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Peer-reviewedCC BY-NCScience Advances

Insights into temporal and spatial dynamics of short association fiber formation in the human fetal brain

  • Bo Li1,2
  • Željka Krsnik3
  • Lana Pierotich1,2
  • Ivica Kostović3
  • Simon K. Warfield1,2
  • P. Ellen Grant2,4,5,6
  • Davood Karimi1,2
6 affiliations
  1. 1Computational Radiology Laboratory, Boston Children’s Hospital, Boston, MA, USA.
  2. 2Harvard Medical School, Boston, MA, USA.
  3. 3Croatian Institute for Brain Research, School of Medicine, University of Zagreb, Zagreb, Croatia.
  4. 4Fetal Neonatal Neuroimaging and Developmental Science Center, Boston Children’s Hospital, Boston, MA, USA.
  5. 5Division of Newborn Medicine, Boston Children’s Hospital, Boston, MA, USA.
  6. 6Division of Neuroradiology, Boston Children’s Hospital, Boston, MA, USA.
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Abstract

Short association fibers (SAFs) form the local scaffold of cortical connectivity and support early functional specialization. However, their development before birth remains largely unknown. Using fetal diffusion magnetic resonance imaging from the Developing Human Connectome Project and histology from the Zagreb Collection of human brains, we present an in utero reconstruction of SAF pathways in the human brain. We tracked their volumetric and microstructural developmental trajectories in 243 fetuses spanning a critical period of connectome formation. We found that SAFs emerge before sulcal folding, initially as flat, loosely arranged pathways along the subplate-white matter interface, and later reorganize into coherent U-shaped bundles. Their maturation followed a sensorimotor-to-association gradient, paralleling cortical development. Nonlinear, bundle-specific trajectories captured multiphasic maturation, with subplate dynamics preceding increases in axonal coherence and early myelination. These findings reveal how the brain's local wiring is established during prenatal development and provide insight into the origins of individual variability.

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Cite

BibTeXRIS
BibTeX
@article{li2026insights,
  title = {{Insights into temporal and spatial dynamics of short association fiber formation in the human fetal brain}},
  author = {Bo Li and Željka Krsnik and Lana Pierotich and Ivica Kostović and Simon K. Warfield and P. Ellen Grant and Davood Karimi},
  journal = {Science Advances},
  year = {2026},
  month = oct,
  doi = {10.1126/sciadv.aee7989},
  url = {https://www.science.org/doi/10.1126/sciadv.aee7989},
  note = {CC BY-NC},
}
RIS
TY  - JOUR
TI  - Insights into temporal and spatial dynamics of short association fiber formation in the human fetal brain
AU  - Bo Li
AU  - Željka Krsnik
AU  - Lana Pierotich
AU  - Ivica Kostović
AU  - Simon K. Warfield
AU  - P. Ellen Grant
AU  - Davood Karimi
PY  - 2026
DA  - 2026/10/09
JO  - Science Advances
DO  - 10.1126/sciadv.aee7989
UR  - https://www.science.org/doi/10.1126/sciadv.aee7989
AB  - Short association fibers (SAFs) form the local scaffold of cortical connectivity and support early functional specialization. However, their development before birth remains largely unknown. Using fetal diffusion magnetic resonance imaging from the Developing Human Connectome Project and histology from the Zagreb Collection of human brains, we present an in utero reconstruction of SAF pathways in the human brain. We tracked their volumetric and microstructural developmental trajectories in 243 fetuses spanning a critical period of connectome formation. We found that SAFs emerge before sulcal folding, initially as flat, loosely arranged pathways along the subplate-white matter interface, and later reorganize into coherent U-shaped bundles. Their maturation followed a sensorimotor-to-association gradient, paralleling cortical development. Nonlinear, bundle-specific trajectories captured multiphasic maturation, with subplate dynamics preceding increases in axonal coherence and early myelination. These findings reveal how the brain's local wiring is established during prenatal development and provide insight into the origins of individual variability.
SN  - 2375-2548
ER  -