Noninvasive, multimodal assessment of physiological responses to transcutaneous auricular vagus nerve stimulation

Stimulating the vagus nerve is of great clinical interest, particularly transcutaneous auricular vagus nerve stimulation (taVNS), a noninvasive method of applying current at the cymba conchae of the outer ear to target the auricular branch of the vagus nerve. Recent efforts have shown therapeutic effects of taVNS on clinical populations, but the mechanism and autonomic nervous system (ANS) responses are not well understood. The ANS maintains physiological homeostasis through control of internal organs, including the heart, blood vessels, and pupils. Instead of invasively accessing neural targets, standard clinical measures can record ANS-dependent signals. Twenty-one individuals were tested in four sessions over two weeks; taVNS was applied at the left ear while noninvasive sensors captured electrocardiography, blood pressure, breathing, electrodermal activity (EDA), and pupil diameter (PD). From raw vitals, heart rate, mean arterial pressure (MAP), heart rate variability, EDA, and PD responses were derived and averaged across all participants. Summary statistics showed increased PD during the ramp up period of stimulation and increased variability in MAP and EDA during stimulation that persisted during recovery. These results suggest that transient PD responses could be candidate biomarkers taVNS optimization. Combining multimodal sensors and controlled autonomic testing may provide insight for objective evaluation of treatment efficacy or measurement of disease progression.