The multiscale brain structural re-organization that occurs from childhood to adolescence correlates with cortical morphology maturation and functional specialization.

Abstract

From childhood to adolescence, the structural organization of the human brain undergoes dynamic and regionally heterogeneous changes across multiple scales, from synapses to macroscale white matter pathways. However, during this period, the developmental process of multiscale structural architecture, its association with cortical morphological changes, and its role in the maturation of functional organization remain largely unknown. Here, using two independent multimodal imaging developmental datasets aged 6-14 years, we investigated developmental process of multiscale cortical organization by constructing an in vivo multiscale structural connectome model incorporating white matter tractography, cortico-cortical proximity, and microstructural similarity. By employing the gradient mapping method, the principal gradient derived from the multiscale structural connectome effectively recapitulated the sensory-association axis. Our findings revealed a continuous expansion of the multiscale structural gradient space during development, characterized by enhanced differentiation between primary sensory and higher-order transmodal regions along the principal gradient. This age-related differentiation paralleled regionally heterogeneous changes in cortical morphology. Furthermore, the developmental changes in coupling between multiscale structural and functional connectivity were correlated with functional specialization refinement, as evidenced by changes in the participation coefficient. Notably, the differentiation of the principal multiscale structural gradient was associated with improved cognitive abilities, such as enhanced working memory and attention performance, and potentially underpinned by synaptic and hormone-related biological processes. These findings advance our understanding of the intricate maturation process of brain structural organization and its implications for cognitive performance.