Analysis of taVNS effects on baroreflex sensitivity and autonomic nervous system regulation during head-up tilt test

Baroreflex dysfunction and autonomic imbalance are key pathophysiological features of hypertension, but current pharmacological approaches often fail to address these neural mechanisms. This study investigated whether transcutaneous auricular vagus nerve stimulation (taVNS) affects autonomic regulation during blood pressure perturbation. In a randomized, single-blind, sham-controlled, crossover design experiment, 32 normotensive adults received 90-min taVNS or sham exposure.

Blood pressure perturbation was induced with the head-up tilt test (supine–tilt–supine). Baroreflex sensitivity (BRS) was analyzed only during the 10-minute tilt phase, whereas heart rate variability (HRV) was analyzed across four 5-minute segments (S-baseline, early-tilt, late-tilt, recovery). In the direct crossover analysis of the primary BRS outcome, pre-to-post changes did not differ significantly between taVNS and sham, and the baseline-adjusted sensitivity analysis yielded the same conclusion.

Among the secondary HRV outcomes, differences averaged across analysis segments were significant only for SDNN and pNN30, whereas no analysis-segment-specific interaction was significant. Descriptive within-visit comparisons showed increases in BRS and several HRV measures during the taVNS visit. These findings provide preliminary evidence compatible with cardiovagal modulation during orthostatic stress, but do not establish a taVNS-specific improvement in BRS or blood pressure regulation.

Further research involving patient cohorts and longitudinal study protocols is needed. This work was supported by a National Research Foundation of Korea (NRF) grant funded by the Korean gov-ernment (MSIT) (RS-2024-00333219) and the Smart HealthCare Program (www.kipot.or.kr), funded by the Korean National Police Agency (KNPA, Korea). [Project Name: Development of wearable system for acquiring lifelog data and customized healthcare service for police officers/Project Number: RS-2022-PT000189]. Geonhee Lee and Donghun Kang have contributed equally to this work.

Department of Electronic Engineering, Hanyang University, Seoul, 04763, Korea Department of Biomedical Engineering, Hanyang University, Seoul, 04763, Korea Donghun Kang, Jongshill Lee & In Young Kim Department of Biomedical Engineering, College of Medicine, Hanyang University, Seoul, 04763, Korea Correspondence to Jeyeon Lee or In Young Kim. The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The clinical trial described in this paper was registered at https://cris.nih.go.kr/cris/index/index.do under the registration number KCT0011752 (first trial registered 20/03/2026, retrospective registration).

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