Macroscale connectome manifold expansion in adolescence

Adolescence is a critical time for the continued maturation of brain networks, and the current work assessed longitudinal reconfigurations of diffusion MRI derived connectomes in a large sample (n = 208). We identified an expansion of structural network representations in lower dimensional manifold spaces, with strongest effects in transmodal cortices and indicative of an increasing differentiation of these networks from the rest of the brain. Findings were shown to relate to mainly an increase in within-module connectivity and increased segregation during adolescence. Connectome findings were consistent when additionally controlling for regional changes in MRI measures of cortical morphology and myelin, despite reductions in effect sizes. On the other hand, cortical areas showing manifold expansion were found to become more closely embedded with subcortical targets, notably the striatum. Identified networks were also found to harbor genes significantly expressed in both cortical and subcortical regions. Using supervised machine learning with cross-validation, we demonstrated that cortico-subcortical manifold features at baseline and their maturational change predicted measures of intelligence at follow-up. Our findings chart adolescent connectome development and suggest that brain-wide network reconfigurations offer intermediary phenotypes between genetic-microstructural processes and cognitive-behavioral outcomes.