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.