Age-dependent effects of intranasal oxytocin administration were revealed by resting brain entropy (BEN)

Oxytocin (OT), a neuropeptide known for its role in social behavior, has unclear neural mechanisms when administered intranasally, especially across different ages. Brain entropy (BEN), a metric of neural irregularity, shows promise for revealing OT's neurophysiological effects. This study examined whether BEN could detect neural changes induced by intranasal OT and how these effects are modulated by age. In a randomized, double-blind, placebo-controlled trial, young adults (YA) and older adults (OA) were assigned to receive intranasal OT or placebo (PL). Using fMRI-based BEN mapping, we identified a significant age-dependent effect in the left temporoparietal junction (TPJ), where OT increased BEN in YA but decreased it in OA. Further analyses showed OT also elevated the fractional amplitude of low-frequency fluctuations (fALFF) in the same region, particularly in YA. Additionally, OT enhanced functional connectivity within the left TPJ and between the left and right TPJ in both age groups. These results establish BEN as a sensitive biomarker capable of capturing age-specific OT effects, providing information beyond traditional measures of oscillatory power and temporal synchronization. The findings suggest that the timing of post-administration brain state changes under OT may vary with age, potentially due to differences in OT receptor density.