Transcutaneous vagal nerve stimulation improvement of sleep quality in veterans with PTSD with or without history of mild TBI

经皮迷走神经刺激可改善患有 PTSD（有或没有轻度 TBI 病史）的退伍军人的睡眠质量

• 批准号: 10490287
• 负责人: John B Williamson
• 金额: --
• 依托单位: VETERANS HEALTH ADMINISTRATION
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-10-01 至 2024-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10490287
• 关键词: Address; Adherence; Affect; Alcohol consumption; Amygdaloid structure; Animals; Apnea; Arthritis; Attenuated; Autonomic nervous system; Behavior; Behavioral; Brain; Cardiovascular Diseases; Chronic; Complex; Continuous Positive Airway Pressure; Crossover Design; Data; Dependence; Development; Diabetes Mellitus; Disease; Dose; Ear; Emotional; Environment; Evaluation; Event; Fostering; Frequencies; Glean; Heart Rate; Heterogeneity; Home; Hour; Human; Impairment; Implant; Individual Differences; Inflammatory; Injury; Investigation; Knowledge; Literature; Measures; Methods; Monitor; Moods; Nerve; Neurotransmitters; Nightmare; Operative Surgical Procedures; Parasympathetic Nervous System; Participant; Patient Self-Report; Patients; Pharmacological Treatment; Phase; Population; Post-Traumatic Stress Disorders; Publishing; Quality of life; REM Sleep; Recording of previous events; Recovery; Regulation; Reporting; Rest; Risk; Role; Safety; Self Assessment; Severities; Sleep; Sleep Architecture; Sleep Deprivation; Sleep Disorders; Sleep disturbances; Sleeplessness; Slow-Wave Sleep; Source; Structure; Sympathetic Nervous System; Symptoms; System; Technology; Testing; Time; Up-Regulation; Vagus nerve structure; Veterans; Visual; Work; actigraphy; addiction; alcohol and other drug; attenuation; clinical care; clinically relevant; cognitive performance; disabling symptom; effective therapy; efficacy evaluation; experience; falls; fighting; heart rate variability; improved; improvement on sleep; innovation; mild traumatic brain injury; multimodality; neurophysiology; neurosurgery; non rapid eye movement; novel; pharmacologic; poor health outcome; poor sleep; post-traumatic symptoms; reduce symptoms; response; side effect; sleep onset; sleep quality; success; tool; translational potential; treatment response; white matter

Problem: Post traumatic stress disorder (PTSD) severely limits quality of life. Current PTSD treatments have limited and variable efficacy. New and more effective treatments are necessary. Patients with PTSD often have disrupted sleep. These patients are more likely to wake up multiple times a night, and have decreased slow wave sleep and increased REM sleep. Further, autonomic and behavioral components during sleep are consistent with a continued fight or flight state while asleep. This includes higher heart rate, lower parasympathetic tone, and greater likelihood of nightmares. PTSD is also associated with higher insomnia severity scores as well as regional neurotransmitter disruptions in systems critical for the regulation of affect. Poor sleep quality is associated with poor health outcomes that overlap with those that are experienced in PTSD. These include associations with the development of cardiovascular disease, diabetes and inflammatory diseases including arthritis. Effective treatment of sleep problems in this population could have substantial impact on these symptoms and improve quality of life. Heterogeneity in PTSD, including hyperarousal symptom expression and prior occurring mild traumatic brain injury (mTBI), may influence individual differences in treatment response. mTBI is a common occurring preceding injury to PTSD and damage to limbic white matter structures may influence presentation of PTSD. Current pharmacological approaches often have side effects like negative impacts on sleep architecture, addiction, and cognitive performance consequences. Further, Veterans often report that they use alcohol and other drugs in order to fall asleep and stop nightmares, compounding the issue. Vagal nerve stimulation (VNS) approaches have potential, especially in this population to improve sleep quality and to also improve hyperarousal symptoms of PTSD. Vagal nerve stimulation (VNS) induces activation of the parasympathetic nervous system and suppression of amygdala activity, addressing the core components of hyperarousal symptoms of PTSD. Conventional VNS requires neurosurgery. However, we will investigate a novel, non-invasive approach: transcutaneous vagal nerve stimulation (tVNS). tVNS has a high potential for success in this population. Preliminary work. Our pilot data demonstrate increased slow wave sleep, and decreased REM sleep and sleep latency after one hour of tVNS at “lights out.” The mechanism for this may be the result of decreasing hyperarousal symptoms during the first hour of sleep; all participants showed increased high frequency heart rate variability during tVNS compared with sham. We have also previously demonstrated tVNS improvement of hyperarousal signs of PTSD including upregulation of parasympathetic nervous system and attenuation of sympathetic nervous system activity during ‘startle’ in Veterans with PTSD with or without history of mTBI. Plan Our objective is to use tVNS in Veterans with PTSD with or without history of mTBI to evaluate its efficacy in changing sleep architecture (aim 1) and hyperarousal symptoms (aim 2). We will also assess the impact of pre-occurring mTBI and heterogeneity of PTSD symptoms on treatment response (aim 3) as well as safety and tolerability features. We will use a within-subject sham-controlled cross-over design to assess the impact of tVNS administered at “lights out” for one hour on several critical sleep variables including sleep onset, slow wave sleep, REM sleep, and autonomic nervous system behavior.

