PROJECT SUMMARY Project 2: Functional Connectivity, Brain Development, and Outcomes in Chiari Type I Malformation Abstract Chiari malformation (CM) is a challenging disease. Despite its anatomically well-defined pathology characterized by herniation of the cerebellar tonsils through the foramen magnum, its clinical symptoms and indications for surgical intervention are highly variable. Here we propose advanced neuroimaging with personalized connectomics acquired longitudinally, in both surgical (pre/post posterior fossa decompression) and non-surgical CM patients, to identify imaging markers for better disease characterization and outcome prediction. We are using resting state functional MRI (rs-fMRI) and diffusion tensor imaging (DTI) to measure resting state functional connectivity (RSFC) and fractional anisotropy (FA), respectively. We are leveraging the protocols of the Adolescent Brain Cognitive Development (ABCD) Study (n = 11,874), to facilitate direct comparisons to age and demographic matched control subjects from the ABCD data set, for both imaging and cognitive/emotional metrics. In addition, we are collecting Chiari Severity Index (CSI) and Chiari Health Index in Pediatrics (CHIP) data, both of which have been developed and validated by our team specifically for CM. The longitudinal arm of this project includes an adult CM cohort, which will expand the number of participants for greater power, and allow us to test developmental CM effects in the pediatric cohort. The imaging and cognitive measures will be compared at baseline before any intervention. Then within-participant comparisons will be made before and after posterior fossa decompression (PFD) surgery to identify novel imaging markers predictive of disease outcomes and response to surgery.