Developmental linearization of functional connectivity and its alteration in males with autism spectrum disorder

Brain development is accompanied by gradual refinement of large-scale functional communication. Recent work indicates that functional connectivity can be characterized by both linear and nonlinear dependencies, raising the possibility that maturation involves a shift toward more linearly organized coupling. Whether this developmental trajectory differs in autism spectrum disorder (ASD) is not yet clear.

We analyzed resting-state fMRI data from the ABIDE cohort, including 188 males with ASD and 216 age-matched typically developing (TD) males. The ASD group had a mean age of 15.66 ± 66.13 years (range = 6-35), and the TD group had a mean age of 15.71 ± 5.97 years (range = 7-35). After standard preprocessing, we estimated linear and nonlinear connectivity for each participant and derived an index reflecting the extent to which nonlinear interactions were accounted for by linear coupling. This index was examined at the whole-brain scale and within canonical large-scale networks defined by the Yeo 7-network framework. Group differences and age-related effects were assessed, with multiple-comparison correction applied to network-level analyses.

At the whole-brain level, ASD participants showed significantly lower R² values than TD participants. At the network level, significant between-group differences were observed in the visual, somatomotor, dorsal attention, ventral attention, and default mode networks. Across the typically developing group, the index increased significantly with age, suggesting a gradual strengthening of linear structure in functional interactions during maturation. In contrast, the ASD group showed only a weak relationship with age. At the network level, age-related associations were more widespread in the TD group than in the ASD group. In TD, significant positive age associations were observed in multiple networks, whereas in ASD they were limited to fewer systems. The clearest between-group inconsistency in age-related pattern was observed in the limbic network.

These findings support the idea that normative brain development is associated with increasing linear organization of functional interactions, and suggest that this pattern is attenuated or altered in males with ASD. The proposed index quantifying the goodness of fit of the linear model predicting distance-correlation-based functional connectivity (FC) from Pearson-correlation-based FC and may provide an operational summary for characterizing atypical maturation of large-scale FC patterns.