MECHANISMS OF MOTOR LEARNING IN NEUROLOGICAL DISEASE

神经系统疾病中运动学习的机制

• 批准号: 6393180
• 负责人: JOHN WALTER KRAKAUER
• 金额: $ 12.96万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-30 至 2004-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6393180
• 关键词: Huntington's disease; behavioral /social science research tag; brain imaging /visualization /scanning; brain metabolism; clinical research; dystonia; functional magnetic resonance imaging; gene expression; human subject; learning disorders; limb movement; neural information processing; neurogenetics; neuropsychology; performance; positron emission tomography; sensorimotor system; stroke

The proposed award is designed to develop the candidate's clinical research skills to prepare him for a career as an independent investigator in the application of motor psychophysics and functional brain imaging to the study of neurological disease. Research Plan: Stroke, Huntington's disease (HD), and Idiopathic Torsion Dystonia (ITD) are diseases that rob people of motor function in the prime of life. Many of the measures of motor performance and functional status commonly used in clinical trials and rehabilitation suffer from subjectivity and lack of scientific validation. The first goal of the proposed study is to characterize and quantify the motor deficit in these diseases using methods previously developed in the study of arm movements in normal subjects. In particular, we will emphasize the importance of examining motor learning abnormalities because we hypothesize that these will give a direct measure of a patient's capacity to compensate or recover from neurological disease. The second goal is to correlate psychophysical parameters of motor performance and motor learning to the degree of expression of brain networks as revealed by functional imaging. This will provide considerable insight into the brain mechanisms underlying abnormalities in motor control. HD and ITD each have an established genetic basis allowing asymptomatic carriers to be identified. Our preliminary studies indicate that these subjects have psychophysical and network abnormalities even though more conventional assessments fail to find any evidence of neurological disturbance. If we confirm and extend these observations, then we will have the tools to follow therapeutic intervention at the earliest stages of disease. In the long term, we hope that our work will lead to the development of a battery of motor tasks that, in conjunction with functional imaging, will be applicable to any neurological disease. This battery will quantify motor deficits; allow monitoring of therapy; provide insight into brain mechanisms: and may serve a rehabilitative function. Educational Plan: By completing this project, I will accomplish six main educational objectives: (1) The design and application of motor psychophysics to neurological disease; (2) Learning PET imaging techniques; (3) The development of skills in brain network analysis and modeling; (4) Learning advanced statistical methods; (5) Learning the principles of functional magnetic resonance imaging; (5) Learning to conduct ethical scientific research, collaborate with colleagues, and produce high quality presentations and publications; and (6) Learning to place experimental findings within their clinical context, and relate them to clinical assessments.

拟议的奖项旨在培养候选人的临床研究技能，为他作为一名独立研究员的职业生涯做准备，将运动心理物理学和脑功能成像应用于神经疾病的研究。研究计划：中风、亨廷顿病(HD)和特发性扭转肌张力障碍(ITD)是剥夺人在壮年运动功能的疾病。临床试验和康复中常用的许多运动表现和功能状态的测量都存在主观性和缺乏科学验证的问题。这项拟议研究的第一个目标是利用先前在研究正常受试者手臂运动时开发的方法来表征和量化这些疾病的运动缺陷。特别是，我们将强调检查运动学习异常的重要性，因为我们假设这些异常将直接衡量患者从神经系统疾病中补偿或恢复的能力。第二个目标是将运动表现和运动学习的心理物理参数与功能成像揭示的大脑网络的表达程度联系起来。这将对运动控制异常背后的大脑机制提供相当大的洞察力。HD和ITD都有既定的遗传基础，可以识别出无症状的携带者。我们的初步研究表明，这些受试者有心理物理和网络异常，尽管更传统的评估未能发现任何神经障碍的证据。如果我们证实并扩大这些观察，那么我们就有了在疾病最早阶段进行治疗干预的工具。从长远来看，我们希望我们的工作将导致一系列运动任务的开发，与功能成像相结合，将适用于任何神经疾病。这种电池将量化运动缺陷；允许监测治疗；提供对大脑机制的洞察：并可能起到康复功能。教育计划：通过完成这个项目，我将完成六个主要的教育目标：(1)运动心理物理学在神经系统疾病中的设计和应用；(2)学习PET成像技术；(3)脑网络分析和建模的技能发展；(4)学习先进的统计学方法；(5)学习功能磁共振成像的原理；(5)学会进行伦理科学研究、与同事合作和制作高质量的演示文稿和出版物；以及(6)学会将实验结果放在临床背景下，并将其与临床评估联系起来。