A neurophysiological model of speech production deficits in fragile X syndrome
- PMID: 32924010
- PMCID: PMC7425415
- DOI: 10.1093/braincomms/fcz042
A neurophysiological model of speech production deficits in fragile X syndrome
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.
Figures







Similar articles
-
Theta Phase Synchrony Is Sensitive to Corollary Discharge Abnormalities in Early Illness Schizophrenia but Not in the Psychosis Risk Syndrome.Schizophr Bull. 2021 Mar 16;47(2):415-423. doi: 10.1093/schbul/sbaa110. Schizophr Bull. 2021. PMID: 32793958 Free PMC article.
-
Altered frontal connectivity as a mechanism for executive function deficits in fragile X syndrome.Mol Autism. 2022 Dec 9;13(1):47. doi: 10.1186/s13229-022-00527-0. Mol Autism. 2022. PMID: 36494861 Free PMC article.
-
Deficient auditory predictive coding during vocalization in the psychosis risk syndrome and in early illness schizophrenia: the final expanded sample.Psychol Med. 2019 Aug;49(11):1897-1904. doi: 10.1017/S0033291718002659. Epub 2018 Sep 25. Psychol Med. 2019. PMID: 30249315
-
Corollary discharge dysfunction in schizophrenia: can it explain auditory hallucinations?Int J Psychophysiol. 2005 Nov-Dec;58(2-3):179-89. doi: 10.1016/j.ijpsycho.2005.01.014. Epub 2005 Aug 31. Int J Psychophysiol. 2005. PMID: 16137779 Review.
-
Communication in fragile X syndrome: Patterns and implications for assessment and intervention.Front Psychol. 2022 Dec 22;13:929379. doi: 10.3389/fpsyg.2022.929379. eCollection 2022. Front Psychol. 2022. PMID: 36619013 Free PMC article. Review.
Cited by
-
Neural Correlates of Auditory Hypersensitivity in Fragile X Syndrome.Front Psychiatry. 2021 Oct 7;12:720752. doi: 10.3389/fpsyt.2021.720752. eCollection 2021. Front Psychiatry. 2021. PMID: 34690832 Free PMC article. Review.
-
Increased aperiodic gamma power in young boys with Fragile X Syndrome is associated with better language ability.Mol Autism. 2021 Feb 25;12(1):17. doi: 10.1186/s13229-021-00425-x. Mol Autism. 2021. PMID: 33632320 Free PMC article.
-
Transcranial direct current stimulation combined with speech therapy in Fragile X syndrome patients: a pilot study.Front Neurol. 2023 Dec 5;14:1268165. doi: 10.3389/fneur.2023.1268165. eCollection 2023. Front Neurol. 2023. PMID: 38116107 Free PMC article.
-
The Relationship between Expressive Language Sampling and Clinical Measures in Fragile X Syndrome and Typical Development.Brain Sci. 2020 Jan 26;10(2):66. doi: 10.3390/brainsci10020066. Brain Sci. 2020. PMID: 31991905 Free PMC article.
-
Sex differences during development in cortical temporal processing and event related potentials in wild-type and fragile X syndrome model mice.J Neurodev Disord. 2024 May 8;16(1):24. doi: 10.1186/s11689-024-09539-8. J Neurodev Disord. 2024. PMID: 38720271 Free PMC article.
References
-
- Abbeduto L, Benson G, Short K, Dolish J.. Effects of sampling context on the expressive language of children and adolescents with mental retardation. Ment Retard 1995; 33: 279–88. - PubMed
-
- Aman MG, Singh NN, Stewart AW, Field CJ.. The Aberrant Behavior Checklist: a behavior rating scale for the assessment of treatment effects. Am J Ment Defic 1985; 89: 485–91. - PubMed
-
- Bear MF, Huber KM, Warren ST.. The mGluR theory of fragile X mental retardation. Trends Neurosci 2004; 27: 370–7. - PubMed