Transcutaneous Vagus Nerve Stimulation (tVNS) Decreases Sympathetic Nerve Activity in Older Healthy Human Subjects
Authors: Murray Aaron R , Clancy Jennifer A , Deuchars Susan A , Deuchars Jim 
Published: November 2023

Increasing age can alter the autonomic balance towards elevated sympathetic nerve activity and reduced parasympathetic activity. This age‐associated autonomic dysfunction is linked with chronic conditions such as cardiovascular disease and impaired mental health. Vagus nerve stimulation (VNS), using a surgically‐implanted bipolar electrode in the neck, is under investigation in a number of chronic conditions but the invasiveness of the procedure and risk of post‐operative complications limits its therapeutic use for age‐associated diseases. The aim of the present study is to investigate the effects of a non‐invasive stimulation technique, transcutaneous vagus nerve stimulation (tVNS) on autonomic activity in older healthy human subjects aged 60 and above.The study was conducted in accordance with the Declaration of Helsinki and approved by the University of Leeds Ethics Committee. tVNS was applied to the tragus of the ear using transcutaneous electrical nerve stimulation (TENS; 20–50mA, 30Hz, 200μs) in 18 healthy subjects (12 female, 6 male; 60–84 years) with no medical history of cardiovascular disease, hypertension or diabetes mellitus. Subjects received either 15 minutes active tVNS or sham stimulation on two separate visits at least one week apart. Three 10 minute recordings of heart rate, blood pressure and respiration were obtained before, during and after stimulation. Heart rate variability (HRV) was calculated from spectral analysis of beat‐to‐beat oscillations in heart rate. The LF/HF ratio was calculated using low frequency power (LF; 0.04–0.15Hz) and high frequency power (HF; 0.15–0.4Hz). A decrease in LF/HF is associated with a reduction in sympathetic activity and a relative increase in parasympathetic activity. Microneurography was used to record single‐unit muscle sympathetic nerve activity (MSNA) and detect changes in MSNA frequency and incidence in 5 subjects who had a decrease in LF/HF during tVNS. Statistical analysis was performed using repeated measures ANOVA with Bonferroni post‐hoc correction or Friedman's and Wilcoxon Signed Ranks tests. All data are presented as mean ± standard error of the mean (SEM) except where indicated.12 of the 18 volunteers (n = 6 male) who received active tVNS had a significant decrease in LF/HF ratio (1.99 ± 0.24 to 1.25 ± 0.14; p = 0.007) during stimulation. The remaining 6 volunteers (all female) did not experience any change in LF/HF. Male volunteers had a higher baseline LF/HF than female volunteers (male = 2.00 ± 0.16, female = 1.47 ± 0.31; p = 0.016). Low frequency power decreased after active tVNS had ceased (p = 0.01) but there was no change in high frequency power. Sham stimulation elicited no change in LF/HF. Microneurography in 5 subjects detected a decrease in MSNA frequency (Z = −2.023; p = 0.043) and incidence (Z = −2.023, p = 0.043) during active tVNS.The results indicate that tVNS reduces muscle sympathetic nerve activity and shifts cardiac autonomic control towards parasympathetic predominance in older healthy subjects. Further studies are needed to determine the long‐term autonomic effects of tVNS in these subjects.Support or Funding InformationThe study was funded by University of Leeds.