An fMRI Model of Naming in Alzheimer's Disease

描述（由申请人提供）：几乎所有阿尔茨海默病（AD）患者最终都会发展为精神失常。最近的文献表明，这种找词问题并不是单一的。阿尔茨海默病患者的词汇和语义缺陷可以独立存在，两者都可能损害词汇发现能力。这个R21应用程序的长期目标是开发一个区域大脑活动和萎缩的模型，以解释AD中不同模式的图片命名缺陷。在功能磁共振成像（fMRI）中，将16例有词汇缺陷的AD患者、16例有语义缺陷的AD患者和16例正常对照进行图片命名任务，并在体素t检验图像中比较各组的活动。主要的假设是：(1)与正常对照相比，有词汇缺陷的患者在支持词汇功能的左脑外围区表现出较低的活动。(2)与正常对照相比，语义缺失患者支持语义功能的左侧下颞叶皮层和支持词汇功能的左侧左脑皮层的活动均有所减少。外围皮层的活动减少并不是因为潜在的神经病理学，而是因为该皮层没有充分受到来自下颞叶皮层的语义输入的刺激。在事后分析中，还将检查额叶皮层的活动，以确定AD组在不同额叶区域是否表现出代偿性活动的增加。此外，左侧颞下皮质和后外侧皮质的功能活动将与语义和词汇缺陷的测量相关联，以确定这种活动是否分别与这两种损伤相关。此外，来自不同组的结构图像将使用基于体素的形态测量（VBM）进行比较，以评估灰质萎缩的区域差异。我们预计，有词汇缺陷的AD患者相对于对照组，左侧左脑皮层的萎缩变化最大，而有语义缺陷的AD患者相对于对照组，左侧下颞叶皮层的萎缩变化最大。最后，生成来自图像命名的fMRI信号强度与来自解剖图像的VBM强度之间的相关图像。在所有受试者组的综合分析中，预计在命名过程中，左侧颞下皮层的fMRI活动减少将与该区域的萎缩程度相关；然而，根据提出的模型，仅在词汇缺陷组中，fMRI活动的减少与该区域的萎缩相关，而不是对所有受试者的综合分析。一旦了解了这些不同的缺陷模式，就可以针对每种模式制定干预措施，以延长疾病过程中功能性沟通的持续时间。在病情进一步恶化时维持功能性沟通将改善患者和家属的生活质量，延长独立性，从而推迟机构化和降低成本。公共卫生相关性：这项研究的长期目标是建立一个区域大脑活动和萎缩的模型，以解释阿尔茨海默病中不同模式的图片命名缺陷。一旦了解了这些不同的缺陷模式，就可以针对每种模式制定不同的干预措施，以延长疾病过程中功能性沟通的持续时间。在疾病过程中进一步保持功能性沟通将改善患者及其家属的生活质量，并延长他们的独立性，从而减少对机构的需求并降低保健费用。

DESCRIPTION (provided by applicant): Almost all Alzheimer's disease (AD) patients eventually develop anomia. Recent literature indicates that such word-finding problems are not monolithic. Lexical and semantic deficits can exist independently in AD patients, and both can impair word finding. The long-term goal of this R21 application is to develop a model of regional brain activity and atrophy that explains different patterns of picture-naming deficit in AD. Sixteen AD patients with lexical deficits, 16 AD patients with semantic deficits, and 16 normal controls will perform a picture naming task during functional MRI (fMRI), and activity from each group will be compared to activity from each other group in voxelwise t-test images. Main hypotheses are: (1) Patients with lexical deficits will demonstrate decreased activity relative to normal controls in left perisylvian regions that support lexical functions. (2) Patients with semantic deficits will show decreased activity relative to normal controls in both left inferior temporal cortex supporting semantic functions and left perisylvian cortex supporting lexical functions. Activity decrease in perisylvian cortex is expected not because of underlying neuropathology, but because this cortex is not adequately stimulated by semantic input from inferior temporal cortex. In post hoc analyses, activity in frontal cortex also will be examined to determine if the AD groups demonstrate compensatory activity increases in different frontal regions. Further, functional activity in the left inferior temporal and posterior perisylvian cortices will be correlated with measures of semantic and lexical deficits to determine if this activity correlates with these two impairments, respectively. In addition, structural images from the different groups will be compared using voxel-based morphometry (VBM) to assess regional differences in gray matter atrophy. It is expected that AD patients with lexical deficits will show the greatest atrophic changes relative to controls in left perisylvian cortex, and AD patients with semantic deficits will show the greatest atrophic changes relative to controls in left inferior temporal cortex. Finally, correlation images between fMRI signal intensities from picture naming and VBM intensities from anatomic images will be generated. It is expected that fMRI activity decreases in the left inferior temporal cortex during naming will correlate with degree of atrophy in this region in a combined analysis of all subject groups; however, according to the proposed model, fMRI activity decreases in the left perisylvian cortex will correlate with atrophy in that region only for the lexical deficit group and not for a combined analysis of all subjects. Once these different patterns of deficit are understood, interventions for each pattern can be developed to extend the duration of functional communication during the course of the disease. Maintenance of functional communication further into the disease will improve quality of life for patients and families and will prolong independence, thereby delayin institutionalization and decreasing costs. PUBLIC HEALTH RELEVANCE: The long-term goal of the proposed research is to develop a model of regional brain activity and atrophy that explains different patterns of picture-naming deficit in Alzheimer's disease. Once these different patterns of deficit are understood, different interventions for each pattern can be developed to extend the duration of functional communication during the course of the disease. Maintenance of functional communication further into the disease process will improve quality of life for patients and their families and will prolong their independence, thereby reducing the need for institutionalization and decreasing health care costs.