Abstract
BackgroundVoxel-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.MethodsWe 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.ResultsGLM 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.LimitationsOnly 55.9% of the participants with autism had complete questionnaire data on continuous parent-reported symptom measures.ConclusionsCovaried areas associated with autism diagnosis and/or symptoms are scattered across the whole brain and include the limbic system, basal ganglia, thalamus, cerebellum, precentral gyrus, and parts of the frontal, parietal, and occipital lobes. Some of these areas potentially subserve social-communicative behavior, whereas others may underpin sensory processing and integration, and motor behavior.
Highlights
Voxel-based morphometry (VBM) studies in autism spectrum disorder have yielded diverging results
Covaried areas associated with autism diagnosis and/or symptoms are scattered across the whole brain and include the limbic system, basal ganglia, thalamus, cerebellum, precentral gyrus, and parts of the frontal, parietal, and occipital lobes
We considered calibrated severity scores g Parent report Social Responsiveness Scale 2nd Edition (SRS) scores were available for 284 participants with autism and 135 typically developing (TD) individuals h RBS scores were available for 277 participants with autism and 133 TD individuals i Sensory Profile (SSP) scores were available for 201 participants with autism and 115 TD individuals g,h,i In all questionnaires, the scores of the autism group only were used in our study, and they are all parent-rated after preprocessing, whereas none of them were observed obvious artifacts, and they were included in the final analyses
Summary
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. Magnetic resonance imaging (MRI) studies have increased our understanding of the neuroanatomical underpinnings of autism and show that autism is associated, at the group level, with brain structural changes [2]. Across whole brain approaches investigating cortical (i.e., cortical thickness and surface area) and subcortical (i.e., volume) features have been inconsistent; two large-scale pooled estimate analytical studies observed diverging results of cortical changes in autism [6, 7]. Even when taking age into account, studies still observed different structural brain alterations in children and adolescents with autism [10, 11]
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