Empirical validation of race-neutral normative brain morphometry models across ethnoracially diverse populations
Abstract
Normative models of brain morphometry quantify individual deviations from typical anatomical patterns and hold promise for enhancing clinical decision-making. However, their clinical utility depends critically on demonstrating generalizability across diverse ethnoracial populations. We previously developed sex-specific, race-neutral normative models for cortical thickness, surface area, and subcortical volumes using brain scans from a large international sample of healthy individuals, as part of the CentileBrain Project, a global initiative to provide open-access, neuroimaging reference models. The primary aim of the present study was to empirically evaluate the generalizability and accuracy of these pretrained models across multiple ethnoracial groups. To this end, we tested model performance in independent samples of healthy individuals from Africa, Asia, Europe, and the Americas, with ethnoracial classification defined either by self-identification or genetic ancestry (N = 4,862). We further compared performance against normative models developed exclusively from a single-population Chinese cohort. Across all groups, as well as in the pooled sample, the pretrained CentileBrain models demonstrated consistently high accuracy, with relative mean absolute error values below 10% for subcortical volume and surface area and below 5% for cortical thickness. Model performance was highly concordant across self-identified and ancestry-defined groups. In a separate analysis, the CentileBrain models performed comparably to a population-specific model when applied to an independent ancestry-matched sample. These findings provide empirical support for the generalizability of race-neutral normative models developed on large and diverse samples and underscore their potential utility for individualized neuroimaging assessment across ethnoracially diverse populations.
Article Details
Journal Info
Proceedings of the National Academy of Sciences
National Academy of Sciences
Authors (35)
Ruiyang Ge
Djavad Mowafaghian Centre for Brain Health, University of British Columbia
Yuetong Yu
Djavad Mowafaghian Centre for Brain Health, University of British Columbia
Faye New
Department of Psychiatry, Icahn School of Medicine
Shalaila S. Haas
Department of Psychiatry, Icahn School of Medicine
Nicole Sanford
Djavad Mowafaghian Centre for Brain Health, University of British Columbia
Kevin Yu
Djavad Mowafaghian Centre for Brain Health, University of British Columbia
Paul Allen
Institute of Psychiatry, Psychology and Neuroscience
Seda Arslan
Department of Psychology, Bilkent University
Mihai Avram
Translational Psychiatry, Department of Psychiatry and Psychotherapy, University of Lübeck
Stefan Borgwardt
Translational Psychiatry, Department of Psychiatry and Psychotherapy, University of Lübeck
Nicolas A. Crossley
Department of Psychiatry, School of Medicine, Pontificia Universidad Católica de Chile
Camilo de la Fuente-Sandoval
Laboratory of Experimental Psychiatry, Instituto Nacional de Neurología y Neurocirugía
Masaki Fukunaga
Section of Brain Function Information, National Institute for Physiological Sciences
Jia-Hong Gao
Changping Laboratory
Alfonso Gonzalez-Valderrama
School of Medicine, Universidad Finis Terrae
Ryota Hashimoto
Department of Pathology of Mental Diseases, National Institute of Mental Health, National Center of Neurology and Psychiatry
Felice Iasevoli
Department of Neuroscience, University School of Naples “Federico II”
Daniel Keeser
Department of Psychiatry and Psychotherapy, LMU University Hospital, LMU Munich
Kader Kubat
National Magnetic Resonance Research Center, Bilkent University
Veena Kumari
Centre for Cognitive and Clinical Neuroscience, Brunel University of London
Junya Matsumoto
Department of Pathology of Mental Diseases, National Institute of Mental Health, National Center of Neurology and Psychiatry
Urvakhsh M. Mehta
Department of Psychiatry, National Institute of Mental Health and Neurosciences
Kiyotaka Nemoto
Department of Medical Informatics and Management and Psychiatry, Institute of Medicine, University of Tsukuba
Giuseppe Pontillo
Department of Advanced Biomedical Sciences, University of Naples “Federico II”
Florian J. Raabe
Department of Psychiatry and Psychotherapy, LMU University Hospital, LMU Munich
Francisco Reyes-Madrigal
Laboratory of Experimental Psychiatry, Instituto Nacional de Neurología y Neurocirugía
Neelabja Roy
Department of Psychiatry, National Institute of Mental Health and Neurosciences
Didenur Şahin-Çevik
National Magnetic Resonance Research Center, Bilkent University
Tuba Sahin-Ilikoglu
National Magnetic Resonance Research Center, Bilkent University
Timothea Toulopoulou
Department of Psychiatry, Icahn School of Medicine
Elias Wagner
Department of Psychiatry, Psychotherapy, and Psychosomatics, Medical Faculty University of Augsburg
Guoyuan Yang
Advanced Research Institute of Multidisciplinary Sciences, School of Medical Technology, School of Life Science, Beijing Institute of Technology
Mariana Zurita
Institute of Psychiatry, Psychology and Neuroscience
Paul M. Thompson
Imaging Genetics Center, Mark & Mary Stevens Institute for Neuroimaging & Informatics, Keck School of Medicine, University of Southern California
Sophia Frangou
Djavad Mowafaghian Centre for Brain Health, University of British Columbia