Mapping Progressive Gray Matter Alterations in Early Childhood Autistic Brain

Xiaonan Guo, Xujun Duan, John Suckling, Jia Wang, Xiaodong Kang, Heng Chen, Bharat B Biswal, Jing Cao, Changchun He, Jinming Xiao, Xinyue Huang, Runshi Wang, Shaoqiang Han, Yun-Shuang Fan, Jing Guo, Jingping Zhao, Lijie Wu, Huafu Chen, Xiaonan Guo, Xujun Duan, John Suckling, Jia Wang, Xiaodong Kang, Heng Chen, Bharat B Biswal, Jing Cao, Changchun He, Jinming Xiao, Xinyue Huang, Runshi Wang, Shaoqiang Han, Yun-Shuang Fan, Jing Guo, Jingping Zhao, Lijie Wu, Huafu Chen

Abstract

Autism spectrum disorder is an early-onset neurodevelopmental condition. This study aimed to investigate the progressive structural alterations in the autistic brain during early childhood. Structural magnetic resonance imaging scans were examined in a cross-sectional sample of 67 autistic children and 63 demographically matched typically developing (TD) children, aged 2-7 years. Voxel-based morphometry and a general linear model were used to ascertain the effects of diagnosis, age, and a diagnosis-by-age interaction on the gray matter volume. Causal structural covariance network analysis was performed to map the interregional influences of brain structural alterations with increasing age. The autism group showed spatially distributed increases in gray matter volume when controlling for age-related effects, compared with TD children. A significant diagnosis-by-age interaction effect was observed in the fusiform face area (FFA, Fpeak = 13.57) and cerebellum/vermis (Fpeak = 12.73). Compared with TD children, the gray matter development of the FFA in autism displayed altered influences on that of the social brain network regions (false discovery rate corrected, P < 0.05). Our findings indicate the atypical neurodevelopment of the FFA in the autistic brain during early childhood and highlight altered developmental effects of this region on the social brain network.

Trial registration: ClinicalTrials.gov NCT02807766.

Keywords: Granger causality; autism spectrum disorder; gray matter volume; neurodevelopment; structural magnetic resonance imaging.

© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.

Figures

Figure 1
Figure 1
Significant main effect of diagnosis in the voxel-based morphometry analysis. Autistic children showed larger gray matter volume than TD children in the bilateral rectus (F(1, 124) = 13.99, P < 0.001), right inferior occipital gyrus (F(1, 124) = 12.73, P = 0.001), right inferior temporal gyrus (F(1, 124) = 14.88, P < 0.001), left lingual gyrus/cerebellum (F(1, 124) = 17.66, P < 0.001), right calcarine (F(1, 124) = 16.39, P < 0.001), right superior temporal gyrus (F(1, 124) = 16.36, P < 0.001), and left cuneus (F(1, 124) = 14.28, P < 0.001). *P < 0.05, **P < 0.01, ***P < 0.001. ASD, autism spectrum disorder; TD, typically developing children.
Figure 2
Figure 2
Significant interaction effects between diagnosis and age identified in the voxel-based morphometry analysis. Clusters in the cerebellum/vermis (F(1, 124) = 12.73, P = 0.001) (A) and FFA (F(1, 124) = 13.57, P < 0.001) (B) showed significant diagnosis-by-age interaction effects. Group differences on gray matter changes with increasing age were compared between ASD and TD groups using Z-tests. The color bar represents F values of the diagnosis-by-age interaction effect in the cerebellum/vermis (A) and FFA (B). ASD, autism spectrum disorder; TD, typically developing children; L, left; R, right.
Figure 3
Figure 3
CaSCN of the FFA. CaSCN of the FFA in ASD (A) and TD (B) groups (P < 0.05, uncorrected). (C) Brain regions with significant differences in CaSCN of the FFA between ASD and TD groups (FDR corrected, P < 0.05). ASD, autism spectrum disorder; TD, typically developing children; L, left; R, right.

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