Accrued Reductions in Heart Rate Following Transcutaneous Vagal Nerve Stimulation in Adults with Posttraumatic Stress Disorder

Srirakshaa Sundararaj ^1* Asim H Gazi ² Viola Vaccarino ^3,4 Amit Jasvant Shah ^3,4,5 Omer T Inan ^6,7 James Douglas Bremner ^5,8,9*

• ¹ College of Sciences, Georgia Institute of Technology, Atlanta, Georgia, United States
• ² School of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts, United States
• ³ Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia, United States
• ⁴ Division of General Internal Medicine, Department of Medicine, School of Medicine, Emory University, Atlanta, Colorado, United States
• ⁵ Atlanta VA Health Care System, Veterans Health Administration, United States Department of Veterans Affairs, Decatur, Georgia, United States
• ⁶ School of Electrical and Computer Engineering, College of Engineering, Georgia Institute of Technology, Atlanta, Georgia, United States
• ⁷ Wallace H. Coulter Department of Biomedical Engineering, College of Engineering, Georgia Institute of Technology, Atlanta, Georgia, United States
• ⁸ Department of Psychiatry and Behavioral Sciences, School of Medicine, Emory University, Atlanta, Georgia, United States
• ⁹ Department of Radiology and Imaging Sciences, School of Medicine, Emory University, Atlanta, Georgia, United States

Background: Post-Traumatic Stress Disorder (PTSD) is a condition marked by chronic autonomic dysregulation, including heightened arousal and increased heart rate, contributing to a higher risk of cardiovascular disease (CVD). TcVNS has been shown in prior work to decrease arousal and reduce heart rate in participants with PTSD during stimulation and two to three minutes afterwards. No studies have investigated effects of tcVNS on objective physiological markers such as heart rate over hour-long timescales.The purpose of this study was to investigate the effects of active versus sham tcVNS on heart rate responses to stress in traumatized individuals with and without PTSD undergoing a three-hour traumatic stress reminder protocol. Understanding the effects of tcVNS on heart rate over extended periods lasting several hours is crucial to better assess its potential cardiovascular benefits and inform treatment strategies for this population.Methods: A total of 41 participants, including 22 with PTSD (sex: 16 female, 6 male; age: 41.5 ± 12.89 years) and 19 without (sex: 9 female, 10 male; age: 32.79 ± 7.10 years), participated in a mechanistic clinical trial that elicited trauma-incited stress responses by replaying recorded traumatic scripts followed by active or sham tcVNS (double-blind, randomized). Continuous electrocardiogram data were collected and used to measure heart rate and temporal alignment and resampling of the beat-by-beat heart rate time series were performed to distinctively enable timepoint by timepoint averaging for the entire three-hour research visit. We then aggregated the responses across participants of the same group (active/sham x PTSD/non-PTSD) and investigated the effects of tcVNS on heart rate over the multi-hour protocol.Results: Analysis revealed accrued reductions in heart rate among participants with PTSD who received active tcVNS compared to those who received sham stimulation (P < 0.05). These effects were not observed in non-PTSD participants. Notably, heart rate reduced approximately 5% below baseline levels for participants with PTSD who received active tcVNS by the end of the ~3-hour-long protocol, indicating accrued effects of tcVNS on cardiac autonomic function.Conclusions: tcVNS induces accrued reductions in heart rate for participants with PTSD, potentially suggesting a temporary reduction of chronic cardiac arousal associated with PTSD.