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. 2020;2(1):fcz042.
doi: 10.1093/braincomms/fcz042. Epub 2019 Dec 9.

A neurophysiological model of speech production deficits in fragile X syndrome

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A neurophysiological model of speech production deficits in fragile X syndrome

Lauren M Schmitt et al. Brain Commun. 2020.

Abstract

Fragile X syndrome is the most common inherited intellectual disability and monogenic cause of autism spectrum disorder. Expressive language deficits, especially in speech production, are nearly ubiquitous among individuals with fragile X, but understanding of the neurological bases for these deficits remains limited. Speech production depends on feedforward control and the synchronization of neural oscillations between speech-related areas of frontal cortex and auditory areas of temporal cortex. Interaction in this circuitry allows the corollary discharge of intended speech generated from an efference copy of speech commands to be compared against actual speech sounds, which is critical for making adaptive adjustments to optimize future speech. We aimed to determine whether alterations in coherence between frontal and temporal cortices prior to speech production are present in individuals with fragile X and whether they relate to expressive language dysfunction. Twenty-one participants with full-mutation fragile X syndrome (aged 7-55 years, eight females) and 20 healthy controls (matched on age and sex) completed a talk/listen paradigm during high-density EEG recordings. During the talk task, participants repeated pronounced short vocalizations of 'Ah' every 1-2 s for a total of 180 s. During the listen task, participants passively listened to their recordings from the talk task. We compared pre-speech event-related potential activity, N1 suppression to speech sounds, single trial gamma power and fronto-temporal coherence between groups during these tasks and examined their relation to performance during a naturalistic language task. Prior to speech production, fragile X participants showed reduced pre-speech negativity, reduced fronto-temporal connectivity and greater frontal gamma power compared to controls. N1 suppression during self-generated speech did not differ between groups. Reduced pre-speech activity and increased frontal gamma power prior to speech production were related to less intelligible speech as well as broader social communication deficits in fragile X syndrome. Our findings indicate that coordinated pre-speech activity between frontal and temporal cortices is disrupted in individuals with fragile X in a clinically relevant way and represents a mechanism contributing to prominent speech production problems in the disorder.

Keywords: EEG; event-related potential; fragile X syndrome; neurophysiology; speech production.

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Figures

Graphical Abstract
Graphical Abstract
Figure 1
Figure 1
Connectivity findings for TDC and FXS. (A) Significant coherence between temporal seed electrodes (pink circle) and frontal electrodes (black ‘X’) for TDC and FXS participants. (B) Time–frequency plot of significant fronto-temporal electrode pairs for TDC, FXS and the comparison of TDC and FXS. Black-outlined area depicts significant clusters in group comparisons. (C) Time–frequency plot of Granger causality analyses in frontal to temporal (F → T) and temporal to frontal (T → F) directions presented on the left. Bar graph showing mean and standard error GCA values for TDC (black) and FXS (grey) on the right. Across all plots, warmer colours depict stronger coherence values.
Figure 2
Figure 2
ERP and Gamma Findings for TDC and FXS. (A) ERP plots for TDC and FXS participants for both the talk task (blue) and listen task (red). Components of interest are labelled in regions in which amplitudes were largest. (B) ERSP time–frequency plots during both the talk and listen tasks (top). Significant task and group × task interaction effects depicted for the Fpz cluster (left), which occurred primarily in frontal regions in FXS participants (right).
Figure 3
Figure 3
Pitch analysis of speech production. (A) Bar graphs for each pitch variable (mean and standard error) analysed for both TDC (blue) and FXS (red) participants in the ‘Ah’/talk task and ELS task. (B) Normalized pitch histograms for TDC (blue) and FXS (red) participants for each speech production task. Asterisk identifies frequency at which groups significantly differed.
Figure 4
Figure 4
Proposed model of speech production deficits in FXS. Schematic representation for forward model/corollary discharge processes prior to speech production in TDC (left) and FXS (right) participants.
Figure 5
Figure 5
Speech production correlations for FXS and TDC. Scatterplots and linear regression findings depicting correlations of between EEG/ERP measures and between EEG/ERP measures and speech production variables separately for TDC (black) and FXS (red) participants.
Figure 6
Figure 6
Clinical correlations for FXS. Scatterplots and linear regression lines depicting correlations of between EEG/ERP measures and clinical features associated with FXS.

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