Gray matter covariations and core symptoms of autism: the EU-AIMS Longitudinal European Autism Project
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RESEARCH
Gray matter covariations and core symptoms of autism: the EU‑AIMS Longitudinal European Autism Project Ting Mei1* , Alberto Llera1,2, Dorothea L. Floris1, Natalie J. Forde1, Julian Tillmann3, Sarah Durston4, Carolin Moessnang5, Tobias Banaschewski6, Rosemary J. Holt7, Simon Baron‑Cohen7, Annika Rausch1, Eva Loth8, Flavio Dell’Acqua8, Tony Charman3, Declan G. M. Murphy8, Christine Ecker8,9, Christian F. Beckmann1,10 and Jan K. Buitelaar1,2* on behalf of the EU-AIMS LEAP group
Abstract Background: Voxel-based morphometry (VBM) studies in autism spectrum disorder (autism) have yielded diverging results. This might partly be attributed to structural alterations being associating with the combined influence of several regions rather than with a single region. Further, these structural covariation differences may relate to continuous measures of autism rather than with categorical case–control contrasts. The current study aimed to identify structural covariation alterations in autism, and assessed canonical correlations between brain covariation patterns and core autism symptoms. Methods: We studied 347 individuals with autism and 252 typically developing individuals, aged between 6 and 30 years, who have been deeply phenotyped in the Longitudinal European Autism Project. All participants’ VBM maps were decomposed into spatially independent components using independent component analysis. A generalized linear model (GLM) was used to examine case–control differences. Next, canonical correlation analysis (CCA) was performed to separately explore the integrated effects between all the brain sources of gray matter variation and two sets of core autism symptoms. Results: GLM analyses showed significant case–control differences for two independent components. The first component was primarily associated with decreased density of bilateral insula, inferior frontal gyrus, orbitofrontal cortex, and increased density of caudate nucleus in the autism group relative to typically developing individuals. The second component was related to decreased densities of the bilateral amygdala, hippocampus, and parahippocampal gyrus in the autism group relative to typically developing individuals. The CCA results showed significant correlations between components that involved variation of thalamus, putamen, precentral gyrus, frontal, parietal, and occipital lobes, and the cerebellum, and repetitive, rigid and stereotyped behaviors and abnormal sensory behaviors in autism individuals. Limitations: Only 55.9% of the participants with autism had complete questionnaire data on continuous parentreported symptom measures.
*Correspondence: [email protected]; [email protected] 1 Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands Full list of author information is available at the end of the article © The Author(s) 2020. Open Access This article is licensed under a Creative Commons Attribution 4.0 Inte
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