Developmental Changes in Gray Matter Microstructure and Local Brain Connectivity Support Inhibitory Control from Adolescence to Young Adulthood

Background: Adolescence is marked by improvements in inhibitory control along with brain maturational processes affecting function and structure of cortical circuitry. Preliminary evidence shows a developmental decrease of local neuronal inputs, suggesting a weakening of local connectivity supporting circuit refinement and mature behavior. Microstructural changes in gray matter, arising from processes such as synaptic pruning and myelination, may support this refinement, though it remains unknown how microstructural features interact with the reconfiguration of functional circuitry, or how this unfolds in vivo in normative development to support mature cognitive functioning. Methods: In this study, 175 participants ages 10-26 (93F; 17.32{+/-}4.82yo) completed an anti-saccade task, a developmentally-validated measure of inhibitory control, as well as a 3T MRI scan involving a multi-shell diffusion weighted imaging acquisition, multi-echo resting state fMRI, and structural (T1w, T2w) scans. We computed measures of neurite density (NDI) in gray matter using neurite orientation dispersion and density imaging, local functional connectivity with surface-based and volumetric regional homogeneity (ReHo), and intracortical myelin using T1w/T2w ratio. Generalized additive models examined non-linear age-related trends across a number of cortical and subcortical regions implicated in inhibitory control, as well as associations with anti-saccade performance. Results: We found that NDI significantly increased with age in all regions while ReHo decreased. Greater NDI was associated with more accurate anti-saccade performance and lower ReHo, which remained after residualizing NDI for T1w/T2w ratio, suggesting that microstructural reorganization beyond myelination may underlie functional specialization throughout adolescence. Lower ReHo, specifically in young adolescents, also resulted in better anti-saccade performance. Finally, an interaction between ReHo and NDI, rather than either measure alone, best predicted inhibitory control performance, such that the maturity of neurite density had the greatest effect when local connectivity was high, suggesting immaturity. Conclusions: Our results suggest that the joint maturation of microstructural elements and associated specialization of local functional circuitry interact to support the emergence of stable adult-level inhibitory control.