Neural mechanisms of balance deficits, falls, and freezing of gait in Parkinson's disease

7.项目摘要/摘要 候选人。我是一名电气工程师，擅长生物医学计算，以前 神经科学、生物力学和生物统计学的跨学科培训。我获得了理科学士学位 (SC.B.)理科硕士(SC.M.)2002年从布朗大学获得电气工程学位，并 2004年，完成了一篇关于脑-计算机接口电路设计的论文，这导致了几项工程 出版，并从佐治亚研究所获得电气和计算机工程博士学位 2010年在丁丽娜博士的指导下，我的学位论文研究应用 回答有关平衡的基础科学问题的肌肉骨骼模拟和优化方法 使用来自清醒猫的遗留数据进行控制。作为一名博士后，我学习了实验室和分析 利用肌电研究人体运动的技术，并开发了一种新的方法和软件 用于时间序列数据的统计分析。2012年，我开始研究个人的平衡控制 与丁博士和帕金森氏病博士玛德琳·哈克尼的一项新合作 康复科学家。这项工作的目标是应用在一个基本的 科学背景下了解年轻健康个体的平衡控制以更好地了解平衡 帕金森病患者的功能障碍，并将模型衍生的生物标记物纳入改善的康复结果 措施。最近，我获得了KL2奖学金，提供临床研究方法的正式培训， 流行病学和生物统计学，使用这些方法回答临床相关问题的关键主题 具有有效性和适当的统计严谨性的问题。 职业目标。我的长期职业目标是成为一名独立的翻译调查员，具有以下专业知识 具有独立实验室空间和强大联系的运动障碍患者的平衡和步态 给专注于帕金森症平衡和步态障碍的临床医生和康复科学家。 需要训练。我需要在这个K25有指导的定量研究中建议的专门培训 发展奖是因为我想以独立调查员的身份提出与疾病相关的问题 需要对帕金森病的病理生理学有详细的了解，并对帕金森病的临床处理有透彻的了解。 我将需要增加我目前在计算神经科学和生物力学方面的专业知识 了解这些高度专业化的主题，以便设计和执行高影响、临床相关、 R01-运动障碍的研究水平。 培训和研究计划的环境和关键要素。拟议的培训和 研究活动将为我回答有关平衡赤字之间相互作用的关键问题做好准备， 在PD中摔倒和冻结步态，建立合作临床研究的跟踪记录，并产生 初步数据将构成我的独立研究组合的基础。在这个奖项下，我将 接受有关基底神经节神经解剖学和病理生理学的正式课程和辅导培训 Thomas Wichmann医学博士在帕金森氏症临床诊断和治疗中的指导 在斯图尔特·因素的指导下，埃默里大学运动障碍诊所的疾病 主要合作者/资源丁博士将为建议的实验提供实验室空间和资源。 研究活动将招募一批帕金森氏症患者，包括弗雷特博士正在进行的 冻结步态，这将为以下领域的合作和探索性分析提供重要机会 除了主要的研究目的之外。 研究项目。这些研究将导致更好地预测PD患者跌倒的风险，并得到改进 理解帕金森病、步态冻结(雾)和跌倒之间的机制关系可能导致新的 治疗。我们目前对帕金森病极限中的平衡缺陷、跌倒和雾的理解存在差距 我们预测跌倒风险以及设计和评估新疗法的能力。因此，我们将表演一场前瞻性的 帕金森病患者有雾与无雾跌倒风险的研究 用于量化年轻健康个体的平衡反应，并在动物模型中预测跌倒风险 作为已建立的行为和神经心理学综合系列的组成部分 对跌倒风险的评估。其他分析将使用来自该队列的数据来定量评估强度 以及客观量化的雾严重程度、姿势反应异常、 和跌倒的风险。这项工作将产生关于帕金森病和帕金森病的中枢病理生理学的新的基础知识 雾会影响运动外周，这将提高我们识别哪些患者是潜在的 康复，这将为更多平衡受损患者群体开辟新的调查路线 并纳入其他研究人员正在开发的成像方法的合作研究中 一队。

7. PROJECT SUMMARY/ABSTRACT CANDIDATE. I am an electrical engineer with expertise in biomedical computation and previous interdisciplinary training in neuroscience, biomechanics, and biostatistics. I received the Bachelor of Science (Sc.B.) and Master of Science (Sc.M.) degrees in Electrical Engineering from Brown University in 2002 and 2004, completing a thesis on circuit design for brain-computer interfaces that resulted in several engineering publications, and received the Ph.D. degree in Electrical and Computer Engineering from the Georgia Institute of Technology in 2010 under the supervision of Lena Ting, Ph.D. My dissertation research applied musculoskeletal simulation and optimization approaches to answer basic science questions about balance control using legacy data from awake cats. As a postdoctoral fellow, I learned laboratory and analysis techniques for human movement studies using electromyography, and developed a new method and software for the statistical analysis of timeseries data. In 2012, I began investigating balance control in individuals with Parkinson's disease (PD) in a new collaboration with Dr. Ting and Madeleine Hackney, Ph.D., a PD rehabilitation scientist. The objectives of this work are to apply engineering models developed in a basic science context to understand balance control in young healthy individuals to better understand balance dysfunction in PD, and to incorporate biomarkers derived from the models into improved rehabilitative outcome measures. Recently, I received a KL2 fellowship that provides formal training in clinical research methods, epidemiology, and biostatistics, critical topics for using these approaches to answer clinically relevant questions with validity and appropriate statistical rigor. CAREER GOAL. My long-term career