问题：创伤后应激障碍(PTSD)严重限制了生活质量。目前的创伤后应激障碍治疗方法有 疗效有限且变化不定。新的、更有效的治疗方法是必要的。患有创伤后应激障碍的患者经常 打乱了睡眠。这些患者更有可能一晚醒来多次，而且病情下降缓慢。 波睡眠和增加的快速眼动睡眠。此外，睡眠期间的自主神经和行为成分 与睡眠中持续战斗或逃跑的状态一致。这包括更高的心率，更低的心率 副交感神经的语调，更有可能做噩梦。创伤后应激障碍还与更严重的失眠有关 严重程度评分以及对情感调节至关重要的系统中的局部神经递质中断。 睡眠质量不佳与健康状况不佳有关，这种情况与睡眠质量不佳的经历有重叠之处。 创伤后应激障碍。这些包括与心血管疾病、糖尿病和炎症性疾病的发展有关。 包括关节炎在内的疾病。在这一人群中有效地治疗睡眠问题可能会有很大的帮助 改善这些症状，提高生活质量。创伤后应激障碍的异质性，包括过度唤醒 症状表现和既往发生的轻度创伤性脑损伤(MTBI)可能会影响个体 治疗反应的差异。MTBI是一种常见的先于创伤后应激障碍和创伤后应激障碍的损伤 边缘白质结构可能影响创伤后应激障碍的表现。 目前的药理学方法通常有副作用，如对睡眠结构的负面影响， 成瘾，以及认知表现的后果。此外，退伍军人经常报告说，他们使用酒精和 其他药物为了入睡和停止噩梦，使问题更加严重。迷走神经刺激(VNS) 方法具有改善睡眠质量和改善睡眠质量的潜力，特别是在这一人群中 创伤后应激障碍的过度觉醒症状。 迷走神经刺激(VNS)引起副交感神经系统的激活和抑制 杏仁核活动，解决创伤后应激障碍高觉醒症状的核心组成部分。常规VNS 需要做神经外科手术。然而，我们将研究一种新的、非侵入性的方法：经皮迷走神经 神经刺激(TVNS)。TVNS在这一人群中具有很高的成功潜力。 前期工作。我们的试验数据显示，慢波睡眠增加，快速眼动睡眠和 在“熄灯”状态下进行一小时的tVNS后的睡眠延迟。这一机制可能是由于 在睡眠的第一个小时内出现高觉醒症状；所有参与者都表现出高频心跳增加 TVNS时与假手术时的心率变异性比较。我们之前还演示了tVNS的改进 创伤后应激障碍的高觉醒症状，包括副交感神经系统的上调和 伴或不伴创伤性脑损伤病史的退伍军人在惊吓时的交感神经系统活动。 计划我们的目标是在有或没有创伤性脑损伤病史的退伍军人中使用TVNS来评估其疗效 改变睡眠结构(目标1)和过度觉醒症状(目标2)。我们还将评估 治疗反应的创伤后应激障碍症状的异质性(目标3)以及安全性和 耐受性特征。我们将使用受试者内假控制的交叉设计来评估 在“熄灯”状态下对几个关键睡眠变量进行一小时的TVNS，包括睡眠开始、缓慢 波动睡眠、快速眼动睡眠和自主神经系统行为。