title: Morphological Alterations in the Thalamus, Striatum, and Pallidum in Autism Spectrum Disorder.
abstract: Autism spectrum disorder (ASD) is a common neurodevelopmental disorder with cognitive, motor, and emotional symptoms. The thalamus and basal ganglia form circuits with the cortex supporting all three of these behavioral domains. Abnormalities in the structure of subcortical regions may suggest atypical development of these networks, with implications for understanding the neural basis of ASD symptoms. Findings from previous volumetric studies have been inconsistent. Here, using advanced surface-based methodology, we investigated localized differences in shape and surface area in the basal ganglia and thalamus in ASD, using T1-weighted anatomical images from the Autism Brain Imaging Data Exchange (373 male participants aged 7-35 years with ASD and 384 typically developing). We modeled effects of diagnosis, age, and their interaction on volume, shape, and surface area. In participants with ASD, we found expanded surface area in the right posterior thalamus corresponding to the pulvinar nucleus, and a more concave shape in the left mediodorsal nucleus. The shape of both caudal putamen and pallidum showed a relatively steeper increase in concavity with age in ASD. Within ASD participants, restricted, repetitive behaviors were positively associated with surface area in bilateral globus pallidus. We found no differences in overall volume, suggesting that surface-based approaches have greater sensitivity to detect localized differences in subcortical structure. This work adds to a growing body of literature implicating corticobasal ganglia-thalamic circuits in the pathophysiology of ASD. These circuits subserve a range of cognitive, emotional, and motor functions, and may have a broad role in the complex symptom profile in ASD.
authors.affiliation: Child and Adolescent Imaging Research (CAIR) Program, University of Calgary, Calgary, AB, Canada.|Alberta Children's Hospital Research Institute, University of Calgary, Calgary, AB, Canada.|Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada.
authors.forename: Manuela
authors.identifier: 0000-0002-3672-388X
authors.initials: M
authors.lastname: Schuetze
authors.affiliation: Cerebral Imaging Centre, Douglas Mental Health University Institute, Montreal, QC, Canada.|Schulich School of Medicine and Dentistry, Western University, London, ON, Canada.
authors.forename: Min Tae M
authors.initials: MT
authors.lastname: Park
authors.affiliation: Child and Adolescent Imaging Research (CAIR) Program, University of Calgary, Calgary, AB, Canada.|Alberta Children's Hospital Research Institute, University of Calgary, Calgary, AB, Canada.
authors.forename: Ivy Yk
authors.initials: IY
authors.lastname: Cho
authors.affiliation: Child and Adolescent Imaging Research (CAIR) Program, University of Calgary, Calgary, AB, Canada.|Alberta Children's Hospital Research Institute, University of Calgary, Calgary, AB, Canada.|Departments of Psychiatry and Pediatrics, University of Calgary, Calgary, AB, Canada.|Mathison Centre for Mental Health Research and Education, Hotchkiss Brain Institute, Calgary, AB, Canada.|Strategic Clinical Network for Addictions and Mental Health, Alberta Health Services, Calgary, AB, Canada.
authors.forename: Frank P
authors.initials: FP
authors.lastname: MacMaster
authors.affiliation: Cerebral Imaging Centre, Douglas Mental Health University Institute, Montreal, QC, Canada.|Departments of Psychiatry and Biomedical Engineering, McGill University, Montreal, QC, Canada.
authors.forename: M Mallar
authors.initials: MM
authors.lastname: Chakravarty
authors.affiliation: Child and Adolescent Imaging Research (CAIR) Program, University of Calgary, Calgary, AB, Canada.|Alberta Children's Hospital Research Institute, University of Calgary, Calgary, AB, Canada.|Departments of Pediatrics and Radiology, University of Calgary, AB, Canada.
authors.forename: Signe L
authors.initials: SL
authors.lastname: Bray
mesh_terms: D000293:Adolescent; D000328:Adult; D000067877:Autism Spectrum Disorder / Q000473:pathology*; D002648:Child; D003342:Corpus Striatum / Q000000981:diagnostic imaging*; D005260:Female; D007839:Functional Laterality; D005917:Globus Pallidus / Q000000981:diagnostic imaging*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D008875:Middle Aged; D059906:Neuroimaging; D013788:Thalamus / Q000000981:diagnostic imaging*; D055815:Young Adult