Basal Ganglia Modulation of Cognitive Systems in Parkinson's disease

帕金森病认知系统的基底神经节调节

• 批准号: 8165070
• 负责人: Kathleen Lombard Poston
• 金额: $ 17.44万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-01 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8165070
• 关键词: Age; Aging; American; Basal Ganglia; Behavioral; Biological Markers; Brain; Brain region; Cell Nucleus; Clinical; Clinical Research; Clinical Trials; Cognitive; Control Groups; Corpus striatum structure; Cross-Sectional Studies; Dementia; Dopamine; Dorsal; Elderly; Ensure; Event; Financial cost; Functional Magnetic Resonance Imaging; Functional disorder; Future; Gender; Goals; Home Nursing Care; Human; Image; Imaging Device; Impaired cognition; Impairment; Lateral; Lead; Memory impairment; Mentored Patient-Oriented Research Career Development Award; Methodology; Midbrain structure; Motor; Neurodegenerative Disorders; Neurosciences; Parkinson Disease; Participant; Patients; Performance; Pharmaceutical Preparations; Population; Prefrontal Cortex; Process; Public Health; Replacement Therapy; Research; Research Methodology; Research Personnel; Research Project Grants; Rest; Role; Severities; Short-Term Memory; Staging; Structure of subthalamic nucleus; Symptoms; System; Time; Training and Education; base; burden of illness; career; cognitive enhancement; cognitive function; cognitive system; executive function; improved; in vivo; mild neurocognitive impairment; mortality; motor deficit; prevent; relating to nervous system; response; skills; stem; success; therapy development; treatment response

DESCRIPTION (provided by applicant): This is an application for a K23 Mentored Patient-Oriented Research Career Development Award titled "Basal ganglia modulation of cognitive systems in Parkinson's disease". The primary goal of the proposed research is to investigate regional and brain network abnormalities associated with mild cognitive impairment (MCI) in Parkinson's disease (PD) patients using event-related and resting state functional MRI (fMRI). The rigorous education and training plan will increase the candidate's expertise in fMRI methodology, statistical analysis, behavioral neuroscience, and clinical research methods, thus providing the candidate the necessary skills to ensure success of the proposed research and to become an independent investigator. The candidate's long term career goal is to use fMRI to elucidate the pathophysiology of cognitive dysfunction in PD and to develop an fMRI based imaging tool that is a sensitive marker of cognitive impairment in PD and an objective biomarker of treatment response. This proposal investigates in vivo functional changes associated with cognitive dysfunction in early PD patients without (PD-noMCI) and with (PD-MCI) mild cognitive impairment, compared to normal controls. Aim 1 uses fMRI tasks targeting executive control processes that require activation of basal ganglia nuclei in normal controls to determine changes in basal ganglia and cortical activation associated with PD cognitive impairment. In addition to changes in regional brain activation, cognitive impairment in PD likely also stems from alterations in connectivity between critical brain regions; therefore in Aim 2 we will investigate functional connectivity between basal ganglia nuclei and the cortex using resting state fMRI. Finally, dopaminergic medications can lead to both cognitive enhancement and further impairment, depending on the cognitive function. Therefore, Aim 3 will investigate changes in basal ganglia and cortical activation, striato- cortical connectivity, and intrinsic networks in the PD-noMCI and PD-MCI groups while ON medications compared to the previously performed OFF medication studies. Changes in basal ganglia activation and functional connectivity associated with PD-MCI identified in this proposed research will help clarify the role of basal ganglia nuclei in early PD cognitive impairment and, thus, have implications on the development of therapies for this currently untreatable symptom. PUBLIC HEALTH RELEVANCE: Cognitive dysfunction in PD patients causes substantial human and financial costs and constitutes a growing public health challenge for the aging American population. The proposed research seeks to clarify the function of the basal ganglia in modulation of PD-associated cognitive impairment, ultimately promoting better treatments for PD patients.

描述（由申请人提供）：这是一份申请K23指导患者导向研究职业发展奖的申请，标题为“帕金森病认知系统的基底神经节调节”。该研究的主要目的是利用事件相关和静息状态功能MRI （fMRI）研究与帕金森病（PD）患者轻度认知障碍（MCI）相关的区域和脑网络异常。严格的教育和培训计划将增加候选人在功能磁共振成像方法学、统计分析、行为神经科学和临床研究方法方面的专业知识，从而为候选人提供必要的技能，以确保拟议研究的成功，并成为一名独立的研究者。候选人的长期职业目标是使用功能磁共振成像来阐明PD认知功能障碍的病理生理学，并开发基于功能磁共振成像的成像工具，作为PD认知功能障碍的敏感标志物和治疗反应的客观生物标志物。本研究旨在研究无（PD- nomci）和（PD- mci）轻度认知障碍的早期PD患者与正常对照组相比，体内功能变化与认知功能障碍的相关性。目的1使用fMRI任务，针对正常对照中需要激活基底神经节核的执行控制过程，以确定与PD认知障碍相关的基底神经节和皮质激活的变化。除了大脑区域激活的变化，PD患者的认知障碍也可能源于关键大脑区域之间连通性的改变；因此，在Aim 2中，我们将使用静息状态fMRI研究基底神经节核和皮层之间的功能连接。最后，根据认知功能的不同，多巴胺类药物既可以增强认知能力，也可以进一步损害认知能力。因此，Aim 3将研究PD-noMCI和PD-MCI组在开药时基底神经节和皮层激活、纹状体-皮层连通性和内在网络的变化，与先前进行的OFF药物研究相比。本研究确定的与PD- mci相关的基底节区激活和功能连接的变化将有助于阐明基底节区核在早期PD认知障碍中的作用，从而对这种目前无法治疗的症状的治疗发展产生影响。