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. 2026 Jan 23.
doi: 10.1038/s41467-026-68714-8. Online ahead of print.

Two axes of white matter development

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Free article

Two axes of white matter development

Audrey C Luo et al. Nat Commun. .
Free article

Abstract

Despite decades of neuroimaging research, how white matter develops along the length of major tracts in humans remains unknown. Here, we identify fundamental patterns of white matter maturation by examining developmental variation along major, long-range cortico-cortical tracts in youth ages 5-23 years using diffusion MRI from three large-scale, cross-sectional datasets (total N = 2716). Across datasets, we delineate two replicable axes of human white matter development. First, we find a deep-to-superficial axis, in which superficial tract regions near the cortical surface exhibit greater age-related change than deep tract regions. Second, we demonstrate that the development of superficial tract regions aligns with the cortical hierarchy defined by the sensorimotor-association axis, with tract ends adjacent to sensorimotor cortices maturing earlier than those adjacent to association cortices. These results reveal developmental variation along tracts that conventional tract-average analyses have previously obscured, challenging the implicit assumption that white matter tracts mature uniformly along their length. Such developmental variation along tracts may have functional implications, including mitigating ephaptic coupling in densely packed deep tract regions and tuning neural synchrony through hierarchical development in superficial tract regions - ultimately refining neural transmission in youth.

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Conflict of interest statement

Competing interests: R.T.S has received consulting income from Octave Bioscience and compensation for scientific reviewing from the American Medical Association. A.A.B. holds equity in Centile Biosciences. The remaining authors declare no competing interests.

Update of

  • Two Axes of White Matter Development.
    Luo AC, Meisler SL, Sydnor VJ, Alexander-Bloch A, Bagautdinova J, Barch DM, Bassett DS, Davatzikos C, Franco AR, Goldsmith J, Gur RE, Gur RC, Hu F, Jaskir M, Kiar G, Keller AS, Larsen B, Mackey AP, Milham MP, Roalf DR, Shafiei G, Shinohara RT, Somerville LH, Weinstein SM, Yeatman JD, Cieslak M, Rokem A, Satterthwaite TD. Luo AC, et al. bioRxiv [Preprint]. 2025 May 20:2025.03.19.644049. doi: 10.1101/2025.03.19.644049. bioRxiv. 2025. Update in: Nat Commun. 2026 Jan 23. doi: 10.1038/s41467-026-68714-8. PMID: 40166142 Free PMC article. Updated. Preprint.

References

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