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. Although these alterations affect multiple and widespread cortical regional asymmetries, the extent to which specific structural networks might be affected remains unknown. Inter-regional morphological covariance analysis can capture network connectivity relations between different cortical areas at the macroscale level. Here, we used cortical thickness data from 1,455 individuals with ASD and 1,560 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 asymmetry of hemispheric networks involving the fusiform, rostral middle frontal, and medial orbitofrontal cortex, driven by shifts toward 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 working memory, executive functions, language, reading, and sensorimotor processes. Taken together, these findings provide new insights into how altered brain left-right asymmetry in ASD affects specific structural and functional brain networks. Altered asymmetrical brain development in ASD may be partly propagated among spatially distant regions through structural connectivity.
Competing Interest Statement
Dr. Anagnostou has served as a consultant or advisory board member for Roche and Quadrant; she has received grant funding from Roche and SynapDx, unrestricted funding from Sanofi, in-kind research support from AMO Pharma; she receives royalties from American Psychiatric Press and Springer and an editorial honorarium from Wiley. Her contribution is on behalf of the POND network.
Dr. Arango has served as a consultant for or received honoraria or grants from Acadia, Abbott, Amgen, CIBERSAM, Fundacin Alicia Koplowitz, Fundacion Familia Alonso, Instituto de Salud Carlos III, Janssen-Cilag, Lundbeck, Merck, Instituto de Salud Carlos III (co-financed by the European Regional Development Fund A way of making Europe, CIBERSAM, the Madrid Regional Government [S2010/BMD-2422 AGES], the European Union Structural Funds, and the European Union Seventh Framework Programmeunder grant agreements FP7-HEALTH-2009-2.2.1-2-241909, FP7-HEALTH-2009-2.2.1-3- 242114, FP7-HEALTH-2013-2.2.1-2-603196, and FP7-HEALTH-2013-2.2.1-2-602478) European Union H2020 Program under the Innovative Medicines Initiative 2 Joint Undertaking (grant agreement No. 115916, Project PRISM, and grant agreement No. 777394, Project AIMS-2-TRIALS), Otsuka, Pfizer, Roche, Servier, Shire, Takeda, and Schering-Plough.
Dr Bolte has acted as an author, consultant or lecturer for Medice and Roche. He receives royalties for text books and diagnostic tools from Hogrefe.
Dr. Buitelaar has served as a consultant, advisory board member, or speaker for Eli Lilly, Janssen-Cilag, Lundbeck, Medice, Novartis, Servier, Shire, and Roche, and he has received research support from Roche and Vifor.
Dr. Freitag receives royalties for books on ASD, ADHD, and MDD. She receives research funding by the DFG (A-FFIP study) and the EU (EU-AIMS2-TRIALS, STIPED).
Dr. Franke has received educational speaking fees from Medice.
Dr. Murphy has received grant funding from Roche, and served on advisory boards for Roche and Servier.
Dr. Rubia has received a grant from Takeda pharmaceuticals for another project and served as a consultant for Lundbeck.
Dr. Thompson received partial research support from Biogen, Inc. (Boston), for research unrelated to the topic of this manuscript.