Neural synchronization deficits linked to cortical hyper-excitability and auditory hypersensitivity in fragile X syndrome

Lauren E. Ethridge, Stormi P. White, Matthew W. Mosconi, Jun Wang, Ernest V. Pedapati, Craig A. Erickson, Matthew J. Byerly, John A. Sweeney

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Background: Studies in the fmr1 KO mouse demonstrate hyper-excitability and increased high-frequency neuronal activity in sensory cortex. These abnormalities may contribute to prominent and distressing sensory hypersensitivities in patients with fragile X syndrome (FXS). The current study investigated functional properties of auditory cortex using a sensory entrainment task in FXS. Methods: EEG recordings were obtained from 17 adolescents and adults with FXS and 17 age- and sex-matched healthy controls. Participants heard an auditory chirp stimulus generated using a 1000-Hz tone that was amplitude modulated by a sinusoid linearly increasing in frequency from 0-100 Hz over 2 s. Results: Single trial time-frequency analyses revealed decreased gamma band phase-locking to the chirp stimulus in FXS, which was strongly coupled with broadband increases in gamma power. Abnormalities in gamma phase-locking and power were also associated with theta-gamma amplitude-amplitude coupling during the pre-stimulus period and with parent reports of heightened sensory sensitivities and social communication deficits. Conclusions: This represents the first demonstration of neural entrainment alterations in FXS patients and suggests that fast-spiking interneurons regulating synchronous high-frequency neural activity have reduced functionality. This reduced ability to synchronize high-frequency neural activity was related to the total power of background gamma band activity. These observations extend findings from fmr1 KO models of FXS, characterize a core pathophysiological aspect of FXS, and may provide a translational biomarker strategy for evaluating promising therapeutics.

Original languageEnglish (US)
Article number22
JournalMolecular Autism
Volume8
Issue number1
DOIs
StatePublished - Jun 7 2017

Fingerprint

Fragile X Syndrome
Hypersensitivity
Auditory Cortex
Aptitude
Interneurons
Cortical Excitability
Electroencephalography
Biomarkers
Communication

Keywords

  • Chirp
  • EEG
  • Fragile X syndrome
  • Gamma
  • Sensory

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Neuroscience
  • Developmental Biology
  • Psychiatry and Mental health

Cite this

Ethridge, L. E., White, S. P., Mosconi, M. W., Wang, J., Pedapati, E. V., Erickson, C. A., ... Sweeney, J. A. (2017). Neural synchronization deficits linked to cortical hyper-excitability and auditory hypersensitivity in fragile X syndrome. Molecular Autism, 8(1), [22]. https://doi.org/10.1186/s13229-017-0140-1

Neural synchronization deficits linked to cortical hyper-excitability and auditory hypersensitivity in fragile X syndrome. / Ethridge, Lauren E.; White, Stormi P.; Mosconi, Matthew W.; Wang, Jun; Pedapati, Ernest V.; Erickson, Craig A.; Byerly, Matthew J.; Sweeney, John A.

In: Molecular Autism, Vol. 8, No. 1, 22, 07.06.2017.

Research output: Contribution to journalArticle

Ethridge, LE, White, SP, Mosconi, MW, Wang, J, Pedapati, EV, Erickson, CA, Byerly, MJ & Sweeney, JA 2017, 'Neural synchronization deficits linked to cortical hyper-excitability and auditory hypersensitivity in fragile X syndrome', Molecular Autism, vol. 8, no. 1, 22. https://doi.org/10.1186/s13229-017-0140-1
Ethridge, Lauren E. ; White, Stormi P. ; Mosconi, Matthew W. ; Wang, Jun ; Pedapati, Ernest V. ; Erickson, Craig A. ; Byerly, Matthew J. ; Sweeney, John A. / Neural synchronization deficits linked to cortical hyper-excitability and auditory hypersensitivity in fragile X syndrome. In: Molecular Autism. 2017 ; Vol. 8, No. 1.
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