title: Altered functional connectivity of the language network in ASD: role of classical language areas and cerebellum.
abstract: The development of language, social interaction and communicative skills is remarkably different in the child with autism spectrum disorder (ASD). Atypical brain connectivity has frequently been reported in this patient population. However, the neural correlates underlying their disrupted language development and functioning are still poorly understood. Using resting state fMRI, we investigated the functional connectivity properties of the language network in a group of ASD patients with clear comorbid language impairment (ASD-LI; N = 19) and compared them to the language related connectivity properties of 23 age-matched typically developing children. A verb generation task was used to determine language components commonly active in both groups. Eight joint language components were identified and subsequently used as seeds in a resting state analysis. Interestingly, both the interregional and the seed-based whole brain connectivity analysis showed preserved connectivity between the classical intrahemispheric language centers, Wernicke's and Broca's areas. In contrast however, a marked loss of functional connectivity was found between the right cerebellar region and the supratentorial regulatory language areas. Also, the connectivity between the interhemispheric Broca regions and modulatory control dorsolateral prefrontal region was found to be decreased. This disruption of normal modulatory control and automation function by the cerebellum may underlie the abnormal language function in children with ASD-LI.
authors.affiliation: Department of Neurosciences, Exp ORL, Catholic University of Leuven, Leuven, Belgium ; Department of Radiology, University Hospitals of the Catholic University of Leuven, Leuven, Belgium.
authors.forename: Marjolein
authors.initials: M
authors.lastname: Verly
authors.affiliation: Department of Radiology, University Hospitals of the Catholic University of Leuven, Leuven, Belgium ; Leuven Autism Research (LAURES) Consortium, Catholic University of Leuven, Leuven, Belgium ; Department of Pediatrics, University Hospitals of the Catholic University of Leuven, Leuven, Belgium.
authors.forename: Judith
authors.initials: J
authors.lastname: Verhoeven
authors.affiliation: Department of Neurosciences, Exp ORL, Catholic University of Leuven, Leuven, Belgium.
authors.forename: Inge
authors.initials: I
authors.lastname: Zink
authors.affiliation: Department of Experimental Psychology, University of Oxford, Oxford OX1 3UD, UK ; Department of Heath Sciences and Technology, ETH Zurich, 8057 Zurich, Switzerland ; Department of Neurosciences, Laboratory for Neuro- and Psychophysiology, KU Leuven, 3000 Leuven, Belgium.
authors.forename: Dante
authors.initials: D
authors.lastname: Mantini
authors.affiliation: Department of Radiology, University Hospitals of the Catholic University of Leuven, Leuven, Belgium.
authors.forename: Ronald
authors.initials: R
authors.lastname: Peeters
authors.affiliation: Department of Radiology, University Hospitals of the Catholic University of Leuven, Leuven, Belgium.
authors.forename: Sabine
authors.initials: S
authors.lastname: Deprez
authors.affiliation: Department of Radiology, University Hospitals of the Catholic University of Leuven, Leuven, Belgium.
authors.forename: Louise
authors.initials: L
authors.lastname: Emsell
authors.affiliation: Leuven Autism Research (LAURES) Consortium, Catholic University of Leuven, Leuven, Belgium ; Parenting and Special Education Research Unit, Catholic University of Leuven, Leuven, Belgium ; Department of Child and Adolescent Psychiatry, University Hospitals of the Catholic University of Leuven, Leuven, Belgium.
authors.forename: Bart
authors.initials: B
authors.lastname: Boets
authors.affiliation: Leuven Autism Research (LAURES) Consortium, Catholic University of Leuven, Leuven, Belgium ; Parenting and Special Education Research Unit, Catholic University of Leuven, Leuven, Belgium ; Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital, Boston, USA.
authors.forename: Ilse
authors.initials: I
authors.lastname: Noens
authors.affiliation: Leuven Autism Research (LAURES) Consortium, Catholic University of Leuven, Leuven, Belgium ; Department of Child and Adolescent Psychiatry, University Hospitals of the Catholic University of Leuven, Leuven, Belgium ; Department of Clinical Genetics, University of Maastricht, Maastricht, The Netherlands.
authors.forename: Jean
authors.initials: J
authors.lastname: Steyaert
authors.affiliation: Department of Pediatrics, University Hospitals of the Catholic University of Leuven, Leuven, Belgium.
authors.forename: Lieven
authors.initials: L
authors.lastname: Lagae
authors.affiliation: Leuven Autism Research (LAURES) Consortium, Catholic University of Leuven, Leuven, Belgium ; Department of Pediatrics, University Hospitals of the Catholic University of Leuven, Leuven, Belgium ; Center for Developmental Disabilities, University Hospitals of the Catholic University of Leuven, Leuven, Belgium.
authors.forename: Paul
authors.initials: P
authors.lastname: De Cock
authors.affiliation: Department of Neurosciences, Exp ORL, Catholic University of Leuven, Leuven, Belgium.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Rommel
authors.affiliation: Department of Radiology, University Hospitals of the Catholic University of Leuven, Leuven, Belgium ; Leuven Autism Research (LAURES) Consortium, Catholic University of Leuven, Leuven, Belgium.
authors.forename: Stefan
authors.initials: S
authors.lastname: Sunaert
mesh_terms: D000293:Adolescent; D000067877:Autism Spectrum Disorder / Q000503:physiopathology*; D002531:Cerebellum / Q000503:physiopathology*; D063132:Connectome / Q000379:methods*; D005260:Female; D006801:Humans; D007802:Language; D007806:Language Disorders / Q000503:physiopathology*; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D009415:Nerve Net / Q000503:physiopathology*; D009434:Neural Pathways / Q000503:physiopathology; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
keywords: Autism spectrum disorders; Cerebellum; Language function; Resting state fMRI