Skip to main content

Main menu

  • Home
  • Articles
    • Current
    • Special Feature Articles - Most Recent
    • Special Features
    • Colloquia
    • Collected Articles
    • PNAS Classics
    • List of Issues
  • Front Matter
    • Front Matter Portal
    • Journal Club
  • News
    • For the Press
    • This Week In PNAS
    • PNAS in the News
  • Podcasts
  • Authors
    • Information for Authors
    • Editorial and Journal Policies
    • Submission Procedures
    • Fees and Licenses
  • Submit
  • Submit
  • About
    • Editorial Board
    • PNAS Staff
    • FAQ
    • Accessibility Statement
    • Rights and Permissions
    • Site Map
  • Contact
  • Journal Club
  • Subscribe
    • Subscription Rates
    • Subscriptions FAQ
    • Open Access
    • Recommend PNAS to Your Librarian

User menu

  • Log in
  • My Cart

Search

  • Advanced search
Home
Home
  • Log in
  • My Cart

Advanced Search

  • Home
  • Articles
    • Current
    • Special Feature Articles - Most Recent
    • Special Features
    • Colloquia
    • Collected Articles
    • PNAS Classics
    • List of Issues
  • Front Matter
    • Front Matter Portal
    • Journal Club
  • News
    • For the Press
    • This Week In PNAS
    • PNAS in the News
  • Podcasts
  • Authors
    • Information for Authors
    • Editorial and Journal Policies
    • Submission Procedures
    • Fees and Licenses
  • Submit
Research Article

A common brain network links development, aging, and vulnerability to disease

Gwenaëlle Douaud, Adrian R. Groves, Christian K. Tamnes, Lars Tjelta Westlye, Eugene P. Duff, Andreas Engvig, Kristine B. Walhovd, Anthony James, Achim Gass, Andreas U. Monsch, Paul M. Matthews, Anders M. Fjell, Stephen M. Smith, and Heidi Johansen-Berg
  1. aFunctional Magnetic Resonance Imaging of the Brain (FMRIB) Centre, Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom;
  2. bResearch Group for Life-Span Changes in Brain and Cognition, Department of Psychology and
  3. cDepartment of Psychology, University of Oslo, 0317 Oslo, Norway;
  4. dNorwegian Centre for Mental Disorders Research (NORMENT), KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital, 0424 Oslo, Norway;
  5. eDepartment of Psychiatry, University of Oxford, Oxford OX3 7JX, United Kingdom;
  6. fDepartment of Neurology, University Hospital Mannheim, University of Heidelberg, 68167 Heidelberg, Germany;
  7. gMemory Clinic, University Center for Medicine of Aging Basel, Felix Platter-Hospital, CH-4031 Basel, Switzerland; and
  8. hDivision of Brain Sciences, Department of Medicine, Imperial College London, London W12 0NN, United Kingdom

See allHide authors and affiliations

PNAS December 9, 2014 111 (49) 17648-17653; first published November 24, 2014; https://doi.org/10.1073/pnas.1410378111
Gwenaëlle Douaud
aFunctional Magnetic Resonance Imaging of the Brain (FMRIB) Centre, Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: douaud@fmrib.ox.ac.uk
Adrian R. Groves
aFunctional Magnetic Resonance Imaging of the Brain (FMRIB) Centre, Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Christian K. Tamnes
bResearch Group for Life-Span Changes in Brain and Cognition, Department of Psychology and
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Lars Tjelta Westlye
cDepartment of Psychology, University of Oslo, 0317 Oslo, Norway;
dNorwegian Centre for Mental Disorders Research (NORMENT), KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital, 0424 Oslo, Norway;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Eugene P. Duff
aFunctional Magnetic Resonance Imaging of the Brain (FMRIB) Centre, Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Andreas Engvig
bResearch Group for Life-Span Changes in Brain and Cognition, Department of Psychology and
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kristine B. Walhovd
bResearch Group for Life-Span Changes in Brain and Cognition, Department of Psychology and
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Anthony James
eDepartment of Psychiatry, University of Oxford, Oxford OX3 7JX, United Kingdom;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Achim Gass
fDepartment of Neurology, University Hospital Mannheim, University of Heidelberg, 68167 Heidelberg, Germany;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Andreas U. Monsch
gMemory Clinic, University Center for Medicine of Aging Basel, Felix Platter-Hospital, CH-4031 Basel, Switzerland; and
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Paul M. Matthews
hDivision of Brain Sciences, Department of Medicine, Imperial College London, London W12 0NN, United Kingdom
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Anders M. Fjell
bResearch Group for Life-Span Changes in Brain and Cognition, Department of Psychology and
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Stephen M. Smith
aFunctional Magnetic Resonance Imaging of the Brain (FMRIB) Centre, Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Heidi Johansen-Berg
aFunctional Magnetic Resonance Imaging of the Brain (FMRIB) Centre, Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  1. Edited by Denise C. Park, University of Texas at Dallas, Dallas, TX and accepted by the Editorial Board October 15, 2014 (received for review June 4, 2014)

