Timing Considerations for Noninvasive Vagal Nerve Stimulation in Clinical Studies.

Noninvasive vagal nerve stimulation (n-VNS) devices have the potential for widespread applicability in improving the well-being of patients with stress-related psychiatric disorders. n-VNS devices are known to affect physiological signals, and, recently, they have been employed in various protocols involving both acute and longitudinal applications. However, questions regarding response time, "dosage," or optimal treatment paradigms remain open. Prior work evaluated noninvasively obtained biomarkers that quantify the stimulation efficacy based on the changes in autonomic tone in a randomized double-blind study. In this work, we extend the state-of-the-art by investigating the onset of action for n-VNS in these same physiological biomarkers through a three-day clinical trial, including 233 administrations on 24 human participants, with and without immediately preceding acute traumatic stress. Determining n-VNS latency serves as a substantial step toward optimizing stimulation delivery with higher temporal resolution for personalized neuromodulation.