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

轻度创伤性脑损伤(MTBI)是退伍军人管理局关注的一个重要问题，它影响 许多退伍军人曾在阿富汗和伊拉克的战斗中服役，经常与 创伤后应激障碍(PTSD)。当这些情况同时发生时，它们与 相当高的发病率、增加的医疗费用和经济生产力的损失。当前的治疗方法 对于mTBI和创伤后应激障碍来说，这是有局限性的，对许多退伍军人来说，这些会成为终生疾病。电气 治疗代表着治疗与神经创伤相关的障碍的新地平线。一种类型的 治疗方法是迷走神经刺激(VNS)，这显示出它促进了神经创伤的前景 神经可塑性，增强新的学习能力，并通过对大脑的影响阻止应激生理 参与调节应激以及减少外周交感神经和炎性反应的区域 副交感神经功能增强。这是通过传入和传出分支的 迷走神经既投射到大脑，也投射到外周炎症和自主系统。早些时候 几代VNS因需要复杂的手术和麻醉程序而受到限制， 费用，以及缺乏保险报销的程序或常规医疗保健后续行动。这 阻碍了这些治疗措施的广泛实施。新型无创迷走神经刺激 (NVNS)装置更经济，不需要手术植入。我们的初步数据 结果显示，nVNS(但不是假刺激)可阻断应激对周围血管收缩的影响，并 通过直接心血管测量(射血前、或 PEP)，降低炎症标记物(IL-6或IL-6)，增强前扣带回功能，阻断 脑岛对压力的反应，提高记忆力，减少创伤后应激障碍症状。本项目将探索 NVNS或Sham治疗对应激反应的脑、心血管/交感神经和免疫反应的影响 患有创伤和创伤后应激障碍的退伍军人。受试者将同时承受压力和 高分辨率正电子发射断层扫描(HR-PET)和放射性标记脑水分测量 血液中的血流量、外周心血管/交感神经功能和免疫生物标志物。我们 假设NVNS而不是假刺激将导致前扣带回和 应激任务中的脑岛功能降低，记忆任务中的海马体功能降低，以及 创伤性脑损伤和创伤后应激障碍患者的心血管/交感和免疫反应。 此外，我们假设，连续三个月的每日nVNS(但不是假的)将导致增强 在记忆功能方面，减少创伤后应激障碍症状，并调节大脑和自主神经反应 压力。该项目将提供有关NVNS机制的神经生物学和 合并创伤后应激障碍的创伤性脑损伤的生理学及改善症状和提高疗效的途径 认知力。这可能是未来神经创伤退伍军人康复的一种很有前途的方法。

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.