Transcutaneous Cervical Vagal Nerve Stimulation Reduces Sympathetic Responses to Stress in Posttraumatic Stress Disorder

Objective Exacerbated autonomic responses to acute stress are prevalent in posttraumatic stress disorder (PTSD). The purpose of this study was to assess the effects of transcutaneous cervical VNS (tcVNS) on autonomic responses to acute stress in patients with PTSD. The authors hypothesized tcVNS would reduce the sympathetic response to stress compared to a sham device. Methods Using a randomized double-blind approach, we studied the effects of tcVNS on physiological responses to stress in patients with PTSD (n=25) using noninvasive sensing modalities. Participants received either sham or active tcVNS after exposure to acute personalized traumatic script stress and mental stress (public speech, mental arithmetic) over a three-day protocol. Physiological parameters related to sympathetic responses to stress were investigated. Results Relative to sham, tcVNS paired to traumatic script stress decreased sympathetic function as measured by: decreased heart rate (adjusted ß=-5.7%; 95% CI: ±3.6%, effect size d=0.43, p<0.01), increased photoplethysmogram amplitude (peripheral vasodilation) (30.8%; ±28%, 0.29, p<0.05), and increased pulse arrival time (vascular function) (6.3%; ±1.9%, 0.57, p<0.0001). Similar (p < 0.05) autonomic, cardiovascular, and vascular effects were observed when tcVNS was applied after mental stress or without acute stress. Conclusion tcVNS attenuates sympathetic arousal associated with stress related to traumatic memories as well as mental stress in patients with PTSD, with effects persisting throughout multiple traumatic stress and stimulation testing days. These findings show that tcVNS has beneficial effects on the underlying neurophysiology of PTSD. Such autonomic metrics may also be evaluated in daily life settings in tandem with tcVNS therapy to provide closed-loop delivery and measure efficacy. ClinicalTrials.gov Registration # NCT02992899 Highlights We studied the effects of tcVNS on physiological responses to stress in patients posttraumatic stress disorder (PTSD). tcVNS modulates physiologic reactivity to traumatic and mental stress in PTSD, and modulates autonomic tone when applied without acute stress. Repeated tcVNS enhances resilience in the face of repeated stress in PTSD as quantified by peripheral autonomic measures which potentially could serve as real-time measures to evaluate the therapy response in longitudinal settings.