Atypicalities in the developmental trajectory of cortico-striatal functional connectivity in autism spectrum disorder

Abstract

The last decades of neuroimaging research has revealed atypical development of intrinsic functional connectivity within and between large-scale cortical networks in autism spectrum disorder, but much remains unknown about cortico-subcortical developmental connectivity atypicalities. This study examined cortico-striatal developmental intrinsic functional connectivity changes in autism spectrum disorder and explored how those changes may be correlated with autistic traits. We studied 49 individuals with autism spectrum disorder and 52 age-, sex-, and head motion–matched typically developing individuals (5–30 years old (14.0 ± 5.6)) using resting-state functional magnetic resonance imaging. Age-related differences in striatal intrinsic functional connectivity were compared between the two groups by adopting functional network–based parcellations of the striatum as seeds. Relative to typically developing individuals, autism spectrum disorder individuals showed atypical developmental changes in intrinsic functional connectivities between almost all striatal networks and sensorimotor network/default network, with connectivity increasing with age in the autism spectrum disorder group and decreasing or constant in typically developing individuals. Age-related degree centrality and voxel-mirrored homotopic connectivity atypicalities in sensorimotor network/default network and voxel-mirrored homotopic connectivity disruptions in striatal regions were also observed in autism spectrum disorder. Significant correlations were found between cortico-striatal intrinsic functional connectivities and Autism Diagnostic Observation Schedule communication/repetitive and restricted-behavior subscores in autism spectrum disorder. Our results indicated that developmental atypicalities of cortico-striatal intrinsic functional connectivities might contribute to the neuropathology of autism spectrum disorder. Lay abstract Autism spectrum disorder has long been conceptualized as a disorder of “atypical development of functional brain connectivity (which refers to correlations in activity levels of distant brain regions).” However, most of the research has focused on the connectivity between cortical regions, and much remains unknown about the developmental changes of functional connectivity between subcortical and cortical areas in autism spectrum disorder. We used the technique of resting-state functional magnetic resonance imaging to explore the developmental characteristics of intrinsic functional connectivity (functional brain connectivity when people are asked not to do anything) between subcortical and cortical regions in individuals with and without autism spectrum disorder aged 6–30 years. We focused on one important subcortical structure called striatum, which has roles in motor, cognitive, and affective processes. We found that cortico-striatal intrinsic functional connectivities showed opposite developmental trajectories in autism spectrum disorder and typically developing individuals, with connectivity increasing with age in autism spectrum disorder and decreasing or constant in typically developing individuals. We also found significant negative behavioral correlations between those atypical cortico-striatal intrinsic functional connectivities and autistic symptoms, such as social-communication deficits, and restricted/repetitive behaviors and interests. Taken together, this work highlights that the atypical development of cortico-subcortical functional connectivity might be largely involved in the neuropathological mechanisms of autism spectrum disorder.