TY - JOUR
T1 - Gray matter covariations and core symptoms of autism
T2 - the EU-AIMS Longitudinal European Autism Project
AU - EU-AIMS LEAP group
AU - Mei, Ting
AU - Llera, Alberto
AU - Floris, Dorothea L.
AU - Forde, Natalie J.
AU - Tillmann, Julian
AU - Durston, Sarah
AU - Moessnang, Carolin
AU - Banaschewski, Tobias
AU - Holt, Rosemary J.
AU - Baron-Cohen, Simon
AU - Rausch, Annika
AU - Loth, Eva
AU - Dell'Acqua, Flavio
AU - Charman, Tony
AU - Murphy, Declan G.M.
AU - Ecker, Christine
AU - Beckmann, Christian F.
AU - Buitelaar, Jan K.
PY - 2020/12/1
Y1 - 2020/12/1
N2 - 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 parent-reported symptom measures. CONCLUSIONS: 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. Some of these areas potentially subserve social-communicative behavior, whereas others may underpin sensory processing and integration, and motor behavior.
AB - 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 parent-reported symptom measures. CONCLUSIONS: 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. Some of these areas potentially subserve social-communicative behavior, whereas others may underpin sensory processing and integration, and motor behavior.
KW - Autism
KW - Canonical correlation analysis
KW - Independent component analysis
KW - Magnetic resonance imaging
KW - Voxel-based morphometry
UR - http://www.scopus.com/inward/record.url?scp=85094983707&partnerID=8YFLogxK
U2 - 10.1186/s13229-020-00389-4
DO - 10.1186/s13229-020-00389-4
M3 - Article
C2 - 33126911
AN - SCOPUS:85094983707
SN - 2040-2392
VL - 11
SP - 86
JO - Molecular Autism
JF - Molecular Autism
IS - 1
M1 - 86
ER -