Functional Studies of Subtypes of Parkinson's Diseasee

帕金森病亚型的功能研究

• 批准号: 6558141
• 负责人: XUEMEI HUANG
• 金额: $ 15.04万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-07-01 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6558141
• 关键词: Parkinson's disease; basal ganglia; bioimaging /biomedical imaging; brain electrical activity; cerebellum; disease /disorder classification; disease /disorder model; dopamine; drug screening /evaluation; frontal lobe /cortex; functional magnetic resonance imaging; human subject; levodopa; patient oriented research; thalamocortical tract

DESCRIPTION (provided by applicant): The long-term objective of this project is to advance the understanding of the pathophysiology and management of Parkinson's disease (PD), and allow the applicant to develop expertise in using functional MRI (fMRI) as a tool to study movement disorders. The primary mentor of this work will be Dr. Frank Longo, Chair of the Department of Neurology, and an established investigator in the area of neurodegenerative disease. Dr. Longo has particular experience in the long-term quantitative follow-up of movement disorder patients. The other mentors are Dr. Gregory McCarthy, a recognized expert in the use of fMRI for the study of cognition and behavior, and Dr. Martin McKeown, a clinical neurologist and an expert in fMRI in studying stroke patients, who will provide guidance in application of these techniques. Drs. Ray Watts, an established PD researcher, will provide critical external consultation. The clinical hallmarks of PD are tremor, muscle rigidity, bradykmesia, and postural instability; cognitive impairment related to frontal lobe dysfunction also clearly occurs. Clinical expression of the disease is not homogenous, however, as tremor-predominant PD (PDT) generally has better long-term motor outcome with fewer motor fluctuations, less levodopa-induced dyskinesias, a slower rate of progression, and fewer cognitive deficits when compared with akinetic-rigid-predominant PD (PDAR). Although most of the symptomatology of PD may be explained by the classic model of basal ganglia-thalamocortical circuitry as related to dopamine neuron degeneration, the resting tremor cannot. I propose a new model involving two segregated, but functionally related parallel loops of the basal ganglia-thalamocortical and cerebello-thalomocortical circuits. My working hypothesis is that the key differences between subtypes of PD are related to the differential involvement of the two major motor regulatory circuits due to different degrees and/or locations of neurodegeneration of melanin-containing neurons in PD. Study of the hypothesis will be accomplished via four specific aims: 1) Stratifiy the patients to PD subtypes 1) according to their clinical features; 2) Compare the differential fMRI activation of the frontal lobe areas (e.g. SMA, DLPFC) in different subtypes of PD patients using a alternative hands squeeze task, and a event-related Go-No-Go paradigm; 3) Compare the differential fMRI activation of cerebellum (i.e.. hemisphere, and anterior vermis/paravermis) in different subtypes of PD patients using a supination/pronation movement paradigm; 4) Assess the effects of levodopa on the clinical symptoms, activation patterns of frontal cortex, and cerebellum in different subtypes of PD patients.

描述（由申请人提供）：该项目的长期目标是提高对帕金森氏病（PD）的病理生理学和管理的理解，并允许申请人在使用功能性MRI（fMRI）方面发展专业知识作为研究运动障碍的工具。这项工作的主要导师将是神经病学系主任弗兰克·朗戈（Frank Longo）博士，也是神经退行性疾病领域的既定研究者。 Longo博士在运动障碍患者的长期定量随访中具有特殊的经验。其他导师是格雷戈里·麦卡锡（Gregory McCarthy）博士，他是使用fMRI进行认知和行为研究的公认专家，以及临床神经科医生，fMRI研究中风患者的专家马丁·麦基恩（Martin McKeown）博士，他们将在应用这些技术方面提供指导。博士。既定的PD研究人员Ray Watts将提供关键的外部咨询。 PD的临床标志是震颤，肌肉僵硬，胸肌和姿势不稳定。与额叶功能障碍有关的认知障碍也显然发生了。然而，由于震颤 - 促销PD（PDT）通常具有更好的长期运动结局，并且与左旋多巴诱导的发育不良，相比，与左旋多巴诱导的发病障碍，相比，与Acikinetic-Rigid-Rigid-PDAR（PDAR相比，较少），这种疾病的临床表达并不是同质的。尽管PD的大多数症状可以通过与多巴胺神经元变性有关的基础神经节 - 丘脑皮层回路的经典模型来解释，但静止震颤不能。我提出了一个新的模型，涉及两个基底神经节 - 丘脑皮层和小脑 - 心脏皮层电路的两个分离但功能相关的平行环。我的工作假设是，PD亚型之间的关键差异与由于不同程度和/或PD中含黑色素神经元神经变性的位置而导致的两个主​​要运动调节回路的差异有关。 该假设的研究将通过四个特定目的来完成：1）患者将PD亚型的患者分类为1）根据其临床特征； 2）使用替代的手挤压任务和事件相关的GO-NO-GO范式比较额叶区域（例如SMA，DLPFC）的差异fMRI激活； 3）比较使用旋转/旋转运动范式在不同亚型的PD患者中，小脑（即半球和前vermis/paravermis）的差异fMRI激活； 4）评估左旋多巴对PD患者不同亚型的临床症状，额叶皮层的激活模式和小脑的影响。