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

Zhiqiang Sha, Daan van Rooij, Evdokia Anagnostou, Celso Arango, Guillaume Auzias, Marlene Behrmann, Boris Bernhardt, Sven Bolte, Geraldo F. Busatto, Sara Calderoni, Rosa Calvo, Eileen Daly, Christine Deruelle, Meiyu Duan, Fabio Luis Souza Duran, Sarah Durston, Christine Ecker, Stefan Ehrlich, Damien Fair, Jennifer FedorJacqueline Fitzgerald, Dorothea L. Floris, Barbara Franke, Christine M. Freitag, Louise Gallagher, David C. Glahn, Shlomi Haar, Liesbeth Hoekstra, Neda Jahanshad, Maria Jalbrzikowski, Joost Janssen, Joseph A. King, Luisa Lazaro, Beatriz Luna, Jane McGrath, Sarah E. Medland, Filippo Muratori, Declan G.M. Murphy, Janina Neufeld, Kirsten O’Hearn, Bob Oranje, Mara Parellada, Jose C. Pariente, Merel C. Postema, Karl Lundin Remnelius, Alessandra Retico, Pedro Gomes Penteado Rosa, Katya Rubia, Devon Shook, Kristiina Tammimies, Margot J. Taylor, Michela Tosetti, Gregory L. Wallace, Fengfeng Zhou, Paul M. Thompson, Simon E. Fisher, Jan K. Buitelaar, Clyde Francks

Research output: Contribution to journalArticlepeer-review

26 Scopus citations


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.

Original languageEnglish
Pages (from-to)2114-2125
Number of pages12
JournalMolecular Psychiatry
Issue number4
StatePublished - Apr 2022
Externally publishedYes


Dive into the research topics of 'Subtly altered topological asymmetry of brain structural covariance networks in autism spectrum disorder across 43 datasets from the ENIGMA consortium'. Together they form a unique fingerprint.

Cite this