Patterns of connectome variability in autism across five functional activation tasks. Findings from the LEAP project

Background Autism spectrum disorder (autism) is a complex neurodevelopmental condition with pronounced behavioural, cognitive, and neural heterogeneities across individuals. Here, our goal was to characterise heterogeneity in autism by identifying patterns of neural diversity as reflected in BOLD fMRI in the way individuals with autism engage with a varied array of cognitive tasks. Methods All analyses were based on the EU-AIMS/AIMS-2-TRIALS multisite Longitudinal European Autism Project (LEAP) with participants with autism and typically developing controls (TD) between 6 and 30 years of age. We employed a novel task-potency approach which combines the unique aspects of both resting-state fMRI and task-fMRI to quantify task-induced variations in the functional connectome. Normative modelling was used to map atypicality of features on an individual basis with respect to their distribution in neurotypical control participants. We applied robust out-of-sample canonical correlation analysis (CCA) to relate connectome data to behavioural data. Results Deviation from the normative ranges of global functional connectivity was greater for individuals with autism compared to TD in each fMRI task paradigm (all tasks p<0.001). The similarity across individuals of the deviation pattern was significantly increased in autistic relative to TD individuals (p<0.002). The CCA identified significant and robust brainbehavior covariation between functional connectivity atypicality and autism-related behavioral features. Conclusions Individuals with autism engage with tasks in a globally atypical way, but the particular spatial pattern of this atypicality is nevertheless similar across tasks. Atypicalities in the tasks originate mostly from prefrontal cortex and default mode network regions, but also speech and auditory networks. We show, moving forward, sophisticated modeling methods such as task-potency and normative modeling will prove key to unravelling complex heterogeneous conditions like autism.