Passive electrical neurofeedback treatment of mTBI: MEG and Behavioral Outcomes

轻度创伤性脑损伤(MTBI)是导致持续的身体、认知、情绪和 退伍军人和普通公众的行为缺陷。然而，潜在的病理生理学 目前还不完全清楚，对脑震荡后症状(PCS)也几乎没有有效的治疗方法。在……里面 此外，在PCS和创伤后应激障碍(PTSD)症状之间有很大的重叠 MTBI。IASIS是一类结合低强度脉冲治疗的被动神经反馈疗法之一 经颅电刺激(LIPTES)和脑电监测。唇语技巧 在减轻患有脑外伤的PCS患者方面显示了有希望的结果。然而，神经机制 由于缺乏神经成像，唇部治疗对脑外伤的影响尚不清楚。 对这种治疗性干预的调查。常规神经成像技术，如MRI和CT 在检测由mTBI引起的生理异常或在评估 MTBI治疗。在急性期和慢性期，CT和MRI通常是阴性的，即使在mTBI患者 持久的PCS。相比之下，越来越多的证据支持静息状态脑磁图。 脑磁图)慢波源成像(增量波段，1-4赫兹)作为神经元的非侵入性成像标志 MTBI异常。本申请的主要目标是使用RS-MEG来识别神经 患有多发性脑损伤的退伍军人接受IASIS治疗后行为改变的基础。使用替身- 盲法安慰剂对照设计，我们将研究IASIS前后异常脑磁图慢波的变化 对患有创伤性脑损伤的退伍军人进行治疗(相对于假治疗组)。此外，我们将检查治疗方法- PCS、创伤后应激障碍症状、神经心理测试成绩的相关变化及其与 脑磁图慢波的变化。我们将首次解决有关该机制的一个基本问题 慢波在脑损伤中的作用，即清醒时慢波的产生是否仅仅是一种负波 神经元损伤的后果，或者如果这是正在进行的神经元重排和愈合的标志 发生在受伤的地方。特定目标1将检测患有mTBI的退伍军人的损伤部位，并评估 RS-MEG慢波治疗IASIS后功能神经影像改变的机制 震源成像。我们假设脑磁慢波源成像将显示出明显更高的灵敏度 在单一受试者基础上确定损伤部位方面优于常规MRI。我们还假设在 觉醒，慢波的产生是正在进行的神经重排/康复的标志，而不是 神经元损伤的负面后果。此外，我们假设IASIS最终将减少异常 在治疗疗程结束时在mTBI中产生脑磁图慢波，这是由于 神经重排/修复。具体目标2将检查PCS和PTSD与治疗相关的变化 患有颅脑损伤的退伍军人的症状。我们推测，与假手术组相比，mTBI退伍军人 IASIS治疗组在PCS和PTSD症状方面的下降幅度将明显更大 基线和治疗后评估。具体目标3将研究IASIS治疗之间的关系- 退伍军人mtbi患者的rs-meg慢波成像、pcs和神经心理学测量的相关变化。 我们假设减少的脑磁图慢波产生将与减少的PCS总分相关， 个人PCS评分(例如，睡眠障碍、创伤后头痛、畏光和记忆问题 症状)，并提高了IASIS后和基线考试之间的神经心理学考试分数。这个 拟议研究的成功将首次证实慢波产生的增强作用 清醒状态对mTBI有显著的治疗效果，包括最终减少异常的慢反应。 伴随着PCS和认知功能改善的电波。

Mild traumatic brain injury (mTBI) is a leading cause of sustained physical, cognitive, emotional, and behavioral deficits in OEF/OIF/OND Veterans and the general public. However, the underlying pathophysiology is not completely understood, and there are few effective treatments for post-concussive symptoms (PCS). In addition, there are substantial overlaps between PCS and post-traumatic stress disorder (PTSD) symptoms in mTBI. IASIS is among a class of passive neurofeedback treatments that combine low-intensity pulses for transcranial electrical stimulation (LIP-tES) with electroencephalography (EEG) monitoring. LIP-tES techniques have shown promising results in alleviating PCS individuals with TBI. However, the neural mechanisms underlying the effects of LIP-tES treatment in TBI are unknown, owing to the dearth of neuroimaging investigations of this therapeutic intervention. Conventional neuroimaging techniques such as MRI and CT have limited sensitivity in detecting physiological abnormalities caused by mTBI, or in assessing the efficacy of mTBI treatments. In acute and chronic phases, CT and MRI are typically negative even in mTBI patients with persistent PCS. In contrast, evidence is mounting in support of resting-state magnetoencephalography (rs- MEG) slow-wave source imaging (delta-band, 1-4 Hz) as a noninvasive imaging marker for neuronal abnormalities in mTBI. The primary goal of the present application is to use rs-MEG to identify the neural underpinnings of behavioral changes associated with IASIS treatment in Veterans with mTBI. Using a double- blind placebo controlled design, we will study changes in abnormal MEG slow-waves before and after IASIS treatment (relative to a ‘sham’ treatment group) in Veterans with mTBI. In addition, we will examine treatment- related changes in PCS, PTSD symptoms, neuropsychological test performances, and their association with changes in MEG slow-waves. We for the first time will address a fundamental question about the mechanism of slow-waves in brain injury, namely whether slow-wave generation in wakefulness is merely a negative consequence of neuronal injury or if it is a signature of ongoing neuronal rearrangement and healing that occurs at the site of the injury. Specific Aim 1 will detect the loci of injury in Veterans with mTBI and assess the mechanisms underlying functional neuroimaging changes related to IASIS treatment using rs-MEG slow-wave source imaging. We hypothesize that MEG slow-wave source imaging will show significantly higher sensitivity than conventional MRI in identifying the loci of injury on a single-subject basis. We also hypothesize that in wakefulness, slow-wave generation is a signature of ongoing neural rearrangement / healing, rather than a negative consequence of neuronal injury. Furthermore, we hypothesize IASIS will ultimately reduce abnormal MEG slow-wave generation in mTBI by the end of the treatment course, owing to the accomplishment of neural rearrangement / healing. Specific Aim 2 will examine treatment-related changes in PCS and PTSD symptoms in Veterans with mTBI. We hypothesize that compared with the sham group, mTBI Veterans in the IASIS treatment group will show significantly greater decreases in PCS and PTSD symptoms between baseline and post-treatment assessments. Specific Aim 3 will study the relationship among IASIS treatment- related changes in rs-MEG slow-wave imaging, PCS, and neuropsychological measures in Veterans with mTBI. We hypothesize that Reduced MEG slow-wave generation will correlate with reduced total PCS score, individual PCS scores (e.g., sleep disturbance, post-traumatic headache, photophobia, and memory problem symptoms), and improved neuropsychological exam scores between post-IASIS and baseline exams. The success of the proposed research will for the first time confirm that potentiation of slow-wave generation in wakefulness leads to significant therapeutic benefits in mTBI, including an ultimate reduction of abnormal slow- waves accompanied by an improvement in PCS and cognitive functioning.