Language behavior and patterns of cortical atrophy in primary progressive aphasia

描述（由申请人提供）：原发性进行性失语症（PPA）是一种退行性神经系统疾病，其特征是语言能力下降，而其他方面的认知能力相对较少。患有PPA的个体在研究语言的大脑行为关系方面具有独特的优势，因为皮质萎缩的区域并不局限于由血管损伤引起的失语区域。本研究旨在探讨PPA区域皮质萎缩模式与语言能力下降之间的关系。在这项研究中，20名PPA患者将接受全面的语言测试，以检查四个关键的语言处理领域：语义学、音韵学、正字法和句法。基于体素的形态测量（VBM）是一种图像分析技术，它允许对患者与健康个体的灰质体积进行体素比较，将用于确定与20组年龄匹配的正常对照相比的区域萎缩区域。在每个领域的行为表现将被检查相对于区域灰质体积的病人组。全脑和感兴趣区域（ROI）方法将用于检查萎缩-行为关系。全脑分析将揭示每个领域中对语言处理至关重要的区域，以及可能涉及某些语言处理的大脑区域网络。使用基于现有病变和神经成像数据创建的roi进行分析，将揭示行为缺陷患者的灰质体积是否与先前研究中确定的对语言至关重要的皮质区域没有缺陷的患者不同。这些分析将有助于确定PPA中语言衰退的神经基础，并通过提供额外的聚合和补充证据来源，可能为当前的语言脑-行为关系模型提供准确性。该项目与公共卫生的相关性在于，它试图阐明PPA（一种相对未被充分研究的痴呆症变体）行为和神经变化的本质。寻找PPA中行为-解剖关系的一致模式是一项相对较新的努力，对于开发更好的诊断程序和为患有该疾病的个体提供最佳护理至关重要。

DESCRIPTION (provided by applicant): Primary progressive aphasia (PPA) is a degenerative neurological condition characterized by a decline in language abilities, with relative sparing of other aspects of cognition. Individuals with PPA represent a unique vantage from which to examine the brain-behavior relations for language, in that areas of cortical atrophy are not confined to regions involved in aphasia resulting from vascular damage. The research proposed herein is designed to explore the relationship between patterns of regional cortical atrophy and language decline in PPA. In this study, 20 individuals with PPA will be administered a comprehensive language battery structured to examine four critical language processing domains: semantics, phonology, orthography, and syntax. Voxel-based morphometry (VBM), an image analysis technique which allows for voxel-wise comparison of gray matter volume in patients relative to healthy individuals, will be used to determine areas of regional atrophy as compared to a set of 20 age-matched normal controls. Behavioral performance in each domain will then be examined relative to regional gray matter volume in the patient group. Both whole-brain and region of interest (ROI) approaches will be utilized to examine atrophy-behavior relationships. Whole-brain analysis will reveal areas critical to language processing in each domain, and possibly networks of brain regions involved in certain language processes. Analysis using ROIs created on the basis of existing lesion and neuroimaging data will reveal whether patients with behavioral deficits differ in gray matter volume from those without deficits in cortical areas identified as critical to language in previous research. These analyses will help to identify the neural bases for language decline in PPA as well as potentially lend veracity to current models of brain-behavior relations for language by providing an additional source of converging and complementary evidence. The relevance of this project to public health lies in its attempts to clarify the nature of behavioral and neurological changes in PPA, a relatively understudied variant of dementia. The search for consistent patterns of behavioral-anatomical relationships in PPA is a relatively new endeavor and one that is critical to the development of better diagnostic procedures and provision of the best care for individuals with the disorder.