ArticlebioRxiv : the preprint server for biology2026
Analytic Bounds on GAMLSS Model Variability of Normative White Matter Brain Charts.
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Article in bioRxiv : the preprint server for biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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39 authors.
Michael E KimVanderbilt University, Department of Computer Science, Nashville, TN, USA.ORCID 0009-0006-3562-2688
Gaurav RudravaramVanderbilt University, Department of Electrical and Computer Engineering, Nashville, TN, USA.
Adam SaundersVanderbilt University, Department of Electrical and Computer Engineering, Nashville, TN, USA.
Chenyu GaoVanderbilt University, Department of Electrical and Computer Engineering, Nashville, TN, USA.ORCID 0000-0003-2098-3035
Karthik RamadassVanderbilt University, Department of Electrical and Computer Engineering, Nashville, TN, USA.
Nancy R NewlinVanderbilt University, Department of Computer Science, Nashville, TN, USA.
Praitayini KanakarajVanderbilt University, Department of Computer Science, Nashville, TN, USA.
Sam BogdanovVanderbilt University, Medical Scientist Training Program, Nashville, TN, USA.
Derek ArcherVanderbilt University Medical Center, Vanderbilt Memory and Alzheimer's Center, Nashville, TN, USA.
Timothy J HohmanVanderbilt University Medical Center, Vanderbilt Memory and Alzheimer's Center, Nashville, TN, USA.ORCID 0000-0002-3377-7014
Angela L JeffersonVanderbilt University Medical Center, Department of Neurology, Nashville, TN, USA.
Victoria L MorganVanderbilt University Medical Center, Department of Radiology and Radiological Sciences, Nashville, TN, USA.
Alexandra RocheVanderbilt University Institute of Imaging Science, Nashville, TN, USA.
Dario J EnglotVanderbilt University Medical Center, Department of Neurological Surgery, Nashville, TN, USA.
Susan M ResnickLaboratory of Behavioral Neuroscience, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.
Lori L Beason HeldLaboratory of Behavioral Neuroscience, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.ORCID 0000-0001-9057-6270
Murat BilgelLaboratory of Behavioral Neuroscience, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.
Laurie E CuttingPeabody College of Education and Human Development, Department of Special Education, Nashville, Tennessee, USA.
Laura A BarqueroPeabody College of Education and Human Development, Department of Special Education, Nashville, Tennessee, USA.
Micah A D'ArchangelPeabody College of Education and Human Development, Department of Special Education, Nashville, Tennessee, USA.
Tin Q NguyenPeabody College of Education and Human Development, Department of Special Education, Nashville, Tennessee, USA.
Kathryn L HumphreysVanderbilt University, Department of Psychology and Human Development, Nashville, TN, USA.
Yanbin NiuVanderbilt University, Department of Psychology and Human Development, Nashville, TN, USA.
Sophia Vinci-BooherVanderbilt University, Department of Psychology and Human Development, Nashville, TN, USA.ORCID 0000-0002-3626-146X
Carissa J CascioUniversity of Kansas, Life Span Institute and Department of Psychology, Lawrence, KS, USA.
Kimberly R PechmanVanderbilt University Medical Center, Vanderbilt Memory and Alzheimer's Center, Nashville, TN, USA.
Niranjana ShashikumarVanderbilt University Medical Center, Vanderbilt Memory and Alzheimer's Center, Nashville, TN, USA.
HABS-HD Study Team
Alzheimer’s Disease Neuroimaging Initiative
BIOCARD Study Team
Zhiyuan LiPark University, Department of Computer Science, Parkville, MO, USA.
Simon N VandekarVanderbilt University Medical Center, Department of Biostatistics, Nashville, TN, USA.
Panpan ZhangVanderbilt University Medical Center, Department of Biostatistics, Nashville, TN, USA.
John C GoreVanderbilt University Medical Center, Department of Radiology and Radiological Sciences, Nashville, TN, USA.
Yihao LiuVanderbilt University, Department of Electrical and Computer Engineering, Nashville, TN, USA.
Lianrui ZuoVanderbilt University, Department of Electrical and Computer Engineering, Nashville, TN, USA.
