Project Summary Chiari malformation (CM) is a challenging disease that frequently presents during development in the pediatric age range. Despite its well-defined anatomic pathology, characterized by ectopic position of the cerebellar tonsils herniating through the foramen magnum, its clinical phenotype is variable. Here we propose an advanced neuroimaging study to seek novel explanations for CM symptomology through personalized connectomics using resting state functional MRI (rs-fMRI). In Aim 1, we will first capitalize on publicly shared data from the Adolescent Brain Cognitive Development (ABCD) Study for incidentally identified CM subjects and typically developing controls. In Aim 2, we will acquire identical ABCD protocol MRI data at presentation and longitudinal timepoints in both surgical and non-surgical subjects who are symptomatic and present for clinical care. We will replicate the imaging and cognitive testing from the ABCD Study in our clinical cohort for direct comparisons. We will also record the Chiari Severity Index (CSI) and Chiari Health Index in Pediatrics (CHIP) metrics, which have been developed and validated specific to CM, in our clinical cohort. Finally, in Aim 3, for a subset of participants we will obtain highly sampled longitudinal data at frequent timepoints after surgical intervention to better characterize the time course of functional connectivity (FC) changes, or potentially confirm if any lack of change could be dependent on timing of data collection. This final aim will be critical for future studies of similar design to optimize decisions on how long after surgery imaging should ideally be acquired to maximize effect measured and avoid missing a transient effect. The FC changes and correlations to natural history, symptoms, and response to treatment will be valuable as potential biomarkers of disease that could be used to guide treatment decisions for future clinical care. While this study is aimed at evaluating FC as a potential marker of cognitive dysfunction specific to CM, its methodology and design will be adapted to several other novel pathologies in the future as my research career develops. Furthermore, the results of this study will provide fundamental knowledge about the relationship between brain structure and function. Specifically, for CM these results relate mechanical compression from ectopic position of the cerebellar tonsils to FC in resting state networks throughout the brain and its related cognitive symptoms. In this manner, we are directly addressing the aims of the NINDS by assessing basic cognitive neuroscience fundamentals of disease in CM and its potential for translation to clinical care of neurologic disease. The data collection and analysis methods are part of a focused plan to advance my career development through training in acquisition of advanced fMRI data, surface-based analysis, and large data analysis from the ABCD Study dataset. In parallel, I will participate in course work...