Language behavior and patterns of cortical atrophy in primary progressive aphasia

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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.