Bogdanov, Sam; Kanakaraj, Praitayini; Kim, Michael E.; Samir, Jessica; Gao, Chenyu; Ramadass, Karthik; Rudravaram, Gaurav; Newlin, Nancy R.; Archer, Derek; Hohman, Timothy J.; Jefferson, Angela L.; Morgan, Victoria L.; Roche, Alexandra; Englot, Dario J.; Resnick, Susan M.; Beason Held, Lori L.; Cutting, Laurie E.; Barquero, Laura A.; D’Archangel, Micah A.; Nguyen, Tin Q.; Humphreys, Kathryn L.; Niu, Yanbin; Vinci-Booher, Sophia; Cascio, Carissa J.; O’Bryant, Sid E.; Yaffe, Kristine; Toga, Arthur; Rissman, Robert; Johnson, Leigh; Braskie, Meredith; King, Kevin; Hall, James R.; Petersen, Melissa; Palmer, Raymond; Barber, Robert; Shi, Yonggang; Zhang, Fan; Nandy, Rajesh; McColl, Roderick; Mason, David; Christian, Bradley; Phillips, Nicole; Large, Stephanie; Lee, Joe; Vardarajan, Badri; Mindt, Monica Rivera; Cheema, Amrita; Barnes, Lisa; Mapstone, Mark; Cohen, Annie; Kind, Amy; Okonkwo, Ozioma; Vintimilla, Raul; Zhou, Zhengyang; Donohue, Michael; Raman, Rema; Borzage, Matthew; Mielke, Michelle; Ances, Beau; Babulal, Ganesh; Llibre-Guerra, Jorge; Hill, Carl; Vig, Rocky; Li, Zhiyuan; Vandekar, Simon N.; Zhang, Panpan; Gore, John C.; Forkel, Stephanie J.; Landman, Bennett A.; Schilling, Kurt G. (2026).听.听Human Brain Mapping, 47(8), e70519.听
The two halves of the brain are not perfectly identical, and these differences in聽white matter鈥攖he bundles of nerve fibers that connect different brain regions鈥攁re thought to support specialized functions such as language and spatial reasoning. Although previous studies have examined white matter asymmetry, most have been limited by small sample sizes, narrow age ranges, or a focus on only a few brain pathways. In this study, the researchers analyzed brain imaging data from more than聽35,000 healthy individuals聽ranging in age from birth to 100 years, creating the most comprehensive maps to date of white matter asymmetry across the lifespan. They examined 30 major white matter pathways and measured multiple features related to both their microscopic tissue structure and overall anatomy. The results showed that asymmetry is present in every pathway studied, but its direction and degree vary depending on the specific pathway and the structural feature being measured. The patterns of asymmetry also changed throughout life, with distinct developmental changes in childhood and adolescence and a general trend toward greater asymmetry with advancing age, particularly in later adulthood. These findings provide a valuable reference for understanding how white matter develops and changes over the lifespan and may help researchers better identify brain changes associated with healthy aging and neurological disorders.
FIGURE 1
Overview of the study datasets, white matter features, and analytical framework. (A) Age distributions for each of the 50 contributing datasets (violin plots), illustrating broad coverage from 0 to 100鈥墆ears. Color encodes the number of participants per dataset (log scale). (B) Features extracted for each of the 30 bilateral pathways. Microstructural indices (e.g., Fractional Anisotropy, and Mean, Axial and Radial diffusivities; FA, MD, AD, and RD) summarize tissue organization and axonal/myelin density; macrostructural indices (e.g., tract volume and length) capture pathway size and geometry. Macrostructural cartoon reproduced under CC-BY from Yeh聽.听(C) Analysis pipeline. For each participant, white matter pathways were segmented, and features were extracted. A Lateralization Index (LI) was calculated for each tract-feature pair. These LIs were used as input for a normative modeling framework (GAMLSS) to generate age-specific population centile curves.