MECHANISMS OF MOTOR LEARNING IN NEUROLOGICAL DISEASE

该奖项旨在培养候选人的临床研究技能，为其在运动心理物理学和功能脑成像应用于神经系统疾病研究方面的独立研究者的职业生涯做好准备。研究计划：中风、亨廷顿氏病（HD）和特发性扭转肌张力障碍（ITD）是在人的壮年时期剥夺运动功能的疾病。许多临床试验和康复中常用的运动表现和功能状态测量存在主观性和缺乏科学验证的问题。该研究的第一个目标是使用先前在正常受试者手臂运动研究中开发的方法来表征和量化这些疾病中的运动缺陷。特别是，我们将强调检查运动学习异常的重要性，因为我们假设这些将直接衡量患者补偿或从神经系统疾病中恢复的能力。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显示的脑网络表达程度联系起来。这将为运动控制异常的大脑机制提供相当大的见解。HD和ITD都有一个既定的遗传基础，可以识别无症状的携带者。我们的初步研究表明，这些受试者有心理生理和网络异常，即使更常规的评估没有发现任何神经障碍的证据。如果我们证实并扩展这些观察结果，那么我们将有工具在疾病的早期阶段跟踪治疗干预。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发展，与功能成像相结合，将适用于任何神经系统疾病。该电池将量化运动缺陷；允许对治疗进行监测；提供对大脑机制的洞察，并可能具有康复功能。教学计划：通过完成本课题，我将实现六个主要教学目标：(1)运动心理物理学在神经系统疾病中的设计与应用；(2)学习PET成像技术；(3)发展脑网络分析和建模技能；(4)学习先进的统计方法；(5)学习功能磁共振成像原理；(5)学会进行合乎伦理的科学研究，与同事合作，制作高质量的报告和出版物；(6)学习将实验结果置于临床环境中，并将其与临床评估联系起来。

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.