PET IN PARKINSONISM: A MULTICENTER COLLABORATIVE STUDY

帕金森症中的宠物：多中心合作研究

• 批准号: 6665063
• 负责人: DAVID EIDELBERG
• 金额: $ 86.37万
• 依托单位: FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-05-15 至 2005-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6665063
• 关键词: Parkinson's disease; bioimaging /biomedical imaging; brain disorder chemotherapy; brain electronic stimulator; brain mapping; brain metabolism; central neural pathway /tract; clinical research; computational neuroscience; cooperative study; human subject; learning; levodopa; longitudinal human study; nervous system disorder therapy; positron emission tomography; psychomotor function; stereotaxic techniques; Parkinson's disease; bioimaging /biomedical imaging; brain disorder chemotherapy; brain electronic stimulator; brain mapping; brain metabolism; central neural pathway /tract; clinical research; computational neuroscience; cooperative study; human subject; learning; levodopa; longitudinal human study; nervous system disorder therapy; positron emission tomography; psychomotor function; stereotaxic techniques

Parkinson's disease (PD) is characterized by the degeneration of dopamine producing cells in the substantia nigra. Although the neurochemical lesion is mainly localized to the nigrostriatal dopamine system, the effects of dopamine loss are widespread and affect non-dopaminoceptive neurons in brain regions constituting crucial elements of motor control and other pathways. These systems, which are still incompletely delineated, play a critical role in mediating the prominent motor and cognitive impairments of PD. In the past funding period, we utilized positron emission tomography (PET) and brain network analysis to identify specific functional alterations in these pathways in PD. Specifically, we utilized an integrated approach involving brain imaging, motor control physiology, and stereotaxic neurosurgery to explore mechanisms of clinical disability in this disease. Using network analysis, we found evidence of abnormal brain-behavior relationships in untreated PD patients at early stages of disease. importantly, we also found that both medical therapy with levodopa as well as surgical therapy with pallidal deep brain stimulation (DBS) improved the manifestations of parkinsonism and corrected PD-related brain network abnormalities. Moreover, we found evidence that DBS procedures may also have a positive effect on motor learning as well as execution. In this continuation application, we seek to expand upon these results to study therapeutic mechanisms for manifestations of PD for which conventional treatments are typically ineffective. We will use our brain imaging methodology in conjunction with DBS to identify the effects of successful therapy on the modulation of PD networks associated with cognition and motor behavior. These studies will utilize on-line psychophysical performance indices of motor performance and learning in conjunction with PET measurements of local cerebral function to evaluate the modulation of specific brain networks in the course of DBS. This integrated approach will allow us to assess changes in brain-behavior relationships brought about by successful interventions utilizing this new therapeutic strategy. In other experiments, we propose to utilize PET imaging with DBS to assess specific pathways associated with the mediation of parkinsonian tremor and levodopa induced dyskinesias. In the proposed studies, we will examine the effects of selected forms of DBS on the modulation of specific brain networks thought to mediate these manifestations. The studies will also utilize state-of-the-art on-line biodynamic measurements in conjunction with dopaminergic therapeutic interventions. Utilizing an integrated approach with network analysis, we will seek to delineate pathways associated with these troubling manifestations of parkinsonism. The proposed studies will allow us to utilize functional imaging, physiologic, and pharmacologic techniques to explore the basis for fixture therapies for parkinsonian manifestations that are currently refractory to existing forms of treatment.

帕金森氏病（PD）的特征是尼格拉底虫中多巴胺产生细胞的变性。尽管神经化学病变主要局限于黑质纹状体多巴胺系统，但多巴胺损失的影响广泛并且影响了构成运动控制和其他途径至关重要的脑区域中的非多巴诺感染性神经元。这些系统仍未完全描述，在介导PD的显着运动和认知障碍中起着至关重要的作用。在过去的资金期间，我们利用正电子发射断层扫描（PET）和脑网络分析来识别PD中这些途径中的特定功能变化。具体而言，我们利用涉及脑成像，运动控制生理和立体定位神经外科的综合方法来探索该疾病中临床障碍的机制。使用网络分析，我们发现疾病早期未经治疗的PD患者的脑行为关系异常的证据。重要的是，我们还发现，左旋多巴的药物治疗以及苍白的深脑刺激（DBS）的手术治疗都改善了帕金森病的表现和纠正与PD相关的脑网络异常。此外，我们发现证据表明DBS程序也可能对运动学习和执行产生积极影响。在此连续应用中，我们试图扩展这些结果，以研究用于常规治疗通常无效的PD表现的治疗机制。我们将使用大脑成像方法与DBS结合使用，以确定成功治疗对与认知和运动行为相关的PD网络调节的影响。这些研究将利用运动性能和学习与局部大脑功能的PET测量的在线心理物理性能指数，以评估DBS过程中特定脑网络的调节。这种综合方法将使我们能够评估通过这种新的治疗策略成功干预措施带来的脑行为关系的变化。在其他实验中，我们建议利用DBS使用PET成像来评估与帕金森震颤和左旋多巴诱发运动障碍的介导相关的特定途径。在拟议的研究中，我们将研究选定形式的DBS对被认为介导这些表现形式的特定大脑网络的调节的影响。这些研究还将利用最新的在线生物动力学测量以及多巴胺能治疗干预措施。利用网络分析的集成方法，我们将寻求描述与这些令人不安的帕金森主义表现相关的途径。拟议的研究将使我们能够利用功能成像，生理和药理学技术来探索帕金森氏症表现固定疗法的基础，而帕金森氏症表现疗法目前对现有的治疗形式难以耐受。