  • Article
  • Figures & SI
  • Info & Metrics
  • PDF
Loading

Significance

Many evolutionary–developmental models have attempted to relate development and aging, with one popular hypothesis proposing that healthy age-related brain decline mirrors developmental maturation. But this elegant hypothesis has so far lacked clear and direct data to support it. Here, we describe intrinsic, entirely data-driven evidence that healthy brain degeneration and developmental process mirror one another in certain brain regions. Specifically, a data-driven decomposition of structural brain images in 484 healthy participants reveals a network of mainly higher-order regions that develop relatively late during adolescence, demonstrate accelerated degeneration in old age, and show heightened vulnerability to disorders that impact on brain structure during adolescence and aging. These results provide a fundamental link between development, aging, and disease processes in the brain.

Abstract

Several theories link processes of development and aging in humans. In neuroscience, one model posits for instance that healthy age-related brain degeneration mirrors development, with the areas of the brain thought to develop later also degenerating earlier. However, intrinsic evidence for such a link between healthy aging and development in brain structure remains elusive. Here, we show that a data-driven analysis of brain structural variation across 484 healthy participants (8–85 y) reveals a largely—but not only—transmodal network whose lifespan pattern of age-related change intrinsically supports this model of mirroring development and aging. We further demonstrate that this network of brain regions, which develops relatively late during adolescence and shows accelerated degeneration in old age compared with the rest of the brain, characterizes areas of heightened vulnerability to unhealthy developmental and aging processes, as exemplified by schizophrenia and Alzheimer’s disease, respectively. Specifically, this network, while derived solely from healthy subjects, spatially recapitulates the pattern of brain abnormalities observed in both schizophrenia and Alzheimer’s disease. This network is further associated in our large-scale healthy population with intellectual ability and episodic memory, whose impairment contributes to key symptoms of schizophrenia and Alzheimer’s disease. Taken together, our results suggest that the common spatial pattern of abnormalities observed in these two disorders, which emerge at opposite ends of the life spectrum, might be influenced by the timing of their separate and distinct pathological processes in disrupting healthy cerebral development and aging, respectively.

  • brain structure
  • development
  • aging
  • schizophrenia
  • Alzheimer's disease

Footnotes

  • ↵1To whom correspondence should be addressed. Email: douaud{at}fmrib.ox.ac.uk.
  • Author contributions: G.D., E.P.D., S.M.S., and H.J.-B. designed research; G.D., C.K.T., L.T.W., A.E., K.B.W., A.J., A.G., A.U.M., P.M.M., and A.M.F. performed research; A.R.G., E.P.D., and S.M.S. contributed new reagents/analytic tools; G.D., A.R.G., and L.T.W. analyzed data; and G.D. wrote the paper.

  • The authors declare no conflict of interest.

  • This article is a PNAS Direct Submission. D.C.P. is a guest editor invited by the Editorial Board.

  • Data deposition: The Z/t stats 3D maps for all three datasets reported in this paper can be found at www.fmrib.ox.ac.uk/analysis/LIFO+AD+AOS/.

