Fig. 1 |. Three brain–behavior dimensions explain individual differences in autism spectrum disorder.

a, Schematic summarizing stabilized feature selection and RCCA in N = 299 ASD participants and N = 907 neurotypical controls. b, Glass brain (left) depicting functional parcellation⁵⁰ spanning the cerebrum, brainstem and cerebellum (colored by functional network). BOLD signal time series extracted from three representative ROIs (middle) and correlation between each ROI and every other ROI (functional connectivity matrix, right) for each participant. c, Glass brain depicting the neuroanatomical distribution of functional connectivity features that were correlated with one or more ASD behaviors, identified in one representative training set (colored by functional network, sized by correlation). d–f, RCCA revealed three dimensions predicting individual differences in verbal IQ (d), social affect (e), and RRB (f) symptoms. Scatterplots depict the association between connectivity scores and behavior scores for each RCCA dimension across participants. Mean scores calculated on held-out data are light, while the average scores calculated on the training set data are dark. Heat maps (left) depict the mean correlation over training sets between each dimension’s behavior scores and each clinical symptom (Fisher z-transformed Spearman correlation coefficients). The canonical correlations (r) for all three dimensions were statistically significant in held-out data (inset also shows Cohen’s d) compared to an empirical null distribution (shuffled held-out test set data; 1,000 shuffles in each of the 1,000 training/test sets). (variate 1: r = 0.269, P <0.0001, d = 1.119; variate 2: r = 0.180, P = 0.0005, d = 0.771; and variate 3: r = 0.115, P = 0.0185, d = 0.484; r indicates mean test set canonical correlation, P indicates P value, and d indicates Cohen’s d). a.u., arbitrary units; BOLD, blood-oxygen-level-dependent; CBL, cerebellum; Cd, caudate; COTC, cerebellar-occipital task control; DMN, default mode network; FPTC, frontoparietal task control; M1, primary motor cortex; MOG, medial orbital gyrus; MTG, middle temporal gyrus; PFC, prefrontal cortex; PPC, posterior parietal cortex; r, canonical correlation; RCCA, regularized canonical correlation; S1, primary somatosensory cortex; SA, social affect.