goal is to be an independent translational investigator with expertise in balance and gait in individuals with movement disorders with independent laboratory space and strong liaison to clinicians and rehabilitation scientists focusing on parkinsonian balance and gait dysfunction. NEED FOR TRAINING. I need the specialized training proposed in this K25 Mentored Quantitative Research Development Award because the disease-related questions I want to ask as an independent investigator require a detailed command of PD pathophysiology and a thorough understanding of PD clinical management. I will need to augment my current expertise in computational neuroscience and biomechanics with a deep understanding these highly specialized topics in order to design and perform high-impact, clinically relevant, R01-level research in movement disorders. ENVIRONMENT AND KEY ELEMENTS OF TRAINING AND RESEARCH PLAN. The proposed training and research activities will prepare me to answer key questions about the interaction between balance deficits, falls, and freezing of gait in PD, establish a track record of collaborative clinical research, and produce preliminary data that will form the foundation of my independent research portfolio. Under this award, I will receive formal coursework and mentored training in basal ganglia neuroanatomy and pathophysiology under the mentorship of Thomas Wichmann, M.D. and in the clinical diagnosis and management of Parkinson's disease at the Emory University Movement Disorders Clinic under the mentorship of Stewart Factor, D.O. My Key Collaborator/Resource Dr. Ting will provide laboratory space and resources for the proposed experiments. Research activities will recruit a cohort of PD patients, including participants in Dr. Factor's ongoing studies of freezing of gait, which will provide significant opportunities for collaboration and exploratory analyses in addition to the primary research aims. RESEARCH PROJECT. These studies will lead to better predictors of fall risk in PD patients and improved understanding of mechanistic relationships between PD, freezing of gait (FOG), and falls that may lead to new treatments. Gaps in our current understanding of balance deficits, falls, and FOG in Parkinson's disease limit our ability to predict fall risk and to design and assess new therapies. Therefore, we will perform a prospective study of fall risk in PD patients with and without FOG to test the ability of advanced engineering tools developed to quantify balance responses in young healthy individuals and in animal models to predict fall risk when included as a component of a comprehensive battery of established behavioral and neuropsychological assessments for fall risk. Additional analyses will use data from this cohort to quantitatively assess the strength and temporality of associations between objectively quantified FOG severity, postural response abnormality, and fall risk. This work will yield new fundamental knowledge about how the central pathophysiology of PD and FOG influences the motor periphery that will improve our ability to identify patients who are candidates for rehabilitation and that will open new lines of investigation into additional balance impaired patient populations and into collaborative studies incorporating imaging approaches being developed by others on the research team.