Reduced Fronto-Temporal Coherence during Speech Production in Fragile-X Syndrome

Background: Fragile X Syndrome (FXS) is the most common inherited intellectual disability and monogenic cause of autism spectrum disorder (ASD). Expressive language deficits are nearly ubiquitous among individuals with FXS, but our 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 left inferior frontal gyrus (IFG) and auditory cortex in left superior temporal gyrus (STG). Fronto-temporal coherence prior to vocalization is thought to reflect the corollary discharge of intended speech generated from an efference copy of the speech command against which the actual speech sound is compared. This process reduces the neural response to self-generated speech (“N1 suppression”) and is critical for making adjustments for future speech.

Objectives: Using the Talk/Listen paradigm during EEG recordings, we aimed to determine whether alterations in coherence between left frontal and temporal cortices prior to speech production are present in individuals with FXS and relate to language dysfunction.

Methods: Twenty-one right-handed participants with full-mutation FXS (8 female, aged 7-55 years old) and 20 healthy controls (HC; matched on age, sex, and handedness) completed the Talk/Listen paradigm during continuous EEG recording using the 132-channel EGI system. During the Talk condition, participants repeatedly pronounced short vocalizations of the phoneme “ah” every 1-2 seconds for a total of 180 seconds. Vocalizations were recorded using a microphone and transmitted back to the participants in real-time. During the Listening condition, participants passively listened to their recordings from the Talk condition. We compared pre-speech ERP activity, N1 suppression, P2 amplitude, single trial gamma power, and fronto-temporal coherence between groups and in relation to performance during a naturalistic expressive language task (narrating a wordless picture book).

Results: Prior to speech production, FXS participants showed reduced pre-speech activity in left IFG and reduced coherent activity between left frontal and temporal cortices as well as greater background gamma activity compared to controls. Though N1 suppression was similar between groups, N1 suppression was associated with greater coherence during talking in HC. In contrast, P2 amplitude was associated with N1 amplitude and fronto-temporal coherence during talking in FXS. Reduced N1 suppression and fronto-temporal coherence and increased gamma activity prior to speech production were related to greater reductions in narrative measures of talkativeness, intelligibility, and lexical complexity in FXS patients.

Conclusions: Our findings indicate that the coordination of pre-speech activity between left frontal and temporal that reflects the transmission of an efference copy of the intended speech sound to auditory cortex is disrupted in FXS. Intact N1 suppression suggests individuals with FXS are able to send a sufficient corollary discharge to auditory cortex to signal impending speech production, but that the signal may be degraded and contain less precise information about intended speech sounds based on its association with the perceptual response to self-generated speech (P2). This degradation and diminished perceptual response may interfere with feedforward processes necessary for making adjustments for future speech, ultimately impacting the overall complexity and intelligibility of speech productions.