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

Accepted version
Peer-reviewed

Type

Article

Change log

Authors

Whitaker, Kirstie J  ORCID logo  https://orcid.org/0000-0001-8498-4059
Romero-Garcia, Rafael 
Váša, František 
Moutoussis, Michael 

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.

Description

Keywords

graph theory, magnetization transfer, microarray, myelinogenesis, partial least squares, Adolescent, Adult, Cerebral Cortex, Cognition, Connectome, Female, Humans, Male, Myelin Sheath, Nerve Net, Schizophrenia, Transcriptome, Young Adult

Journal Title

Proc Natl Acad Sci U S A

Conference Name

Journal ISSN

0027-8424
1091-6490

Volume Title

113

Publisher

Proceedings of the National Academy of Sciences
Sponsorship
Wellcome Trust (095844/Z/11/Z)
Medical Research Council (MR/K020706/1)
Medical Research Council (G1000183)
Medical Research Council (G1100464)
Wellcome Trust (093875/Z/10/Z)
Medical Research Council (G0001354)
Medical Research Council (G1100464/1)
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. Additional support was provided by the NIHR Cambridge Biomedical Research Centre and the MRC/Wellcome Trust Behavioural & Clinical Neuroscience Institute. PEV is supported by the MRC (MR/K020706/1). We used the Darwin Supercomputer of the University of Cambridge High Performance Computing Service provided by Dell Inc. using Strategic Research Infrastructure Funding from the Higher Education Funding Council for England and funding from the Science and Technology Facilities Council.