Atypical Functional Covariance Connectivity Between Gray and White Matter in Children With Autism Spectrum Disorder

Autism spectrum disorder (ASD) is a type of neurodevelopmental disorder with atypical gray matter (GM) and white matter (WM) functional developmental course. However, the functional co-developmental pattern between GM and WM in ASD is unclear. Here, we utilized a functional covariance connectivity method to explore the concordance pattern between GM and WM function in individuals with ASD. A multi-center resting-state fMRI dataset composed of 105 male children with ASD and 102 well-matched healthy controls (HCs) from six sites of the ABIDE dataset was utilized. GM and WM ALFF maps were calculated for each subject. Voxel by voxel functional covariance connectivity of the ALFF values across subjects was calculated between GM and WM for children with ASD and HCs. A Z-test combining FDR multi-comparison correction was then employed to determine whether the functional covariance is significantly different between the two groups. A "bundling" strategy was utilized to ensure that the GM/WM clusters showing atypical functional covariance were larger than 5 voxels. Finally, canonical correlation analysis was conducted to explore whether the atypical GM/WM functional covariance is related to ASD symptoms. Results showed atypical functional covariance connections between specific GM and WM regions, whereas the ALFF values of these regions indicated no significant difference between the two groups. Canonical correlation analysis revealed a significant relationship between the atypical functional covariance and stereotyped behaviors of ASD. The results indicated an altered functional co-developmental pattern between WM and GM in ASD. Lay Summary White matter (WM) and gray matter (GM) are two major human brain organs supporting brain function. WM and GM functions show a specific co-developmental pattern in typical developed individuals. This study showed that this GM/WM co-developmental pattern was altered in children with ASD, while this altered GM/WM co-developmental pattern was related to stereotyped behaviors. These findings may help understand the GM/WM functional development of ASD.