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

Kana Matsumura; Hiroyuki Matsuta; Ryushin Kawasoe; Tomoyuki Fumuro; Kojiro Matsushita; Nobuhiro Hata; Yoshiki Asayama; Tsuyoshi Shimomura; Minoru Fujiki; Hisato Sugata

doi:10.3389/fnhum.2026.1731345

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

Front Hum Neurosci. 2026 Feb 18:20:1731345. doi: 10.3389/fnhum.2026.1731345. eCollection 2026.

Authors

Kana Matsumura¹, Hiroyuki Matsuta^{2

3}, Ryushin Kawasoe^{1

4}, Tomoyuki Fumuro⁵, Kojiro Matsushita⁶, Nobuhiro Hata³, Yoshiki Asayama⁷, Tsuyoshi Shimomura², Minoru Fujiki³, Hisato Sugata^{1

8

9}

Affiliations

¹ Graduate School of Welfare and Health Science, Oita University, Oita, Japan.
² Hospital Informatics Center, Oita University Hospital, Oita, Japan.
³ Department of Neurosurgery, School of Medicine, Oita University, Oita, Japan.
⁴ Division of Health Sciences, Graduate School of Medicine, Osaka University, Osaka, Japan.
⁵ Faculty of Medicine, Department of Advanced Medical Sciences, Oita University, Oita, Japan.
⁶ Department of Mechanical Engineering, Gifu University, Gifu, Japan.
⁷ Faculty of Medicine, Department of Radiology, Oita University, Oita, Japan.
⁸ Faculty of Welfare and Health Science, Oita University, Oita, Japan.
⁹ Graduate School of Medicine, Oita University, Oita, Japan.

Abstract

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 (¹H-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.

Keywords: gamma-aminobutyric acid; glutamate; motor learning; neuromodulation; proton magnetic resonance spectroscopy; tVNS.