Identification of autonomic biomarkers of transcutaneous auricular vagus nerve stimulation

Transcutaneous auricular vagus nerve stimulation (taVNS) is a non-invasive neuromodulatory technique with promising therapeutic applications, particularly in neurorehabilitation, as it can elicit physiological effects comparable to invasive VNS without requiring surgical implantation. However, the lack of reliable biomarkers confirming effective vagal engagement during taVNS remains a barrier to its clinical translation. Such biomarkers are essential to identify responders, optimize stimulation parameters, and improve reproducibility across studies. Heart Rate Variability (HRV), derived from electrocardiography (ECG), provides a non-invasive way to investigate the autonomic nervous system activity and has been widely explored as a candidate biomarker of vagal activation. This thesis systematically investigates the effects of short (2 s) and longer (30 s) taVNS bursts on HRV in healthy adults. Data were analyzed from two independent experiments involving healthy adults. HRV features, primarily the root mean square of successive differences (RMSSD), were computed within short (5 s) and longer (30 s) windows to assess transient changes in autonomic activity. Our results show that neither short nor longer taVNS bursts produced consistent changes in HRV metrics compared to sham stimulation. These results provide insights into the complexity of taVNS-induced autonomic effects and indicate that HRV may have limited sensitivity as an acute biomarker of vagal engagement under these conditions. Overall, this work advances our understanding of the autonomic effects of taVNS and underscore the need for future research to identify reliable physiological markers to guide personalized, clinically relevant stimulation protocols, particularly in movement-paired neurorehabilitation settings.