Adolescence is associated with genomically patterned consolidation of the hubs of the human brain connectome

NSPN Consortium3, Kirstie J. Whitaker*, Petra E. Vértes, Rafael Romero-Garciaa, František Váša, Michael Moutoussis, Gita Prabhu, Nikolaus Weiskopf, Martina F. Callaghan, Konrad Wagstyl, Timothy Rittman, Roger Tait, Cinly Ooi, John Suckling, Becky Inkster, Peter Fonagy, Raymond J. Dolan, Peter B. Jones, Ian M. Goodyer, Edward T. BullmoreEran Eldar

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

289 Scopus citations

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.

Original languageEnglish
Pages (from-to)9105-9110
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume113
Issue number32
DOIs
StatePublished - 9 Aug 2016

Bibliographical note

Funding Information:
We thank Dr. Amy Orsborn for her graphic design of Fig. 2C and Dr. Fred Dick for helpful discussions of MRI analyses. We also thank the AIBS for use of the Allen Human Brain Atlas available from human.brain-map.org. We used the Darwin Supercomputer of the University of Cambridge High Performance Computing Service provided by Dell Inc. and funded by Higher Education Funding Council for England and Science and Technology Facilities Council. Study data were collected and managed using REDCap electronic data capture tools hosted at the University of Cambridge. This study was supported by the Neuroscience in Psychiatry Network, a strategic award by the Wellcome Trust to the University of Cambridge and University College London (095844/Z/11/Z). Additional support was provided by the National Institute for Health Research Cambridge Biomedical Research Centre and the Medical Research Council (MRC)/Wellcome Trust Behavioural and Clinical Neuroscience Institute. P.E.V. is supported by the MRC Grant MR/ K020706/1. F.V. is supported by the Gates Cambridge Trust. M.M. is supported by the Biomedical Research Council.

Keywords

  • Graph theory
  • Magnetization transfer
  • Microarray
  • Myelinogenesis
  • Partial least squares

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