Non-Invasive Vagal Nerve Stimulation in Veterans with Mild Traumatic Brain Injury (mTBI)

对患有轻度创伤性脑损伤 (mTBI) 的退伍军人进行无创迷走神经刺激

• 批准号: 10543080
• 负责人: James Douglas Bremner
• 金额: --
• 依托单位: VETERANS HEALTH ADMINISTRATION
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-11-01 至 2025-10-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10543080
• 关键词: Address; Affect; Afghanistan; Anesthetics; Anterior; Area; Biological Markers; Blood; Brain; Brain imaging; Brain region; Cardiovascular system; Cerebrovascular Circulation; Cognition; Cognitive; Data; Devices; Disease; Economics; Exposure to; Feeling suicidal; Future; Generations; Government; Guidelines; Headache; Health; Health Care Costs; Healthcare; Hippocampus; Home; Image; Immune response; Immunologic Markers; Impaired cognition; Implant; Inflammation; Inflammatory; Inflammatory Response; Insula of Reil; Insurance; Interleukin-6; Intervention; Iraq; Learning; Measurement; Measures; Mediating; Memory; Morbidity - disease rate; Nerve; Nervous System Trauma; Neurobiology; Neuronal Plasticity; Operative Surgical Procedures; Outcome; Patients; Peripheral; Pharmaceutical Preparations; Photoplethysmography; Physiological; Physiology; Placebos; Positron-Emission Tomography; Post-Concussion Syndrome; Post-Traumatic Stress Disorders; Procedures; Productivity; Publishing; Radiolabeled; Randomized; Rehabilitation therapy; Resistance; Resolution; Stress; Surgical complication; Sympathetic Nerve Block; Symptoms; Syndrome; System; United States Department of Veterans Affairs; Vagus nerve structure; Veterans; Water; biological adaptation to stress; cognitive function; combat; combat veteran; comorbidity; cost; effective therapy; follow-up; implantation; inflammatory marker; memory encoding; memory recall; mild traumatic brain injury; neuroregulation; novel; pain reduction; prevent; progression risk; reduce symptoms; response; restoration; suicidal; vasoconstriction; Address; Affect; Afghanistan; Anesthetics; Anterior; Area; Biological Markers; Blood; Brain; Brain imaging; Brain region; Cardiovascular system; Cerebrovascular Circulation; Cognition; Cognitive; Data; Devices; Disease; Economics; Exposure to; Feeling suicidal; Future; Generations; Government; Guidelines; Headache; Health; Health Care Costs; Healthcare; Hippocampus; Home; Image; Immune response; Immunologic Markers; Impaired cognition; Implant; Inflammation; Inflammatory; Inflammatory Response; Insula of Reil; Insurance; Interleukin-6; Intervention; Iraq; Learning; Measurement; Measures; Mediating; Memory; Morbidity - disease rate; Nerve; Nervous System Trauma; Neurobiology; Neuronal Plasticity; Operative Surgical Procedures; Outcome; Patients; Peripheral; Pharmaceutical Preparations; Photoplethysmography; Physiological; Physiology; Placebos; Positron-Emission Tomography; Post-Concussion Syndrome; Post-Traumatic Stress Disorders; Procedures; Productivity; Publishing; Radiolabeled; Randomized; Rehabilitation therapy; Resistance; Resolution; Stress; Surgical complication; Sympathetic Nerve Block; Symptoms; Syndrome; System; United States Department of Veterans Affairs; Vagus nerve structure; Veterans; Water; biological adaptation to stress; cognitive function; combat; combat veteran; comorbidity; cost; effective therapy; follow-up; implantation; inflammatory marker; memory encoding; memory recall; mild traumatic brain injury; neuroregulation; novel; pain reduction; prevent; progression risk; reduce symptoms; response; restoration; suicidal; vasoconstriction

