Deconstructing Post-Stroke Hemiparesis for Precision Neurorehabilitation

项目摘要/摘要 David Lin博士是退伍军人管理局普罗维登斯健康中心的神经危重护理和神经康复专业神经科专家 职业目标是进行神经康复技术的机械性临床试验的护理系统，以 为中风后有运动障碍的退伍军人最大限度地发挥神经再生潜能和功能恢复。一位批评者 朝着这个目标迈进的一步是林博士在上肢表型方面进行研究并获得培训 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项 上肢卒中运动恢复的自然史研究，他在其中证明了 招募180多名手臂无力的急性中风患者参加研究并追踪他们的上肢 从急性期到慢性期的肢体损伤。林博士正在完成对模式的分析 在他的VA CDA-1项目中，研究了中风后脑电皮质连接性的变化。在这个职业发展奖中-2 (CDA-2)项目中，林博士建议测试特定系统的神经科学，模型驱动的关于 卒中后上肢偏瘫的表型与解剖学的关系 扩散磁共振成像)和生理学(通过经颅磁刺激进行评估) 特定的下行运动通路(皮质脊髓和皮质网状脊髓)。具体地说，他将(1) 卒中后偏瘫的各个组成部分解构(2)运动束下行解剖图 卒中后偏瘫的不同组成部分和(3)下行运动束生理图 中风后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 弗吉尼亚州普罗维登斯对75名中风后慢性偏瘫退伍军人的专门横断面研究。 拟议的CDA-2项目将为林博士提供运动控制、结构 神经影像、运动系统、神经生理学和神经康复研究的应用生物统计学 以及领导独立退伍军人管理局实验室和临床所需的研究技能的进一步经验 审判。林博士将在世界级和 多学科指导团队。Leigh Hochberg博士(主要导师)和John Krakauer博士(主要合作伙伴 Mentor)将协调一个内容导师小组(神经成像-Jennifer Barredo博士，神经生理学-Dr。 诺亚·菲利普和运动学和运动控制-史蒂文·考茨博士)和主题顾问(神经成像-博士)。 运动系统生理学-莫妮卡·佩雷斯博士，神经技术-卡鲁内什·甘古利博士，应用 生物统计学--杰夫·戈德史密斯博士)。林博士制定了一项系统的指导和教学计划 补充他提议的项目中的科学活动。所有这些活动都将利用广泛的 退伍军人研究开发中心(CfNN)的资源和世界级环境 在弗吉尼亚州普罗维登斯及其附属研究机构，马萨诸塞州总医院，哈佛医学院。因此， 拟议的退伍军人管理局以患者为导向的研究项目，与指导和培训计划相结合，将提供 林博士具有发展成为独立退伍军人管理局所必需的科学洞察力和技能 在中风神经康复和系统神经科学的前沿领域的内科科学家生涯。

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.