Neuromodulation of heart rate variability: A systematic review

BACKGROUND: Autonomic nervous system (ANS) dysfunction contributes to an increased risk of cardiovascular events. Non-invasive neuromodulation methods, such as transcranial direct current stimulation (tDCS), transcranial magnetic stimulation (TMS), and transcutaneous vagus nerve stimulation (tVNS), have been used to modulate the ANS. However, their comparative efficacy and optimal protocols remain uncertain due to study heterogeneity. This study aimed to verify the level of evidence for the effect of these neuromodulation methods on heart rate variability (HRV) and sympathovagal balance. METHODS: This systematic review and meta-analysis followed PRISMA guidelines and was registered in PROSPERO. Databases including Cochrane Library, Web of Science, PubMed, and Embase were searched up to October 2024. Randomized controlled trials (RCTs) that compared tDCS, TMS, or tVNS against control or sham conditions in humans, with HRV variables as an outcome, were included. RESULTS: Thirteen RCTs were included: 5 used tDCS, 6 used tVNS, and 2 used TMS. Significant heterogeneity was observed in the neuromodulation protocols. The meta-analysis found no statistically significant effects of tDCS on frequency-domain variables. Similarly, tVNS showed no significant effect on frequency- or time-domain variables. The quality of evidence for the main outcomes was rated as moderate for both tDCS and tVNS. CONCLUSION: The current evidence on the effects of tDCS, TMS, and tVNS on HRV is limited and heterogeneous. These findings reinforce the need for methodological standardization in stimulation protocols and for studies with larger sample sizes to provide more robust clinical findings.