Atypical brain asymmetry in autism - a candidate for clinically meaningful stratification

  • Background: Autism Spectrum Disorder (henceforth ‘autism’) is a highly heterogeneous neurodevelopmental condition with few effective treatments for core and associated features. To make progress we need to both identify and validate neural markers that help to parse heterogeneity to tailor therapies to specific neurobiological profiles. Atypical hemispheric lateralization is a stable feature across studies in autism, however its potential of lateralization as a neural stratification marker has not been widely examined. Methods: In order to dissect heterogeneity in lateralization in autism, we used the large EU-AIMS Longitudinal European Autism Project dataset comprising 352 individuals with autism and 233 neurotypical (NT) controls as well as a replication dataset from ABIDE (513 autism, 691 NT) using a promising approach that moves beyond mean-group comparisons. We derived grey matter voxelwise laterality values for each subject and modelled individual deviations from the normative pattern of brain laterality across age using normative modeling. Results: Results showed that individuals with autism had highly individualized patterns of both extreme right- and leftward deviations, particularly in language-, motor- and visuospatial regions, associated with symptom severity. Language delay (LD) explained most variance in extreme rightward patterns, whereas core autism symptom severity explained most variance in extreme leftward patterns. Follow-up analyses showed that a stepwise pattern emerged with individuals with autism with LD showing more pronounced rightward deviations than autism individuals without LD. Conclusion: Our analyses corroborate the need for novel (dimensional) approaches to delineate the heterogeneous neuroanatomy in autism, and indicate atypical lateralization may constitute a neurophenotype for clinically meaningful stratification in autism.

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Author:Dorothea L. FlorisORCiDGND, Thomas WolfersORCiDGND, Mariam ZabihiORCiD, Nathalie E. HolzORCiDGND, Marcel P. ZwiersORCiD, Tony CharmanORCiDGND, Julian TillmannORCiDGND, Christine EckerORCiD, Flavio Dell'AcquaORCiDGND, Tobias BanaschewskiORCiDGND, Carolin Ulrike MößnangORCiDGND, Simon Baron-CohenORCiDGND, Rosemary Holt, Sarah Durston, Eva LothORCiDGND, Declan G. M. MurphyORCiD, Andre F. MarquandORCiD, Jan K. BuitelaarORCiDGND, Christian F. BeckmannORCiDGND
Parent Title (English):bioRxiv
Document Type:Preprint
Date of Publication (online):2020/03/25
Date of first Publication:2020/03/25
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Contributing Corporation:the EU-AIMS LEAP group
Release Date:2023/07/23
Page Number:44
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - CC BY-NC-ND - Namensnennung - Nicht kommerziell - Keine Bearbeitungen 4.0 International