Introduction: While global topological properties of brain networks reach relative maturity early in development, functional reconfigurations at the regional level continue throughout adolescence to support cognitive maturation. However, regional age and sex-specific developmental patterns of functional reconfiguration remain incompletely understood. Methods: We analyzed resting-state fMRI data from 528 participants aged 5-21 years from the Human Connectome Project in Development. Three regional graph-theory metrics (betweenness centrality, hub score, and local efficiency) were computed for each individual's functional network. Cognition was measured using NIH toolbox. Parallel factor analysis was employed to decompose an individual-by-region-by-metric array into factors representing distinct developmental properties in the full sample and separately for males and females. Brain-cognition associations were examined in developmental subgroups (<13, 13-18, >18 years). Results: Three factors emerged, characterizing visual, multimodal integration, and higher-order factors. Across development, metrics capturing network integration (betweenness centrality and hubness) showed general stability, while metrics capturing segregation (local efficiency) presented distinct peaks, particularly in the visual factor. Females showed earlier peaks and declines in higher-order factor, while males exhibited greater variability and protracted maturation in multimodal and higher-order factors. Brain-cognition associations were modest with early childhood and crystallized cognition composites showed small negative correlations with hub score in entire sample (r=-0.212) and local efficiency in males aged <13 years (r=-0.215). Conclusion: Findings highlight nonlinear, sex-specific functional reconfiguration at region-level during childhood and adolescence, underscoring the importance of sex-stratified analyses in developmental and providing a crucial foundation for future investigations of developmental disorders.
Fang, C. Z., Nakua, H., Ma, X., Zhang, A., Lee, S.
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