Assessing aberrant motor learning in Parkinson's patients

评估帕金森病患者的异常运动学习

基本信息

批准号：
8848150
负责人：
JEFF A. BEELER
金额：
$ 23.26万
依托单位：
QUEENS COLLEGE
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-05-15 至 2017-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8848150
关键词：
Adopted Affect Alzheimer&apos s Disease Animal Model Clinical Clinical Research Complement Corpus striatum structure Data Denervation Development Disease Progression Distress Dopamine Drug Kinetics Dyskinetic syndrome Effectiveness Functional disorder Future Goals Health Home environment Hospitals Human Impairment Knowledge Learning Levodopa Mediating Methods Modeling Motor Motor Skills Movement Nature Parkinson Disease Participant Patients Performance Pharmaceutical Preparations Pharmacologic Substance Phase Pilot Projects Play Population Process Publishing Reaction Time Regimen Rehabilitation therapy Replacement Therapy Role Sensory Serial Learning Signal Pathway Speed Symptoms Synapses Task Performances Testing Therapeutic Time Treatment Efficacy Validation Variant Weight base cost design drug development improved innovation insight motor control motor deficit motor learning motor skill learning novel novel strategies novel therapeutics rehabilitation strategy research study response sequence learning

项目摘要

DESCRIPTION (provided by applicant): This project will investigate the contribution of aberrant motor learning to the motor deficits associated with Parkinson's disease (PD) and the role that correcting aberrant learning plays in treatment efficacy. Though human studies have demonstrated motor learning impairments in PD, the extent and nature of learning impairments and their relationship to disease progression and treatment have been controversial. This project proposes the hypothesis that dopamine denervation induces abnormal corticostriatal plasticity, as has been observed in animal models, that results in aberrant, inappropriate inhibitory learning in the dorsolateral striatum that impedes rather than optimizes motor performance. As a consequence, under decreased dopamine, aberrant motor learning will gradually replace the established learning (encoded as synaptic strengths) that enables effective movement with learning and synaptic weights that disable movement. In contrast, dopamine replacement therapy corrects this aberrant learning and re-enables the optimization function associated with the dorsolateral striatum and facilitates movement. The human studies in this project will utilize a strategy of testing subjects at home using two novel iPad based task in order to conduct extended testing across time and to test subjects during different phases in the daily pharmacokinetic fluctuations in their daily medication regimen (i.e., peak vs. trough medication). The intent is to clearly distinguish the effects of these fluctuations on motor learning and performance and to assess the contribution of the motor learning component, independent of the direct performance effects of medication. Knowledge gained from these studies will contribute to greater understanding of (a) the role of learning mechanisms in the core symptoms and progression of PD and (b) the contribution of learning to the therapeutic efficacy of current treatments. Establishing a role for aberrant learning in the pathophysiology and treatment of PD will open new avenues for the development novel pharmaceuticals targeting signaling pathways that underlie aberrant learning. Finally, as rehabilitative therapies are ultimately based on practice, they are fundamentally based on learning. Understanding how practice-based learning may be optimized could potentially provide insight to enhance strategies for rehabilitation treatments.

描述（由申请人提供）：该项目将调查异常运动学习对与帕金森氏病（PD）相关的运动缺陷的贡献，以及纠正异常学习在治疗功效中起作用的作用。尽管人类的研究表明，PD的运动障碍，但学习障碍的程度和性质及其与疾病进展和治疗的关系一直存在争议。该项目提出了这样一个假设，即在动物模型中观察到的那样，多巴胺神经氨基诱导的皮质纹状体可塑性异常，从而导致背外侧纹状体中异常，不适当的抑制性学习会阻碍而不是优化运动性能。结果，在减少的多巴胺下，异常运动学习将逐渐取代已建立的学习（被编码为突触强度），从而可以通过学习和突触权重有效地运动，从而使运动。相比之下，多巴胺替代疗法纠正了这种异常学习和重新启用与背外侧纹状体相关的优化功能并促进运动。该项目中的人类研究将利用一种基于iPad的任务在家中测试受试者的策略，以便跨时间进行扩展测试，并在每日药物治疗方案中的每日药代动力学波动中的不同阶段进行测试（即峰值与槽药物）。目的是清楚地区分这些波动对运动学习和性能的影响，并评估运动学习成分的贡献，而与药物的直接性能效应无关。从这些研究中获得的知识将有助于对（a）学习机制在PD的核心症状和进展中的作用以及（b）学习对当前治疗的治疗功效的贡献。在PD的病理生理学和治疗中确立异常学习的作用将为开发新型药物靶向基于异常学习的信号通路的新途径。最后，由于康复疗法最终是基于实践的，因此从根本上讲，它们是基于学习的。了解如何优化基于实践的学习可能会提供洞察力，以增强康复治疗的策略。

项目成果

期刊论文数量（1）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Chronic Nicotine Alters Corticostriatal Plasticity in the Striatopallidal Pathway Mediated By NR2B-Containing Silent Synapses.

慢性尼古丁改变由含有 NR2B 的沉默突触介导的纹状体苍白球通路中的皮质纹状体可塑性。

DOI：
10.1038/npp.2017.87
发表时间：
2017
期刊：
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
影响因子：
0
作者：
Xia,Jianxun;Meyers,AllisonM;Beeler,JeffA
通讯作者：
Beeler,JeffA