title: Adolescence is associated with genomically patterned consolidation of the hubs of the human brain connectome.
abstract: How does human brain structure mature during adolescence? We used MRI to measure cortical thickness and intracortical myelination in 297 population volunteers aged 14-24 y old. We found and replicated that association cortical areas were thicker and less myelinated than primary cortical areas at 14 y. However, association cortex had faster rates of shrinkage and myelination over the course of adolescence. Age-related increases in cortical myelination were maximized approximately at the internal layer of projection neurons. Adolescent cortical myelination and shrinkage were coupled and specifically associated with a dorsoventrally patterned gene expression profile enriched for synaptic, oligodendroglial- and schizophrenia-related genes. Topologically efficient and biologically expensive hubs of the brain anatomical network had greater rates of shrinkage/myelination and were associated with overexpression of the same transcriptional profile as cortical consolidation. We conclude that normative human brain maturation involves a genetically patterned process of consolidating anatomical network hubs. We argue that developmental variation of this consolidation process may be relevant both to normal cognitive and behavioral changes and the high incidence of schizophrenia during human brain adolescence.
authors.affiliation: Department of Psychiatry, University of Cambridge, Cambridge CB2 0SZ, United Kingdom; kw401@cam.ac.uk.
authors.forename: Kirstie J
authors.identifier: 0000-0001-8498-4059
authors.initials: KJ
authors.lastname: Whitaker
authors.affiliation: Department of Psychiatry, University of Cambridge, Cambridge CB2 0SZ, United Kingdom;
authors.forename: Petra E
authors.identifier: 0000-0002-0992-3210
authors.initials: PE
authors.lastname: Vértes
authors.affiliation: Department of Psychiatry, University of Cambridge, Cambridge CB2 0SZ, United Kingdom;
authors.forename: Rafael
authors.initials: R
authors.lastname: Romero-Garcia
authors.affiliation: Department of Psychiatry, University of Cambridge, Cambridge CB2 0SZ, United Kingdom;
authors.forename: František
authors.initials: F
authors.lastname: Váša
authors.affiliation: Wellcome Trust Centre for Neuroimaging, University College London, London WC1N 3BG, United Kingdom;
authors.forename: Michael
authors.initials: M
authors.lastname: Moutoussis
authors.affiliation: Wellcome Trust Centre for Neuroimaging, University College London, London WC1N 3BG, United Kingdom;
authors.forename: Gita
authors.initials: G
authors.lastname: Prabhu
authors.affiliation: Wellcome Trust Centre for Neuroimaging, University College London, London WC1N 3BG, United Kingdom; Department of Neurophysics, Max Planck Institute for Human Cognitive and Brain Sciences, 04103 Leipzig, Germany;
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Weiskopf
authors.affiliation: Wellcome Trust Centre for Neuroimaging, University College London, London WC1N 3BG, United Kingdom;
authors.forename: Martina F
authors.initials: MF
authors.lastname: Callaghan
authors.affiliation: Department of Psychiatry, University of Cambridge, Cambridge CB2 0SZ, United Kingdom;
authors.forename: Konrad
authors.initials: K
authors.lastname: Wagstyl
authors.affiliation: Department of Clinical Neurosciences, University of Cambridge, Cambridge CB2 3EB, United Kingdom;
authors.forename: Timothy
authors.initials: T
authors.lastname: Rittman
authors.affiliation: Department of Psychiatry, University of Cambridge, Cambridge CB2 0SZ, United Kingdom;
authors.forename: Roger
authors.initials: R
authors.lastname: Tait
authors.affiliation: Department of Psychiatry, University of Cambridge, Cambridge CB2 0SZ, United Kingdom;
authors.forename: Cinly
authors.initials: C
authors.lastname: Ooi
authors.affiliation: Department of Psychiatry, University of Cambridge, Cambridge CB2 0SZ, United Kingdom; Cambridgeshire and Peterborough National Health Service Foundation Trust, Cambridge, CB21 5EF, United Kingdom; Medical Research Council/Wellcome Trust Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge CB2 3EB, United Kingdom;
authors.forename: John
authors.initials: J
authors.lastname: Suckling
authors.affiliation: Department of Psychiatry, University of Cambridge, Cambridge CB2 0SZ, United Kingdom;
authors.forename: Becky
authors.initials: B
authors.lastname: Inkster
authors.affiliation: Research Department of Clinical, Educational and Health Psychology, University College London, London WC1E 6BT, United Kingdom;
authors.forename: Peter
authors.initials: P
authors.lastname: Fonagy
authors.affiliation: Wellcome Trust Centre for Neuroimaging, University College London, London WC1N 3BG, United Kingdom; Max Planck University College London Centre for Computational Psychiatry and Ageing Research, University College London, London WC1B 5EH, United Kingdom;
authors.forename: Raymond J
authors.initials: RJ
authors.lastname: Dolan
authors.affiliation: Department of Psychiatry, University of Cambridge, Cambridge CB2 0SZ, United Kingdom; Cambridgeshire and Peterborough National Health Service Foundation Trust, Cambridge, CB21 5EF, United Kingdom;
authors.forename: Peter B
authors.initials: PB
authors.lastname: Jones
authors.affiliation: Department of Psychiatry, University of Cambridge, Cambridge CB2 0SZ, United Kingdom; Cambridgeshire and Peterborough National Health Service Foundation Trust, Cambridge, CB21 5EF, United Kingdom;
authors.forename: Ian M
authors.initials: IM
authors.lastname: Goodyer
authors.affiliation: Department of Psychiatry, University of Cambridge, Cambridge CB2 0SZ, United Kingdom; Cambridgeshire and Peterborough National Health Service Foundation Trust, Cambridge, CB21 5EF, United Kingdom; Medical Research Council/Wellcome Trust Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge CB2 3EB, United Kingdom; ImmunoPsychiatry, GlaxoSmithKline Research and Development, Stevenage SG1 2NY, United Kingdom.
authors.forename: Edward T
authors.identifier: 0000-0002-8955-8283
authors.initials: ET
authors.lastname: Bullmore
mesh_terms: D000293:Adolescent; D000328:Adult; D002540:Cerebral Cortex / Q000033:anatomy & histology* / Q000502:physiology; D003071:Cognition; D063132:Connectome / Q000379:methods*; D005260:Female; D006801:Humans; D008297:Male; D009186:Myelin Sheath / Q000502:physiology; D009415:Nerve Net / Q000033:anatomy & histology / Q000502:physiology; D012559:Schizophrenia / Q000503:physiopathology; D059467:Transcriptome; D055815:Young Adult
keywords: graph theory; magnetization transfer; microarray; myelinogenesis; partial least squares