Two axes of white matter development
- PMID: 41578121
- DOI: 10.1038/s41467-026-68714-8
Two axes of white matter development
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.
© 2026. The Author(s).
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
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Two Axes of White Matter Development.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
-
- Knickmeyer, R. C. et al. A structural MRI study of human brain development from birth to 2 years. J. Neurosci. 28, 12176–12182 (2008).
-
- Lebel, C. & Beaulieu, C. Longitudinal development of human brain wiring continues from childhood into adulthood. J. Neurosci. 31, 10937–10947 (2011).
-
- Sydnor, V. J. et al. Neurodevelopment of the association cortices: patterns, mechanisms, and implications for psychopathology. Neuron 109, 2820–2846 (2021).
-
- Luo, A. C. et al. Functional connectivity development along the sensorimotor-association axis enhances the cortical hierarchy. Nat. Commun. 15, 3511 (2024).
-
- Sydnor, V. J. et al. Intrinsic activity development unfolds along a sensorimotor–association cortical axis in youth. Nat. Neurosci. 1–12 https://doi.org/10.1038/s41593-023-01282-y. (2023).
Grants and funding
- R01MH120482/U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH)
- R01MH112847/U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH)
- RF1MH116920/U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH)
- R01MH113550/U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH)
- R37MH125829/U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH)
- 5T32MH019112/U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH)
- T32MH018951/U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH)
- T32MH016804/U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH)
- R01MH132934/U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH)
- R01MH133843/U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH)
- F31MH136685/U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH)
- U01MH109589/U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH)
- R01MH119219/U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH)
- R01MH119219/U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH)
- 5T32MH019112/U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH)
- 1L30MH131061-01/U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH)
- R00MH127293/U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH)
- R01MH120482/U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH)
- R01MH120174/U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH)
- R01MH123550/U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH)
- R01MH123563/U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH)
- R01MH112847/U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH)
- U01MH109589/U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH)
- RF1MH121867/U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH)
- RF1MH126699/U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH)
- RF1MH121868/U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH)
- R01EB022573/U.S. Department of Health & Human Services | NIH | National Institute of Biomedical Imaging and Bioengineering (NIBIB)
- R01EB027585/U.S. Department of Health & Human Services | NIH | National Institute of Biomedical Imaging and Bioengineering (NIBIB)
- U24NS130411/U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS)
- R01NS060910/U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS)
- T32GM007170/U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS)
- 1934292/National Science Foundation (NSF)
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