Dynamic brain connectivity patterns induced by oxytocin: An fMRI Co-Activation pattern analysis study

Oxytocin (OT) is a neuropeptide widely implicated in emotional regulation and social cognition. However, its effects on dynamic brain connectivity remain poorly understood. In this study, we applied co-activation pattern (CAP) analysis to resting-state fMRI data to examine how a single intranasal dose of OT modulates whole-brain functional dynamics. Participants included healthy young (18-31 years) and older (63-81 years) adults, with analyses conducted at both the group level and across age subgroups. OT significantly altered temporal properties of brain states, including increased frequency, in-degree, and out-degree in multiple CAPs, indicating enhanced network flexibility and switching. Notably, OT modulated states involving the amygdala, medial prefrontal cortex, and salience network, regions critical for emotion regulation, and increased self-transition probabilities, suggesting greater within-state stability. Age-stratified analysis revealed differential sensitivity: young adults exhibited more pronounced modulation and greater dynamic flexibility, while older adults showed more sustained engagement with emotion-related states. Importantly, only in the elderly OT and combined young subgroups did time spent in these states significantly correlate with cognitive performance on the Digit Symbol Substitution Test, suggesting that OT-enhanced engagement in these networks supports compensatory mechanisms during aging. No such correlations were found in young participants or in either age group under placebo, highlighting the specificity of oxytocin's functional relevance in older adults. Meta-analytic decoding using Neurosynth confirmed that OT-modulated regions are closely associated with emotion, memory, and social cognition. These findings demonstrate that OT shapes transient brain dynamics in age- and function-specific ways. CAP analysis provides a powerful approach for capturing such neuromodulatory effects.