Functional Electrical Stimulation Mediated Neuroplasticity

描述(由申请人提供)：这份K23申请书建议支持候选人Lynne R.Sheffler，MD的研究培训目标。一个为期5年的科研培训计划被勾勒出来，其中包括教育课程、重点科学指导和临床研究。候选人的主要长期科学目标是成为一名独立的临床研究人员，在1)神经肌肉电刺激(NMES)对中枢神经系统(CNS)瘫痪患者的运动再学习和神经整形效应方面具有专业知识，以及2)应用功能磁共振成像(FMRI)技术对NMES和其他康复干预措施的神经整形反应进行量化。作为K23职业发展计划的基础，候选人的短期科学目标是1)发展NMES介导的运动再学习方面的专业知识；2)熟练使用功能磁共振成像作为NMES介导的神经可塑性的测试；以及3)获得成功过渡到独立的额外研究技能。研究的重点是脚部下垂，这是一种常见的中风后踝关节背屈功能障碍，其特征是在行走过程中拖拽脚，导致低效和不安全的步态模式。一系列为期5年的研究方案被提出，以开发和实施中风幸存者的踝关节背屈功能磁共振成像范式，该范式将允许比较对侧控制的NMES(CCNMES)和环状腓骨NMES的治疗效果，以促进中风后急性期踝关节的运动恢复。方案1将开发踝关节背屈功能磁共振成像范例。方案2将把功能磁共振成像范式应用于急性中风后患者，以记录与自然恢复相关的皮质和皮质下激活模式的变化。方案3是一项先导性随机试验，将比较CCNMES和周期性腓骨NMES对运动障碍和fMRI激活模式的影响。神经可塑性文献表明，NMES影响皮质重组和运动恢复的能力可能在急性卒中后时期(定义为卒中后3个月)最大。应用功能磁共振踝关节背屈功能磁共振成像范式识别和表征NMES介导的卒中后急性期肢体运动再学习的中枢机制，将在卒中患者的临床护理中具有广泛的意义。K23职业发展计划确定了三名由NIH资助的临床研究人员，他们是John Chae医学博士、Stephen M.Rao博士和Jayme S.Knutson博士，负责监督候选人在K23颁奖期间的职业发展和培训活动。候选人还得到了包括克利夫兰FES中心、凯斯西储大学、MetroHealth医疗中心和Schey认知神经成像中心(克利夫兰诊所)在内的研究基础设施的进一步支持。这一K23应用程序将探索有关中风后运动再学习和NMES介导的神经可塑性的关键问题，并将为候选人过渡到独立临床研究人员状态提供坚实的培训基础。

DESCRIPTION (provided by applicant): This K23 application proposes to support the research training goals of candidate Lynne R. Sheffler, MD. A 5-year research training plan is outlined which includes educational coursework, focused scientific mentoring and clinical research. The candidate's primary long-term scientific goal is to become an independent clinician researcher with expertise in 1) the motor relearning and neuroplastic effects of neuromuscular electrical stimulation (NMES) for persons with central nervous system (CNS) paralysis and 2) the application of functional magnetic resonance imaging (fMRI) techniques to quantitate neuroplastic responses to NMES and other rehabilitation interventions. The candidate's short-term scientific goals, which form the basis of the K23 career development plan, are 1) to develop expertise in NMES-mediated motor relearning; 2) to gain proficiency with fMRI as an assay for NMES-mediated neuroplasticity; and 3) to acquire additional research skills for successful transition to independence. The research focus is on footdrop, a common post-stroke impairment of ankle dorsiflexion characterized by dragging of the foot during walking, which results in an inefficient and unsafe gait pattern. A series of three research protocols is proposed, over a 5 year period, to develop and implement an ankle dorsiflexion fMRI paradigm in stroke survivors which will allow the comparison of the therapeutic effect of Contralaterally-controlled NMES (CCNMES) versus cyclic peroneal NMES to enhance motor recovery of the ankle when applied in the acute post-stroke period. Protocol 1 will develop the ankle dorsiflexion fMRI paradigm. Protocol 2 will apply the fMRI paradigm to acute post-stroke patients to document changes in cortical and subcortical activation patterns associated with natural recovery. Protocol 3 is a pilot randomized trial which will compare the effect of CCNMES to cyclic peroneal NMES on motor impairment and fMRI activation patterns. The neuroplasticity literature suggests that the ability of NMES to affect cortical reorganization and motor recovery may be greatest in the acute post-stroke period (defined as < 3 months post-stroke). The application of an fMRI ankle dorsiflexion fMRI paradigm to identify and characterize a central mechanism for NMES-mediated lower extremity motor relearning in the acute post-stroke period will have broad implications in the clinical care of stroke patients. The K23 career development plan identifies three NIH-funded clinical researchers, John Chae, MD, Stephen M. Rao, PhD, and Jayme S. Knutson, PhD, to oversee the candidate's career development and training activities during the K23 award period. The candidate is further supported by a research infrastructure that includes the Cleveland FES Center, Case Western Reserve University, MetroHealth Medical Center and the Schey Center for Cognitive Neuroimaging (Cleveland Clinic). This K23 application will explore critical questions regarding post-stroke motor relearning and NMES-mediated neuroplasticity and will provide a solid training foundation to transition the candidate to independent clinical researcher status.