Functional Electrical Stimulation Mediated Neuroplasticity

描述（由申请人提供）：此K23申请旨在支持候选人Lynne R. Sheffler， MD的研究培训目标。概述了5年的研究培训计划，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医生研究人员，专长于：1)中枢神经系统（CNS）瘫痪患者神经肌肉电刺激（NMES）的运动再学习和神经可塑性效应；2)应用功能磁共振成像（fMRI）技术量化NMES和其他康复干预措施的神经可塑性反应。作为K23职业发展计划的基础，候选人的短期科学目标是：1)培养nmes介导的运动再学习的专业知识；2)熟练使用fMRI作为nmes介导的神经可塑性的检测方法；3)获得额外的研究技能，以成功过渡到独立。研究的重点是足下垂，这是一种常见的中风后踝关节背屈损伤，其特征是步行时脚的拖拽，导致低效和不安全的步态模式。在5年的时间里，提出了一系列的三个研究方案，以开发和实施中风幸存者的踝关节背屈fMRI范式，这将允许比较对侧控制的NMES （CCNMES）与循环腓侧NMES的治疗效果，以增强急性中风后时期踝关节的运动恢复。方案1将发展踝关节背屈的fMRI范例。方案2将对急性脑卒中后患者应用功能磁共振成像范式，以记录与自然恢复相关的皮层和皮层下激活模式的变化。方案3是一项试点随机试验，将比较CCNMES与循环腓骨NMES对运动损伤和fMRI激活模式的影响。神经可塑性的文献表明，NMES对脑卒中后急性期（定义为脑卒中后< 3个月）大脑皮层重组和运动恢复的影响最大。应用功能磁共振成像（fMRI）踝关节背曲模式来识别和表征脑卒中后急性期nmes介导的下肢运动再学习的中心机制，将对脑卒中患者的临床护理具有广泛的意义。K23职业发展计划确定了三位美国国立卫生研究院资助的临床研究人员，John Chae， MD, Stephen M. Rao， PhD和Jayme S. Knutson, PhD，在K23奖励期间监督候选人的职业发展和培训活动。该候选人得到了包括克利夫兰FES中心、凯斯西储大学、MetroHealth医学中心和谢伊认知神经成像中心（克利夫兰诊所）在内的研究基础设施的进一步支持。这项K23申请将探讨脑卒中后运动再学习和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的临床研究人员地位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. PUBLIC HEALTH RELEVANCE: There is a critical need to train physician researchers capable of bridging basic neuroscience and engineering research and clinical care so as to facilitate the translation of rehabilitation interventions that may enhance motor function and quality of life for patients with CNS paralysis. The K23 funding mechanism will provide the candidate with a unique set of skills as an expert in NMES-mediated motor relearning, post-stroke neuroplasticity and the application of functional MRI to elucidate cortical mechanisms of post-stroke motor recovery.