Charting brain growth and aging at high spatial precision

  1. Saige Rutherford  Is a corresponding author
  2. Charlotte Fraza
  3. Richard Dinga
  4. Seyed Mostafa Kia
  5. Thomas Wolfers
  6. Mariam Zabihi
  7. Pierre Berthet
  8. Amanda Worker
  9. Serena Verdi
  10. Derek Andrews
  11. Laura Han
  12. Johanna MM Bayer
  13. Paola Dazzan
  14. Phillip McGuire
  15. Roel T Mocking
  16. Aart Schene
  17. Chandra Sripada
  18. Ivy F Tso
  19. Elizabeth R Duval
  20. Soo-Eun Chang
  21. Brenda W. Pennix
  22. Mary M. Heitzeg
  23. S Alexandra Burt
  24. Luke Hyde
  25. David Amaral
  26. Christine Wu Nordahl
  27. Ole A Andreasssen
  28. Lars T Westlye
  29. Roland Zahn
  30. Henricus G Ruhe
  31. Christian Beckmann
  32. Andre F Marquand
  1. Radboud University Medical Center, Netherlands
  2. University of Oslo, Norway
  3. King's College London, United Kingdom
  4. University College London, United Kingdom
  5. University of California, Davis, United States
  6. Amsterdam University Medical Center, Netherlands
  7. University of Melbourne, Australia
  8. University of Michigan, United States
  9. Michigan State University, United States

Abstract

Defining reference models for population variation, and the ability to study individual deviations is essential for understanding inter-individual variability and its relation to the onset and progression of medical conditions. In this work, we assembled a reference cohort of neuroimaging data from 82 sites (N=58,836; ages 2-100) and use normative modeling to characterize lifespan trajectories of cortical thickness and subcortical volume. Models are validated against a manually quality checked subset (N=24,354) and we provide an interface for transferring to new data sources. We showcase the clinical value by applying the models to a transdiagnostic psychiatric sample (N=1,985), showing they can be used to quantify variability underlying multiple disorders whilst also refining case-control inferences. These models will be augmented with additional samples and imaging modalities as they become available. This provides a common reference platform to bind results from different studies and ultimately paves the way for personalized clinical decision making.

Data availability

All pre-trained models and code for transferring to new sites are shared online via GitHub (https://github.com/predictive-clinical-neuroscience/braincharts). We have also shared the models on Zenodo (https://zenodo.org/record/5535467#.YVRECmYzZhF).

The following data sets were generated
The following previously published data sets were used
    1. Adriana Di Martino
    (2012) ABIDE
    http://fcon_1000.projects.nitrc.org/indi/abide/.
    1. Michael Millham
    (2011) ADHD200
    https://fcon_1000.projects.nitrc.org/indi/adhd200/.
    1. Michael Millham
    (2020) CMI-HBN
    http://fcon_1000.projects.nitrc.org/indi/cmi_healthy_brain_network/About.html.
    1. Beau Ances et al
    (2021) HCP-Aging
    https://nda.nih.gov/general-query.html?q=query=featured-datasets:HCP%20Aging%20and%20Development.
    1. Deanna Barch et al
    (2021) HCP-Development
    https://nda.nih.gov/general-query.html?q=query=featured-datasets:HCP%20Aging%20and%20Development.
    1. Alan Breier
    (2021) HCP-Early Psychosis
    https://nda.nih.gov/general-query.html?q=query=featured-datasets:Connectomes%20Related%20to%20Human%20Disease.
    1. Imperial College London
    (2010) IXI
    https://brain-development.org/ixi-dataset/.
    1. Mike Millham
    (2017) NKI-RS
    http://fcon_1000.projects.nitrc.org/indi/enhanced/access.html.
    1. Randy Buckner
    (2007) Oasis
    https://direct.mit.edu/jocn/article/19/9/1498/4427/Open-Access-Series-of-Imaging-Studies-OASIS-Cross.
    1. Saori Tanaka
    (2021) SRPBS
    https://bicr-resource.atr.jp/srpbsopen/.
    1. Steve Smith
    (2014) UKbiobank
    https://biobank.ndph.ox.ac.uk/showcase/.

