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Vagus nerve stimulation strengthens beta- and gamma-rate auditory steady-state responses in rat cortex

Abstract

Background: Gamma entrainment using sensory stimulation (GENUS) is under study as a treatment for neurological disease, but cortical engagement is variable. Vagus nerve stimulation (VNS) modulates cortical state and sound-evoked beta-gamma activity, suggesting that it may strengthen responses to rhythmic sensory input. Objective: To determine whether VNS strengthens auditory steady-state responses across beta and gamma rates and whether the effect depends on cortical region and sensory drive. Methods: Electrocorticography (ECoG) was recorded from core and belt auditory cortex, insular auditory field (IAF), and anterior insular cortex (AIC) in seven isoflurane-anesthetized rats before and 90 min after initiation of 30-Hz cervical VNS. Responses to 500-ms click trains at 20 and 40 Hz were quantified using inter-trial phase clustering (ITPC), event-related spectral perturbation (ERSP), and debiased weighted phase-lag index (WPLI). Results: VNS increased click-evoked P1-N1 amplitude. During 40-Hz trains, 40-Hz ITPC and ERSP increased only in auditory core. During 20-Hz trains, 20-Hz ITPC increased in core, belt, and IAF, whereas ERSP increased only in core; 40-Hz harmonic responses increased only in core. AIC showed no change. Within auditory cortex, WPLI increased selectively at frequencies present in each click train and not in the alpha band. Conclusions: VNS strengthened beta- and gamma-rate stimulus-locked responses in auditory-driven cortex without globally increasing synchrony. VNS may therefore enhance auditory cortical target engagement during GENUS, although effects on disease pathology or clinical outcomes remain untested.

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BibTeX
@misc{kumagai2026vagus,
  title = {{Vagus nerve stimulation strengthens beta- and gamma-rate auditory steady-state responses in rat cortex}},
  author = {Shinichi Kumagai and Tomoyo Isoguchi Shiramatsu and Karin Oshima and Yohei Ishishita and Kenji Ibayashi and Yoshiyuki Onuki and Naoto Kunii and Kensuke Kawai and Hirokazu Takahashi},
  howpublished = {arXiv},
  year = {2026},
  month = oct,
  doi = {10.48550/arxiv.2610.29042},
  eprint = {2610.29042},
  archivePrefix = {arXiv},
  url = {https://arxiv.org/abs/2610.29042},
}
RIS
TY  - UNPB
TI  - Vagus nerve stimulation strengthens beta- and gamma-rate auditory steady-state responses in rat cortex
AU  - Shinichi Kumagai
AU  - Tomoyo Isoguchi Shiramatsu
AU  - Karin Oshima
AU  - Yohei Ishishita
AU  - Kenji Ibayashi
AU  - Yoshiyuki Onuki
AU  - Naoto Kunii
AU  - Kensuke Kawai
AU  - Hirokazu Takahashi
PY  - 2026
DA  - 2026/10/21
PB  - arXiv
DO  - 10.48550/arxiv.2610.29042
UR  - https://arxiv.org/abs/2610.29042
AB  - Background: Gamma entrainment using sensory stimulation (GENUS) is under study as a treatment for neurological disease, but cortical engagement is variable. Vagus nerve stimulation (VNS) modulates cortical state and sound-evoked beta-gamma activity, suggesting that it may strengthen responses to rhythmic sensory input. Objective: To determine whether VNS strengthens auditory steady-state responses across beta and gamma rates and whether the effect depends on cortical region and sensory drive. Methods: Electrocorticography (ECoG) was recorded from core and belt auditory cortex, insular auditory field (IAF), and anterior insular cortex (AIC) in seven isoflurane-anesthetized rats before and 90 min after initiation of 30-Hz cervical VNS. Responses to 500-ms click trains at 20 and 40 Hz were quantified using inter-trial phase clustering (ITPC), event-related spectral perturbation (ERSP), and debiased weighted phase-lag index (WPLI). Results: VNS increased click-evoked P1-N1 amplitude. During 40-Hz trains, 40-Hz ITPC and ERSP increased only in auditory core. During 20-Hz trains, 20-Hz ITPC increased in core, belt, and IAF, whereas ERSP increased only in core; 40-Hz harmonic responses increased only in core. AIC showed no change. Within auditory cortex, WPLI increased selectively at frequencies present in each click train and not in the alpha band. Conclusions: VNS strengthened beta- and gamma-rate stimulus-locked responses in auditory-driven cortex without globally increasing synchrony. VNS may therefore enhance auditory cortical target engagement during GENUS, although effects on disease pathology or clinical outcomes remain untested.
ER  -