Optimizing transcutaneous vagus nerve stimulation parameters for sleep and autonomic function in veterans with posttraumatic stress disorder with or without mild traumatic brain injury

Sarah A Bottari; Erin R Trifilio; Brittany Rohl; Samuel S Wu; Dolores Miller-Sellers; Isabella Waldorff; Susheela Hadigal; Michael S Jaffee; Raffaele Ferri; Damon G Lamb; Eric C Porges; John B Williamson

doi:10.1093/sleep/zsaf152

Optimizing transcutaneous vagus nerve stimulation parameters for sleep and autonomic function in veterans with posttraumatic stress disorder with or without mild traumatic brain injury

Sleep. 2025 Jun 9:zsaf152. doi: 10.1093/sleep/zsaf152. Online ahead of print.

Authors

Sarah A Bottari^{1

2

3}, Erin R Trifilio^{2

3}, Brittany Rohl³, Samuel S Wu⁴, Dolores Miller-Sellers², Isabella Waldorff², Susheela Hadigal⁵, Michael S Jaffee⁶, Raffaele Ferri⁷, Damon G Lamb^{1

2}, Eric C Porges^{2

8}, John B Williamson^{1

2

3

8}

Affiliations

¹ Center for OCD, Anxiety, and Related Disorders, Department of Psychiatry, University of Florida, Gainesville, FL, USA.
² Brain Rehabilitation Research Center, Malcom Randall VA Medical Center, Gainesville, FL, USA.
³ Department of Clinical and Health Psychology, College of Public Health and Health Professions, University of Florida, Gainesville, FL, USA.
⁴ Department of Biostatistics, College of Public Health and Health Professions, College of Medicine, University of Florida, Gainesville, FL, USA.
⁵ Division of Pulmonary, Critical Care and Sleep Medicine, University of Florida, Gainesville, Florida, USA.
⁶ Department of Neurology, University of Florida, Gainesville, FL, USA.
⁷ Sleep Research Center, Oasi Research Institute - IRCCS, Troina, Italy.
⁸ Center for Cognitive Aging and Memory, College of Medicine, University of Florida, Gainesville, FL, USA.

PMID: 40489292
DOI: 10.1093/sleep/zsaf152

Abstract

Study objectives: Transcutaneous vagus nerve stimulation (tVNS) has emerged as a potential therapeutic intervention for posttraumatic stress disorder (PTSD), yet optimal stimulation parameters remain undetermined. This study aimed to identify the most effective tVNS parameters for enhancing sleep architecture and autonomic function in veterans with PTSD.

Methods: Twenty-one veterans with PTSD underwent three nights of polysomnography with tVNS administered for one hour at lights out. Nine combinations of pulse width (100μs, 500μs), frequency (10Hz, 20Hz, 25Hz), and intensity threshold (80% discomfort, 100% sensory, 200% sensory) were tested against sham stimulation. Primary outcomes were percentage of slow wave (N3) sleep, next-day resting respiratory sinus arrhythmia (RSA), and electrodermal activity during an emotionally-modulated startle task.

Results: The parameter combination of 20Hz, 100μs pulse width, and 80% discomfort threshold was associated with the most optimal outcomes across both intent-to-treat and per protocol analyses. This combination significantly improved slow wave sleep percentage and next-day startle response compared to sham, but not next-day resting RSA. The 80% discomfort threshold setting outperformed other intensity thresholds. While frequency and pulse width combinations did not significantly differ, 20Hz, 100μs allowed for higher stimulation intensity due to greater tolerability.

Conclusions: A single session of tVNS using 20Hz, 100μs, and 80% discomfort threshold parameters improved sleep and autonomic features of PTSD compared to sham stimulation. This combination may be preferred due to allowing higher stimulation intensity while maintaining tolerability. These findings further our understanding of the neurophysiological effects of different tVNS parameter settings and may inform parameter selection in future clinical trials of tVNS.

Keywords: parameter optimization; posttraumatic stress disorder; sleep; transcutaneous auricular vagus nerve stimulation; transcutaneous vagus nerve stimulation; vagus nerve stimulation; veterans.

Published by Oxford University Press on behalf of Sleep Research Society (SRS) 2025. This work is written by (a) US Government employee(s) and is in the public domain in the US.