Subtly altered topological asymmetry of brain structural covariance networks in autism spectrum disorder across 43 datasets from the ENIGMA consortium

Abstract

Small average differences in the left-right asymmetry of cerebral cortical thickness have been reported in individuals with autism spectrum disorder (ASD) compared to typically developing controls, affecting widespread cortical regions. The possible impacts of these regional alterations in terms of structural network effects have not previously been characterized. Inter-regional morphological covariance analysis can capture network connectivity between different cortical areas at the macroscale level. Here, we used cortical thickness data from 1455 individuals with ASD and 1560 controls, across 43 independent datasets of the ENIGMA consortium’s ASD Working Group, to assess hemispheric asymmetries of intra-individual structural covariance networks, using graph theory-based topological metrics. Compared with typical features of small-world architecture in controls, the ASD sample showed significantly altered average asymmetry of networks involving the fusiform, rostral middle frontal, and medial orbitofrontal cortex, involving higher randomization of the corresponding right-hemispheric networks in ASD. A network involving the superior frontal cortex showed decreased right-hemisphere randomization. Based on comparisons with meta-analyzed functional neuroimaging data, the altered connectivity asymmetry particularly affected networks that subserve executive functions, language-related and sensorimotor processes. These findings provide a network-level characterization of altered left-right brain asymmetry in ASD, based on a large combined sample. Altered asymmetrical brain development in ASD may be partly propagated among spatially distant regions through structural connectivity.

Coordinated cortical thickness alterations across six neurodevelopmental and psychiatric disorders

“…Last, we aimed to understand the degree to which cortical alterations observed in individual disorders are reflected in described transdiagnostic features. To this end, we first examined cross-cortical similarities of illness effects within disorders 101 , 102 , via absolute differences in Cohen’s d values between regions. We then correlated each parcel’s disorder-specific whole-brain covariance profile with the previously described transdiagnostic covariance profile of the same parcel.…”

Changes in the geometry and robustness of diffusion tensor imaging networks: Secondary analysis from a randomized controlled trial of young autistic children receiving an umbilical cord blood infusion

“…We found that cord blood treatment was associated with changes in connectivity among a number of networks connected to the dlPFC. The dlPFC is a critical hub for supporting attention, memory, and other aspects of cognition in the brain and has been implicated as a critical region in the neurobiology of autism ( 62 , 63 ). Studies employing resting state MRI have demonstrated that differential connectivity in networks involving the dlPFC correlate with social and communication abilities in autistic children ( 64 ).…”

Proteomic-Based Approach Reveals the Involvement of Apolipoprotein A-I in Related Phenotypes of Autism Spectrum Disorder in the BTBR Mouse Model

“…The etiology and pathogenesis of ASD remain unknown, and studies have focused on genomics, metabolomics [ 4 ], and imaging investigations [ 5 ]. Abnormalities in lipid metabolism contribute to the pathogenesis of ASD [ 6 , 7 ].…”