Fixel-wise Differences in White Matter Fiber-bundle Cross-section identified in Children who Stutter
Abstract
Developmental stuttering has been repeatedly linked to decreased white matter integrity and structural connectivity differences in major white matter tracts. Prior diffusion-weighted MRI studies reporting such white matter structural differences involved voxel-averaged tensor measures (e.g., fractional anisotropy (FA)). A well-acknowledged limitation of this approach, however, has been that it cannot resolve distinct fiber populations within crossing-fiber regions. Fixel-based analysis addresses this limitation by quantifying individual fiber populations within a voxel and providing complementary measures of fiber density (FD), fiber-bundle cross-section (FC), and their combined measure (FDC).
Here we applied Fixel-based analysis to diffusion MRI data from 171 children aged 3–13 years, including 84 children who stutter and 87 typically developing controls, to test whether white-matter differences associated with developmental stuttering were expressed as differences in FD, FC, and FDC and whether these measures show group-specific age-related patterns. We evaluated this at both the whole-brain level and within a priori white-matter tracts.
FC, but not FD or FDC, showed significant Group and Group × Age effects, indicating that white-matter differences were primarily expressed in fiber-bundle macrostructure. Tract-of-interest analyses identified developmental differences in bilateral arcuate fasciculus FC that remained significant across tracts, with controls showing greater age-related increases in FC than children who stutter. Additional FC differences were observed across corticospinal and thalamocortical pathways, although these tract-wise effects were less robust to across-tract correction.
These findings suggest that white-matter differences in developmental stuttering are prominently expressed in fiber-bundle macrostructure rather than fiber density and highlight divergent development of bilateral arcuate pathways. FBA provides fiber-specific information that complements conventional tensor-based diffusion measures and may improve characterization of white-matter development in childhood stuttering.
Significance Statement: Developmental stuttering has repeatedly been associated with white-matter differences, but conventional diffusion measures cannot readily distinguish changes in individual fiber populations within regions containing crossing fibers. Using Fixel-based analysis in children who stutter, we show that these differences are primarily expressed in fiber-bundle cross-section rather than fiber density, implicating macrostructural differences in white-matter organization. The strongest tract-wise developmental effects were observed bilaterally in the arcuate fasciculus, a major pathway supporting auditory-motor integration, where children who stutter showed divergent age-related trajectories relative to typically developing children. These findings provide a fiber-specific perspective on the neurodevelopmental basis of stuttering and refine the interpretation of white-matter differences previously identified using conventional diffusion imaging.
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BibTeX
@misc{weerathunge2026fixelwise,
title = {{Fixel-wise Differences in White Matter Fiber-bundle Cross-section identified in Children who Stutter}},
author = {Hasini Weerathunge and Yanni Liu and Fiona Höbler and Mike Angstadt and Andrew Jahn and Ho Ming Chow and Soo-Eun Chang},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.29.762844},
url = {https://www.biorxiv.org/content/10.64898/2026.10.29.762844v1},
note = {CC BY-NC},
}
RIS
TY - UNPB
TI - Fixel-wise Differences in White Matter Fiber-bundle Cross-section identified in Children who Stutter
AU - Hasini Weerathunge
AU - Yanni Liu
AU - Fiona Höbler
AU - Mike Angstadt
AU - Andrew Jahn
AU - Ho Ming Chow
AU - Soo-Eun Chang
PY - 2026
DA - 2026/10/29
PB - bioRxiv
DO - 10.64898/2026.10.29.762844
UR - https://www.biorxiv.org/content/10.64898/2026.10.29.762844v1
AB - Developmental stuttering has been repeatedly linked to decreased white matter integrity and structural connectivity differences in major white matter tracts. Prior diffusion-weighted MRI studies reporting such white matter structural differences involved voxel-averaged tensor measures (e.g., fractional anisotropy (FA)). A well-acknowledged limitation of this approach, however, has been that it cannot resolve distinct fiber populations within crossing-fiber regions. Fixel-based analysis addresses this limitation by quantifying individual fiber populations within a voxel and providing complementary measures of fiber density (FD), fiber-bundle cross-section (FC), and their combined measure (FDC). Here we applied Fixel-based analysis to diffusion MRI data from 171 children aged 3–13 years, including 84 children who stutter and 87 typically developing controls, to test whether white-matter differences associated with developmental stuttering were expressed as differences in FD, FC, and FDC and whether these measures show group-specific age-related patterns. We evaluated this at both the whole-brain level and within a priori white-matter tracts. FC, but not FD or FDC, showed significant Group and Group × Age effects, indicating that white-matter differences were primarily expressed in fiber-bundle macrostructure. Tract-of-interest analyses identified developmental differences in bilateral arcuate fasciculus FC that remained significant across tracts, with controls showing greater age-related increases in FC than children who stutter. Additional FC differences were observed across corticospinal and thalamocortical pathways, although these tract-wise effects were less robust to across-tract correction. These findings suggest that white-matter differences in developmental stuttering are prominently expressed in fiber-bundle macrostructure rather than fiber density and highlight divergent development of bilateral arcuate pathways. FBA provides fiber-specific information that complements conventional tensor-based diffusion measures and may improve characterization of white-matter development in childhood stuttering. Significance Statement: Developmental stuttering has repeatedly been associated with white-matter differences, but conventional diffusion measures cannot readily distinguish changes in individual fiber populations within regions containing crossing fibers. Using Fixel-based analysis in children who stutter, we show that these differences are primarily expressed in fiber-bundle cross-section rather than fiber density, implicating macrostructural differences in white-matter organization. The strongest tract-wise developmental effects were observed bilaterally in the arcuate fasciculus, a major pathway supporting auditory-motor integration, where children who stutter showed divergent age-related trajectories relative to typically developing children. These findings provide a fiber-specific perspective on the neurodevelopmental basis of stuttering and refine the interpretation of white-matter differences previously identified using conventional diffusion imaging.
SN - 2692-8205
ER -