Mild Traumatic Brain Injury (mTBI) is an important concern of the Veterans Administration that affects many veterans who served in combat in Afghanistan and Iraq and is frequently associated with Posttraumatic stress disorder (PTSD). When these conditions occur together they are associated with considerable morbidity, increased healthcare costs and loss of economic productivity. Current treatments for mTBI and PTSD have limitations, and in many veterans these become lifelong disorders. Electrical treatments represent a new horizon in the approach to disorders related to neurotrauma. One type of treatment is Vagal Nerve Stimulation (VNS), which shows promise for neurotrauma in that it promotes neuroplasticity, enhances new learning, and blocks stress physiology both through effects on brain regions involved in modulation of stress as well reduction of peripheral sympathetic and inflammatory and enhancement of parasympathetic function. This is mediated through afferent and efferent branches of the vagus nerve that project to both the brain and peripheral inflammatory and autonomic systems. Earlier generations of VNS were limited by the need for complicated surgical and anesthetic procedures, high cost, and lack of reimbursement by insurance for procedures or routine healthcare follow-up. This prevented wide-spread implementation of these treatments. New non-invasive Vagal Nerve Stimulation (nVNS) devices are more economical and do not require surgical implantation. Our preliminary data shows that nVNS (but not sham stimulation) blocks effects of stress on peripheral vasoconstriction and increased sympathetic tone as measured with direct cardiovascular measures (pre-ejection period, or PEP), reduces inflammatory markers (interleukin-6, or IL-6), enhances anterior cingulate function, blocks insula response to stress, promotes memory and reduces PTSD symptoms. This project will explore the effects of nVNS or sham treatment on brain, cardiovascular / sympathetic and immune response to stress in combat veterans with mTBI and PTSD. Subjects will undergo exposure to stress in conjunction with High Resolution Positron Emission Tomography (HR-PET) and radiolabeled water measurement of brain blood flow, and peripheral cardiovascular /sympathetic function and immune biomarkers in blood. We hypothesize that nVNS but not sham stimulation will result in an increase in anterior cingulate and reduced insula function with stress tasks and hippocampal function with memory tasks, and block cardiovascular / sympathetic and immune response to stress in patients with mTBI and PTSD. Furthermore we hypothesize that daily nVNS (but not sham) for three months will lead to an enhancement in memory function, reduction in PTSD symptoms, and modulate brain and autonomic responses to stress. This project will provide information about mechanisms of nVNS on the neurobiology and physiology of mTBI with comorbid PTSD and ways in which it may ameliorate symptoms and enhance cognition. This may be a promising future approach for rehabilitation of veterans with neurotrauma.

轻度创伤性脑损伤（MTBI）是退伍军人管理的重要关注 许多在阿富汗和伊拉克战斗的退伍军人，经常与 创伤后应激障碍（PTSD）。当这些条件一起出现时，它们与 相当大的发病率，增加医疗保健成本和经济生产力损失。当前治疗 对于MTBI和PTSD来说，有局限性，在许多退伍军人中，这些都是终身疾病。电气 治疗代表了与神经疾病有关的疾病方法的新视野。一种类型 治疗是迷走神经刺激（VNS），它显示出神经曲的希望 神经可塑性，增强新学习并阻止压力生理，既通过对大脑的影响 涉及压力调节的区域以及外周交感神经和炎症的减少 增强副交感神经功能。这是通过传入和传出的分支来介导的 迷走神经对大脑和周围炎症和自主性系统的神经神经。较早 几代VN的限制受到复杂的外科手术和麻醉程序的需求，高 费用，缺乏保险偿还程序或常规医疗保健随访。这 阻止了这些治疗方法的广泛实施。新的非侵入性迷走神经刺激 （NVN）设备更经济，不需要手术植入。我们的初步数据 表明NVN（但不是假刺激）阻止了压力对周围血管收缩和 通过直接心血管措施（注射前期或 PEP），减少炎症标记（白介素-6或IL-6），增强了前扣带回功能，块 岛对压力的反应，促进记忆力并减少PTSD症状。这个项目将探索 NVN或假治疗对大脑的影响，心血管 /交感神经和免疫反应 在与MTBI和PTSD的战斗退伍军人中。受试者将与 高分辨率的正电子发射断层扫描（HR-PET）和大脑的放射标记水测量值 血流，外周心血管 /交感神经功能和血液中的免疫生物标志物。我们 假设NVN而不是假手术刺激会导致前扣带回和 通过压力任务和海马功能降低了岛的功能，并通过内存任务进行阻止 MTBI和PTSD患者的心血管 /交感神经和免疫反应。 此外，我们假设每天的NVN（但不是假）将导致增强 在记忆功能，减少PTSD症状以及调节大脑和对自主的反应 压力。该项目将提供有关神经生物学机制和神经生物学机制的信息 MTBI的生理学与合并症PTSD以及可以改善症状并增强的方式 认识。这可能是与Neurotrauma恢复退伍军人的未来方法。