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

Kana Matsumura¹Hiroyuki Matsuta^1*Ryushin Kawasoe¹Tomoyuki Fumuro¹Kojiro Matsushita²Nobuhiro Hata¹Yoshiki Asayama¹Tsuyoshi Shimomura¹Minoru Fujiki¹Hisato Sugata^1*

• ¹Oita University, Oita, Japan
• ²Gifu Daigaku, Gifu, Japan

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 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 (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 minutes 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.