Motor Learning in Parkinson's Disease

帕金森病的运动学习

• 批准号: 6341399
• 负责人: M. Felice Marina GHILARDI
• 金额: $ 10.19万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-09-30 至 2003-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6341399
• 关键词: Parkinson's disease; afferent nerve; basal metabolism; behavioral /social science research tag; bioimaging /biomedical imaging; brain imaging /visualization /scanning; clinical research; cognition; corpus striatum; deoxyglucose; dopamine; dystonia; extrapyramidal disorder; human subject; learning; levodopa; longitudinal human study; magnetic resonance imaging; memory disorders; motor cortex; neural information processing; neuropsychology; positron emission tomography; psychophysiology; short term memory

DESCRIPTION (provided by applicant): The specific aims of the original proposal were: 1. To determine the effect of Parkinson's disease (PD) on the learning of spatial and temporal features of motor learning tasks, compared to a normally aging population. 2. To test the hypothesis that the deficits in motor learning in PD result from the altered function of specific cortical and subcortical networks whose expression correlates with task performance in age-matched controls. 3. To assess the effect on motor learning of new therapies, such as pallidal ablation and pallidal stimulation. Over the past two and a half year, we have made extensive progress in accomplishing these aims, as described in Progress Report and in the publication track record. In this competing continuation application, we plan to complete the initial research and educational aims and to extend our work. Specifically, we will pursue the following aims: 1. To study the effects of DBS and levodopa administration on motor learning in PD. We have shown that aspects of motor learning are defective in the earliest stages of PD and are associated with abnormal brain organization. Preliminary data indicate that these abnormalities are not rectified by levodopa, but, GPi DBS can improve sequence learning and increase activity in brain regions normally involved in this process. Here we ask if STN DBS (which drives GPi and other structures mediating simple and complex motor behavior) can improve performance in PD by modulating the brain circuits involved in sequence learning, similarly to GPi DBS. PET recordings during motor tasks will be conducted in a group of PD patients with STN DBS, a group with GPi DBS, and a group treated with levodopa infusion in on and off conditions. Brain network expression and performance will be compared across groups and conditions. 2. To characterize the progression of motor and cognitive dysfunction in PD. We found that PD patients in stage I and 11 require longer time and need to recruit more brain areas to learn a motor sequence. Here we ask how performance and brain network activation change in relation to disease progression. In this longitudinal study, we will also evaluate changes in acquisition of motor skills other than sequence learning, such as adaptation to new reference frames or novel inertial configuration. We will use tasks we have recently developed and tested in a population of young normal subjects. We will ask the following questions: Which are the normal brain networks involved in the different types of learning? Are they independent or share some common bases? Does their expression change in PD patients in early stages? Does brain network expression in PD change with disease progression? These studies psychophysical and imaging studies will be conducted in the group of PD patients and age-matched controls we have tested in the previous grant period. 3. To study motor learning and execution in hyperkinetic basal ganglia disorders. Studies with "F-fluoro-deoxyglucose (FDG) and PET have demonstrated an abnormal metabolic network in clinically non-manifesting carriers of Idiopathic Torsion Dystonia (ITD) DYT I gene. In preliminary studies, we have found that motor sequence learning may be impaired in these same gene carriers. We plan to complete the psychophysical studies in non-manifesting DYTI carriers and to assess the effect of GPiDBS on rcbf in affected DYTI patients. Specifically, we will ask the following questions: Will non-manifesting DYTI carriers show motor learning and network activation abnormalities that parallel their resting metabolic abnormalities? Will non-manifesting DYT I carriers and dystonic patients show differences in motor learning and network activation? By comparing rcbf before and during pallidal stimulation, we will determine how altering pallidal function affects the expression of activation patterns subserving motor learning in ITD. Overall, these studies will provide the bases for a comprehensive understanding of basal ganglia and related cicuitry in motor learning and execution, as well as for the development of new therapeutical strategies for basal ganglia disorders.

描述（由申请人提供）：原始提案的具体目标 为： 1.为了确定帕金森病（PD）对学习的影响， 运动学习任务的空间和时间特征，与正常 人口老龄化 2.为了验证帕金森病运动学习障碍是由 特定皮质和皮质下网络的功能改变， 在年龄匹配的对照组中，表达与任务表现相关。 3.评估新疗法对运动学习的影响，如苍白球 消融和苍白球刺激。 在过去两年半，我们在以下方面取得了广泛的进展： 实现这些目标，如进度报告和 出版跟踪记录。在这个竞争性的延续申请中，我们计划 完成最初的研究和教育目标，并扩大我们的工作。 具体而言，我们将努力实现以下目标： 1.研究DBS和左旋多巴给药对运动学习的影响， 警局我们已经证明，运动学习的各个方面在最早的时候是有缺陷的， PD的阶段，并与异常的大脑组织有关。初步 数据表明这些异常不能被左旋多巴纠正，但是GPi DBS可以改善序列学习并增加大脑区域的活动 通常参与这个过程。在这里，我们问，如果你的DBS（驱动GPi和 其他调节简单和复杂运动行为的结构）可以改善 通过调节参与序列的大脑回路来改善PD的表现 学习，类似于GPi DBS。运动任务期间的PET记录将 在一组使用DBS的PD患者中进行，一组使用GPi DBS， 左旋多巴组在开、关状态下静脉滴注左旋多巴。脑网络 将在各组和不同条件下比较表达和表现。 2.描述PD患者运动和认知功能障碍的进展。我们 发现I期和11期PD患者需要更长的时间并且需要 招募更多的大脑区域来学习运动序列。在这里，我们问如何性能 以及与疾病进展相关的脑网络激活变化。在这 纵向研究，我们还将评估运动能力获取的变化 序列学习以外的技能，如适应新的参考框架 或新颖的惯性配置。我们将使用我们最近开发的任务 并在年轻的正常受试者中进行测试。我们将提出以下问题 问题：哪些是参与不同类型的正常大脑网络 学习？它们是独立的还是有共同的基础？做他们 PD患者早期的表达变化？大脑网络表达 PD随疾病进展而变化？这些研究心理物理学和成像 研究将在PD患者组和年龄匹配的对照组中进行 我们在上一个资助期进行了测试。 3.研究基底神经节运动功能亢进时的运动学习和执行功能 紊乱使用氟脱氧葡萄糖（FDG）和PET的研究表明， 在临床上无表现的携带者中的异常代谢网络 特发性扭转性肌张力障碍（ITD）DYT I基因。在初步研究中， 发现运动序列学习可能在这些相同的基因携带者中受损。 我们计划完成对未表现DYTI携带者的心理物理学研究 并评估GPiDBS对DYTI患者rcbf的影响。 具体来说，我们会问以下问题： 携带者表现出运动学习和网络激活异常， 他们的静息代谢异常将非表现DYT I携带者和 肌张力障碍患者在运动学习和网络激活方面表现出差异？通过 比较苍白球刺激前后的rcbf，我们将确定 改变苍白球功能影响激活模式的表达 在ITD中辅助运动学习。 总的来说，这些研究将为全面了解 基底神经节和相关的cicuitry在运动学习和执行，以及 至于基底神经节新的治疗策略的发展， 紊乱