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

轻度创伤性脑损伤（mTBI）是退伍军人管理局的一个重要问题， 许多曾在阿富汗和伊拉克作战的退伍军人， 创伤后应激障碍。当这些情况同时发生时，它们与 相当高的发病率、增加的医疗保健成本和经济生产力的损失。当前治疗 对于mTBI和PTSD有局限性，在许多退伍军人中，这些成为终身障碍。电 治疗代表了治疗与神经创伤有关的疾病的方法的新视野。一种类型的 治疗是迷走神经刺激（VNS），它显示了神经创伤的希望，因为它促进了 神经可塑性，增强新的学习，并通过对大脑的影响阻断压力生理学 参与调节应激以及减少外周交感神经和炎症的区域， 增强副交感神经功能。这是通过传入和传出分支的介导的 迷走神经投射到大脑和周围炎症和自主系统。早些时候 几代VNS受到需要复杂手术和麻醉程序的限制， 费用，以及缺乏保险对程序或常规医疗保健随访的报销。这 阻止了这些治疗方法的广泛应用。新型无创迷走神经刺激 （nVNS）设备更经济，并且不需要手术植入。我们的初步数据 显示nVNS（但不是假刺激）阻断应激对外周血管收缩的作用， 通过直接心血管测量测量的交感神经张力增加（射血前期，或 PEP），减少炎症标志物（白细胞介素-6或IL-6），增强前扣带功能，阻断 减少对压力的反应，促进记忆，减少创伤后应激障碍症状。本项目将探讨 nVNS或假治疗对脑、心血管/交感神经和免疫应激反应的影响 mTBI和创伤后应激障碍的退伍军人。受试者将暴露于压力下， 脑的高分辨率正电子发射断层扫描（HR-PET）和放射性标记水测量 血流和外周心血管/交感神经功能以及血液中的免疫生物标志物。我们 假设nVNS而不是假刺激将导致前扣带回增加， 应激任务的海马功能和记忆任务的海马功能降低， mTBI和PTSD患者对应激的心血管/交感神经和免疫反应。 此外，我们假设每天nVNS（而不是假）三个月将导致增强 在记忆功能，减少创伤后应激障碍症状，调节大脑和自主反应， 应力本项目将提供有关nVNS在神经生物学上的机制， mTBI与共病PTSD的生理学以及它可以改善症状和增强 认知.这可能是一个有前途的未来的方法，为退伍军人神经创伤的康复。

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.