PROJECT SUMMARY AND ABSTRACT Developmental dyslexia, or reading disability (RD), is characterized by unexpected reading impairments, and dyscalculia, or math disability (MD), is characterized by unexpected impairment in arithmetic abilities. Both learning disabilities (LDs) are associated with differences in gray matter (GM) structure compared to typically developing (TD) children. Intensive reading intervention (tutoring) in children with RD has been shown to improve reading skills and change brain structure, but it is unknown whether math intervention results in similar neuroanatomical changes in children with MD. It is also not yet known how intervention-induced changes in brain structure in these LDs compare to the developmental trajectory of brain structure in TD children, specifically whether the mechanisms of intervention in LD involve normalization or compensation. In the proposed study, we will (1) investigate intervention-induced changes in reading and math skills, (2) study how two GM properties (e.g., gray matter volume and cortical thickness) change in response to successful interventions in children with LDs, and (3) compare these GM findings to those occurring over the course of typical development. In Aim 1, we will characterize the behavioral data collected from children with RD and MD undergoing 90 hours of reading or math intervention, respectively. We will build on prior analyses to determine the role of related academic skills (e.g., phonemic awareness) and sex on behavioral gains made during each intervention. In Aim 2, we will measure intervention-induced changes in GM structure in the same children with RD and MD. We will test for correlations between behavioral gains and changes in GM structure in each group. We expect to observe intervention-induced GM changes (and correlations with behavioral gains) in left hemisphere reading-related areas in RD following the reading intervention, and changes in bilateral fronto- parietal regions associated with arithmetic following the math intervention. We will also determine whether pre- intervention GM properties are associated with the magnitude of behavioral gains made during each intervention. In Aim 3, we will compare our findings of anatomical changes in LD to changes in TD children observed over time to contextualize our intervention results as “normalization,” “compensation,” or some combination of both. Specifically, we will test for changes in the same brain regions identified in Aim 2. One TD group, which underwent the same structural MRI protocol as the RD and MD groups, will be used for direct comparison. A second, larger TD group (from an NIH database) will be used for replication of the first TD group. Overall, all three Aims will lead to an increased understanding of the brain mechanisms underlying interventions in LDs, and how these brain changes relate to typical development.