Identifying brain functional subtypes and corresponding task performance profiles in autism spectrum disorder

Abstract

Refining the classification of autism spectrum disorder (ASD) subtypes is essential for advancing personalized interventions strategies, given the substantial heterogeneity in phenotypic clinical symptoms among individuals with ASD. Thus, the current study integrated normative modeling, resting-state fMRI data, clinical assessment, and eye-gaze patterns to investigate potential ASD subtypes. By incorporating both static and instant dynamic (strength and variability) functional connectivity as predictive variables within the normative models, we aimed to delineate multi-level functional developmental trajectories. Our comprehensive analysis of 1046 participants (479 with ASD, 567 typical development) identified two distinct neural ASD subtypes with unique functional brain network profiles despite comparable clinical presentations. One ASD subtype was characterized by positive deviations in the occipital network and cerebellar network, coupled with negative deviations in the frontoparietal network, default mode network, and cingulo-opercular network. Conversely, the other subtype exhibited an inverse pattern of functional deviations across these networks. Furthermore, an independent cohort of 21 ASD individuals revealed that these neural subtypes were also associated with distinct gaze patterns assessed by two autism-sensitive eye-tracking tasks focused on preference for social cues. These findings emphasize the complexity and heterogeneity of ASD, uncovering the presence of neurobehavioral subtypes that extend beyond simple neural variations and manifest in diverse functional developmental patterns and behavioral presentations. This study underscores the importance of adopting personalized intervention strategies that cater to the individual needs of each person, rather than relying on a standardized, one-size-fits-all approach, despite the presence of similar clinical symptoms.