Diffusion trajectory of atypical morphological development in autism spectrum disorder

Brain development from childhood through adolescence is crucial for understanding autism spectrum disorder (ASD). Yet how functional networks regulate developmental changes in brain morphology remains unclear. Here, we analyzed gray matter volume (GMV) and functional connectivity (FC) in 301 individuals with ASD and 375 typically developing controls (TDCs), aged 8-18 years, from the Autism Brain Imaging Data Exchange (ABIDE). Using a sliding-window approach, participants were stratified by age, and GMV distribution deviations (DEV) were quantified with Kullback-Leibler divergence and expected value analysis. Network diffusion modeling (NDM) was applied to predict developmental alterations and evaluate how functional networks constrain atypical neurodevelopment. Results revealed a developmental shift in GMV divergence: during early adolescence, ASD participants showed positive GMV deviations relative to TDCs, which shifted to negative in late adolescence. The largest DEV were observed in the superior temporal sulcus, cingulate gyrus, insula, and superior parietal lobule. Furthermore, NDM demonstrated cross-stage predictability, as DEV values of atypical brain regions at preceding age stages significantly predicting subsequent ones, constrained by network architecture. These findings highlight a dynamic developmental shift from GMV overgrowth to delayed maturation during adolescence in ASD and revealing the role of intrinsic functional networks in constraining atypical anatomical development.