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

Author: Nil Z Gurel1, Matthew T Wittbrodt2, Hewon Jung1, Md Mobashir H Shandhi1, Emily G Driggers2, Stacy L Ladd2,3, Minxuan Huang4, Yi-An Ko5, Lucy Shallenberger4, Joy Beckwith2, Jonathon A Nye3, Bradley D Pearce4, Viola Vaccarino4,6, Amit J Shah4,6,7, Omer T Inan1,8, J Douglas Bremner2,3,7
1 School of Electrical and Computer Engineering, Georgia Institute of Technology, Atlanta, GA, USA.
2 Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA.
3 Department of Radiology, Emory University School of Medicine, Atlanta, GA, USA.
4 Department of Epidemiology, Rollins School of Pu;blic Health, Atlanta, GA, USA.
5 Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Atlanta, GA, USA.
6 Department of Internal Medicine, Emory University School of Medicine, Atlanta, GA, USA.
7 Atlanta VA Medical Center, Decatur, GA, USA.
8 Coulter Department of Bioengineering, Georgia Institute of Technology, Atlanta, GA, USA.
Conference/Journal: Neurobiol Stress
Date published: 2020 Oct 20
Other: Volume ID: 13 , Pages: 100264 , Special Notes: doi: 10.1016/j.ynstr.2020.100264. , Word Count: 277

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.

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.

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.

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 Registration # NCT02992899.

Keywords: Electroceuticals; Posttraumatic stress disorder; Stress; Transcutaneous cervical stimulation; Vagus nerve stimulation; Wearable bioelectronic medicine.

PMID: 33344717 PMCID: PMC7739181 DOI: 10.1016/j.ynstr.2020.100264