Non-Pharmacological Mitigation of Acute Mental Stress-Induced Sympathetic Arousal: Comparison Between Median Nerve Stimulation and Auricular Vagus Nerve Stimulation.

Acute mental stress is a common experience in daily life, significantly affecting both physiological and psychological well-being. While traditional pharmacological interventions can be effective, they often accompany undesirable side effects. Non-pharmacological alternatives, such as non-invasive transcutaneous peripheral neuromodulation, have promise in mitigating acute stress-induced arousal, possibly with fewer side effects. Median nerve stimulation (MNS) and auricular vagus nerve stimulation (AVNS), in particular, have demonstrated notable potential. However, efficacy and mechanism of action pertaining to MNS and AVNS remain largely unknown. This paper comparatively investigated MNS and AVNS in terms of efficacy and mechanism of action in the context of mitigating acute stress-induced arousal. Using an experimental dataset collected from 19 healthy participants who experienced acute mental stressors as well as MNS and AVNS, we showed that (i) MNS and AVNS are both effective in mitigating acute stress-induced cardiovascular arousal with MNS modestly superior to AVNS in terms of a synthetic multi-modal variable derived from physio-markers representing heart rate, blood pressure, stroke volume, cardiac output, and peripheral vasoconstriction: 74% vs. 71% in explainability; 86% vs. 69% in stimulation consistency; 0.77 vs. 0.40 in stimulation sensitivity; and 34% vs. 19% in stimulation effectiveness, respectively; and that (ii) MNS and AVNS mitigate acute stress-induced cardiovascular arousal in a distinct mechanism of action: MNS primarily mitigates the arousal pertaining to the physio-markers representing heart rate and peripheral vasoconstriction, while AVNS mitigates the arousal pertaining to the physio-markers representing heart rate, blood pressure, stroke volume, cardiac output, and peripheral vasoconstriction. These findings may help to support future device development for addressing acute mental stress-induced arousal through MNS or AVNS, and they pave the way toward a better understanding of how to quantify the efficacy of such interventions.