Altered Connectivity Between Cerebellum, Visual, and Sensory-Motor Networks in Autism Spectrum Disorder: Results from the EU-AIMS Longitudinal European Autism Project

Abstract : BACKGROUND: Resting-state functional magnetic resonance imaging-based studies on functional connectivity in autism spectrum disorder (ASD) have generated inconsistent results. Interpretation of findings is further hampered by small samples and a focus on a limited number of networks, with networks underlying sensory processing being largely underexamined. We aimed to comprehensively characterize ASD-related alterations within and between 20 well-characterized resting-state networks using baseline data from the EU-AIMS (European Autism Interventions-A Multicentre Study for Developing New Medications) Longitudinal European Autism Project. METHODS: Resting-state functional magnetic resonance imaging data was available for 265 individuals with ASD (7.5-30.3 years; 73.2% male) and 218 typically developing individuals (6.9-29.8 years; 64.2% male), all with IQ > 70. We compared functional connectivity within 20 networks-obtained using independent component analysis-between the ASD and typically developing groups, and related functional connectivity within these networks to continuous (overall) autism trait severity scores derived from the Social Responsiveness Scale Second Edition across all participants. Furthermore, we investigated case-control differences and autism trait-related alterations in between-network connectivity. RESULTS: Higher autism traits were associated with increased connectivity within salience, medial motor, and orbitofrontal networks. However, we did not replicate previously reported case-control differences within these networks. The between-network analysis did reveal case-control differences showing on average 1) decreased connectivity of the visual association network with somatosensory, medial, and lateral motor networks, and 2) increased connectivity of the cerebellum with these sensory and motor networks in ASD compared with typically developing subjects. CONCLUSIONS: We demonstrate ASD-related alterations in within- and between-network connectivity. The between-network alterations broadly affect connectivity between cerebellum, visual, and sensory-motor networks, potentially underlying impairments in multisensory and visual-motor integration frequently observed in ASD.