Article and author information

Author details

  1. Saige Rutherford

    Donders Institute for Brain, Cognition, and Behavior, Radboud University Medical Center, Nijmegen, Netherlands
    For correspondence
    saige.rutherford@donders.ru.nl
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3006-9044
  2. Charlotte Fraza

    Donders Institute for Brain, Cognition, and Behavior, Radboud University Medical Center, Nijmegen, Netherlands
    Competing interests
    No competing interests declared.
  3. Richard Dinga

    Donders Institute for Brain, Cognition, and Behavior, Radboud University Medical Center, Nijmegen, Netherlands
    Competing interests
    No competing interests declared.
  4. Seyed Mostafa Kia

    Donders Institute for Brain, Cognition, and Behavior, Radboud University Medical Center, Nijmegen, Netherlands
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7128-814X
  5. Thomas Wolfers

    Department of Psychology, University of Oslo, Oslo, Norway
    Competing interests
    No competing interests declared.
  6. Mariam Zabihi

    Donders Institute for Brain, Cognition, and Behavior, Radboud University Medical Center, Nijmegen, Netherlands
    Competing interests
    No competing interests declared.
  7. Pierre Berthet

    Department of Psychology, University of Oslo, Oslo, Norway
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6878-6842
  8. Amanda Worker

    Department of Psychological Medicine, King's College London, London, United Kingdom
    Competing interests
    No competing interests declared.
  9. Serena Verdi

    Centre for Medical Image Computing, University College London, London, United Kingdom
    Competing interests
    No competing interests declared.
  10. Derek Andrews

    Department of Psychiatry and Behavioral Sciences, University of California, Davis, Davis, United States
    Competing interests
    No competing interests declared.
  11. Laura Han

    Amsterdam University Medical Center, Amsterdam, Netherlands
    Competing interests
    No competing interests declared.
  12. Johanna MM Bayer

    Centre for Youth Mental Health, University of Melbourne, Melbourne, Australia
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4891-6256
  13. Paola Dazzan

    Department of Psychological Medicine, King's College London, London, United Kingdom
    Competing interests
    No competing interests declared.
  14. Phillip McGuire

    Department of Psychosis Studies, King's College London, London, United Kingdom
    Competing interests
    No competing interests declared.
  15. Roel T Mocking

    Amsterdam University Medical Center, Amsterdam, Netherlands
    Competing interests
    No competing interests declared.
  16. Aart Schene

    Department of Psychiatry, Radboud University Medical Center, Nijmegen, Netherlands
    Competing interests
    No competing interests declared.
  17. Chandra Sripada

    Department of Psychiatry, University of Michigan, Ann Arbor, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9025-6453
  18. Ivy F Tso

    Department of Psychiatry, University of Michigan, Ann Arbor, United States
    Competing interests
    No competing interests declared.
  19. Elizabeth R Duval

    Department of Psychiatry, University of Michigan, Ann Arbor, United States
    Competing interests
    No competing interests declared.
  20. Soo-Eun Chang

    Department of Psychiatry, University of Michigan, Ann Arbor, United States
    Competing interests
    No competing interests declared.
  21. Brenda W. Pennix

    Amsterdam University Medical Center, Amsterdam, Netherlands
    Competing interests
    No competing interests declared.
  22. Mary M. Heitzeg

    Department of Psychiatry, University of Michigan, Ann Arbor, United States
    Competing interests
    No competing interests declared.
  23. S Alexandra Burt

    Department of Psychology, Michigan State University, East Lansing, United States
    Competing interests
    No competing interests declared.
  24. Luke Hyde

    Department of Psychology, University of Michigan, Ann Arbor, United States
    Competing interests
    No competing interests declared.
  25. David Amaral

