Abraham Tonny Hagan ¹ Lei Xu ² Benjamin Klugah-Brown ¹ Jialin Li ¹ Xi Jiang ^1* Keith Maurice Kendrick ^1*

• ¹ Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, Sichuan, China
• ² Sichuan Normal University, Chengdu, Sichuan Province, China

Neuroimaging studies have demonstrated that intranasal oxytocin has extensive effects on the resting state functional connectivity of social and emotional processing networks and may have therapeutic potential. However, the extent to which intranasal oxytocin modulates functional connectivity network topology remains less explored, with inconsistent findings in the existing literature. To address this gap, we conducted an exploratory data-driven study. We recruited 142 healthy males and administered 24 IU of intranasal oxytocin or placebo in a randomized controlled double-blind design. Resting-state functional MRI data were acquired for each subject. Network-based statistical analysis and graph theoretical approaches were employed to evaluate oxytocin's effects on whole-brain functional connectivity and graph topological measures. Our results revealed that oxytocin altered connectivity patterns within brain networks involved in sensory and motor processing, attention, memory, emotion and reward functions as well as social cognition including the default mode, limbic, frontoparietal, cerebellar, and visual networks. Furthermore, oxytocin increased local efficiency, clustering coefficients, and small-world propensity in specific brain regions including the cerebellum, left thalamus, posterior cingulate cortex, right orbitofrontal cortex, right superior frontal gyrus, left inferior frontal gyrus and right middle orbitofrontal cortex, while decreasing nodal path topological measures in the left and right caudate. These findings suggest that intranasal oxytocin may produce its functional effects through influencing the integration and segregation of information flow within small-world brain networks, particularly in regions closely associated with social cognition and motivation.