Deconstructing Post-Stroke Hemiparesis for Precision Neurorehabilitation

项目总结/摘要 博士大卫林是一个神经重症监护和神经康复专业神经学家在弗吉尼亚州普罗维登斯健康 护理系统，其职业目标是进行神经康复技术的机械临床试验， 最大限度地发挥神经可塑性潜力，并为中风后运动障碍的退伍军人提供功能恢复。一个关键 林博士朝着这个目标迈出的一步是进行上肢表型的研究和训练 中风偏瘫及其神经解剖学和神经生理学基础。林博士目前领导着一个 上肢中风运动恢复的自然史研究，他已经证明了 招募了180多名手臂无力的急性中风患者参加一项研究， 从急性到慢性恢复阶段的肢体损伤。林博士正在完成一项模式分析 中风后脑电图皮层连接性变化的研究。在这个职业发展奖-2 （CDA-2）项目，林博士提出测试特定的系统神经科学，模型驱动的假设， 脑卒中后上肢轻偏瘫的表型与解剖学之间的关系（由 扩散磁共振成像）和生理学（经颅磁刺激评估） 特异性下行运动通路（皮质脊髓和皮质网状脊髓）。具体而言，他将（1） 将卒中后轻偏瘫分解为各个组成部分（2）绘制下行运动束解剖图 脑卒中后轻偏瘫的不同组成部分;（3）将下行运动束生理学映射到 中风后轻偏瘫的不同组成部分。为了实现这些目标，林博士计划进行一项新的和 在普罗维登斯VA进行的一项专门的横断面研究，研究对象为N = 75名卒中后慢性轻偏瘫退伍军人。 拟议中的CDA-2项目将为林博士提供运动控制、结构控制、 神经影像学、运动系统神经生理学和神经康复研究的应用生物统计学 以及领导独立VA实验室和临床所需的研究技能的进一步经验 审判林博士将实现科学和培训提出的支持下，一个世界级的， 多学科指导团队。Leigh Hochberg博士（主要导师）和John Krakauer博士（主要合作者） 导师）将协调一个内容导师小组（神经成像-詹妮弗巴雷多博士，神经生理学-博士。 诺亚菲利普，运动学和运动控制-史蒂芬考茨博士）和主题顾问（神经影像学-博士。 Sanes，运动系统生理学-Monica Perez博士，神经技术-Karunesh Ganguly博士，应用 生物统计学-Jeff金匠博士）。林博士已经制定了一个系统的指导和教学计划， 在他提出的项目中补充科学活动。所有这些活动都将利用广泛的 VA RR&D神经修复和神经技术中心（CfNN）的资源和世界一流的环境 在普罗维登斯弗吉尼亚州和研究附属机构，马萨诸塞州总医院，哈佛医学院。因此 拟议的退伍军人事务部以病人为导向的研究项目，与指导和培训计划相一致，将提供 博士林与科学的见解和技能，是必不可少的，他发展成为一个独立的VA 在中风神经康复和系统神经科学的前沿医生科学家的职业生涯。

PROJECT SUMMARY / ABSTRACT Dr. David Lin is a Neurocritical Care and Neurorehabilitation specialized Neurologist at VA Providence Health Care System whose career goal is to conduct mechanistic clinical trials of neurorehabilitation technologies, to maximize neuroplastic potential and functional recovery for Veterans with motor deficits after stroke. A critical step towards this goal is for Dr. Lin to perform research and acquire training in the phenotype of upper extremity stroke hemiparesis as well as its neuroanatomic and neurophysiologic underpinnings. Dr. Lin currently leads a natural history study of upper extremity stroke motor recovery in which he has demonstrated the feasibility of recruiting over 180 acute stroke patients with arm weakness into a research study and tracking their upper extremity impairments from the acute to chronic stages of recovery. Dr. Lin is completing an analysis of patterns of EEG cortical connectivity change after stroke in his VA CDA-1 project. In this Career Development Award-2 (CDA-2) project, Dr. Lin proposes to test specific systems neuroscience, model-driven hypothesis about the relationship between the phenotype of post-stroke upper extremity hemiparesis with anatomy (assessed by diffusion magnetic resonance imaging) and physiology (assessed by transcranial magnetic stimulation) of specific descending motor pathways (corticospinal and corticoreticulospinal). Specifically, he will (1) Deconstruct post-stroke hemiparesis into its individual components (2) Map descending motor tract anatomy onto distinct components of post-stroke hemiparesis and (3) Map descending motor tract physiology onto distinct components of post-stroke hemiparesis. To achieve these aims, Dr. Lin plans to conduct a new and dedicated cross-sectional study at Providence VA of N = 75 Veterans with chronic hemiparesis after stroke. The proposed CDA-2 project will provide Dr. Lin with fundamental training in motor control, structural neuroimaging, motor systems neurophysiology, and applied biostatistics for neurorehabilitation research as well as further experience with research skills necessary to lead an independent VA laboratory and clinical trials. Dr. Lin will achieve the science and training proposed with the support of a world-class and multidisciplinary mentorship team. Dr. Leigh Hochberg (primary mentor) and Dr. John Krakauer (primary co- mentor) will coordinate a panel of content mentors (neuroimaging- Dr. Jennifer Barredo, neurophysiology- Dr. Noah Philip, and kinematics and motor control - Dr. Steven Kautz) and subject advisors (neuroimaging- Dr. Sanes, motor systems physiology- Dr. Monica Perez, neurotechnology- Dr. Karunesh Ganguly, applied biostatistics- Dr. Jeff Goldsmith). Dr. Lin has developed a systematic mentoring and didactic plan to complement the scientific activities in his proposed project. All of these activities will leverage the extensive resources and world-class environment of VA RR&D Center for Neurorestoration and Neurotechnology (CfNN) at Providence VA and research affiliate, Massachusetts General Hospital, Harvard Medical School. Thus, the proposed VA patient-oriented research project, in concert with the mentorship and training plan, will provide Dr. Lin with the scientific insights and skills that are essential for him to develop into an independent VA physician-scientist career at the cutting edge of stroke neurorehabilitation and systems neuroscience.