    Department of Psychiatry and Behavioral Sciences, University of California, Davis, Davis, United States
    Competing interests
    No competing interests declared.
  26. Christine Wu Nordahl

    Department of Psychiatry and Behavioral Sciences, University of California, Davis, Davis, United States
    Competing interests
    No competing interests declared.
  27. Ole A Andreasssen

    Norwegian Center for Mental Disorders Research, University of Oslo, Oslo, Norway
    Competing interests
    Ole A Andreasssen, is a consultant for HealthLytix and received speaker's honorarium from Lundbeck and Sunovion..
  28. Lars T Westlye

    Norwegian Center for Mental Disorders Research, University of Oslo, Oslo, Norway
    Competing interests
    No competing interests declared.
  29. Roland Zahn

    Centre for Affective Disorders, King's College London, London, United Kingdom
    Competing interests
    No competing interests declared.
  30. Henricus G Ruhe

    Department of Psychiatry, Radboud University Medical Center, Nijmegen, Netherlands
    Competing interests
    Henricus G Ruhe, received speaker's honorarium from Lundbeck and Janssen..
  31. Christian Beckmann

    Donders Institute for Brain, Cognition, and Behavior, Radboud University Medical Center, Nijmegen, Netherlands
    Competing interests
    Christian Beckmann, is director and shareholder of SBGNeuro Ltd..
  32. Andre F Marquand

    Donders Institute for Brain, Cognition, and Behavior, Radboud University Medical Center, Nijmegen, Netherlands
    Competing interests
    No competing interests declared.

Funding

H2020 European Research Council (10100118)

  • Andre F Marquand

Medical Research Council (G0902304)

  • Roland Zahn

National Institute of Mental Health (K23MH108823)

  • Ivy F Tso

National Institute on Deafness and Other Communication Disorders (R01DC011277)

  • Soo-Eun Chang

National Institute of Mental Health (R01MH107741)

  • Chandra Sripada

Michigan Institute for Clinical and Health Research (UL1TR002240)

  • Elizabeth R Duval

National Institute of Mental Health (UG3MH114249)

  • S Alexandra Burt
  • Luke Hyde

Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD093334)

  • S Alexandra Burt
  • Luke Hyde

H2020 European Research Council (802998)

  • Lars T Westlye

Wellcome Trust (215698/Z/19/Z)

  • Andre F Marquand

Wellcome Trust (098369/Z/12/Z)

  • Christian Beckmann

Nederlandse Organisatie voor Wetenschappelijk Onderzoek (VIDI grant 016.156.415)

  • Andre F Marquand

National Institute of Mental Health (R01MH104438)

  • David Amaral
  • Christine Wu Nordahl

National Institute of Mental Health (R01MH103371)

  • David Amaral
  • Christine Wu Nordahl

Eunice Kennedy Shriver National Institute of Child Health and Human Development (P50 HD093079)

  • David Amaral
  • Christine Wu Nordahl

H2020 Marie Skłodowska-Curie Actions (895011)

  • Thomas Wolfers

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Human subjects: Ethical approval for the public data were provided by the relevant local research authorities for the studies contributing data. For full details see the main study publications given in the main text. For all clinical studies, approval was obtained via the local ethical review authorities, i.e.: TOP: Regional Committee for Medical & Health Research Ethics South East Norway. Approval number: 2009/2485- C, KCL: South Manchester NHS National Research Ethics Service. Approval number: 07/H1003/194. Delta: The local ethics committee of the Academic Medical Center of the University of Amsterdam (AMC-METC) Nr.:11/050, UMich_IMPS: University of Michigan Institution Review Board HUM00088188, UMich_SZG: University of Michigan Institution Review Board HUM00080457, UMich_MLS: University of Michigan Institution Review Board HUM00040642, UMich_CWS: MSU Biomedical and Health Institutional Review Board (BIIRB) IRB#09-810, UMich_MTWiNS: University of Michigan Institution Review HUM00163965, UCDavis: University of California Davis Institutional Review Board IRB ID: 220915, 592866, 1097084.​

