title: Frontal networks in adults with autism spectrum disorder.
abstract: It has been postulated that autism spectrum disorder is underpinned by an 'atypical connectivity' involving higher-order association brain regions. To test this hypothesis in a large cohort of adults with autism spectrum disorder we compared the white matter networks of 61 adult males with autism spectrum disorder and 61 neurotypical controls, using two complementary approaches to diffusion tensor magnetic resonance imaging. First, we applied tract-based spatial statistics, a 'whole brain' non-hypothesis driven method, to identify differences in white matter networks in adults with autism spectrum disorder. Following this we used a tract-specific analysis, based on tractography, to carry out a more detailed analysis of individual tracts identified by tract-based spatial statistics. Finally, within the autism spectrum disorder group, we studied the relationship between diffusion measures and autistic symptom severity. Tract-based spatial statistics revealed that autism spectrum disorder was associated with significantly reduced fractional anisotropy in regions that included frontal lobe pathways. Tractography analysis of these specific pathways showed increased mean and perpendicular diffusivity, and reduced number of streamlines in the anterior and long segments of the arcuate fasciculus, cingulum and uncinate--predominantly in the left hemisphere. Abnormalities were also evident in the anterior portions of the corpus callosum connecting left and right frontal lobes. The degree of microstructural alteration of the arcuate and uncinate fasciculi was associated with severity of symptoms in language and social reciprocity in childhood. Our results indicated that autism spectrum disorder is a developmental condition associated with abnormal connectivity of the frontal lobes. Furthermore our findings showed that male adults with autism spectrum disorder have regional differences in brain anatomy, which correlate with specific aspects of autistic symptoms. Overall these results suggest that autism spectrum disorder is a condition linked to aberrant developmental trajectories of the frontal networks that persist in adult life.
authors.affiliation: 1 Sackler Institute for Translational Neurodevelopment, and Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, King's College, London, UK 2 NatBrainLab, Centre for Neuroimaging Sciences, Institute of Psychiatry, King's College, London, UK.
authors.forename: Marco
authors.initials: M
authors.lastname: Catani
authors.affiliation: 2 NatBrainLab, Centre for Neuroimaging Sciences, Institute of Psychiatry, King's College, London, UK.
authors.forename: Flavio
authors.initials: F
authors.lastname: Dell'Acqua
authors.affiliation: 1 Sackler Institute for Translational Neurodevelopment, and Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, King's College, London, UK.
authors.forename: Sanja
authors.initials: S
authors.lastname: Budisavljevic
authors.affiliation: 1 Sackler Institute for Translational Neurodevelopment, and Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, King's College, London, UK.
authors.forename: Henrietta
authors.initials: H
authors.lastname: Howells
authors.affiliation: 1 Sackler Institute for Translational Neurodevelopment, and Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, King's College, London, UK.
authors.forename: Michel
authors.initials: M
authors.lastname: Thiebaut de Schotten
authors.affiliation: 1 Sackler Institute for Translational Neurodevelopment, and Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, King's College, London, UK.
authors.forename: Seán
authors.initials: S
authors.lastname: Froudist-Walsh
authors.affiliation: 1 Sackler Institute for Translational Neurodevelopment, and Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, King's College, London, UK.
authors.forename: Lucio
authors.initials: L
authors.lastname: D'Anna
authors.affiliation: 1 Sackler Institute for Translational Neurodevelopment, and Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, King's College, London, UK.
authors.forename: Abigail
authors.initials: A
authors.lastname: Thompson
authors.affiliation: 1 Sackler Institute for Translational Neurodevelopment, and Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, King's College, London, UK.
authors.forename: Stefano
authors.initials: S
authors.lastname: Sandrone
authors.affiliation: 3 Cambridgeshire and Peterborough NHS Foundation Trust 4 Brain Mapping Unit, Department of Psychiatry, University of Cambridge, UK.
authors.forename: Edward T
authors.initials: ET
authors.lastname: Bullmore
authors.affiliation: 3 Cambridgeshire and Peterborough NHS Foundation Trust 4 Brain Mapping Unit, Department of Psychiatry, University of Cambridge, UK 5 Autism Research Centre, Department of Psychiatry, University of Cambridge, UK.
authors.forename: John
authors.initials: J
authors.lastname: Suckling
authors.affiliation: 3 Cambridgeshire and Peterborough NHS Foundation Trust 5 Autism Research Centre, Department of Psychiatry, University of Cambridge, UK.
authors.forename: Simon
authors.initials: S
authors.lastname: Baron-Cohen
authors.affiliation: 5 Autism Research Centre, Department of Psychiatry, University of Cambridge, UK 6 Department of Psychology and Center for Applied Neuroscience, University of Cyprus, Cyprus.
authors.forename: Michael V
authors.initials: MV
authors.lastname: Lombardo
authors.affiliation: 5 Autism Research Centre, Department of Psychiatry, University of Cambridge, UK.
authors.forename: Sally J
authors.initials: SJ
authors.lastname: Wheelwright
authors.affiliation: 5 Autism Research Centre, Department of Psychiatry, University of Cambridge, UK 7 Centre for Integrative Neuroscience and Neurodynamics, School of Psychology and Clinical Language Sciences, University of Reading, Reading, UK.
authors.forename: Bhismadev
authors.initials: B
authors.lastname: Chakrabarti
authors.affiliation: 5 Autism Research Centre, Department of Psychiatry, University of Cambridge, UK 8 Centre for Addiction and Mental Health and Department of Psychiatry, University of Toronto, Canada 9 Department of Psychiatry, National Taiwan University Hospital and College of Medicine, Taiwan.
authors.forename: Meng-Chuan
authors.initials: MC
authors.lastname: Lai
authors.affiliation: 5 Autism Research Centre, Department of Psychiatry, University of Cambridge, UK.
authors.forename: Amber N V
authors.initials: AN
authors.lastname: Ruigrok
authors.affiliation: 10 Image Sciences Institute, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Alexander
authors.initials: A
authors.lastname: Leemans
authors.affiliation: 1 Sackler Institute for Translational Neurodevelopment, and Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, King's College, London, UK.
authors.forename: Christine
authors.initials: C
authors.lastname: Ecker
authors.forename: Mrc Aims
authors.initials: MA
authors.lastname: Consortium
authors.affiliation: 1 Sackler Institute for Translational Neurodevelopment, and Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, King's College, London, UK 11 National Autism Unit, South London and Maudsley NHS Foundation Trust, Bethlem Royal Hospital, Beckenham, UK.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Craig
authors.affiliation: 1 Sackler Institute for Translational Neurodevelopment, and Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, King's College, London, UK m.catani@iop.kcl.ac.uk.
authors.forename: Declan G M
authors.initials: DG
authors.lastname: Murphy
mesh_terms: D000293:Adolescent; D000328:Adult; D000067877:Autism Spectrum Disorder / Q000175:diagnosis* / Q000378:metabolism*; D003430:Cross-Sectional Studies; D056324:Diffusion Tensor Imaging / Q000379:methods; D005625:Frontal Lobe / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009415:Nerve Net / Q000378:metabolism* / Q000473:pathology; D066127:White Matter / Q000378:metabolism* / Q000473:pathology; D055815:Young Adult
keywords: arcuate fasciculus; autism spectrum disorder; diffusion tractography; frontal networks; language