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bioRxiv · 10.1101/2025.08.05.668742

Testing the auditory steady-state response (ASSR) to 40-Hz and 27-Hz click trains in children with autism spectrum disorder and their first-degree biological relatives: A high-density electroencephalographic (EEG) study

Abstract

MotivationAltered auditory processing likely contributes to core social and attentional impairments in autism spectrum disorder (ASD). The auditory steady-state response (ASSR)-- a neural measure of auditory processing and cortical excitatory-inhibitory balance--has yielded mixed results in ASD. This study uses high density electroencephalography (EEG) to evaluate ASSR in ASD and unaffected siblings to clarify neural mechanisms underlying auditory deficits in autism. MethodsHigh-density 70-channel EEG was recorded in children (8-12 years, IQ >80) with ASD (n=53), typically developing (TD) peers (n=35), and unaffected biological siblings (n=26) during 500-ms binaural click trains (27- and 40-Hz) in an active oddball task. ResultsNo group differences were observed in frequency-following responses (FFR) to 27- or 40-Hz stimuli, although higher 40-Hz power was associated with older age and better behavioral performance in ASD. The broad-band response from 180-250 ms was reduced in ASD for both stimulation frequencies--particularly in the low-frequency (<8 Hz) range--and significantly correlated with IQ and age. Siblings showed intermediate broad-band responses. DiscussionWhile FFRs appeared intact in ASD, we observed reduced broad-band response in the transition period to the steady state FFR, which was specific to low (<8-Hz) frequencies--potentially reflecting reduced synchronization at timescales that correspond with slower, syllabic rhythms ([~]4-8 Hz) occurring in natural speech. Intermediate responses in first-degree relatives suggest that this is related to genetic vulnerability for ASD and highlights its clinical relevance. These findings suggest intact sensory processing in ASD alongside possible top-down auditory feedback deficits, which may serve as heritable neurophysiological markers. Lay AbstractChildren with autism may process sounds differently, which could contribute to challenges with attention and communication. Here, electroencephalography (EEG) measured how the brain responds to rapidly repeating sounds and found that, while basic sound processing was intact, children with autism showed significantly reduced low-frequency responses that may reflect difficulty tracking speech rhythm. Interestingly, unaffected siblings showed an intermediate response, suggesting this may be a heritable marker of neural differences in autism.

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Darrell, M., Vanneau, T., Cregin, D., Lecaj, T., Foxe, J. J., Molholm, S.. 2025-08-05. Testing the auditory steady-state response (ASSR) to 40-Hz and 27-Hz click trains in children with autism spectrum disorder and their first-degree biological relatives: A high-density electroencephalographic (EEG) study. https://doi.org/10.1101/2025.08.05.668742

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