An fMRI Model of Naming in Alzheimer's Disease

阿尔茨海默病命名的功能磁共振成像模型

• 批准号: 7667093
• 负责人: BRUCE A. CROSSON
• 金额: $ 21.03万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-01 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7667093
• 关键词: Affect; Alzheimer' s Disease; Anatomy; Anomia; Area; Atrophic; Brain; Cognitive; Communication; Disease; Family; Functional Magnetic Resonance Imaging; Goals; Health Care Costs; Image; Impaired cognition; Impairment; Inferior; Institutionalization; Intervention; Language; Language Disorders; Learning; Left; Literature; Magnetic Resonance Imaging; Maintenance; Measures; Modeling; Names; Nature; Pathology; Patients; Pattern; Performance; Pilot Projects; Play; Process; Quality of life; Relative (related person); Research; Retrieval; Role; Semantics; Signal Transduction; Site; Structure; System; Temporal Lobe; Testing; base; cost; experience; frontal lobe; gray matter; improved; lexical; lexical retrieval; morphometry; neuropathology; phonology; public health relevance; regional difference; relating to nervous system; semantic processing; success

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.

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，这样的找词问题并不是铁板一块的。在AD患者中，词汇和语义缺陷可以独立存在，并且两者都会损害单词发现。这个R21应用的长期目标是开发一个区域大脑活动和萎缩的模型，解释AD中图片命名缺陷的不同模式。16名有词汇缺陷的AD患者、16名有语义缺陷的AD患者和16名正常对照将在功能磁共振成像(FMRI)中执行图片命名任务，并在体素方向的t检验图像中将每组的活动与其他组的活动进行比较。主要的假说是：(1)与正常对照组相比，词汇缺陷患者在支持词汇功能的左侧视周区表现出活动减少。(2)与正常对照组相比，语义缺陷患者在支持语义功能的左侧颞叶下部皮质和支持词汇功能的左侧乙状旁叶皮质的活动均降低。大脑皮质的活动减少并不是因为潜在的神经病理，而是因为这个皮质没有被来自下颞叶皮质的语义输入充分地刺激。在专案分析中，还将检查额叶皮质的活动，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，左下颞叶和后颞叶周围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。预计伴有词汇缺陷的AD患者左侧大脑皮质萎缩程度最大，伴有语义缺陷的AD患者左侧颞叶下部皮质萎缩程度最大。最后，由图像命名得到的fMRI信号强度与来自解剖图像的VBM信号强度之间的相关图像将被生成。在对所有受试者的联合分析中，预计命名过程中左侧颞叶下部皮质的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，只有在词汇缺陷组，而不是对所有受试者的综合分析中，左侧颞叶周围皮质的fMRI活动减少将与该区域的萎缩相关。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。在疾病中进一步维持功能沟通将改善患者和家属的生活质量，并将延长独立性，从而延迟住院和降低成本。与公共健康相关：这项拟议研究的长期目标是开发一个区域大脑活动和萎缩的模型，解释阿尔茨海默病图片命名缺陷的不同模式。一旦了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沟通的持续时间。在疾病过程中进一步保持功能沟通将提高患者及其家人的生活质量，延长他们的独立性，从而减少制度化的需要，并降低保健费用。