Oxytocin Modulates Inhibitory Control Under Anxiety via Stage-Specific Neural Mechanisms

Impaired inhibitory control is a hallmark of anxiety disorders, impacting decision-making and emotional regulation. Current anxiolytics often have broad effects, lacking specificity for cognitive deficits. Oxytocin (OXT), a neuropeptide known for its role in social behavior and anxiety modulation, has shown promise in influencing emotional processing. However, the precise neural-temporal dynamics through which OXT modulates inhibitory control, especially under acute threat, remain poorly understood, representing a critical gap in optimizing its therapeutic potential.

This randomized, double-blind, placebo-controlled study involved 100 healthy male university students. Participants received a single dose of oxytocin 24 IU intranasally or placebo. They then performed an interference-inhibition working memory task under both threat-of-shock (anxiety) and safe conditions. The task required attention to either emotional faces (social stimuli) or house scenes (non-social stimuli) while ignoring superimposed irrelevant distractors. Neural activity was measured using event-related potentials (ERP) across distinct processing stages, specifically analyzing N1, P2, N2, and N450 components.

While oxytocin did not significantly affect behavioral performance on the inhibitory control task, it produced stage-specific, context-dependent neuromodulatory effects on neural processing. Specifically, OXT: (1) modulated early perceptual processing of social stimuli under anxiety, indicated by a reduced P2 amplitude to faces. (2) influenced conflict-monitoring, reflected by an anxiety-dependent attenuation of the N2 response during the non-social task. (3) modulated later conflict resolution processes, evidenced by a double dissociation in the N450 component. Under threat, OXT prevented the anxiety-induced increase in N450 for houses while simultaneously enhancing the N450 response to faces. This suggests OXT's influence is not a general anxiolytic effect, but rather a targeted modulation of multi-stage neural processes.

Oxytocin prevented the anxiety-induced increase in N450 for non-social stimuli (houses) while enhancing N450 for social stimuli (faces) under threat-of-shock.