Project Summary Incomplete understanding of patient-specific factors that determine whether someone will respond well to language therapy after stroke limits the development of methods to target or account for sources of variability. There is a strong likelihood that genetics play a role in language recovery after stroke, but very little research has been dedicated to investigating this link. The long-term goal of this line of work is to maximize response to aphasia therapy by incorporating patient-specific factors into decisions related to treatment planning. The overall objective of this application is to identify patterns of patient-specific factors including two candidate genes and cognitive skills that show a relationship with treatment outcomes. The central hypothesis is that there will be a relationship between ApoE and BDNF genotypes, and working memory on stimulus generalization. The rationale for the proposed project is that the identification of factors that impact treatment responsiveness will allow for better estimation of prognosis, improved triage of individuals into appropriate therapy regimens and direct targeting of cognitive factors to maximize behavioral gains. The two specific aims of the project are to determine the degree to which (1) ApoE and BDNF genotypes influence how individuals with aphasia respond to therapy, and (2) working memory abilities are related to stimulus acquisition and stimulus generalization after anomia therapy. Individuals with chronic post-stroke aphasia will undergo cognitive and language assessment, and provide a saliva sample for genetic analysis prior to participating in a cued picture-naming therapy for anomia. The expected outcomes are to integrate cognitive scores and genotypes for BDNF and ApoE into formulating probabilities of individual patient responsiveness to restorative therapy. This contribution is expected to be significant because it will allow for more informed clinical decision making and better allocation of resources to appropriate treatments, thereby making advances in the field toward more personalized medicine, as opposed to a one-size-fits-all clinical approach. The proposed research is innovative, in the applicants' opinions, because it represents a substantive departure from the status quo by quantifying sources of genetic and cognitive variability that may influence responsiveness to restorative therapy, which the applicants propound can be used both clinically and in research to improve patient outcomes.