Transcutaneous vagus nerve stimulation reduces total striatal GABA content and facilitates early-phase motor learning

Background: Transcutaneous vagus nerve stimulation (tVNS) has emerged as a promising non-invasive technique for modulating neuroplasticity. Previous studies have suggested that changes in regional brain GABA signaling contribute to these effects, but empirical neurophysiological evidence remains limited. Methods: We investigated the neurophysiological and behavioral effects of tVNS (200 microsecond pulses at 20 Hz, alternating 30 s ON, 1 s OFF cycles, 30 min total duration) in healthy adults using two experimental paradigms. In Experiment 1, GABA levels were measured in the left striatum (STR), dorsolateral prefrontal cortex (DLPFC), and sensorimotor cortex (SM) of 34 participants by magnetic resonance spectroscopy (MRS) before and after ipsilateral tVNS. In Experiment 2, 28 participants performed a right-hand force-control motor learning task before, during, and after tVNS. Results: Administration of tVNS significantly reduced GABA levels in the left STR compared to sham stimulation (p < 0.05), and also significantly improved motor task performance compared to the sham group at 10 minutes after stimulus onset (p < 0.05). Conclusion: Transcutaneous VNS may facilitate early-phase motor learning by reducing striatal GABA levels and consequently inducing corticobasal circuit disinhibition. These findings support tVNS as a potential noninvasive intervention to enhance motor learning for neurorehabilitation and motor disorder treatment.