A study of the reproducibility and etiology of diffusion anisotropy differences in developmental stuttering: a potential role for impaired myelination

Abstract

Several diffusion tensor imaging (DTI) studies have reported fractional anisotropy (FA) reductions within the left perisylvian white matter (WM) of persistent developmental stutterers (PSs). However, these studies have not reached the same conclusions in regard to the presence, spatial distribution (focal/diffuse), and directionality (elevated/reduced) of FA differences outside of the left perisylvian region. In addition, supplemental DTI measures (axial and radial diffusivities, diffusion trace) have yet to be utilized to examine the potential etiology of these FA reductions. Therefore, the present study sought to reexamine earlier findings through a sex- and age-controlled replication analysis and then to extend these findings with the aforementioned non-FA measures. The replication analysis showed that robust FA reductions in PSs were largely focal, left hemispheric, and within late-myelinating associative and commissural fibers (division III of the left superior longitudinal fasciculus, callosal body, forceps minor of the corpus callosum). Additional DTI measures revealed that these FA reductions were attributable to an increase in diffusion perpendicular to the affected fiber tracts (elevated radial diffusivity). These findings suggest a hypothesis that will be testable in future studies: that myelogenesis may be abnormal in PSs within left-hemispheric fiber tracts that begin a prolonged course of myelination in the first postnatal year.

Figure 1

Axial (rows 1 and 2), coronal (row 3), and sagittal (row 4) views of fiber tracts where fractional anisotropy (FA) was significantly reduced in PSs relative to normally fluent speakers NSs. The axial images are displayed in neurological format (the left of the brain is on left-hand side) using the Montreal Neurological Institute (MNI) coordinate system. The affected regions are displayed using both a red-to-yellow overlay (corrected, one-tailed results) and blue-to-white overlay (corrected, two-tailed results). For clarity, these affected regions have been “thickened” for display purposes using the using tools in the FMRIB software library (FSL). Axial slices are separated by 5 mm, coronal slices by 3 mm, and sagittal slices by 11 mm.

Figure 2

Significant FA reductions in PSs as compared to NSs across four studies of developmental stuttering. The significant results of the present study are overlain as thickened voxels (see Figure 1 and caption). For the remaining three studies, the peak coordinates reported per study were used to generate spherical regions-of-interest and are color-coded with a legend at the bottom of the figure.