title: Atypical age-dependent effects of autism on white matter microstructure in children of 2-7 years.
abstract: Atypical age-dependent changes of white matter (WM) microstructure play a central role in abnormal brain maturation of the children with autism spectrum disorder (ASD), but their early manifestations have not been systematically characterized. The entire brain core WM voxels were surveyed to detect differences in WM microstructural development between 31 children with ASD of 2-7 years and 19 age-matched children with typical development (TD), using measurements of fractional anisotropy (FA) and radial diffusivity (RD) from diffusion tensor imaging (DTI). The anatomical locations, distribution, and extent of the core WM voxels with atypical age-dependent changes in a specific tract or tract group were delineated and evaluated by integrating the skeletonized WM with a digital atlas. Exclusively, unidirectional FA increases and RD decreases in widespread WM tracts were revealed in children with ASD before 4 years, with bi-directional changes found for children with ASD of 2-7 years. Compared to progressive development that raised FA and lowered RD during 2-7 years in the TD group, flattened curves of WM maturation were found in multiple major WM tracts of all five tract groups, particularly associational and limbic tracts, in the ASD group with trend lines of ASD and TD crossed around 4 years. We found atypical age-dependent changes of FA and RD widely and heterogeneously distributed in WM tracts of children with ASD. The early higher WM microstructural integrity before 4 years reflects abnormal neural patterning, connectivity, and pruning that may contribute to aberrant behavioral and cognitive development in ASD. Hum Brain Mapp 37:819-832, 2016. © 2015 Wiley Periodicals, Inc.
authors.affiliation: Department of Radiology, Children's Hospital of Philadelphia, Pennsylvania.|Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Texas.|Biomedical Engineering Joint Graduate Program, University of Texas at Arlington-University of Texas Southwestern Medical Center, Texas.
authors.forename: Minhui
authors.initials: M
authors.lastname: Ouyang
authors.affiliation: Department of Radiology, Beijing Children's Hospital, Capital Medical University, Beijing, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Cheng
authors.affiliation: Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Texas.
authors.forename: Virendra
authors.initials: V
authors.lastname: Mishra
authors.affiliation: State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing, China.
authors.forename: Gaolang
authors.initials: G
authors.lastname: Gong
authors.affiliation: Center for Autism and Developmental Disabilities, University of Texas Southwestern Medical Center, Dallas, Texas.|Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, Texas.
authors.forename: Matthew W
authors.initials: MW
authors.lastname: Mosconi
authors.affiliation: Center for Autism and Developmental Disabilities, University of Texas Southwestern Medical Center, Dallas, Texas.|Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, Texas.
authors.forename: John
authors.initials: J
authors.lastname: Sweeney
authors.affiliation: Department of Radiology, Beijing Children's Hospital, Capital Medical University, Beijing, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Peng
authors.affiliation: Department of Radiology, Children's Hospital of Philadelphia, Pennsylvania.|Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Texas.|Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Pennsylvania.
authors.forename: Hao
authors.initials: H
authors.lastname: Huang
mesh_terms: D000067877:Autism Spectrum Disorder / Q000473:pathology*; D001921:Brain / Q000254:growth & development* / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D016000:Cluster Analysis; D056324:Diffusion Tensor Imaging; D006801:Humans; D007091:Image Processing, Computer-Assisted; D016014:Linear Models; D008297:Male; D009434:Neural Pathways / Q000254:growth & development / Q000473:pathology; D012720:Severity of Illness Index; D066127:White Matter / Q000254:growth & development* / Q000473:pathology*
keywords: atypical; autism; children; development; microstructure; white matter