Autism Is Associated With Interindividual Variations of Gray and White Matter Morphology
Ting Mei, Natalie J. Forde, Dorothea L. Floris, Flavio Dell’Acqua, Richard Stones, Iva Ilioska, Sarah Durston, Carolin Moessnang, Tobias Banaschewski, Rosemary Holt, Simon Baron‐Cohen, Annika Rausch, Eva Loth, Bethany Oakley, Tony Charman, Christine Ecker, Declan Murphy, Jan K. Buitelaar, Jumana Ahmad, Sara Ambrosino, Bonnie Auyeung, Tobias Banaschewski, Simon Baron‐Cohen, Sarah Baumeister, Christian F. Beckmann, Sven Bölte, Thomas Bourgeron, Carsten Bours, Michael Brammer, Daniel Brandeis, Claudia Brogna, Yvette de Bruijn, Bhismadev Chakrabarti, Tony Charman, Ineke Cornelissen, Daisy Crawley, Flavio Dell’Acqua, Guillaume Dumas, Sarah Durston, Christine Ecker, Jessica Faulkner, Vincent Frouin, Pilar Garcés, David Goyard, Lindsay Ham, Hannah Hayward, Joerg F. Hipp, Rosemary Holt, Mark H. Johnson, Emily J. H. Jones, Prantik Kundu, Meng‐Chuan Lai, Xavier Liogier D’ardhuy, Michael Lombardo, Eva Loth, David J. Lythgoe, René C.W. Mandl, André F. Marquand, Luke Mason, Maarten Mennes, Andreas Meyer‐Lindenberg, Carolin Moessnang, Nico Mueller, Declan Murphy, Bethany Oakley, Laurence O’Dwyer, Marianne Oldehinkel, Bob Oranje, Gahan Pandina, Antonio M. Persico, Annika Rausch, Barbara Ruggeri, Amber Ruigrok, Jessica Sabet, Roberto Sacco, Antonia San José Cáceres, Emily Simonoff, Will Spooren, Julian Tillmann, Roberto Toro, Heike Tost, Jack Waldman, Steven Williams, Caroline Wooldridge, Iva Ilioska, Ting Mei, Marcel P. Zwiers, Christian F. Beckmann, Alberto Llera, Jan K. Buitelaar
Abstract
BACKGROUND: Although many studies have explored atypicalities in gray matter (GM) and white matter (WM) morphology of autism, most of them relied on unimodal analyses that did not benefit from the likelihood that different imaging modalities may reflect common neurobiology. We aimed to establish brain patterns of modalities that differentiate between individuals with and without autism and explore associations between these brain patterns and clinical measures in the autism group. METHODS: We studied 183 individuals with autism and 157 nonautistic individuals (age range, 6-30 years) in a large, deeply phenotyped autism dataset (EU-AIMS LEAP [European Autism Interventions-A Multicentre Study for Developing New Medications Longitudinal European Autism Project]). Linked independent component analysis was used to link all participants' GM volume and WM diffusion tensor images, and group comparisons of modality shared variances were examined. Subsequently, we performed univariate and multivariate brain-behavior correlation analyses to separately explore the relationships between brain patterns and clinical profiles. RESULTS: One multimodal pattern was significantly related to autism. This pattern was primarily associated with GM volume in bilateral insula and frontal, precentral and postcentral, cingulate, and caudate areas and co-occurred with altered WM features in the superior longitudinal fasciculus. The brain-behavior correlation analyses showed a significant multivariate association primarily between brain patterns that involved variation of WM and symptoms of restricted and repetitive behavior in the autism group. CONCLUSIONS: Our findings demonstrate the assets of integrated analyses of GM and WM alterations to study the brain mechanisms that underpin autism and show that the complex clinical autism phenotype can be interpreted by brain covariation patterns that are spread across the brain involving both cortical and subcortical areas.