Development of structure-function coupling in human brain networks during youth

Abstract

The protracted development of structural and functional brain connectivity within distributed association networks coincides with improvements in higher-order cognitive processes such as executive function. However, it remains unclear how white-matter architecture develops during youth to directly support coordinated neural activity. Here, we characterize the development of structure-function coupling using diffusion-weighted imaging and n-back functional MRI data in a sample of 727 individuals (ages 8 to 23 y). We found that spatial variability in structure-function coupling aligned with cortical hierarchies of functional specialization and evolutionary expansion. Furthermore, hierarchy-dependent age effects on structure-function coupling localized to transmodal cortex in both cross-sectional data and a subset of participants with longitudinal data (n = 294). Moreover, structure-function coupling in rostrolateral prefrontal cortex was associated with executive performance and partially mediated age-related improvements in executive function. Together, these findings delineate a critical dimension of adolescent brain development, whereby the coupling between structural and functional connectivity remodels to support functional specialization and cognition.

Keywords: MRI; brain development; connectome; cortical organization; structure–function.

Fig. 1.

Measuring structure–function coupling in human brain networks. Nodes in structural and functional brain networks were defined using a 400-region cortical parcellation based on functional homogeneity in fMRI data (22). For each participant, regional connectivity profiles were extracted from each row of the structural or functional connectivity matrix and represented as vectors of connectivity strength from a single network node to all other nodes in the network. Structure–function coupling was then measured as the Spearman rank correlation between nonzero elements of regional structural and functional connectivity profiles.

Fig. 2.

Variability in structure–function coupling reflects cortical hierarchies of functional specialization. The coupling between regional structural and functional connectivity profiles during the n-back working memory task varied widely across the cortex. (A) Primary sensory and medial prefrontal cortex exhibited relatively high structure–function coupling, while lateral temporal and frontoparietal regions had relatively low coupling. (B) Structure–function coupling was significantly associated with the structural participation coefficient (PC) and the functional participation coefficient (C), a measure of the diversity of intermodule connectivity. (D) Variability in structure–function coupling reflected a brain region’s position along the macroscale functional gradient from unimodal to transmodal processing, and (E) recapitulated patterns of evolutionary expansion in cortical surface area from macaques to humans. The significance of regional correlations was evaluated using nonparametric spatial permutation testing, and associated P values are denoted p_spin.

Fig. 3.

Hierarchy-dependent development of structure–function coupling. Age-related differences in structure–function coupling were broadly distributed across the cerebral cortex. (A) Age-related increases in structure–function coupling were observed bilaterally in the temporoparietal junction and prefrontal cortex, while age-related decreases in coupling were observed in visual, motor, and insular cortex. (B) Notably, age-related increases in coupling were disproportionately enriched within the default mode network compared to other functional systems (F = 12.54, P < 10⁻¹⁰). (C) The magnitude of age-related differences in structure–function coupling was significantly correlated with the functional participation coefficient (PC), (D) the functional gradient from unimodal to transmodal processing, and (E) evolutionary expansion of cortical surface area. The significance of regional correlations was evaluated using nonparametric spatial permutation testing, and associated P values are denoted p_spin. Red points in C–E correspond to default mode regions, and blue points correspond to brain regions in other functional systems. Asterisks in B indicate P < 0.001. VIS, visual; SOM, somatomotor; DOR, dorsal attention; VEN, ventral attention; LIM, limbic; FPC, frontoparietal control; DMN, default mode network.

Fig. 4.

Longitudinal change in structure–function coupling is associated with longitudinal change in the diversity of regional functional connectivity. (A) We observed a significant correspondence between cross-sectional (n = 727) and longitudinal age effects on structure–function coupling estimated with a linear mixed-effects model (n = 294). We used linear regression to test whether longitudinal change in structure–function coupling (B) was associated with longitudinal change in the functional participation coefficient (C). Longitudinal increases in coupling were associated with increased participation coefficient (functional integration) in lateral frontoparietal and temporal regions and decreased participation coefficient (functional segregation) in medial visual and prefrontal regions (D).

Fig. 5.

Individual differences in structure–function coupling are associated with executive function. (A) We found that executive performance was associated with higher structure–function coupling in the rlPFC, anterior insula, posterior cingulate, and medial occipital cortex, while better performance was associated with lower structure–function coupling in areas of somatomotor cortex. (B) Higher structure–function coupling in the rlPFC (circled in A) partially mediated age-related improvements in executive function. Mediation results are reported as standardized regression coefficients, and statistical significance was assessed using 95% bootstrapped CIs.