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. Bullmore; Eran Eldar

doi:10.1073/pnas.1601745113

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 journal › Article › peer-review

338 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 language	English
Pages (from-to)	9105-9110
Number of pages	6
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	113
Issue number	32
DOIs	https://doi.org/10.1073/pnas.1601745113
State	Published - 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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10.1073/pnas.1601745113

Cite this

NSPN Consortium3, Whitaker, K. J., Vértes, P. E., Romero-Garciaa, R., Váša, F., Moutoussis, M., Prabhu, G., Weiskopf, N., Callaghan, M. F., Wagstyl, K., Rittman, T., Tait, R., Ooi, C., Suckling, J., Inkster, B., Fonagy, P., Dolan, R. J., Jones, P. B., Goodyer, I. M., ... Eldar, E. (2016). Adolescence is associated with genomically patterned consolidation of the hubs of the human brain connectome. Proceedings of the National Academy of Sciences of the United States of America, 113(32), 9105-9110. https://doi.org/10.1073/pnas.1601745113

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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.",

keywords = "Graph theory, Magnetization transfer, Microarray, Myelinogenesis, Partial least squares",

author = "{NSPN Consortium3} and Whitaker, {Kirstie J.} and V{\'e}rtes, {Petra E.} and Rafael Romero-Garciaa and Franti{\v s}ek V{\'a}{\v s}a and Michael Moutoussis and Gita Prabhu and Nikolaus Weiskopf and Callaghan, {Martina F.} and Konrad Wagstyl and Timothy Rittman and Roger Tait and Cinly Ooi and John Suckling and Becky Inkster and Peter Fonagy and Dolan, {Raymond J.} and Jones, {Peter B.} and Goodyer, {Ian M.} and Bullmore, {Edward T.} and Eran Eldar",

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.",

year = "2016",

month = aug,

day = "9",

doi = "10.1073/pnas.1601745113",

language = "אנגלית",

volume = "113",

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NSPN Consortium3, Whitaker, KJ, Vértes, PE, Romero-Garciaa, R, Váša, F, Moutoussis, M, Prabhu, G, Weiskopf, N, Callaghan, MF, Wagstyl, K, Rittman, T, Tait, R, Ooi, C, Suckling, J, Inkster, B, Fonagy, P, Dolan, RJ, Jones, PB, Goodyer, IM, Bullmore, ET & Eldar, E 2016, 'Adolescence is associated with genomically patterned consolidation of the hubs of the human brain connectome', Proceedings of the National Academy of Sciences of the United States of America, vol. 113, no. 32, pp. 9105-9110. https://doi.org/10.1073/pnas.1601745113

Adolescence is associated with genomically patterned consolidation of the hubs of the human brain connectome. / NSPN Consortium3; Whitaker, Kirstie J.; Vértes, Petra E. et al.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 113, No. 32, 09.08.2016, p. 9105-9110.

Research output: Contribution to journal › Article › peer-review

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T1 - Adolescence is associated with genomically patterned consolidation of the hubs of the human brain connectome

AU - NSPN Consortium3

AU - Whitaker, Kirstie J.

AU - Vértes, Petra E.

AU - Romero-Garciaa, Rafael

AU - Váša, František

AU - Moutoussis, Michael

AU - Prabhu, Gita

AU - Weiskopf, Nikolaus

AU - Callaghan, Martina F.

AU - Wagstyl, Konrad

AU - Rittman, Timothy

AU - Tait, Roger

AU - Ooi, Cinly

AU - Suckling, John

AU - Inkster, Becky

AU - Fonagy, Peter

AU - Dolan, Raymond J.

AU - Jones, Peter B.

AU - Goodyer, Ian M.

AU - Bullmore, Edward T.

AU - Eldar, Eran

N1 - 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.

PY - 2016/8/9

Y1 - 2016/8/9

N2 - 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.

AB - 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.

KW - Graph theory

KW - Magnetization transfer

KW - Microarray

KW - Myelinogenesis

KW - Partial least squares

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JF - Proceedings of the National Academy of Sciences of the United States of America

IS - 32

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

Abstract

Bibliographical note

Keywords

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