Reviewing Editor

  1. Chris I Baker, National Institute of Mental Health, National Institutes of Health, United States

Publication history

  1. Preprint posted: August 8, 2021 (view preprint)
  2. Received: August 19, 2021
  3. Accepted: January 26, 2022
  4. Accepted Manuscript published: February 1, 2022 (version 1)
  5. Version of Record published: February 9, 2022 (version 2)

Copyright

© 2022, Rutherford et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 3,234
    Page views
  • 557
    Downloads
  • 2
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Saige Rutherford
  2. Charlotte Fraza
  3. Richard Dinga
  4. Seyed Mostafa Kia
  5. Thomas Wolfers
  6. Mariam Zabihi
  7. Pierre Berthet
  8. Amanda Worker
  9. Serena Verdi
  10. Derek Andrews
  11. Laura Han
  12. Johanna MM Bayer
  13. Paola Dazzan
  14. Phillip McGuire
  15. Roel T Mocking
  16. Aart Schene
  17. Chandra Sripada
  18. Ivy F Tso
  19. Elizabeth R Duval
  20. Soo-Eun Chang
  21. Brenda W. Pennix
  22. Mary M. Heitzeg
  23. S Alexandra Burt
  24. Luke Hyde
  25. David Amaral
  26. Christine Wu Nordahl
  27. Ole A Andreasssen
  28. Lars T Westlye
  29. Roland Zahn
  30. Henricus G Ruhe
  31. Christian Beckmann
  32. Andre F Marquand
(2022)
Charting brain growth and aging at high spatial precision
eLife 11:e72904.
https://doi.org/10.7554/eLife.72904

Further reading

    1. Neuroscience
    Anita Siller et al.
    Research Article

    In dopaminergic (DA) substantia nigra (SN) neurons Cav2.3 R-type Ca2+-currents contribute to somatodendritic Ca2+-oscillations. This activity may contribute to the selective degeneration of these neurons in Parkinson's disease (PD) since Cav2.3-knockout is neuroprotective in a PD mouse model. Here we show that in tsA-201-cells the membrane-anchored β2-splice variants β2a and β2e are required to stabilize Cav2.3 gating properties allowing sustained Cav2.3 availability during simulated pacemaking and enhanced Ca2+-currents during bursts. We confirmed the expression of β2a- and β2e-subunit transcripts in the mouse SN and in identified SN DA neurons. Patch-clamp recordings of mouse DA midbrain neurons in culture and SN DA neurons in brain slices revealed SNX-482-sensitive R-type Ca2+-currents with voltage-dependent gating properties that suggest modulation by β2a- and/or β2e-subunits. Thus, β-subunit alternative splicing may prevent a fraction of Cav2.3 channels from inactivation in continuously active, highly vulnerable SN DA neurons, thereby also supporting Ca2+ signals contributing to the (patho)physiological role of Cav2.3 channels in PD.

    1. Neuroscience
    Sunwoo Kwon et al.
    Research Article Updated

    The visual pathways that guide actions do not necessarily mediate conscious perception. Patients with primary visual cortex (V1) damage lose conscious perception but often retain unconscious abilities (e.g. blindsight). Here, we asked if saccade accuracy and post-saccadic following responses (PFRs) that automatically track target motion upon saccade landing are retained when conscious perception is lost. We contrasted these behaviors in the blind and intact fields of 11 chronic V1-stroke patients, and in 8 visually intact controls. Saccade accuracy was relatively normal in all cases. Stroke patients also had normal PFR in their intact fields, but no PFR in their blind fields. Thus, V1 damage did not spare the unconscious visual processing necessary for automatic, post-saccadic smooth eye movements. Importantly, visual training that recovered motion perception in the blind field did not restore the PFR, suggesting a clear dissociation between pathways mediating perceptual restoration and automatic actions in the V1-damaged visual system.