Alterations of visual and auditory evoked potentials in fragile X syndrome

Knoth, Inga Sophia; Vannasing, Phetsamone; Major, Philippe; Michaud, Jacques L.; Lippé, Sarah

doi:10.1016/j.ijdevneu.2014.05.003

Cited by 56 publications

(65 citation statements)

References 37 publications

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“…FXS patients showed significantly increased phase-locking in alpha frequencies during the stimulus onset time period and decreased theta frequency phase-locking and increased alpha frequency phase-locking after stimulus offset (Fig. 2c), consistent with increased ERP amplitudes found in previous work [40, 41]. As expected, FXS showed decreased gamma phase-locking to the chirp stimulus from 30–58 Hz and decreased gamma phase-locking to the chirp harmonic from 47–58 Hz (Fig.…”

Section: Resultssupporting

confidence: 91%

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

et al. 2017

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BackgroundStudies 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.MethodsEEG 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.ResultsSingle 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.ConclusionsThis 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s13229-017-0140-1) contains supplementary material, which is available to authorized users.

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Section: Resultssupporting

confidence: 91%

“…The increased alpha phase-locking is consistent with previous findings of increased amplitude early ERP components in response to brief auditory stimuli in FXS [26, 40, 41]. Decreased theta frequency phase-locking simultaneous to stimulus offset is a novel finding in FXS.…”

Section: Discussionsupporting

confidence: 90%

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

et al. 2017

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“…Two studies of auditory evoked potentials (AEPs) and VEPs found that the amplitudes in both modalities were increased in FXS compared to both chronological (VEP only) and developmental (both VEP and AEP) control groups (Knoth et al, 2014). This profile suggests disruptions in sensory processing in FXS and supports the notion of a hyper-reactive nervous system.…”

Section: Local Circuits and Networkmentioning

confidence: 99%

Altered Neuronal and Circuit Excitability in Fragile X Syndrome

Contractor

Klyachko

Portera‐Cailliau

2015

Neuron

371

365

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Fragile X syndrome (FXS) results from a genetic mutation in a single gene, yet produces a phenotypically complex disorder with a range of neurological and psychiatric problems. Efforts to decipher how perturbations in signaling pathways lead to the myriad alterations in synaptic and cellular functions have provided insights into the molecular underpinnings of this disorder. From this large body of data the theme of circuit hyperexcitability has emerged as a potential explanation for many of the neurological and psychiatric symptoms in FXS. The mechanisms for hyperexcitability range from alterations in the expression or activity of ion channels to changes in neurotransmitters and receptors. Contributions of these processes are often brain region- and cell type-specific, resulting in complex effects on circuit function that manifest as altered excitability. Here, we review the current state of knowledge of the molecular, synaptic and circuit-level mechanisms underlying hyperexcitability and their contributions to the FXS phenotypes.

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“…Individuals with mutations of NLGN4X-coding genes, expressed in inhibitory and excitatory synapses(84), were more likely to exhibit ASD and showed abnormal ERP to auditory deviance detection. In Fragile X syndrome, both auditory and visual ERP amplitudes were increased(85). This finding suggests hyper-excitable neural responses, most prominent in audition, in a genetic syndrome with known glutamate disruption and causing ASD.…”

Section: Electrophysiology and Magnetoencephalographymentioning

confidence: 99%

Searching for Cross-Diagnostic Convergence: Neural Mechanisms Governing Excitation and Inhibition Balance in Schizophrenia and Autism Spectrum Disorders

Foss‐Feig

Adkinson

et al. 2017

Biological Psychiatry

247

183

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Recent theoretical accounts have proposed excitation (E) and inhibition (I) imbalance as a possible mechanistic, network-level hypothesis underlying neural and behavioral dysfunction across neurodevelopmental disorders, particularly autism spectrum disorder (ASD) and schizophrenia (SCZ). These two disorders share some overlap in their clinical presentation as well as convergence in their underlying genes and neurobiology. However, there are also clear points of dissociation in terms of phenotypes and putatively affected neural circuitry. Here we highlight emerging work from the clinical neuroscience literature examining neural correlates of E/I imbalance across children and adults with ASD and adults with both chronic and early-course SCZ. We discuss findings from diverse neuroimaging studies across distinct modalities, conducted with EEG, MEG, 1H-MRS, and fMRI, including effects observed both during task and at rest. Throughout this review we discuss points of convergence and divergence in the ASD and SCZ literature, with a focus on disruptions in neural E/I balance. We also consider these findings in relation to predictions generated by theoretical neuroscience, particularly computational models predicting E/I imbalance across disorders. Finally, we discuss how human non-invasive neuroimaging can benefit from pharmacological challenge studies to reveal mechanisms in ASD and SCZ. Collectively, we attempt to shed light on shared and divergent neuroimaging effects across disorders with the goal of informing future research examining the mechanisms underlying the E/I imbalance hypothesis across neurodevelopmental disorders. We posit that such translational efforts are vital to facilitate development of neurobiologically informed treatment strategies across neuropsychiatric conditions.

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Alterations of visual and auditory evoked potentials in fragile X syndrome

Cited by 56 publications

References 37 publications

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

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

Altered Neuronal and Circuit Excitability in Fragile X Syndrome

Searching for Cross-Diagnostic Convergence: Neural Mechanisms Governing Excitation and Inhibition Balance in Schizophrenia and Autism Spectrum Disorders

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