Evidence of left inferior frontal-premotor structural and functional connectivity deficits in adults who stutter

Abstract

The neurophysiological basis for stuttering may involve deficits that affect dynamic interactions among neural structures supporting fluid speech processing. Here, we examined functional and structural connectivity within corticocortical and thalamocortical loops in adults who stutter. For functional connectivity, we placed seeds in the left and right inferior frontal Brodmann area 44 (BA44) and in the ventral lateral nucleus (VLN) of the thalamus. Subject-specific seeds were based on peak activation voxels captured during speech and nonspeech tasks using functional magnetic resonance imaging. Psychophysiological interaction (PPI) was used to find brain regions with heightened functional connectivity with these cortical and subcortical seeds during speech and nonspeech tasks. Probabilistic tractography was used to track white matter tracts in each hemisphere using the same seeds. Both PPI and tractrography supported connectivity deficits between the left BA44 and the left premotor regions, while connectivity among homologous right hemisphere structures was significantly increased in the stuttering group. No functional connectivity differences between BA44 and auditory regions were found between groups. The functional connectivity results derived from the VLN seeds were less definitive and were not supported by the tractography results. Our data provide strongest support for deficient left hemisphere inferior frontal to premotor connectivity as a neural correlate of stuttering.

Figure 1.

Functional connections of the left BA44 shown with PPI analysis. (A) Conjunction map showing regions that significantly increased functional connectivity (PPI) with left BA44 in normally fluent controls during speech (red), nonspeech (blue), and for both speech and nonspeech (yellow). (B) Conjunction map showing regions that significantly increased functional connectivity with the left BA44 in stuttering speakers during speech (red), nonspeech (blue), and both speech and nonspeech (yellow). (C) Contrast of PPI results between stuttering and control groups during speech production. Warmer color blobs show regions, where the control group exhibited higher functional connectivity than the stuttering group and the blue blobs show, where stuttering speakers had more functional connectivity than the control group (P < 0.01, corrected).

Figure 2.

Probabilistic tractography results are shown for tracts generated using the left BA44 seed (upper row) and right BA44 seed (lower row). The color bar shows the relationship between colors of the tracts and the extent of agreement among subjects in each cohort. The majority of control participants exhibited robust tracts in the left hemisphere corresponding to the SLF. There was more variability in the tracts, and only a minority of stuttering speakers had robust tracts that reached the inferior parietal regions. The results from the right BA44 were similar for the 2 groups.

Figure 3.

ROI analysis showing significantly increased tract density in the left SLF in control relative to stuttering group. Error bars depict the standard error. Tract density was quantitatively measured by taking the number of voxels that passed through the premotor (BA6) and precentral gyrus (4p) ROIs within each tract for each participant and comparing the groups using repeated measures ANOVA (see Materials and Methods). Here, the results from both the left BA6 and the left 4p significantly differed between the groups.

Figure 4.

ROI analysis of tracts generated using bilateral pSTG seeds. Error bars depict the standard error. Tract density was quantitatively measured by taking the number of voxels that passed through the inferior frontal (BA44) and precentral gyrus (4p) ROIs within each tract for each participant and comparing the groups using repeated measures ANOVA (see Materials and Methods). Here, the results from the left BA44 significantly differed between the groups.

Figure 5.

Functional connections of the right BA44 shown with PPI analysis. (A) Conjunction map showing regions with significantly increased functional connectivity (PPI) with the right BA44 in normally fluent controls during speech (red), nonspeech (blue), and common regions for speech and nonspeech (yellow). (B) Conjunction map showing regions with significantly increased functional connectivity in stuttering speakers during speech (red), nonspeech (blue), and common regions for speech and nonspeech (yellow). (C) Contrast of PPI between stuttering and control groups during speech production. Warmer color blobs show regions, where the control group exhibited higher functional connectivity than stuttering group and the blue blobs show, where stuttering speakers had more functional connectivity than the control group (P < 0.01, corrected).

Figure 6.

Functional connections of the LVLN region shown with PPI analysis. Warmer color blobs show regions showing positive functional connectivity, whereas the blue blobs show regions with negative functional connectivity with the seed region. (A) PPI results for speech production. (B) PPI results for nonspeech production.

Figure 7.

Functional connections of the RVLN region shown with PPI analysis. Warmer color blobs show regions showing positive functional connectivity, whereas the blue blobs show regions with negative functional connectivity with the seed region. (A) PPI results for speech production. (B) PPI results for nonspeech production.