Atypical brain responses to 40-Hz click trains in girls with Rett syndrome: Auditory steady-state response and sustained wave

Aim: The current study aimed to infer neurophysiological mechanisms of auditory processing in children with Rett syndrome (RTT)-rare neurodevelopmental disorders caused by MECP2 mutations. We examined two brain responses elicited by 40-Hz click trains: auditory steady-state response (ASSR), which reflects fine temporal analysis of auditory input, and sustained wave (SW), which is associated with integral processing of the auditory signal. Methods: We recorded electroencephalogram findings in 43 patients with RTT (aged 2.92-17.1 years) and 43 typically developing children of the same age during 40-Hz click train auditory stimulation, which lasted for 500 ms and was presented with interstimulus intervals of 500 to 800 ms. Mixed-model ancova with age as a covariate was used to compare amplitude of ASSR and SW between groups, taking into account the temporal dynamics and topography of the responses. Results: Amplitude of SW was atypically small in children with RTT starting from early childhood, with the difference from typically developing children decreasing with age. ASSR showed a different pattern of developmental changes: the between-group difference was negligible in early childhood but increased with age as ASSR increased in the typically developing group, but not in those with RTT. Moreover, ASSR was associated with expressive speech development in patients, so that children who could use words had more pronounced ASSR. Conclusion: ASSR and SW show promise as noninvasive electrophysiological biomarkers of auditory processing that have clinical relevance and can shed light onto the link between genetic impairment and the RTT phenotype.