Transcutaneous vagus nerve stimulation reduces total striatal GABA+ content, increases DLPFC Glu content, and facilitates early-phase motor learning

Objectives 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. Materials and methods We investigated the neurophysiological and behavioral effects of tVNS (200-μs 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+ and Glutamate (Glu) levels were measured in the left striatum (STR), dorsolateral prefrontal cortex (DLPFC), and sensorimotor cortex (SM) of 34 participants by proton magnetic resonance spectroscopy ( 1 H-MRS), before and after ipsilateral tVNS. In Experiment 2, 27 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 ( p < 0.05), increased Glu levels in the DLPFC ( p < 0.05), and significantly improved motor task performance compared to the sham group at 10 min after stimulus onset ( p < 0.05). Conclusion tVNS (1) reduced striatal GABA+ levels and increased DLPFC Glu in healthy adults, and (2) facilitated early-phase motor learning. These findings support the use of tVNS as a noninvasive intervention that enhances motor learning in neurorehabilitation and the treatment of motor disorders.