Scaling and Sequencing Motor Output in Humans: fMRI Study

人类运动输出的缩放和排序：功能磁共振成像研究

• 批准号: 8320108
• 负责人: David E Vaillancourt
• 金额: $ 32.53万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-08-01 至 2016-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8320108
• 关键词: Address; Affect; Age; Alzheimer' s Disease; Anterior; Antiparkinson Agents; Area; Basal Ganglia; Biological Markers; Bradykinesia; Brain; Brain Diseases; Brain imaging; Cell Nucleus; Cells; Cognition; Cognitive; Cognitive deficits; Data; Development; Diffusion Magnetic Resonance Imaging; Disease; Disease Progression; Dorsal; Functional Magnetic Resonance Imaging; Funding; Globus Pallidus; Goals; Grant; Human; Image; Knowledge; Laboratories; Levodopa; Link; Longitudinal Studies; Measures; Memory; Motor; Motor Cortex; Motor output; Movement; Natural History; Nerve Degeneration; Outcome; Parkinson Disease; Patients; Pharmaceutical Preparations; Physicians; Positioning Attribute; Prefrontal Cortex; Preparation; Rehabilitation therapy; Research; Staging; Structure; Structure of subthalamic nucleus; Substantia nigra structure; Subthalamic structure; Symptoms; Testing; Thalamic structure; Time; Tremor; United States; United States National Institutes of Health; executive function; falls; frontal lobe; grasp; in vivo Model; innovation; motor deficit; putamen; sex

DESCRIPTION (provided by applicant): Longitudinal studies in Parkinson's disease (PD), that document how changes in structure and function of the brain relate to changes in movement and cognition, represent a critical component to developing new therapies that will slow the rate of progression of PD. Unfortunately, longitudinal studies of brain structure and function in PD are very rare. In years 7-12 of this renewal R01, our laboratory is well-positioned to conduct a longitudinal study since we have already tested 40 patients with PD and 40 age and sex-matched control subjects at baseline. Our research team has used diffusion tensor imaging (DTI) to show that the structural integrity of the dorsal substantia nigra is reduced with age, and that the ventral substantia nigra is reduced in early stage, de novo PD. Further, our laboratory has used functional magnetic resonance imaging (fMRI) to show that the functional activity of all basal ganglia nuclei are reduced in PD during specific grip force switching tasks. We have shown that the functional activity of basal ganglia nuclei relates to specific motor signs in PD, such as bradykinesia and tremor. In this renewal, we will compare our baseline DTI and fMRI data in 40 de novo patients with PD and 40 control subjects longitudinally to a 4 year time point. In year 4, patients will be tested off and on antiparkinsonian medication. We test the hypothesis that alterations in the structural integrity of the substantia nigra and anterior thalamus are linked to disease progression changes in motor signs and cognitive signs. As a consequence, disease progression changes in motor signs and cognitive signs will be related to region-specific changes in functional activity of the basal ganglia, thalamus, motor cortex, and frontal cortex in PD. Aim 1a will use DTI to examine the structural integrity of the substantia nigra in relation to motor signs of PD. Aim 1B will use fMRI during a well-defined force switching task to examine the relation between functional activity of the basal ganglia, thalamus, and motor cortex to motor signs of PD. Aim 2a will use DTI to examine the structural integrity of the thalamus in relation to cognitive signs of PD. Aim 2b will use fMRI during a cognitive-motor task to examine the functional activity of the caudate and frontal cortex in relation to cognitive signs of PD. The proposed research is both significant and innovative because it will be the first comprehensive study to use structural and functional brain imaging at 3 Tesla to focus on how subcortical and cortical brain structures change in patients with PD after 4 years.

描述（由申请人提供）：帕金森氏病（PD）中的纵向研究，记录了大脑结构和功能的变化与运动和认知的变化有关，代表了开发新疗法的关键组成部分，以减缓PD进展的速度。不幸的是，PD中大脑结构和功能的纵向研究非常罕见。在此续签R01的7 - 12年级中，我们的实验室对进行了纵向研究，因为我们已经在基线测试了40例PD和40岁和40岁的患者，并且在基线时进行了性匹配的对照组受试者。我们的研究团队使用扩散张量成像（DTI）表明，背态尼格拉的结构完整性随着年龄的增长而降低，并且腹侧黑质在早期阶段降低，从头pd。此外，我们的实验室使用功能性磁共振成像（fMRI）表明，在特定的握力切换任务中，PD中所有基底神经节核的功能活性均降低。我们已经表明，基底神经节核的功能活性与Bradykinesia和Tremor等PD中的特定运动符号有关。在此续签中，我们将比较40名NOVO患者的基线DTI和fMRI数据，纵向与40名对照组受试者与4年的时间点进行比较。在第4年中，将对患者进行测试和抗帕金森氏药物。我们测试了一个假设，即黑质和丘脑前的结构完整性的改变与运动体征和认知迹象的疾病进展变化有关。结果，疾病的进展变化和认知迹象将与PD中基底神经节，丘脑，运动皮层和额叶皮质的功能活性的区域特异性变化有关。 AIM 1A将使用DTI来检查黑质Nigra与PD的运动迹象有关的结构完整性。 AIM 1B将在定义明确的力切换任务期间使用fMRI来检查基底神经节，丘脑和运动皮层的功能活动与PD的运动符号之间的关系。 AIM 2A将使用DTI来检查丘脑与PD认知迹象有关的结构完整性。 AIM 2B将在认知运动任务期间使用fMRI来检查与PD的认知迹象有关的尾状和额叶皮层的功能活性。拟议的研究既重要又具有创新性，因为它将是首次使用3特斯拉的结构和功能性脑成像的全面研究，以关注4年后PD患者的皮质下和皮质脑结构如何变化。