Kurt G SchillingVanderbilt University Medical Center, Department of Radiology and Radiological Sciences, Nashville, TN, USA.ORCID 0000-0003-3686-7645
Daniel C MoyerVanderbilt University, Department of Computer Science, Nashville, TN, USA.
Bennett A LandmanVanderbilt University, Department of Computer Science, Nashville, TN, USA.
Funding
The Health & Aging Brain Study - Health Disparities (HABS-HD)U19AG078109 · NIA · UNIVERSITY OF NORTH TEXAS HLTH SCI CTR · PI Sid E O'Bryant · 2022 to 2026
$181.1MVanderbilt Institute for Clinical and Translational Research (VICTR) -Identifying correlates of functional immunity in SARS-CoV-2 convalescent plasmaUL1TR002243 · NCATS · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Paul A. Harris, Wesley H Self · 2017 to 2026
$130.7MAlzheimer's Disease Neuroimaging Initiative - SupplementU01AG024904 · NIA · NORTHERN CALIFORNIA INSTITUTE RES &EDUC · PI WEINER, MICHAEL W · 2004 to 2015
$121.0MTechnology and Remote Assessment CoreU19AG063911 · NIA · MAYO CLINIC ROCHESTER · PI Bradley F Boeve · 2019 to 2026
$120.9MEarly Onset AD Consortium - the LEAD Study (LEADS)U01AG057195 · NIA · INDIANA UNIVERSITY INDIANAPOLIS · PI APOSTOLOVA, LIANA G, CARRILLO, MARIA C · 2018 to 2023
$70.3MSmartphone-Based "Burst" Cognitive AssessmentsP01AG003991 · NIA · WASHINGTON UNIVERSITY · PI Suzanne Elizabeth Schindler · 1985 to 2026
$69.5MThe Clinical Significance of Incidental White Matter Lesions on MRI Amongst a Diverse Population with Cognitive Complaints (INDEED)U19NS120384 · NINDS · UNIVERSITY OF CALIFORNIA AT DAVIS · PI DAVID K JOHNSON · 2020 to 2026
$61.9MTHERAPEUTIC EFFECTS OF INTRA-NASAL INSULIN DETEMIRP50AG005136 · NIA · UNIVERSITY OF WASHINGTON · PI GRABOWSKI, THOMAS J. · 1985 to 2019
$57.2MCellular and molecular mechanisms governing cortical surface area overgrowth in iPSC-derived neural cells from longitudinally characterized individuals with autismR01HD055741 · NICHD · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Joseph Piven · 2007 to 2026
$52.6MThe natural history of AB accumulation in preclinical ADP01AG026276 · NIA · WASHINGTON UNIVERSITY · PI MORRIS, JOHN · 2005 to 2025
$49.5MSUPPLEMENT TO RUSH ALZHEIMERS DISEASE CENTER COREP30AG010161 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI LEURGANS, SUE E. · 1991 to 2020
$49.1MSatellite Diagnostic and Treatment Clinic CoreP50AG008702 · NIA · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI DE JAGER, PHILIP L · 1989 to 2019
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Abstract
Brain charts, or normative models of quantitative neuroimaging measures, can identify trajectories of brain development and abnormalities in groups and individuals by leveraging large populations. Recent work has extended these brain charts to model microstructural and macrostructural features of white matter. Assessments of variance for these brain charts are necessary to determine whether the models being used for these data are stable. We implement an analytic approach to characterize variability of the parameters in previously released brain charts created using the generalized additive models for location, scale, and shape (GAMLSS) framework. Additionally, we empirically validate the accuracy of each analytic model through a comparison to a bootstrapping approach from 0.2 to 90 years of age. We find that across all models, the analytic coefficient of variation (COV) remains below 5% for ages greater than 0.25 years, with the maximum empirical observed COV reaching 7% at 0.2 years of age. Further, the empirical assessment shows high agreement with the analytic assessment, with COV estimates averaged across the lifespan for all models having a Pearson correlation coefficient of 0.776 and a mean difference of 4 × 10
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model variabilitynormative modelingwhite matter
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