2026 ECNP Congress

PS01-1159

Closed-loop respiratory-gated transcutaneous auricular vagus nerve stimulation reduces beta power in healthy volunteers

Tiago Costa — J. Steyn, F. Hutchings, B. Hall, B.D.S. Anderson, M. Baker, P. Taylor, Y. Wang, A. Jackson, S. Watson, R.H. McAllister-Williams · Newcastle University, Translational and Clinical Research Institute, Newcastle Upon Tyne, United Kingdom

2026 ECNP Congress

Introduction

Transcutaneous auricular vagus nerve stimulation (taVNS) may modulate cortical dynamics via afferent brainstem arousal pathways. Respiratory-gated taVNS has been proposed as a strategy to couple stimulation to physiological fluctuations in vagal afferent traffic related to breathing. However, the electrophysiological effects of respiratory phase-specific stimulation remain poorly characterised. With funding and support from the UK closeNIT Network+ and the UK NIHR Newcastle Biomedical Research Centre, we developed a closed-loop respiratory-gated taVNS system and examined resting-state electroencephalography (EEG) changes in healthy volunteers. Here we focus on analysis of global/regional band-power and secondary beta-power metrics. Motivated by reports linking frontal beta reduction to antidepressant effects of rTMS [1], we hypothesised that active taVNS would modulate resting-state beta power, particularly in the frontal region, with respiratory-gated stimulation producing paradigm-specific effects.

Methods

In a single-blind, sham-controlled randomised pilot study, participants received active left cymba concha taVNS or sham left earlobe stimulation. Each participant completed stimulation blocks in random order: open-loop continuous stimulation, inspiratory-gated stimulation, and expiratory-gated stimulation. Stimulation was delivered at 10 Hz with 300 microsecond pulse width and individually titrated intensity. Respiratory gating used a thoracic transducer belt and custom control software (github.com/NewcastleRSE/Java_taVNS). Thirty-two-channel EEG was recorded continuously. Five-minute resting-state pre- and post-stimulation segments were extracted around each block. EEG was average-referenced, notch-filtered at 50/100/150 Hz, band-pass filtered from 0.5-80 Hz, resampled to 256 Hz, and cleaned using independent component analysis. Power spectral density was estimated using Welch’s method over 1-80 Hz. Per-channel spectra were normalised across 1-80 Hz, integrated into canonical bands, and log10-transformed. Inferential analyses used participant-level post-minus-pre change scores, paired tests within condition, independent active-versus-sham contrasts, and Benjamini-Hochberg false discovery rate (FDR) correction.

Results

Thirty-two participants received stimulation. Sixty-one stimulation blocks were analysable, of which 54 met the prespecified inferential criterion of at least 60 seconds of clean paired pre- and post-stimulation EEG. No global or regional active-versus-sham contrast survived FDR correction across the primary band-power family. The strongest primary directional finding was reduced beta power after active inspiratory-gated stimulation: frontal change -0.129, effect size -1.52, p<0.001, q=0.088; global change -0.099, effect size -1.27, p=0.001, q=0.093. In the secondary beta analysis, these active inspiratory reductions were FDR-corrected significant in frontal and global summaries: frontal q=0.023; global q=0.034. Comparable corrected reductions were not detected in sham inspiratory blocks, although active-versus-sham beta contrasts did not survive correction.

Conclusions

Closed-loop respiratory-gated taVNS was feasible with concurrent EEG acquisition and showed preliminary evidence of inspiratory-gated beta-power modulation. The most robust within-condition finding was an FDR-corrected reduction in frontal and global beta power after active inspiratory-gated stimulation. This converges directionally with reports of frontal beta reduction with rTMS in people with depression [1]. However, our study delivered taVNS in a small sample of healthy volunteers and should be interpreted as pilot and preliminary. Larger balanced studies should test whether respiratory phase, stimulation site, and clinical state determine beta-related cortical responses to taVNS.

References

  1. Kratter, I.H., Austelle, C.W., Lissemore, J.I., Wada, M., Geoly, A.D., Chaiken, A., et al., 2026. Stanford neuromodulation therapy for treatment-resistant depression: a randomized controlled trial confirming efficacy, and an EEG study providing insight into mechanism of action and a potentially predictive biomarker of efficacy. World Psychiatry 25 (1), 105-116. https://doi.org/10.1002/wps.70032