Charting brain growth and aging at high spatial precision
- Radboud University Medical Center, Netherlands
- University of Oslo, Norway
- King's College London, United Kingdom
- University College London, United Kingdom
- University of California, Davis, United States
- Amsterdam University Medical Center, Netherlands
- University of Melbourne, Australia
- University of Michigan, United States
- 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).
-
ABIDEhttp://fcon_1000.projects.nitrc.org/indi/abide/.
-
ADHD200https://fcon_1000.projects.nitrc.org/indi/adhd200/.
-
CAMCANhttps://camcan-archive.mrc-cbu.cam.ac.uk/dataaccess/.
-
CMI-HBNhttp://fcon_1000.projects.nitrc.org/indi/cmi_healthy_brain_network/About.html.
-
HCP-Aginghttps://nda.nih.gov/general-query.html?q=query=featured-datasets:HCP%20Aging%20and%20Development.
-
HCP-Developmenthttps://nda.nih.gov/general-query.html?q=query=featured-datasets:HCP%20Aging%20and%20Development.
-
HCP-Early Psychosishttps://nda.nih.gov/general-query.html?q=query=featured-datasets:Connectomes%20Related%20to%20Human%20Disease.
-
NKI-RShttp://fcon_1000.projects.nitrc.org/indi/enhanced/access.html.
-
Oasishttps://direct.mit.edu/jocn/article/19/9/1498/4427/Open-Access-Series-of-Imaging-Studies-OASIS-Cross.
-
Philadelphia Neurodevelopmental Cohorthttps://www.med.upenn.edu/bbl/philadelphianeurodevelopmentalcohort.html.
Article and author information
Author details
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
- Chris I Baker, National Institute of Mental Health, National Institutes of Health, United States
Publication history
- Preprint posted: August 8, 2021 (view preprint)
- Received: August 19, 2021
- Accepted: January 26, 2022
- Accepted Manuscript published: February 1, 2022 (version 1)
- 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)
Charting brain growth and aging at high spatial precision
eLife 11:e72904.
https://doi.org/10.7554/eLife.72904
Further reading
-
- Neuroscience
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.
-
- Neuroscience
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.
