Characterizing pubertal and age mechanisms of neurodevelopment and association with rising internalizing symptoms

PROJECT SUMMARY Building comprehensive accounts of human brain development from childhood to early adulthood is crucial to our understanding of both healthy neurodevelopment and the mechanisms underlying threats to youths’ mental health. Brain development unfolds on multiple levels, but the field lacks a comprehensive understanding of whether the trajectories of development are fundamentally similar or different across modalities (e.g., structure and function), and how they reflect developmental mechanisms associated with puberty or age (or both). The proposed research aims to generate a systematic and comprehensive multimodal account of typical neurodevelopment from ages 5 to 21, with a particular focus on a) identifying age versus pubertal- and hormonal-based mechanisms that undergird development in childhood and adolescence; b) systematic analyses across brain structure, function, and connectivity using state-of-the-art acquisition and analysis approaches; and c) evaluation of maturational variation in multimodal coupling across brain systems/ modalities as a function of development. Once established, this multimodal model of typical neurodevelopment will be used to test a conceptual model proposing that early pubertal timing leads to intensification of internalizing symptoms due to disruptions in brain development, including alterations in multimodal coupling. Specifically, models of the impact of early pubertal timing predict either further enhanced coupling with early puberty (neurodevelopmental acceleration) or disruptions in coupling due to neurodevelopmental delays. To compare these competing models and advance our understanding of the neurodevelopmental pathways by which early pubertal timing contributes to the rise of internalizing symptoms during adolescence, the research will use both hypothesis-driven methods and novel validated analysis pipelines for data-driven exploration of developmental changes in coupling, with careful attention to robustness and replication. The primary dataset will be the Human Connectome Project in Development (HCPD), a large, NIH funded, multimodal brain imaging dataset that includes a comprehensive assessment of brain structure, function, and connectivity paired with pubertal and hormonal measures and extensive behavioral and clinical measures in both a cross-sectional cohort of N=1300+ youth ages 5 to 21, and a longitudinal cohort (N=252) spanning ages 9 to 17 capturing the pubertal transition. This sample is purposefully strong diversity in race, ethnicity, and socioeconomic status. Key findings will be replicated to ensure robustness and generalizability in the Adolescent Brain and Cognitive Development (ABCD) longitudinal study. Our Specific Aims are to: A1) Establish a comprehensive, systematic account of age-and pubertal-linked pathways of brain development across multiple modalities of brain structure and function; A2) Test hypotheses about the relations of age and pubertal development to coupling across brain modalities; and A3) Test hypotheses about the neurodevelopmental mechanisms contributing to the rise in internalizing symptoms during the pubertal transition.