 years, range = 55-83) were randomly assigned to self-administer either IN-OT or placebo twice daily via nasal spray over four weeks. Chronic IN-OT reduced resting-state functional connectivity (rs-FC) of both the right insula and the left middle cingulate cortex with the salience network but enhanced rs-FC of the left medial prefrontal cortex with the default mode network as well as the left thalamus with the basal ganglia-thalamus network. No significant chronic IN-OT effects were observed for between-network rs-FC. However, chronic IN-OT increased selective rs-FC of the basal ganglia-thalamus network with the salience network and the default mode network, indicative of more specialized, efficient communication between these networks. Directly comparing chronic vs. acute IN-OT, reduced rs-FC of the right insula with the salience network and between the default mode network and the basal ganglia-thalamus network, and greater selective rs-FC of the salience network with the default mode network and the basal ganglia-thalamus network, were more pronounced after chronic than acute IN-OT. Our results delineate the modulatory role of IN-OT on large-scale brain networks among older adults.