Functional neural circuits that underlie developmental stuttering

Jianping Qiao,Zhishun Wang,Yuankai Huo,Bradley S Peterson,Guihu Zhao,Carl L Herder,Chamonix O Sikora,J Bruce Morton

doi:10.1371/journal.pone.0179255

Abstract

The aim of this study was to identify differences in functional and effective brain connectivity between persons who stutter (PWS) and typically developing (TD) fluent speakers, and to assess whether those differences can serve as biomarkers to distinguish PWS from TD controls. We acquired resting-state functional magnetic resonance imaging data in 44 PWS and 50 TD controls. We then used Independent Component Analysis (ICA) together with Hierarchical Partner Matching (HPM) to identify networks of robust, functionally connected brain regions that were highly reproducible across participants, and we assessed whether connectivity differed significantly across diagnostic groups. We then used Granger Causality (GC) to study the causal interactions (effective connectivity) between the regions that ICA and HPM identified. Finally, we used a kernel support vector machine to assess how well these measures of functional connectivity and granger causality discriminate PWS from TD controls. Functional connectivity was stronger in PWS compared with TD controls in the supplementary motor area (SMA) and primary motor cortices, but weaker in inferior frontal cortex (IFG, Broca’s area), caudate, putamen, and thalamus. Additionally, causal influences were significantly weaker in PWS from the IFG to SMA, and from the basal ganglia to IFG through the thalamus, compared to TD controls. ICA and GC indices together yielded an accuracy of 92.7% in classifying PWS from TD controls. Our findings suggest the presence of dysfunctional circuits that support speech planning and timing cues for the initiation and execution of motor sequences in PWS. Our high accuracy of classification further suggests that these aberrant brain features may serve as robust biomarkers for PWS.

Highlights

Developmental stuttering is a speech disorder in which sounds, syllables, or words are repeated or prolonged, disrupting the normal flow of speech [1–2]
We performed a one-sample t-test on each of the 10 clusters to generate independent components (ICs) maps that represented statistically significant functional connectivity in this dataset (Fig 1). These maps yielded 12 ICs located in primary motor cortex (PMC), supplementary motor cortex (SMA), inferior frontal gyrus (IFG), primary somatosensory cortex (PSC), caudate, putamen, thalamus, anterior cingulate cortex (ACC), superior temporal gyrus (STG), inferior parietal lobule (IPL), Heschl’s gyrus, and posterior cingulate cortex (PCC)
Functional connectivity was significantly stronger in people who stutter (PWS) in the left supplementary motor area (SMA) and primary motor cortex (PMC) (Fig 2)

Summary

Introduction

Developmental stuttering is a speech disorder in which sounds, syllables, or words are repeated or prolonged, disrupting the normal flow of speech [1–2] These speech disruptions may be accompanied by behaviors representing effortful motor control, such as rapid eye blinking or lip tremor. Voxel-based morphometry studies using anatomical Magnetic Resonance Imaging (MRI) have reported atypical leftward asymmetry [8, 12–13] and increased white matter volumes in the superior temporal gyrus (STG), middle temporal gyrus (MTG), inferior frontal gyrus (IFG), middle frontal gyrus (MFG) and corpus callosum [14–16] of adults who stutter compared with controls. Diffusion Tensor Imaging (DTI) has shown that children who stutter have reduced fractional anisotropy in the region of the left superior longitudinal fasciculus and bilateral corticospinal tracts [18, 20]. Our recent spectroscopy study in the same participants of the present study reported reduced levels of N-acetyl aspartate (NAA), an index of neural density, in inferior and superior frontal cortices (including Broca’s region) and caudate nucleus, and increased NAA in the posterior cingulate, lateral parietal, and parahippocampal cortices, as well as the hippocampus and amygdala [5]

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