Transcutaneous vagus nerve stimulation modulates fear memory extinction and neural responses in humans

Abstract Previous research has shown that transcutaneous auricular vagus nerve stimulation (tVNS) promotes declarative fear extinction, but its neural mechanisms in this process are still unclear. This study aimed to explore tVNS’s impacts on physiological (skin conductance response [SCR]) and neural (event-related potentials, ERP) fear-related responses. Forty healthy participants were randomly assigned to the tVNS or Sham group. During a fear-conditioned memory paradigm, electroencephalograph (EEG) and SCR were measured. We analyzed SCR amplitude, ERP components, EEG signal spectral analysis, and the correlation between SCR and EEG metrics. Results showed that compared with the Sham group, the tVNS group had a remarkable decrease in SCR amplitudes for conditioned stimuli (CS+) during retrieval and recall, suggesting reduced sympathetic arousal. ERP analysis revealed a notable decline in late positive potential (LPP) (400–800 ms) amplitudes for CS+ in the tVNS group during these phases, indicating weakened neural reactivity. A significant group-by-phase interaction showed that tVNS effectively suppressed immediate and sustained fear responses, maintaining lower fear-related physiological and neural activity levels. These findings suggest that tVNS modulates neural circuits involved in fear processing, clarifies the mechanisms underlying fear extinction, and highlights its therapeutic potential for fear-related disorders.