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

帕金森病平衡缺陷、跌倒和冻结步态的神经机制

• 批准号: 9179981
• 负责人: Johnathan Lucas McKay
• 金额: $ 12.73万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-19 至 2020-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9179981
• 关键词: Acceleration; Agonist; Animal Model; Area; Award; Basal Ganglia; Basic Science; Behavioral; Biological Markers; Biomechanics; Biomedical Computing; Biometry; Brain Stem; Clinic; Clinical Management; Clinical Research; Collaborations; Computer software; Computers; Data; Disease; Doctor of Medicine; Doctor of Philosophy; Electrical Engineering; Electromyography; Elements; Engineering; Environment; Epidemiologic Methods; Equilibrium; Fall prevention; Felis catus; Fellowship; Foundations; Freezing; Functional disorder; Gait; Goals; Human; Image; Individual; Institutes; Investigation; K-Series Research Career Programs; Knowledge; Laboratories; Lead; Learning; Link; Master of Science; Mentors; Mentorship; Methods; Modeling; Morbidity - disease rate; Motion; Motor; Movement; Movement Disorders; Multivariate Analysis; Muscle; Musculoskeletal; Neuroanatomy; Neurosciences; Outcome Measure; Parkinson Disease; Parkinsonian Disorders; Participant; Patient Self-Report; Patients; Pharmaceutical Preparations; Pharmacotherapy; Physiological; Postdoctoral Fellow; Postural response; Prospective Studies; Protocols documentation; Publications; Quality of life; Recruitment Activity; Rehabilitation therapy; Research; Research Activity; Research Methodology; Research Personnel; Research Training; Resources; Risk Factors; Science; Scientist; Severities; Staging; Statistical Data Interpretation; Supervision; Symptoms; Techniques; Technology; Testing; Therapeutic; Time; Training; Training Activity; Tremor; Universities; Work; abstracting; awake; brain computer interface; career; clinical Diagnosis; clinically relevant; cohort; computational neuroscience; cost; design; equilibration disorder; fall risk; falls; foot; improved; loved ones; mortality; neuromechanism; neuropsychological; new therapeutic target; novel therapeutics; patient population; prevent; research and development; research study; response; sensor; simulation; tool

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.

7.项目总结/摘要 候选人我是一名电气工程师，擅长生物医学计算， 神经科学、生物力学和生物统计学的跨学科培训。我获得了理学学士学位 （Sc.B.）Master of Science（Sc.M.）2002年获得布朗大学电气工程学位， 2004年，完成了一篇关于脑机接口电路设计的论文，并获得了多项工程成果 出版物，并获得博士学位。在格鲁吉亚学院获得电子和计算机工程学位 2010年，在Lena Ting博士的监督下，我的论文研究应用于 肌肉骨骼模拟和优化方法来回答有关平衡的基础科学问题 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 技术的人体运动研究使用肌电图，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。在2012年，我开始调查个人的平衡控制， 帕金森病（PD）在一个新的合作与丁博士和马德琳哈克尼，博士，的PD 康复科学家这项工作的目标是应用工程模型开发的一个基本的 了解年轻健康个体的平衡控制，以更好地了解平衡 PD功能障碍，并将来自模型的生物标志物纳入改善的康复结果 措施最近，我收到了一个KL 2奖学金，提供正式的临床研究方法的培训， 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 问题的有效性和适当的统计严谨性。 职业目标。我的长期职业目标是成为一名独立的翻译研究者， 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 临床医生和康复科学家专注于帕金森平衡和步态功能障碍。 需要培训。我需要K25指导定量研究中提出的专业培训 发展奖，因为我想问的疾病相关的问题作为一个独立的调查员 需要对PD病理生理学的详细掌握和对PD临床管理的透彻理解。 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力，临床相关， R 01级运动障碍研究。 环境与培训和研究的关键要素拟议的培训和 研究活动将使我准备好回答有关平衡赤字之间相互作用的关键问题， 福尔斯，以及PD步态冻结，建立合作临床研究的跟踪记录，并产生 这些初步数据将构成我独立研究组合的基础。在这个奖项下，我将 接受正式的课程和指导下的基底神经节神经解剖学和病理生理学培训 医学博士托马斯·威希曼的指导以及帕金森氏症的临床诊断和治疗 疾病在埃默里大学运动障碍诊所的指导下斯图尔特因素，D. O。我 丁博士将为拟议的实验提供实验室空间和资源。 研究活动将招募一组PD患者，包括Factor博士正在进行的以下研究的参与者： 步态冻结，这将为合作和探索性分析提供重要机会 除了主要的研究目的。 研究项目。这些研究将导致更好的预测PD患者的跌倒风险，并改善 了解PD、步态冻结（FOG）和福尔斯之间的机制关系，可能导致新的 治疗。我们目前对帕金森病的平衡缺陷、福尔斯和FOG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，我们将执行前瞻性 研究有和无FOG的PD患者的跌倒风险，以测试先进工程工具的能力 开发用于量化年轻健康个体和动物模型的平衡反应，以预测跌倒风险 当作为一个组成部分，包括一个全面的电池建立行为和神经心理 评估跌倒风险。其他分析将使用该队列的数据来定量评估强度 以及客观量化的FOG严重程度，姿势反应异常， 跌倒的风险这项工作将产生新的基础知识，如何中央病理生理学的PD和 FOG影响运动外周，这将提高我们识别候选患者的能力。 康复，这将为额外的平衡受损患者人群开辟新的调查途径 并将其他研究人员正在开发的成像方法纳入合作研究， 团队