Neural systems of stuttering

Abstract

Persistent developmental stuttering is a neurobiologically based speech disorder. Although previous neuroimaging studies have demonstrated functional and structural abnormalities in multiple cortical and subcortical regions supporting speech processing in people who stutter (PWS), how these neural abnormalities lead to stuttering remains unclear. Intrinsically, speech is a serial order action that involves sequencing a set of individual sound units into large expressions, leading us to postulate that stuttering would be associated with the problem in sequence processing. This hypothesis has been corroborated by empirical evidence from behavioral studies demonstrating the impairment in sequence processing during speech and motor execution in PWS. However, the neuroanatomical mechanisms underlying sequence processing deficit in PWS remain unknown. Combining functional and structural magnetic resonance imaging (MRI), the present research examined the neural mechanisms of sequence processing in PWS (N=19) and fluent speakers (N=19). In Study 1, using a syllable repetition task, we examined activation and functional connectivity associated with sequence processing in speech production. Results showed that, compared with controls, PWS exhibited higher activation in the bilateral IFG and right insula. Functional connectivity analysis showed that sequence processing yielded weaker functional connectivity between the left cerebellum and right MFG and between the right cerebellum and left insula, but stronger connectivity between the left IPL and left IFG and between the left insula and left SFG in PWS than in controls. These findings suggested that PWS have abnormal neural responses to sequence processing during speech production. In Study 2, using a syllable sequence judgment task, we investigated the neural correlates of sequence processing in phonological working memory. PWS and controls did not differ in activation and functional connectivity, implying that PWS have an intact ability in temporary storage of syllable sequence, or alternatively, the sequence processing deficit is speech production-dependent in PWS. In Study 3, using resting-state fMRI, we examined the intrinsic functional connectivity in neural networks supporting sequence processing in speech production identified by Study 1. Results showed that PWS and controls differed in resting state functional connectivity (RSFC) within the auditory-motor circuits, cerebellar-cortical circuits and basal-ganglia-thalamocortical circuits. The significant correlation between RSFC and the performance of sequential syllable production confirmed their contributions to sequence processing deficit in speech production in PWS. In Study 4, the structure basis for the abnormalities of sequence processing in speech production in PWS was examined using voxel-based morphometry. Results demonstrated that PWS exhibited increased gray matter in the bilateral cerebellum and right insula, but had reduced gray matter in the supplementary motor area (SMA) relative to controls. A correlation analysis indicated significant correlation between gray matter volume of cerebellum and SMA and sequential syllable production, suggesting the roles of these anatomical alternations in sequence processing deficit in PWS. Collectively, converging evidence from functional and structural imaging studies supported the hypothesis that stuttering is associated with aberrant sequence processing in speech production. These findings provided novel evidence for a specific speech processing deficit in PWS, shedding new light on the causes and better treatment strategies of stuttering.