title: Atypical lateralization of motor circuit functional connectivity in children with autism is associated with motor deficits.
abstract: BACKGROUND
  Atypical lateralization of language-related functions has been repeatedly found in individuals with autism spectrum conditions (ASC). Few studies have, however, investigated deviations from typically occurring asymmetry of other lateralized cognitive and behavioural domains. Motor deficits are among the earliest and most prominent symptoms in individuals with ASC and precede core social and communicative symptoms.
  
  
  METHODS
  Here, we investigate whether motor circuit connectivity is (1) atypically lateralized in children with ASC and (2) whether this relates to core autistic symptoms and motor performance. Participants comprised 44 right-handed high-functioning children with autism (36 males, 8 females) and 80 typically developing control children (58 males, 22 females) matched on age, sex and performance IQ. We examined lateralization of functional motor circuit connectivity based on homotopic seeds derived from peak activations during a finger tapping paradigm. Motor performance was assessed using the Physical and Neurological Examination for Subtle Signs (PANESS).
  
  
  RESULTS
  Children with ASC showed rightward lateralization in mean motor circuit connectivity compared to typically developing children, and this was associated with poorer performance on all three PANESS measures.
  
  
  CONCLUSIONS
  Our findings reveal that atypical lateralization in ASC is not restricted to language functions but is also present in circuits subserving motor functions and may underlie motor deficits in children with ASC. Future studies should investigate whether this is an age-invariant finding extending to adolescents and adults and whether these asymmetries relate to atypical lateralization in the language domain.
authors.affiliation: Autism Research Centre, Department of Psychiatry, University of Cambridge, Cambridge, UK ; Department of Child and Adolescent Psychiatry, the Child Study Center, New York University Langone Medical Center, New York, NY USA.
authors.forename: Dorothea L
authors.initials: DL
authors.lastname: Floris
authors.affiliation: Center for Neurodevelopmental and Imaging Research, Kennedy Krieger Institute, Baltimore, MD USA ; Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD USA ; Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD USA.
authors.forename: Anita D
authors.initials: AD
authors.lastname: Barber
authors.affiliation: Center for Neurodevelopmental and Imaging Research, Kennedy Krieger Institute, Baltimore, MD USA ; Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD USA ; Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD USA.
authors.forename: Mary Beth
authors.initials: MB
authors.lastname: Nebel
authors.affiliation: Center for Neurodevelopmental and Imaging Research, Kennedy Krieger Institute, Baltimore, MD USA ; Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD USA ; Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD USA.
authors.forename: Mary
authors.initials: M
authors.lastname: Martinelli
authors.affiliation: Autism Research Centre, Department of Psychiatry, University of Cambridge, Cambridge, UK ; Child, Youth and Family Services, Centre for Addiction and Mental Health and Department of Psychiatry, University of Toronto, Toronto, Canada ; Department of Psychiatry, College of Medicine, National Taiwan University Hospital, Taipei City, Taiwan.
authors.forename: Meng-Chuan
authors.initials: MC
authors.lastname: Lai
authors.affiliation: Center for Neurodevelopmental and Imaging Research, Kennedy Krieger Institute, Baltimore, MD USA ; Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD USA ; Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD USA.
authors.forename: Deana
authors.initials: D
authors.lastname: Crocetti
authors.affiliation: Autism Research Centre, Department of Psychiatry, University of Cambridge, Cambridge, UK ; Cambridgeshire and Peterborough NHS Foundation Trust, Cambridge, UK ; National Institute of Health Research, Cambridge Biomedical Research Centre, Cambridge, UK ; Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK.
authors.forename: Simon
authors.initials: S
authors.lastname: Baron-Cohen
authors.affiliation: Cambridgeshire and Peterborough NHS Foundation Trust, Cambridge, UK ; National Institute of Health Research, Cambridge Biomedical Research Centre, Cambridge, UK ; Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK ; Brain Mapping Unit, Department of Psychiatry, University of Cambridge, Cambridge, UK.
authors.forename: John
authors.initials: J
authors.lastname: Suckling
authors.affiliation: F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, USA ; Department of Radiology, Johns Hopkins School of Medicine, Baltimore, USA.
authors.forename: James J
authors.initials: JJ
authors.lastname: Pekar
authors.affiliation: Center for Neurodevelopmental and Imaging Research, Kennedy Krieger Institute, Baltimore, MD USA ; Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD USA ; Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD USA.
authors.forename: Stewart H
authors.initials: SH
authors.lastname: Mostofsky
mesh_terms: D000067877:Autism Spectrum Disorder / Q000503:physiopathology*; D001921:Brain / Q000000981:diagnostic imaging / Q000503:physiopathology; D016022:Case-Control Studies; D002648:Child; D005260:Female; D007839:Functional Laterality / Q000502:physiology; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007802:Language; D008279:Magnetic Resonance Imaging; D008297:Male; D009483:Neuropsychological Tests
keywords: Autism; Hemispheric specialization; Intrinsic functional connectivity; Lateralization; Motor deficits