Development of frontoparietal connectivity predicts longitudinal symptom changes in young people with autism spectrum disorder

Structural neuroimaging studies suggest altered brain maturation in autism spectrum disorder (ASD) compared with typically developing controls (TDC). However, the prognostic value of whole-brain structural connectivity analysis in ASD has not been established. Diffusion magnetic imaging data were acquired in 27 high-functioning young ASD participants (2 females) and 29 age-matched TDC (12 females; age 8-18 years) at baseline and again following 3-7 years. Whole-brain structural connectomes were reconstructed from these data and analyzed using a longitudinal statistical model. We identified distinct patterns of widespread brain connections that exhibited either significant increases or decreases in connectivity over time (p < 0.001). There was a significant interaction between diagnosis and time in brain development (p < 0.001). This was expressed by a decrease in structural connectivity within the frontoparietal network-and its broader connectivity-in ASD during adolescence and early adulthood. Conversely, these connections increased with time in TDC. Crucially, stronger baseline connectivity in this subnetwork predicted a lower symptom load at follow-up (p = 0.048), independent of the expression of symptoms at baseline. Our findings suggest a clinically meaningful relationship between the atypical development of frontoparietal structural connections and the dynamics of the autism phenotype through early adulthood. These results highlight a potential marker of future outcome.