Widespread Focal Cortical Alterations in Autism Spectrum Disorder with Intellectual Disability Detected by Threshold-Free Cluster Enhancement.
In the past decades, a large body of work aimed at investigating brain structural anomalies accrued in autism spectrum disorder. Autism spectrum disorder is associated with intellectual disability in up to 50% of cases. However, only a few neuroimaging studies were conducted in autism spectrum disorder with intellectual disability, and none of them benefited from a nonsyndromic intellectual disability control group.



We performed a voxelwise investigation of the structural alterations in 25 children with autism spectrum disorder with intellectual disability by comparing them with 25 typically developing children and 25 nonsyndromic children with an intellectual disability. Besides a classic voxel-based morphometry statistical approach, the threshold-free cluster enhancement statistical approach was adopted.



Classic voxel-based morphometry results did not survive family-wise error correction. The threshold-free cluster enhancement-based analysis corrected for family-wise error highlighted the following: 1) widespread focal cortical anomalies and corpus callosum alteration detected in autism spectrum disorder with intellectual disability; 2) basal ganglia and basal forebrain alteration detected both in autism spectrum disorder with intellectual disability and in nonsyndromic intellectual disability; and 3) differences in the frontocingulate-parietal cortex between autism spectrum disorder with intellectual disability and nonsyndromic intellectual disability.



The present study suggests that the frontocingulate-parietal cortex may be the eligible key region for further investigations aiming at detecting imaging biomarkers in autism spectrum disorder with intellectual disability. The detection of structural alterations in neurodevelopmental disorders may be dramatically improved by using a threshold-free cluster enhancement statistical approach.
From the Neuroradiology Department (V.E.C., A.E.) contarino.v@istituto-besta.it.
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0000-0002-8922-657X
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Contarino
Developmental Neurology Division (S.B., S.A., D.R.), Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Neurologico C. Besta, Milano, Italy.
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0000-0002-5998-2200
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Bulgheroni
Developmental Neurology Division (S.B., S.A., D.R.), Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Neurologico C. Besta, Milano, Italy.
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0000-0002-0213-9810
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Annunziata
From the Neuroradiology Department (V.E.C., A.E.).
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0000-0003-0295-3596
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Erbetta
Developmental Neurology Division (S.B., S.A., D.R.), Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Neurologico C. Besta, Milano, Italy.
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0000-0002-9113-894X
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Riva
D000067877:Autism Spectrum Disorder / Q000000981:diagnostic imaging* / Q000523:psychology; D001479:Basal Ganglia / Q000000981:diagnostic imaging; D001921:Brain / Q000000981:diagnostic imaging*; D002648:Child; D002675:Child, Preschool; D016000:Cluster Analysis; D003337:Corpus Callosum / Q000000981:diagnostic imaging; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008607:Intellectual Disability / Q000000981:diagnostic imaging* / Q000523:psychology; D007361:Intelligence Tests; D008279:Magnetic Resonance Imaging; D008297:Male; D009483:Neuropsychological Tests; D010296:Parietal Lobe / Q000000981:diagnostic imaging