Fixel-wise differences in White Matter Fiber-bundle Cross-section identified in Children who Stutter

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.

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.