P3 Abnormality in fragile X syndrome

Clair, David Malcolm St; Blackwood, Douglas; Oliver, Chris; Dickens, Paul

doi:10.1016/0006-3223(87)90148-x

Cited by 46 publications

(46 citation statements)

References 30 publications

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“…The published work is primarily on temporal and amplitude properties of the auditory ERPs (Knoth and Lippe, 2012; Rotschafer and Razak, 2014). A consistent observation across studies is that the N1 component has larger average amplitude and shows reduced habituation to repeated sounds in humans with FXS compared to control subjects (Castrén et al, 2003; Ethridge et al, 2016; Rojas et al, 2001; St Clair et al, 1987; Van der Molen et al, 2012a,b). A study using MEG also revealed enlargement and reduced latency of the N100 m (the MEG equivalent of the N1 in EEG) in adults with FXS (Rojas et al, 2001).…”

Section: Sensory Processing In Individuals With Asd and Fxssupporting

confidence: 54%

Sensory processing in autism spectrum disorders and Fragile X syndrome—From the clinic to animal models

Sinclair

Oranje

Razak

et al. 2017

Neuroscience & Biobehavioral Reviews

156

148

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Brains are constantly flooded with sensory information that needs to be filtered at the pre-attentional level and integrated into endogenous activity in order to allow for detection of salient information and an appropriate behavioral response. People with Autism Spectrum Disorder (ASD) or Fragile X Syndrome (FXS) are often over- or under-reactive to stimulation, leading to a wide range of behavioral symptoms. This altered sensitivity may be caused by disrupted sensory processing, signal integration and/or gating, and is often being neglected. Here, we review translational experimental approaches that are used to investigate sensory processing in humans with ASD and FXS, and in relevant rodent models. This includes electroencephalographic measurement of event related potentials, neural oscillations and mismatch negativity, as well as habituation and pre-pulse inhibition of startle. We outline robust evidence of disrupted sensory processing in individuals with ASD and FXS, and in respective animal models, focusing on the auditory sensory domain. Animal models provide an excellent opportunity to examine common mechanisms of sensory pathophysiology in order to develop therapeutics.

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Section: Sensory Processing In Individuals With Asd and Fxssupporting

confidence: 54%

Sensory processing in autism spectrum disorders and Fragile X syndrome—From the clinic to animal models

Sinclair

Oranje

Razak

et al. 2017

Neuroscience & Biobehavioral Reviews

156

148

View full text Add to dashboard Cite

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“…Cortical evoked responses to tones differ from controls (Castrén et al, 2003; Rojas et al, 2001; St Clair et al, 1987; Van der Molen et al, 2012a, 2012b). However, the specifics of the experimental design appear to influence which peaks in the evoked potential are significantly larger and which are significantly smaller than controls (Knoth and Lippé, 2012).…”

Section: Discussionmentioning

confidence: 78%

“…Neurophysiology studies have established that both children and adults with fragile X syndrome have cortical deficits in auditory processing (Castrén et al, 2003; Knoth and Lippé, 2012; Rojas et al, 2001; St Clair et al, 1987; Van der Molen et al, 2012a, 2012b) in spite of normal auditory brainstem responses (Roberts et al, 2005). It is not clear how these observed cortical impairments impact speech sound processing.…”

Section: Introductionmentioning

confidence: 99%

Degraded speech sound processing in a rat model of fragile X syndrome

Engineer

Centanni

et al. 2014

Brain Research

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Fragile X syndrome is the most common inherited form of intellectual disability and the leading genetic cause of autism. Impaired phonological processing in fragile X syndrome interferes with the development of language skills. Although auditory cortex responses are known to be abnormal in fragile X syndrome, it is not clear how these differences impact speech sound processing. This study provides the first evidence that the cortical representation of speech sounds is impaired in Fmr1 knockout rats, despite normal speech discrimination behavior. Evoked potentials and spiking activity in response to speech sounds, noise burst trains, and tones were significantly degraded in primary auditory cortex, anterior auditory field and the ventral auditory field. Neurometric analysis of speech evoked activity using a pattern classifier confirmed that activity in these fields contains significantly less information about speech sound identity in Fmr1 knockout rats compared to control rats. Responses were normal in the posterior auditory field, which is associated with sound localization. The greatest impairment was observed in the ventral auditory field, which is related to emotional regulation. Dysfunction in the ventral auditory field may contribute to poor emotional regulation in fragile X syndrome and may help explain the observation that later auditory evoked responses are more disturbed in fragile X syndrome compared to earlier responses. Rodent models of fragile X syndrome are likely to prove useful for understanding the biological basis of fragile X syndrome and for testing candidate therapies.

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“…Sensory abnormalities can be objectively assessed using electroencephalography (EEG) in both humans with FXS and Fmr1 KO mice. Humans with FXS show evidence of auditory hypersensitivity, disrupted preattentive stimulus recognition, and altered novelty detection by EEG (St Clair et al 1987; Castrén et al 2003; Van der Molen et al 2012a, b; Ethridge et al 2016), as do Fmr1 KO mice (Chen and Toth, 2001; Frankland et al 2004; Gibson et al 2008; Lovelace et al 2016). Because abnormalities of sensory processing are likely to contribute to sensory hypersensitivity and other deficits in FXS, they are an important potential target for baclofen treatment.…”

Section: Introductionmentioning

confidence: 99%

GABA-B Agonist Baclofen Normalizes Auditory-Evoked Neural Oscillations and Behavioral Deficits in theFmr1Knockout Mouse Model of Fragile X Syndrome

Sinclair

Featherstone

Naschek

et al. 2017

eNeuro

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Fragile X syndrome is a genetic condition resulting from FMR1 gene mutation that leads to intellectual disability, autism-like symptoms, and sensory hypersensitivity. Arbaclofen, a GABA-B agonist, has shown efficacy in some individuals with FXS but has become unavailable after unsuccessful clinical trials, prompting interest in publicly available, racemic baclofen. The present study investigated whether racemic baclofen can remediate abnormalities of neural circuit function, sensory processing, and behavior in Fmr1 knockout mice, a rodent model of fragile X syndrome. Fmr1 knockout mice showed increased baseline and auditory-evoked high-frequency gamma (30–80 Hz) power relative to C57BL/6 controls, as measured by electroencephalography. These deficits were accompanied by decreased T maze spontaneous alternation, decreased social interactions, and increased open field center time, suggestive of diminished working memory, sociability, and anxiety-like behavior, respectively. Abnormal auditory-evoked gamma oscillations, working memory, and anxiety-related behavior were normalized by treatment with baclofen, but impaired sociability was not. Improvements in working memory were evident predominantly in mice whose auditory-evoked gamma oscillations were dampened by baclofen. These findings suggest that racemic baclofen may be useful for targeting sensory and cognitive disturbances in fragile X syndrome.

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P3 Abnormality in fragile X syndrome

Cited by 46 publications

References 30 publications

Sensory processing in autism spectrum disorders and Fragile X syndrome—From the clinic to animal models

Sensory processing in autism spectrum disorders and Fragile X syndrome—From the clinic to animal models

Degraded speech sound processing in a rat model of fragile X syndrome

GABA-B Agonist Baclofen Normalizes Auditory-Evoked Neural Oscillations and Behavioral Deficits in theFmr1Knockout Mouse Model of Fragile X Syndrome

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