  • This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1410378111/-/DCSupplemental.

Freely available online through the PNAS open access option.

View Full Text
PreviousNext
Back to top
Article Alerts
Email Article

Thank you for your interest in spreading the word on PNAS.

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
A common brain network links development, aging, and vulnerability to disease
(Your Name) has sent you a message from PNAS
(Your Name) thought you would like to see the PNAS web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Linking brain development, aging, and disease
Gwenaëlle Douaud, Adrian R. Groves, Christian K. Tamnes, Lars Tjelta Westlye, Eugene P. Duff, Andreas Engvig, Kristine B. Walhovd, Anthony James, Achim Gass, Andreas U. Monsch, Paul M. Matthews, Anders M. Fjell, Stephen M. Smith, Heidi Johansen-Berg
Proceedings of the National Academy of Sciences Dec 2014, 111 (49) 17648-17653; DOI: 10.1073/pnas.1410378111

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Request Permissions
Share
Linking brain development, aging, and disease
Gwenaëlle Douaud, Adrian R. Groves, Christian K. Tamnes, Lars Tjelta Westlye, Eugene P. Duff, Andreas Engvig, Kristine B. Walhovd, Anthony James, Achim Gass, Andreas U. Monsch, Paul M. Matthews, Anders M. Fjell, Stephen M. Smith, Heidi Johansen-Berg
Proceedings of the National Academy of Sciences Dec 2014, 111 (49) 17648-17653; DOI: 10.1073/pnas.1410378111
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Mendeley logo Mendeley

Article Classifications

  • Biological Sciences
  • Neuroscience

This article has a Letter. Please see:

  • Relationship between Research Article and Letter - May 04, 2015
Proceedings of the National Academy of Sciences: 111 (49)
Table of Contents

Submit

Sign up for Article Alerts

Jump to section

  • Article
    • Abstract
    • Results
    • Discussion
    • Materials and Methods
    • Acknowledgments
    • Footnotes
    • References
  • Figures & SI
  • Info & Metrics
  • PDF

You May Also be Interested in

Water from a faucet fills a glass.
News Feature: How “forever chemicals” might impair the immune system
Researchers are exploring whether these ubiquitous fluorinated molecules might worsen infections or hamper vaccine effectiveness.
Image credit: Shutterstock/Dmitry Naumov.
Reflection of clouds in the still waters of Mono Lake in California.
Inner Workings: Making headway with the mysteries of life’s origins
Recent experiments and simulations are starting to answer some fundamental questions about how life came to be.
Image credit: Shutterstock/Radoslaw Lecyk.
Cave in coastal Kenya with tree growing in the middle.
Journal Club: Small, sharp blades mark shift from Middle to Later Stone Age in coastal Kenya
Archaeologists have long tried to define the transition between the two time periods.
Image credit: Ceri Shipton.
Illustration of groups of people chatting
Exploring the length of human conversations
Adam Mastroianni and Daniel Gilbert explore why conversations almost never end when people want them to.
Listen
Past PodcastsSubscribe
Panda bear hanging in a tree
How horse manure helps giant pandas tolerate cold
A study finds that giant pandas roll in horse manure to increase their cold tolerance.
Image credit: Fuwen Wei.

Similar Articles

Site Logo
Powered by HighWire
  • Submit Manuscript
  • Twitter
  • Facebook
  • RSS Feeds
  • Email Alerts

Articles

  • Current Issue
  • Special Feature Articles – Most Recent
  • List of Issues

PNAS Portals

  • Anthropology
  • Chemistry
  • Classics
  • Front Matter
  • Physics
  • Sustainability Science
  • Teaching Resources

Information

  • Authors
  • Editorial Board
  • Reviewers
  • Subscribers
  • Librarians
  • Press
  • Cozzarelli Prize
  • Site Map
  • PNAS Updates
  • FAQs
  • Accessibility Statement
  • Rights & Permissions
  • About
  • Contact

Feedback    Privacy/Legal

Copyright © 2021 National Academy of Sciences. Online ISSN 1091-6490