Intranasal oxytocin modulates the salience network in aging.

Growing evidence supports a role of the neuropeptide oxytocin in promoting social cognition and prosocial behavior, possibly via modulation of the salience of social information. The effect of intranasal oxytocin administration on the salience network, however, is not well understood, including in the aging brain. To address this research gap, 42 young (22.52 ± 3.02 years; 24 in the oxytocin group) and 43 older (71.12 ± 5.25 years; 21 in the oxytocin group) participants were randomized to either self-administer intranasal oxytocin or placebo prior to resting-state functional imaging. The salience network was identified using independent component analysis (ICA). Independent t-tests showed that individuals in the oxytocin compared to the placebo group had lower within-network resting-state functional connectivity, both for left amygdala (MNI coordinates: x = -18, y = 0, z = -15; corrected p < 0.05) within a more ventral salience network and for right insula (MNI coordinates: x = 39, y = 6, z = -6; corrected p < 0.05) within a more dorsal salience network. Age moderation analysis furthermore demonstrated that the oxytocin-reduced functional connectivity between the ventral salience network and the left amygdala was only present in older participants. These findings suggest a modulatory role of exogenous oxytocin on resting-state functional connectivity within the salience network and support age-differential effects of acute intranasal oxytocin administration on this network.