title: Cerebellar gray matter differentiates children with early language delay in autism.
abstract: Early language delay (ELD) is one of the earliest indicators of autism spectrum disorder (ASD), and predicts later cognitive and behavioral outcomes. We aimed to determine the neural correlates of ELD in autism, and examine the relationships between gray matter (GM), age of first word/phrase, and core ASD symptoms. We used voxel-based morphometry to examine whole-brain differences in GM in 8-13 year old children with autism (n = 13 ELD; n = 22 non-ELD) and 35 age-matched typically developing (TD) children. Multiple regression analyses examined the relationships between GM, age of first word/phrase, and autism diagnostic observation schedule (ADOS) scores. Composite age of first word/phrase negatively correlated with GM throughout the cerebellum. Both ASD groups (ELD and non-ELD) had reduced GM in right cerebellar Crus I/II when compared to TD children. Left cerebellar Crus I/II was the only region in the brain that differentiated ELD and non-ELD children, with ELD children showing reduced GM relative to both non-ELD and TD groups. Group×score interactions converged in left Crus I/II, such that the non-ELD group showed poorer ADOS scores with increasing GM, whereas the ELD group showed poorer ADOS scores as GM decreased. Reduced GM in right cerebellar Crus I/I was related ASD diagnosis, while children with ELD showed additional reduced GM in left Crus I/II. These findings highlight the importance of specific cerebellar networks in both ASD and early language development, and suggest that bilateral disruption in cerebellar regions that interconnect with fronto-parietal networks could impact language acquisition in ASD. Autism Res 2016, 9: 1191-1204. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
authors.affiliation: Developmental Neuroscience Lab, Department of Psychology, and Center for Behavioral Neuroscience, American University, Washington, DC.
authors.forename: Anila M
authors.initials: AM
authors.lastname: D'Mello
authors.affiliation: Developmental Neuroscience Lab, Department of Psychology, and Center for Behavioral Neuroscience, American University, Washington, DC.
authors.forename: Dorothea M
authors.initials: DM
authors.lastname: Moore
authors.affiliation: Center for Neurodevelopmental and Imaging Research (CNIR), Kennedy Krieger Institute, Baltimore, Maryland.
authors.forename: Deana
authors.initials: D
authors.lastname: Crocetti
authors.affiliation: Center for Neurodevelopmental and Imaging Research (CNIR), Kennedy Krieger Institute, Baltimore, Maryland.|Department of Neurology, Johns Hopkins University School of Medicine, Johns Hopkins University, Baltimore, Maryland.|Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Stewart H
authors.initials: SH
authors.lastname: Mostofsky
authors.affiliation: Developmental Neuroscience Lab, Department of Psychology, and Center for Behavioral Neuroscience, American University, Washington, DC.
authors.forename: Catherine J
authors.initials: CJ
authors.lastname: Stoodley
mesh_terms: D000293:Adolescent; D001321:Autistic Disorder / Q000150:complications* / Q000503:physiopathology; D002531:Cerebellum / Q000000981:diagnostic imaging / Q000503:physiopathology*; D002648:Child; D003937:Diagnosis, Differential; D005260:Female; D066128:Gray Matter / Q000000981:diagnostic imaging / Q000503:physiopathology*; D006801:Humans; D007805:Language Development Disorders / Q000150:complications* / Q000175:diagnosis* / Q000503:physiopathology; D008279:Magnetic Resonance Imaging; D008297:Male; D012044:Regression Analysis; D012720:Severity of Illness Index
keywords: ADOS; autism; cerebellum; early language delay; imaging; voxel-based morphometry