Transcutaneous cervical vagal nerve stimulation reduces sympathetic responses to stress in posttraumatic stress disorder: A double-blind, randomized, sham controlled trial

• Authors: Nil Z. Gurel, Georgia Institute of Technology; Matthew T. Wittbrodt, Emory University; Hewon Jung, Georgia Institute of Technology; Md. Mobashir H. Shandhi, Georgia Institute of Technology; Emily G. Driggers, Emory University; Stacy L. Ladd, Emory University; Minxuan Huang, Emory University; Yi-An Ko, Emory University; Lucy Shallenberger, Emory University; Joy Beckwith, Emory University; Jonathon Nye, Emory University; Bradley Pearce, Emory University; Viola Vaccarino, Emory University; Amit Shah, Emory University; Omer T. Inan, Georgia Institute of Technology; J. Douglas Bremner, Emory University
• Journal Title: NEUROBIOLOGY OF STRESS
• Volume: Volume 13
• Publisher: ELSEVIER SCIENCE INC | 2020-11-01, Pages 100264-100264
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.1016/j.ynstr.2020.100264
• Subjects: Biology, Neuroscience; Psychology, Developmental; Psychology, Physiological
• Keywords: Science & Technology; Life Sciences & Biomedicine; Neurosciences; Neurosciences & Neurology; Posttraumatic stress disorder; Wearable bioelectronic medicine; Vagus nerve stimulation; Transcutaneous cervical stimulation; Stress; Electroceuticals; HEART-RATE-VARIABILITY; BAROREFLEX SENSITIVITY; ELECTRICAL-STIMULATION; BARORECEPTOR SENSITIVITY; EXPOSURE THERAPY; MENTAL STRESS; FMRI EVIDENCE; PTSD; EXTINCTION; MORTALITY

Abstract

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 (n = 12) or active tcVNS (n = 13) 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 β = −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.