Genetic and MRI biomarkers of neuroplasticity predict aphasia recovery and phenotypes

Project Abstract Aphasia is an acquired neurologic language disorder that is among the most challenging long-term disabilities for stroke survivors, often leading to social isolation and reduced quality of life. Recovery from aphasia relies on plasticity in residual brain networks. However, neuroplasticity varies substantially across individuals, making the presence, severity, and phenotype of language impairments challenging to predict. A vital step toward post-stroke precision medicine is identifying neuroplasticity-related biological markers that can improve prognostic models and targeted neurorehabilitation therapies for people with aphasia. The proposed research will test the central hypothesis that individual differences in neuroplasticity, measured through genetic polymorphisms and longitudinal neuroimaging connectivity biomarkers, will account for significant variance in post-stroke aphasia recovery. This 5-year project will include three specific aims. Aim 1 is to index spontaneous recovery by determining relationships between genetic biomarkers of plasticity, longitudinal neural network connectivity, and changes in language during sub-acute to chronic stroke recovery. Aim 2 is to identify genetic and MRI biomarkers predictive of chronic post-stroke aphasia severity and phenotypes. Aim 3 is to characterize genetic and MRI biomarkers associated with verbal learning variability in chronic aphasia. These data will support the development of a larger, multi-site R01 study to examine interactions between multiple biomarkers of neuroplasticity that inform longitudinal aphasia prognostics and treatment efficacy. This career development proposal is designed to provide Haley C. Dresang, Ph.D., a clinical neuroscientist and aphasiologist, with the training required for success as an independent patient-oriented scientist conducting neurotranslational aphasia research. As a junior faculty member at the University of Wisconsin– Madison, Dr. Dresang is in an ideal environment with extensive infrastructure to support early-stage investigator training and research. The proposed career development plan includes both coursework and mentored training in the areas of 1) MRI neuroplasticity biomarkers, 2) genetic polymorphisms associated with neuroplasticity, 3) longitudinal clinical trials design and analysis, and 4) professional skills for an independent translational neuroscientist. To ensure success, she has identified committed, expert mentors in these disciplines and secured protected time for this work. This award addresses a significant clinical dilemma and serious gap in neurobiologically motivated aphasia research, while affording the education and mentored research experience critical for Dr. Dresang to lead an independent aphasia research program.