{
  "abstract": "Normative models of brain metrics based on large populations could be extremely valuable for detecting brain abnormalities in patients with a variety of disorders, including degenerative, psychiatric and neurodevelopmental conditions, but no such models exist for the brain's white matter (WM) microstructure. Here we present the first large-scale normative model of brain WM microstructure - based on 19 international diffusion MRI datasets covering almost the entire lifespan (totaling N=54,583 individuals; age: 4-91 years). We extracted regional diffusion tensor imaging (DTI) metrics using a standardized analysis and quality control protocol and used hierarchical Bayesian regression (HBR) to model the statistical distribution of derived WM metrics as a function of age and sex. We extracted the average lifespan trajectories and corresponding centile curves for each WM region. We illustrate the utility of the method by applying it to detect and visualize profiles of WM microstructural deviations in a variety of contexts: in mild cognitive impairment, Alzheimer's disease, and 22q11.2 deletion syndrome - a neurogenetic condition that markedly increases risk for schizophrenia. The resulting large-scale model provides a common reference to identify disease effects on the brain's microstructure in individuals or groups, and to compare disorders, and discover factors affecting WM abnormalities. The derived normative models are a new resource publicly available to the community, adaptable and extendable to future datasets as the available data expands.",
  "abstract_shown": true,
  "affiliations": [
    "Imaging Genetics Center, Mark & Mary Stevens Institute for Neuroimaging & Informatics, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. julio.villalon@ini.usc.edu",
    "Laboratory of Brain eScience, Mark & Mary Stevens Institute for Neuroimaging & Informatics, Keck School of Medicine, University of Southern California, Los Angeles, USA",
    "Imaging Genetics Center, Mark & Mary Stevens Institute for Neuroimaging & Informatics, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA",
    "Centre de recherche Azrieli, CHU Sainte-Justine, Department of Psychiatry and Addictology, University of Montreal, Montreal, QC, Canada",
    "Semel Institute for Neuroscience and Human Behavior, Departments of Psychiatry and Biobehavioral Sciences and Psychology, University of California, Los Angeles, CA, USA",
    "Multimodal Brain Image Analysis Laboratory, Department of Psychiatry, National Institute of Mental Health and Neuro Sciences, Bengaluru, India",
    "Center of Cognitive Science and Artificial Intelligence, Tilburg School of Humanities and Digital Sciences, Tilburg University, Tilburg, The Netherlands",
    "Donders Centre for Cognitive Neuroimaging, Donders Institute for Brain, Cognition and Behaviour. Radboud University, Nijmegen, The Netherlands",
    "Imaging Genetics Center, Mark & Mary Stevens Institute for Neuroimaging & Informatics, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. pthomp@usc.edu"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 20,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Julio E. Villalón‐Reina",
      "orcid": "0009-0005-9039-4924"
    },
    {
      "affs": [
        1
      ],
      "name": "Alyssa H. Zhu",
      "orcid": "0000-0003-0083-5107"
    },
    {
      "affs": [
        2
      ],
      "name": "Leila Nabulsi",
      "orcid": "0000-0001-9448-7769"
    },
    {
      "affs": [
        2
      ],
      "name": "Sophia I. Thomopoulos",
      "orcid": "0000-0002-0046-4070"
    },
    {
      "affs": [
        3
      ],
      "name": "Clara A. Moreau",
      "orcid": "0000-0001-6217-731X"
    },
    {
      "affs": [
        2
      ],
      "name": "Yixue Feng",
      "orcid": "0000-0003-1015-4209"
    },
    {
      "affs": [
        2
      ],
      "name": "Tamoghna Chattopadhyay",
      "orcid": "0000-0002-3146-6845"
    },
    {
      "affs": [
        2
      ],
      "name": "Sebastian M. Benavidez"
    },
    {
      "affs": [
        4
      ],
      "name": "Leila Kushan",
      "orcid": "0000-0002-2650-7147"
    },
    {
      "affs": [
        5
      ],
      "name": "John P. John",
      "orcid": "0000-0001-6756-0297"
    },
    {
      "affs": [
        5
      ],
      "name": "Himanshu Joshi",
      "orcid": "0000-0003-2624-7821"
    },
    {
      "affs": [
        1
      ],
      "name": "Iyad Ba Gari",
      "orcid": "0000-0003-1443-8786"
    },
    {
      "affs": [
        2
      ],
      "name": "Katherine E. Lawrence",
      "orcid": "0000-0002-0156-353X"
    },
    {
      "affs": [
        1
      ],
      "name": "Talia M. Nir",
      "orcid": "0000-0002-7106-7443"
    },
    {
      "affs": [
        1
      ],
      "name": "Neda Jahanshad",
      "orcid": "0000-0003-4401-8950"
    },
    {
      "affs": [
        4
      ],
      "name": "Carrie E. Bearden",
      "orcid": "0000-0002-8516-923X"
    },
    {
      "affs": [
        6,
        7
      ],
      "name": "Seyed Mostafa Kia",
      "orcid": "0000-0002-7128-814X"
    },
    {
      "affs": [
        7
      ],
      "name": "André F. Marquand",
      "orcid": "0000-0001-5903-203X"
    },
    {
      "name": "the Frontotemporal Lobar Degeneration Neuroimaging Initiative"
    },
    {
      "affs": [
        8
      ],
      "name": "Paul M. Thompson",
      "orcid": "0000-0002-4720-8867"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/1d1m5r0gjvdem.bib",
  "cited_by": 15,
  "doi": "10.1038/s41467-026-72875-x",
  "fulltext_url": null,
  "id": "1d1m5r0gjvdem",
  "issns": [
    "2041-1723"
  ],
  "landing_url": "https://doi.org/10.1038/s41467-026-72875-x",
  "language": "en",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2741|Advanced Neuroimaging Techniques and Applications"
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  "pdf_url": "https://www.nature.com/articles/s41467-026-72875-x.pdf",
  "pmcid": "PMC12621655",
  "pmid": "41256711",
  "published": "2026-05-27",
  "publisher": "Nature Portfolio",
  "ris": "https://research.draconitic.com/paper/1d1m5r0gjvdem.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T13:26:56Z",
      "native_id": "W7162560706",
      "source": "openalex",
      "url": "https://doi.org/10.1038/s41467-026-72875-x"
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  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2741|Advanced Neuroimaging Techniques and Applications",
      "subfield": "imaging"
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  ],
  "title": "Lifespan normative modeling of brain microstructure",
  "title_text": "Lifespan normative modeling of brain microstructure",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T13:21:16Z",
  "url": "https://research.draconitic.com/paper/1d1m5r0gjvdem",
  "venue": "Nature Communications",
  "versions": []
}