title: Periventricular white matter abnormalities and restricted repetitive behavior in autism spectrum disorder.
abstract: Malformations of cortical development are found at higher rates in autism spectrum disorder (ASD) than in healthy controls on postmortem neuropathological evaluation but are more variably observed on visual review of in-vivo MRI brain scans. This may be due to the visually elusive nature of many malformations on MRI. Here, we utilize a quantitative approach to determine whether a volumetric measure of heterotopic gray matter in the white matter is elevated in people with ASD, relative to typically developing controls (TDC). Data from a primary sample of 48 children/young adults with ASD and 48 age-, and gender-matched TDCs, selected from the Autism Brain Imaging Data Exchange (ABIDE) open-access database, were analyzed to compare groups on (1) blinded review of high-resolution T1-weighted research sequences; and (2) quantitative measurement of white matter hypointensity (WMH) volume calculated from the same T1-weighted scans. Groupwise WMH volume comparisons were repeated in an independent, multi-site sample (80 ASD/80 TDC), also selected from ABIDE. Visual review resulted in equivalent proportions of imaging abnormalities in the ASD and TDC group. However, quantitative analysis revealed elevated periventricular and deep subcortical WMH volumes in ASD. This finding was replicated in the independent, multi-site sample. Periventricular WMH volume was not associated with age but was associated with greater restricted repetitive behaviors on both parent-reported and clinician-rated assessment inventories. Thus, findings demonstrate that periventricular WMH volume is elevated in ASD and associated with a higher degree of repetitive behaviors and restricted interests. Although the etiology of focal WMH clusters is unknown, the absence of age effects suggests that they may reflect a static anomaly.
authors.affiliation: NYU Comprehensive Epilepsy Center, Department of Neurology, New York University School of Medicine, New York, NY 10016, USA.
authors.forename: Karen
authors.initials: K
authors.lastname: Blackmon
authors.affiliation: NYU Comprehensive Epilepsy Center, Department of Neurology, New York University School of Medicine, New York, NY 10016, USA ; Department of Psychology, New York University, New York, NY 10003, USA.
authors.forename: Emma
authors.initials: E
authors.lastname: Ben-Avi
authors.affiliation: NYU Comprehensive Epilepsy Center, Department of Neurology, New York University School of Medicine, New York, NY 10016, USA.
authors.forename: Xiuyuan
authors.initials: X
authors.lastname: Wang
authors.affiliation: NYU Comprehensive Epilepsy Center, Department of Neurology, New York University School of Medicine, New York, NY 10016, USA.
authors.forename: Heath R
authors.initials: HR
authors.lastname: Pardoe
authors.affiliation: Department of Child and Adolescent Psychiatry, Child Study Center at NYU Langone Medical Center, New York, NY 10016, USA.
authors.forename: Adriana
authors.initials: A
authors.lastname: Di Martino
authors.affiliation: Department of Radiology, University of California at San Diego, La Jolla, CA 92069, USA ; Department of Neurosciences, University of California at San Diego, La Jolla, CA 92069, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Halgren
authors.affiliation: NYU Comprehensive Epilepsy Center, Department of Neurology, New York University School of Medicine, New York, NY 10016, USA.
authors.forename: Orrin
authors.initials: O
authors.lastname: Devinsky
authors.affiliation: NYU Comprehensive Epilepsy Center, Department of Neurology, New York University School of Medicine, New York, NY 10016, USA ; Department of Radiology, New York University School of Medicine, New York, NY 10016, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Thesen
authors.affiliation: NYU Comprehensive Epilepsy Center, Department of Neurology, New York University School of Medicine, New York, NY 10016, USA.
authors.forename: Ruben
authors.initials: R
authors.lastname: Kuzniecky
mesh_terms: D000293:Adolescent; D000328:Adult; D000067877:Autism Spectrum Disorder / Q000473:pathology* / Q000523:psychology*; D001921:Brain / Q000473:pathology*; D002552:Cerebral Ventricles / Q000473:pathology*; D002648:Child; D005260:Female; D066128:Gray Matter / Q000473:pathology; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D009483:Neuropsychological Tests; D012720:Severity of Illness Index; D066127:White Matter / Q000473:pathology*; D055815:Young Adult
keywords: Autism spectrum disorder; Magnetic resonance imaging; Malformations of cortical development; Periventricular heterotopia; Restricted repetitive behaviors; White matter hypointensities