Bottari Sarah A, Trifilio Erin R, Rohl Brittany, Wu Samuel S, Miller-Sellers Dolores, Waldorff Isabella, Hadigal Susheela, Jaffee Michael S, Ferri Raffaele, Lamb Damon G, Porges Eric C, Williamson John B
Center for OCD, Anxiety, and Related Disorders, Department of Psychiatry, University of Florida, Gainesville, FL, USA.
Brain Rehabilitation Research Center, Malcom Randall VA Medical Center, Gainesville, FL, USA.
Sleep. 2025 Aug 14;48(8). doi: 10.1093/sleep/zsaf152.
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.
Twenty-one veterans with PTSD underwent three nights of polysomnography with tVNS administered for 1 hour at lights out. Nine combinations of pulse width (100μs, 500μs), frequency (10, 20, 25 Hz), 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.
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, 20 Hz, 100 μs allowed for higher stimulation intensity due to greater tolerability.
A single session of tVNS using 20 Hz, 100 μs, 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.
Non-invasive Nerve Stimulation and Sleep (NINS), NCT04021537; https://clinicaltrials.gov/study/NCT04021537.
经皮迷走神经刺激（tVNS）已成为创伤后应激障碍（PTSD）的一种潜在治疗干预手段，但最佳刺激参数仍未确定。本研究旨在确定在患有创伤后应激障碍的退伍军人中，增强睡眠结构和自主神经功能的最有效tVNS参数。
21名患有创伤后应激障碍的退伍军人接受了三晚的多导睡眠图检查，在熄灯时给予tVNS刺激1小时。针对假刺激测试了脉冲宽度（100μs、500μs）、频率（10、20、25Hz）和强度阈值（80%不适、100%感觉、200%感觉）的九种组合。主要结局指标为慢波（N3）睡眠百分比、次日静息时的呼吸性窦性心律不齐（RSA）以及情绪调节惊跳任务期间的皮肤电活动。
在意向性分析和符合方案分析中，20Hz、100μs脉冲宽度和80%不适阈值的参数组合均与最优化结局相关。与假刺激相比，该组合显著提高了慢波睡眠百分比和次日惊跳反应，但未改善次日静息时的RSA。80%不适阈值设置优于其他强度阈值。虽然频率和脉冲宽度组合无显著差异，但20Hz、100μs由于耐受性更高，允许更高的刺激强度。
与假刺激相比，使用20Hz、100μs和80%不适阈值参数进行单次tVNS治疗可改善创伤后应激障碍的睡眠和自主神经特征。该组合可能更受青睐，因为在保持耐受性的同时允许更高的刺激强度。这些发现进一步加深了我们对不同tVNS参数设置的神经生理效应的理解，并可能为未来tVNS临床试验中的参数选择提供参考。
非侵入性神经刺激与睡眠（NINS），NCT04021537；https://clinicaltrials.gov/study/NCT04021537 。
