Endogenous and exogenous oxytocin modulate interpersonal motor resonance in autism: A context-dependent and person-specific approach

Understanding and interpreting non-verbal actions are critical components of social cognition, which are often challenging for autistic individuals. Oxytocin, a neuropeptide known to modulate social behavior and enhance the salience of social stimuli, is being explored as a therapeutic option for improving social mirroring. However, its effects are mediated by context- and person-dependent factors. This study examines the impact of a single intranasal dose of oxytocin (24 IU) on interpersonal motor resonance in young adult men with and without autism. Neurophysiological assessments of corticomotor excitability were performed using transcranial magnetic stimulation while participants observed real-time hand movements displayed by an experimenter demonstrating varying social intent (i.e. showing direct vs averted gaze). While no overall effect of oxytocin on interpersonal motor resonance was observed across groups, person-specific factors significantly influenced outcomes. In the autism group, individuals with higher endogenous oxytocin levels exhibited greater motor resonance during action observation. Autistic individuals with heightened social difficulties or avoidant attachment styles showed enhanced motor resonance following oxytocin administration. These findings highlight the nuanced role of both endogenous and exogenous oxytocin in shaping neurophysiological motor resonance and emphasize the importance of individual variability in assessing oxytocin’s therapeutic potential for addressing social challenges in autism. Lay abstract This study explores how oxytocin, a hormone that influences social behaviors, affects the ability to interpret and respond to non-verbal cues, particularly in autistic adults. Understanding others’ actions and intentions, often guided by observing body language and eye contact, is a critical part of social interaction. Autistic individuals frequently face challenges in these areas. Using a safe, non-invasive brain stimulation technique, the study measured participants’ brain responses as they observed real-time hand movements paired with the interaction partner’s direct eye contact or averted gaze. Participants included young autistic and non-autistic adult men who received a placebo and a single dose of oxytocin via nasal spray. Results showed no overall differences between the two groups in their brain responses to these movements. However, in the autism group, several factors significantly influenced the effects of oxytocin. Participants with higher natural oxytocin levels or those who reported greater social challenges showed stronger responses after oxytocin administration, particularly when observing hand movements combined with direct gaze. These findings suggest that oxytocin may enhance social understanding in autistic individuals, especially for those experiencing greater difficulties. This highlights the potential of personalized approaches when considering oxytocin as a therapeutic option to improve social interactions.