Language production disorders are the most common symptoms of aphasia due to stroke or neurodegenerative disease. Difficulty finding and articulating the right word or speaking in sentences can significantly hinder communication and social participation. In our current NIDCD R01 being conducted at the UC Berkeley, we are evaluating the neural mechanisms that accompany the recovery of language production during the first year after stroke. In particular, we are testing the hypothesis that certain white matter pathways play a significant role in language processing, and that detailed examination of these pathways using diffusion MRI will help determine their role in language recovery. In this supplement, we will parallel the approach we are taking in our parent R01, but now will investigate the role of white matter pathways in the decline of language production skills in neurodegenerative disease. Here, we will follow the changes that occur in primary progressive aphasia (PPA) over the course of one year using the same language and diffusion imaging analyses that are being applied in our parent R01. In collaboration with our colleague, Dr. Maria Luisa Gorno-Tempini, at the University of California, San Francisco (UCSF), we will capitalize on the excellent recruitment and diagnostics already being done with her cohort of PPA patients. With the incorporation of additional language tests, slight modification of their diffusion imaging protocol, and our own imaging analysis pipeline, we will test whether the same fiber pathways that change (for the better) in relation to language production recovery will also change (for the worse) in language production decline. Thirty individuals with PPA will undergo an identical set of language and imaging assessments to those currently being administered to our stroke cohort at UC Berkeley, conducted at two time points, 1 year apart. Measures of white matter microstructure in individual tracts at Time 1 will be evaluated as predictors of the type of language change that occurs during the subsequent year. Changes in white matter microstructure metrics that occur from Time 1 to Time 2 will be correlated with language change to assess the role of each tract in language decline. One of the many benefits of this Supplement is that we will be able to leverage existing NIH-funded projects to extract additional gains. We will take advantage of the testing and imaging already being done at both sites, as well as the infrastructure and resources that currently exist. Yet, this Supplement goes beyond the scope of the two currently-funded projects by adding additional language tests and neuroimaging analyses to both patient cohorts. By combining them in this novel way to evaluate the microstructure of particular fiber pathways in both language recovery and decline, we will provide strong evidence for the causal role that these important connections play in language processing.
Individuals with Primary Progressive Aphasia suffer from a gradual and insidious decline in their ability to produce words and sentences that profoundly impairs their ability to communicate with others. The proposed Supplemental project will apply the same language and neuroimaging tools used in our parent R01 that evaluates recovery in aphasic stroke patients to examine the underlying changes in the brain's fiber pathways that occur as language production declines. This novel approach of comparing language recovery in stroke with language decline in neurodegenerative disease will provide strong evidence for the causal role that these important neural connections play in language processing.
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