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

15 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

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, 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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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.",
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