DESCRIPTION (provided by applicant): This Clinical Research Center (P50) proposal is focused on providing a neuroimaging-based examination of language recovery in individuals with chronic aphasia resulting from stroke. The goal of the Center is to bring together the expertise of clinical investigators with mutual scientific interest and complementary expertise in understanding the cognitive and neural correlates of stroke-induced language recovery, the effects of language treatment on these processes, and cognitive and neural factors (biomarkers) of language/brain recovery. The proposal includes three subprojects, which examine language recovery in three language domains, with experts in each serving as PI: Subproject 1. The neurobiology of recovery of spoken naming in aphasia, Swathi Kiran (Boston University) and David Caplan (Harvard, MGH); Subproject 2. The neurobiology of recovery of written naming in acquired dysgraphia, Brenda Rapp (Johns Hopkins); and Subproject 3. The neurobiology of recovery of sentence processing in agrammatism, Cynthia Thompson (Northwestern). Combining the expertise and efforts of the PIs on this project will allow us to study aphasia recovery in a comprehensive manner. At the heart of the approach is a common set of cognitive and neuroimaging measures, including functional magnetic resonance imaging (fMRI), structural and perfusion imaging, and diffusion tensor imaging (DTI), which we will use as tools for identifying, monitoring and evaluating cognitive-brain changes at several time points, coinciding with treatment application and spanning a one-year period. Cross-project data will be deposited into a centralized Neuroimaging and Data Analysis Core (Core B) where they will be analyzed by an expert team of neuroimaging specialists and statisticians, led by Todd Parnsh (PI; neurophysicist at Northwestern), using state-of-the art neuroimaging acquisition and analysis methods. This will allow us to examine the effects of treatment designed to improve specific aphasic language deficits and to answer questions relevant to the relation between language and brain variables and treatment-induced versus natural recovery in chronic aphasia. The work will highly impact clinical intervention practices for individuals with aphasia, providing importan information relevant to the effects of treatment and prognosis for recovery, and contribute to knowledge about brain plasticity and the reorganization of language functions in the adult brain.

PUBLIC HEALTH RELEVANCE: Understanding the neurobiology of language recovery in stroke-induced language impairment (aphasia) is critical for advancing clinical practice for this devastating disorder. The comprehensive, innovative and theoretically grounded set of experiments examining how treatment impacts recovery coupled with state-of-the- art neuroimaging methodology that will be used in this Clinical Research Center are expected to significantly move forward our understanding of the effects of treatment on the stroke-recovering brain and the cognitive and neural factors that affect it, enhancing the ability to provide accurat prognosis for recovery and prescribe effect treatment. Subproject 1 The Neurobiology of Recovery of Naming Impairments Lead Investigators: Swathi Kiran & David Caplan