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）患者最终都会出现命名障碍。最近的文献表明，这样的单词查找问题是不是铁板一块。词汇和语义缺陷可以独立存在于AD患者，都可以损害词的发现。这项R21应用的长期目标是开发一个局部脑活动和萎缩的模型，以解释AD中图片命名缺陷的不同模式。16例AD患者与词汇缺陷，16例AD患者与语义缺陷，和16名正常对照将执行功能性MRI（fMRI）期间的图片命名任务，并从每组的活动将进行比较，从每个其他组在voxelwise t-检验图像的活动。主要假设是：（1）与正常对照组相比，词汇缺陷患者的左侧大脑外侧裂周区支持词汇功能的活动减少。(2)与正常对照组相比，语义缺陷患者支持语义功能的左下颞叶皮层和支持词汇功能的左外侧裂周皮层的活动均降低。大脑外侧裂周皮层的活动减少并不是因为潜在的神经病理学，而是因为大脑外侧裂周皮层没有受到来自下颞叶皮层的语义输入的充分刺激。在事后分析中，还将检查额叶皮层的活动，以确定AD组是否在不同的额叶区域表现出代偿性活动增加。此外，左下颞叶和后外侧裂周皮质的功能活动将与语义和词汇缺陷的测量相关，以确定该活动是否分别与这两种损伤相关。此外，将使用基于体素的形态测定法（VBM）比较不同组的结构图像，以评估灰质萎缩的区域差异。预期具有词汇缺陷的AD患者相对于对照组在左侧外侧裂周皮层中将显示最大的萎缩变化，并且具有语义缺陷的AD患者相对于对照组在左侧下颞叶皮层中将显示最大的萎缩变化。最后，将生成来自图片命名的fMRI信号强度与来自解剖图像的VBM强度之间的相关图像。在对所有受试者组的综合分析中，预计在命名过程中左下颞叶皮层的fMRI活动减少将与该区域的萎缩程度相关;然而，根据所提出的模型，左外侧裂周皮层的fMRI活动减少仅与词汇缺陷组的萎缩相关，而不是与所有受试者的综合分析相关。一旦理解了这些不同的缺陷模式，就可以开发针对每种模式的干预措施，以延长疾病过程中功能性沟通的持续时间。在疾病进一步发展的过程中保持功能性沟通将提高患者和家庭的生活质量，并将延长独立性，从而推迟住院时间并降低成本。公共卫生相关性：这项研究的长期目标是建立一个局部脑活动和萎缩的模型，以解释阿尔茨海默病中图片命名缺陷的不同模式。一旦理解了这些不同的缺陷模式，就可以针对每种模式开发不同的干预措施，以延长疾病过程中功能性沟通的持续时间。在疾病过程中保持功能性沟通将提高患者及其家属的生活质量，延长他们的独立性，从而减少对住院治疗的需求，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.