Does non-invasive vagus nerve stimulation affect heart rate variability? A living and interactive Bayesian meta-analysis

Abstract

Non-invasive brain stimulation techniques, such as transcutaneous auricular vagus nerve stimulation (taVNS), have considerable potential for clinical use. Beneficial effects of taVNS have been demonstrated on symptoms in patients with mental or neurological disorders as well as transdiagnostic dimensions, including mood and motivation. However, since taVNS research is still an emerging field, the underlying neurophysiological processes are not yet fully understood, and the replicability of findings on biomarkers of taVNS effects has been questioned. Here, we perform a living Bayesian random effects meta-analysis to synthesize the current evidence concerning the effects of taVNS on heart rate variability (HRV), a candidate biomarker that has, so far, received most attention in the field. To keep the synthesis of evidence transparent and up to date as new studies are being published, we developed a Shiny web app that regularly incorporates new results and enables users to modify study selection criteria to evaluate the robustness of the inference across potential confounds. Our analysis focuses on 17 single-blind studies comparing taVNS versus sham in healthy participants. These newly synthesized results provide strong evidence for the null hypothesis (g = 0.011, CIshortest = [−0.103, 0.125], BF01 = 25.587), indicating that acute taVNS does not alter HRV compared to sham. To conclude, based on a synthesis of the available evidence to date, there is no support for the hypothesis that HRV is a robust biomarker for acute taVNS. By increasing transparency and timeliness, we believe that the concept of living meta-analyses can lead to transformational benefits in emerging fields such as non-invasive brain stimulation.

Non-invasive vagal nerve stimulation enhances cognitive emotion regulation

“…Given the crucial role of the vagus nerve in HRV, an increase in HRV during taVNS has been hypothesized (Burger, D'Agostini, et al, 2020). However, inconsistent findings have been found in the literature (see Wolf et al, 2021 for a recent preprint meta-analysis), questioning the suitability of HRV as taVNS biomarker. Other proposed candidates are based on the hypothesized effects of taVNS on the locus coeruleus norepinephrinergic (LC-NE) system (Colzato & Vonck, 2017), with LC-NE activity being assessed by indirect markers such as pupil dilation, salivary alpha-amylase and the P300 event-related potential (Burger, D'Agostini, et al, 2020).…”

“…For example, Clancy et al (2014) found that bilateral taVNS of the tragus reduces muscle sympathetic nerve activity and enhances heart rate variability, an index of cardiac vagal control (Burger, D'Agostini, et al, 2020) related to successful emotion regulation (Mather & Thayer, 2018). Yet, findings have been conflicting given that enhancing effects of taVNS on heart rate variability parameters have not been found in other studies (e.g., Borges et al, 2020Borges et al, , 2019Burger et al, 2019, see also this recent meta-analysis preprint by Wolf et al, 2021). Taken together, although previous research provides evidence for the modulatory effects of taVNS on various processes related to cognitive control, required for successful cognitive emotion regulation, fundamental studies in healthy samples investigating the behavioral and psychophysiological effects of taVNS on cognitive emotion regulation strategies, for which cognitive reappraisal is one of the most studied, are lacking.…”

Auricular Vagus Neuromodulation—A Systematic Review on Quality of Evidence and Clinical Effects

“…Overall, the effects of aVNS on sympathovagal balance conflict between studies. Similarly, Wolf et al (2021), in a meta-analysis pre-print, concluded that there was "no support for the hypothesis that HRV is a robust biomarker for acute [aVNS]. "…”

State- and frequency-dependence in autonomic rebalance mediated by intradermal auricular electroacupuncture stimulation

“…Therefore, we hypothesized that statedependency in iaES would be a distinct feature in normal and autonomic imbalance models. HRV and HR are biomarkers of ANS activity (Wolf et al, 2021). We used heart rate variability (HRV) monitoring (Michael et al, 2017;Capilupi et al, 2020) to determine the effects of different iaES frequencies in normal and ANS imbalance model rats.…”