Normative Modeling of Brain Morphometry Across the Lifespan Using CentileBrain: Algorithm Benchmarking and Model Optimization
Authors: Ge Ruiyang , Yu Yuetong , Qi Yi Xuan , Fan Yunan Vera , Chen Shiyu , Gao Chuntong , Haas Shalaila S , Modabbernia Amirhossein , New Faye , Agartz Ingrid , Asherson Philip , Ayesa-Arriola Rosa , Banaj Nerisa , Banaschewski Tobias , Baumeister Sarah , Bertolino Alessandro , Boomsma Dorret I , Borgwardt Stefan , Bourque Josiane , Brandeis Daniel , Breier Alan , Brodaty Henry , Brouwer Rachel M , Buckner Randy , Buitelaar Jan K , Cannon Dara M , Caseras Xavier , Cervenka Simon , Conrod Patricia J , Crespo-Facorro Benedicto , Crivello Fabrice , Crone Eveline A , de Haan Liewe , de Zubicaray Greig I , Di Giorgio Annabella , Erk Susanne , Fisher Simon E , Franke Barbara , Frodl Thomas , Glahn David C , Grotegerd Dominik , Gruber Oliver , Gruner Patricia , Gur Raquel E , Gur Ruben C , Harrison Ben J , Hatton Sean N , Hickie Ian , Howells Fleur M , Hulshoff Pol Hilleke E , Huyser Chaim , Jernigan Terry L , Jiang Jiyang , Joska John A , Kahn René S , Kalnin Andrew J , Kochan Nicole A , Koops Sanne , Kuntsi Jonna , Lagopoulos Jim , Lazaro Luisa , Lebedeva Irina S , Lochner Christine , Martin Nicholas G , Mazoyer Bernard , McDonald Brenna C , McDonald Colm , McMahon Katie L , Nakao Tomohiro , Nyberg Lars , Piras Fabrizio , Portella Maria J , Qiu Jiang , Roffman Joshua L , Sachdev Perminder S , Sanford Nicole , Satterthwaite Theodore D , Saykin Andrew J , Schumann Gunter , Sellgren Carl M , Sim Kang , Smoller Jordan W , Soares Jair , Sommer Iris E , Spalletta Gianfranco , Stein Dan J , Tamnes Christian K , Thomopolous Sophia I , Tomyshev Alexander S , Tordesillas-Gutiérrez Diana , Trollor Julian N , van ’t Ent Dennis , van den Heuvel Odile A , van Erp Theo GM , van Haren Neeltje EM , Vecchio Daniela , Veltman Dick J , Walter Henrik , Wang Yang , Weber Bernd , Wei Dongtao , Wen Wei , Westlye Lars T , Wierenga Lara M , Williams Steven CR , Wright Margaret J , Medland Sarah , Wu Mon-Ju , Yu Kevin , Jahanshad Neda , Thompson Paul M , Frangou Sophia 
Published: February 2023

We present an empirically benchmarked framework for sex-specific normative modeling of brain morphometry that can inform about the biological and behavioral significance of deviations from typical age-related neuroanatomical changes and support future study designs. This framework was developed using regional morphometric data from 37,407 healthy individuals (53% female; aged 3–90 years) following a comparative evaluation of eight algorithms and multiple covariate combinations pertaining to image acquisition and quality, parcellation software versions, global neuroimaging measures, and longitudinal stability. The Multivariate Factorial Polynomial Regression (MFPR) emerged as the preferred algorithm optimized using nonlinear polynomials for age and linear effects of global measures as covariates. The MFPR models showed excellent accuracy across the lifespan and within distinct age-bins, and longitudinal stability over a 2-year period. The performance of all MFPR models plateaued at sample sizes exceeding 3,000 study participants. The model and scripts described here are freely available through CentileBrain (https://centilebrain.org/).