PROJECT SUMMARY Adolescence is typically defined as the transition period between childhood and adulthood. It is a critical period for neural changes, including maturation of the brain’s cognitive networks, but also a period of increased vulnerability to psychopathology. It is well accepted that the brain is functionally organized into multiple interacting networks and extensive literature has demonstrated that the spatial and functional organization of these networks shows major age-related changes across the lifespan, but particularly during adolescence. Yet, there is currently no reference functional brain atlas derived from typically-developing adolescents, which is especially problematic as the reliable and reproducible identification of functional brain networks crucially depends on the use of such reference functional atlases. Furthermore, the use of atlases derived from adults may undermine the validity and reliability of developmental neuroimaging research. Using preliminary data for this application and previous works, we show that an age-appropriate functional brain atlas will improve the characterization of the brain functional connectome and its links to neuropsychiatric traits in youth. In this context, the aim of this application is to construct and validate the first reference functional brain atlas in typically-developing youth between the age of 8 and 17 years. To achieve this, we will use resting-state functional MRI (rs-fMRI) from the three largest developmental neuroimaging datasets. Our first aim (Aim 1) is to generate a reference atlas, called “Dev-Atlas”, using the rs-fMRI datasets from approximately 2,000 youths. We will then (Aim 2) demonstrate the replicability of Dev-Atlas in two independent large samples of typically- developing youth (Dev-Cog: n=230; Dev-MIND: n=310), collected at Boys Town National Research Hospital and the Mind Research Network. Because girls, on average, enter puberty one to two years earlier than boys, we will test (Aim 3) whether girls show brain network differences compared to boys. In the event of significant sex differences, we will create the first sex-specific functional brain atlases for youth. Finally, we will demonstrate the superiority of network connectivity features derived from Dev-Atlas compared to atlases based on data from adults in predicting a greater amount of the variance in psychiatric traits (Aim 4). The successful completion of this project will provide the first reliable functional brain atlas for youth aged 8-17 years old, which will be made freely available to the research community. By mapping the brain functional connectome underlying childhood and adolescence, this work has the potential to elucidate how brain network dysfunction contributes to psychiatric traits and the risk for mental health disorders in adolescence.

PROJECT NARRATIVE Understanding developmental changes in the brain’s functional architecture during childhood and adolescence is a major public health challenge, as adolescence encompasses a critical developmental period during which many mental health disorders emerge. This project aims to construct and validate the first ever functional reference brain atlas for typically-developing youth aged 8 to 17 years old (Dev-Atlas) and to demonstrate its value in predicting neuropsychiatric traits in this age window.