Abstract

A number of studies have indicated alterations of brain morphology in individuals with autism spectrum disorder (ASD); however, how ASD influences the topological organization of the brain cortex at different developmental stages is not yet well characterized. In this study, we used structural images of 492 high‐functioning participants in the Autism Brain Imaging Data Exchange database acquired from 17 international imaging centers, including 75 autistic children (age 7–11 years), 91 adolescents with ASD (age 12–17 years), and 80 young adults with ASD (age 18–29 years), and 246 typically developing controls (TDCs) that were age, gender, handedness, and full‐scale IQ matched. Cortical thickness (CT) and surface area (SA) were extracted and the covariance between cortical regions across participants were treated as a network to examine developmental patterns of the cortical topological organization at different stages. A center‐paired resampling strategy was developed to control the center bias during the permutation test. Compared with the TDCs, network of SA (but not CT) of individuals with ASD showed reduced small‐worldness in childhood, and the network hubs were reorganized in the adulthood such that hubs inclined to connect with nonhub nodes and demonstrated more dispersed spatial distribution. Furthermore, the SA network of the ASD cohort exhibited increased segregation of the inferior parietal lobule and prefrontal cortex, and insular‐opercular cortex in all three age groups, resulting in the emergence of two unique modules in the autistic brain. Our findings suggested that individuals with ASD may undergo remarkable remodeling of the cortical topology from childhood to adulthood, which may be associated with the altered social and cognitive functions in ASD.

Highlights

  • Autism spectrum disorder (ASD) is a pervasive neurodevelopmental disorder characterized by impaired social–emotional functioning and related behavior throughout the lifespan, including deficits in social communication, restricted interest, and repetitive and stereotyped behaviors (Association, 2013; Baron-Cohen, 2000)

  • We found that there was a significant reduction in network assortativity in adults with autism spectrum disorder (ASD) compared to the matched controls (q < 0.05, permutation test, false discovery rate (FDR) corrected, Figure 4), suggesting hub nodes tended to cluster more with nonhub nodes and cluster less with other hubs in adults with ASD

  • Our results suggested that ASD (a) resulted in substantial changes in cortical structural organization in the childhood, including reduced small-worldness, centralized hubs in the orbitofrontal cortex, and reduced network assortativity in the adulthood; and (b) caused disordered module organization that formed a specific module including brain regions associated with socio-emotional processing and cognitive functions

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Summary

Introduction

Autism spectrum disorder (ASD) is a pervasive neurodevelopmental disorder characterized by impaired social–emotional functioning and related behavior throughout the lifespan, including deficits in social communication, restricted interest, and repetitive and stereotyped behaviors (Association, 2013; Baron-Cohen, 2000). Other studies showed that the gray matter (GM) may still undergo evident changes in the adults with ASD, especially in the amygdala and frontal brain regions (Courchesne et al, 2011; Ecker, Ginestet, et al, 2013; Eilam-Stock, Wu, Spagna, Egan, & Fan, 2016; Freitag et al, 2009; Hazlett, Poe, Gerig, Smith, & Piven, 2006) These findings primarily concerned about the changes in GM morphology but did not address how the brain morphological networks were altered in terms of connectivity, hub topology (the spatial distribution of important brain regions and their connective pattern), and modularity (measures the decomposability of a network into several sparsely interconnected communities) at different stages of development

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