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Abstract

We compared the N1 responses of the auditory event-related brain potentials (ERPs) in school-aged children with fragile X syndrome to age-matched controls in order to assess auditory processing. Event-related potentials to non-attended standard and deviant tone stimuli were recorded with EEG electrodes and here the standard tones were analysed. The amplitude of the N1 component to standard tones was significantly larger in children with fragile X syndrome than in control children. In addition, the global field power maximum of ERP corresponding to the N2 component was significantly (p<0.05) larger in fragile X children than in controls. The N2 scalp distribution in children with fragile X syndrome appeared more frontal than that in controls. Furthermore, the fragile X children exhibited no habituation of N1 and an absence of N2 sensitization for repeated tones. Increased responsiveness observed in the N1 evoked potential together with abnormal habituation of auditory responses in childhood may indicate increased sensory sensitivity for auditory stimuli in fragile X syndrome. The data, though very limited, suggest that stimulus processing in the auditory afferent pathways and/or in the corresponding cortical receiving areas is abnormal in children with fragile X syndrome.

Matrix metalloproteinase-9 deletion rescues auditory evoked potential habituation deficit in a mouse model of Fragile X Syndrome

“…The reduced habituation of N1 amplitude in Fmr1 KO mice is similar to observations in humans with FXS providing, for the first time, an analogous functional sensory outcome measure in mice and humans (Castren et al, 2003; Van der Molen et al, 2012; Schneider et al, 2013). Likewise, the lack of differences in N1 latency between Fmr1 KO and WT recordings is consistent with observations in humans (Van der Molen et al, 2012a,b).…”

“…Behavioral and functional studies indicate abnormal auditory sensitivity in humans with FXS (St Clair et al, 1987; Castren et al, 2003; Van der Molen et al, 2012a,b; Schneider et al, 2013; Rotschafer and Razak, 2014). A consistent observation in FXS is that the amplitude of the N1 component of auditory event related potentials (ERP) shows reduced habituation with sound repetition compared to the control group, suggesting neural correlates of auditory hypersensitivity.…”

Altered Neuronal and Circuit Excitability in Fragile X Syndrome

“…These seizures are possibly triggered by elevated responsiveness of neurons in the auditory cortex to sound (Rotschafer and Razak, 2013), providing another example of how increased neuronal excitability in sensory cortices underlies a behavioral phenotype. Similar increases in responses in the auditory cortex are observed in the event related brain potential (ERP) recorded in the EEG in humans with FXS (Castren et al, 2003), consistent with hyperexcitability of auditory circuits associated with loss of FMRP in both mice and humans.…”

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

“…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).…”

“…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.…”