Targeting Neuroplasticity with Brain Computer Interfaces to Maximize Motor Recovery for Veterans with Stroke

中风每年影响超过15，000名退伍军人，是获得性成人残疾的主要原因 在美国改善中风退伍军人的功能残疾是VA的高度优先事项 医疗保健系统。中风后上肢无力是功能性残疾的主要来源， 三分之二的中风幸存者在6个月时无法将其受影响的手臂纳入日常生活活动 中风后与近年来急性卒中护理的变革性进展相反， 中风后的康复仍然有限。脑卒中后手臂运动功能的临床研究现状 康复仍然是职业和物理治疗。这些标准方法目前还没有 由中风后神经解剖学损伤或神经生理学告知。 脑机接口（BCI）是一种很有前途的脑卒中康复新技术。超出 通过让人们控制电脑光标来恢复交流， 或机器人假肢来恢复运动，BCI也有可能增强神经康复。的 康复BCI的基本原理是将预期手臂运动的神经活动（即， 通过EEG）到实际手臂运动的感觉运动反馈（即通过手臂矫形器）， 环境需要最大限度地参与神经回路和恢复神经功能。小型研究 脑机接口改善中风患者的康复已经显示出一些希望，但脑机接口的机制， 哪些BCI能够实现恢复尚未得到充分研究。因此，重大问题仍然摆在面前。 可以发生用于中风康复的BCI的有意义的临床转化。哪些病人会 最佳受益于BCI神经康复？脑卒中后进行BCI训练的最佳时间段是什么？ 在这份职业发展申请中，我将利用一项独特的、正在进行的临床研究， 普罗维登斯退伍军人医疗中心和马萨诸塞州总医院的基础设施， 在2.5年中，我们对120多名手臂无力的急性中风患者进行了随访， 他们第一年的恢复过程，手臂运动结果测量包括Fugl-Meyer和上肢 肢体运动学、神经影像学和神经生理学。我将通过添加脑电图直接扩展这项研究- 在四个研究时间点进行BCI手臂矫形器治疗，第一次治疗发生在中风的几天内。 我的第一个目标是识别由单次- EEG-BCI手臂矫形器培训课程。我将研究特定的神经回路， EEG-BCI训练和脑卒中后时间窗，其中电路对训练最敏感。我的第二 目的是评估基线手臂运动严重程度和卒中神经解剖学如何调节EEG的影响， 脑机接口手臂矫形器训练对皮质功能连接的影响。我会调查手臂的影响Fugl-Meyer 和特定解剖结构的结构损伤对EEG-BCI诱发的回路改变的影响。而且这 该项目将使我能够将我的研究和临床生涯融入VA系统，并将为我提供 量化大脑网络、神经工程和纵向分析的基础科学工具 运动表现和恢复结果，由一个特殊的VA为基础的导师团队的支持。 该项目是（1）创新的，因为它直接扩展了一个独特的临床研究基础设施， 普罗维登斯VAMC和MGH的神经技术和神经恢复的特殊环境， 据我所知，在世界其他地方是不可用的（2）有影响力，因为对 本文的研究结果将进一步完善脑电脑机接口治疗手臂运动神经康复的神经机制 将BCI神经技术转化为临床;（3）重要，因为它是VA整合的第一步 这将最终为我提供机会，领导一个VA团队在临床上翻译BCI 技术，使最大限度地恢复功能，提高生活质量的退伍军人中风后。

Stroke affects more than 15,000 Veterans per year and is the leading cause of acquired adult disability in the United States. Improving functional disability for Veterans with stroke is a high priority for the VA healthcare system. Upper extremity weakness after stroke is a major source of functional disability with over two-thirds of stroke survivors unable to incorporate their affected arm into activities of daily life at six months post-stroke. In contrast to transformative advances in acute stroke care in recent years, novel therapies for rehabilitation after stroke remain limited. The current clinical state-of-the-art for post-stroke arm motor rehabilitation remains occupational and physical therapies. These standard approaches are not currently informed by post-stroke neuroanatomic injury or neurophysiology. Brain computer interfaces (BCIs) are a promising novel technology for stroke rehabilitation. Beyond substituting for lost motor function by allowing people to control computer cursors to regain communication or robot prosthetics to restore movement, BCIs also have the potential to enhance neurorehabilitation. The underlying principle of a rehabilitative BCI is that linking the neural activity of intended arm movement (i.e. via EEG) to the sensorimotor feedback of actual arm movement (i.e. via arm orthosis) recreates the Hebbian environment needed to maximally engage neural circuits and restore neurologic function. Small studies of BCIs to improve rehabilitation for patients with stroke have shown some promise, but the mechanisms by which BCIs enable recovery have been understudied. As a result, significant questions remain before meaningful clinical translation of BCIs for stroke rehabilitation can occur. Who are the patients who would optimally benefit from BCI neurorehabilitation? What is the optimal time period post-stroke for BCI training? In this proposed career development application, I will leverage a unique and ongoing clinical-research infrastructure at Providence VA Medical Center and Massachusetts General Hospital, which has recruited over 120 acute stroke patients with arm weakness in 2.5 years and followed these patients through the course of their first year of recovery with arm motor outcome measures including Fugl-Meyer and upper extremity kinematics, neuroimaging, and neurophysiology. I will directly extend this study by adding EEG- BCI arm orthosis sessions at four study time points, with the first session occurring within days of stroke. My first aim is to identify longitudinal changes in cortical functional connectivity induced by single- sessions of EEG-BCI arm orthosis training. I will investigate specific neural circuits that are strengthened by EEG-BCI training and the post-stroke time window in which circuits are most sensitive to training. My second aim is to evaluate how baseline arm motor severity and stroke neuroanatomy modulate the effects of EEG- BCI arm orthosis training on cortical functional connectivity. I will investigate the effects of arm Fugl-Meyer and structural injury to specific anatomic structures on EEG-BCI induced circuit changes. Furthermore, this project will allow me to integrate my research and clinical career into the VA system and will provide me with fundamental scientific tools in quantification of brain networks, neural engineering, and longitudinal analysis of motor performance and recovery outcomes, supported by an exceptional VA-based mentorship team. This project is (1) innovative because it directly extends a unique clinical-research infrastructure within an exceptional environment for neurotechnology and neurorestoration at Providence VAMC and MGH that, to my knowledge, is unavailable elsewhere in the world (2) impactful because the fundamental insights into the neural mechanisms of EEG-BCI therapy for arm motor neurorehabilitation gained here will advance translation of BCI neurotechnology to the clinic and (3) significant because it is the first step in VA integration of my career that will ultimately provide the opportunity for me to lead a VA team to clinically translate BCI technologies to enable maximal recovery of function and improve quality of life for Veterans after stroke.