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的研究培训目标。Sheffler，MD.一个为期5年的研究培训计划概述，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，具有以下专业知识：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可塑性影响，2）应用功能性磁共振成像（fMRI）技术定量NMES和其他康复干预措施的神经可塑性反应。候选人的短期科学目标，形成了K23职业发展计划的基础，是1）发展NMES介导的运动再学习的专业知识; 2）熟练掌握功能磁共振成像作为NMES介导的神经可塑性的测定;和3）获得额外的研究技能，成功过渡到独立。研究的重点是足下垂，一种常见的中风后踝关节背屈损伤，其特征是行走时拖着脚，导致效率低下和不安全的步态模式。提出了一系列的三个研究方案，在5年的时间内，开发和实施踝关节背屈功能磁共振成像范式中风幸存者，这将允许比较的治疗效果的双侧控制的NMES（CCNMES）与周期性腓神经NMES，以提高运动恢复的踝关节时，应用于急性中风后时期。方案1将开发踝关节背屈功能磁共振成像范例。方案2将对急性卒中后患者应用功能磁共振成像范例，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是一项初步随机试验，将比较CCNMES与周期性腓神经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。应用踝关节背屈功能磁共振成像范式来识别和表征急性卒中后NMES介导的下肢运动再学习的中枢机制，将对卒中患者的临床护理产生广泛的影响。K23职业发展计划确定了三名NIH资助的临床研究人员，John Chae，MD，Stephen M。Rao博士和Jayme S. Knutson博士，负责监督候选人在K23奖项期间的职业发展和培训活动。候选人还得到了研究基础设施的支持，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）。该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的临床研究人员状态提供坚实的培训基础。 公共卫生相关性：迫切需要培训能够将基础神经科学和工程研究与临床护理联系起来的医生研究人员，以促进康复干预措施的转化，从而提高CNS瘫痪患者的运动功能和生活质量。K23资助机制将为候选人提供一套独特的技能，作为NMES介导的运动再学习，卒中后神经可塑性和功能性MRI应用的专家，以阐明卒中后运动恢复的皮质机制。

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.