Darrell Megan, Vanneau Theo, Cregin Dennis, Lecaj Tringa, Foxe John J, Molholm Sophie
Medical Scientist Training Program, Albert Einstein College of Medicine, Bronx, NY, USA.
Rose F. Kennedy Center, Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY, USA.
bioRxiv. 2025 Aug 5:2025.08.05.668742. doi: 10.1101/2025.08.05.668742.
Altered 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.
High-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.
No 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.
While 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.
听觉处理改变可能导致自闭症谱系障碍（ASD）的核心社交和注意力缺陷。听觉稳态反应（ASSR）——一种听觉处理和皮质兴奋-抑制平衡的神经测量指标——在ASD研究中结果不一。本研究使用高密度脑电图（EEG）评估ASD患儿及其未受影响的兄弟姐妹的ASSR，以阐明自闭症听觉缺陷背后的神经机制。
在一项主动式oddball任务中，对患有ASD的儿童（8至12岁，智商>80，n=53）、发育正常（TD）的同龄人（n=35）和未受影响的亲生兄弟姐妹（n=26）进行500毫秒双耳点击序列（27赫兹和40赫兹）时，记录70通道高密度EEG。
在对27赫兹或40赫兹刺激的频率跟随反应（FFR）方面未观察到组间差异，尽管在ASD中，较高的40赫兹功率与年龄较大和行为表现较好相关。对于两种刺激频率，ASD患儿在180至250毫秒的宽带反应均降低，尤其是在低频（<8赫兹）范围内，且与智商和年龄显著相关。兄弟姐妹表现出中等程度的宽带反应。
虽然ASD患儿的FFR似乎未受影响，但我们观察到在向稳态FFR过渡期间宽带反应降低，这在低频（<8赫兹）时尤为明显，可能反映了在与自然语音中较慢的音节节奏（约4至8赫兹）相对应的时间尺度上同步性降低。一级亲属的中等反应表明这与ASD的遗传易感性有关，并突出了其临床相关性。这些发现表明ASD患儿的感觉处理完好，但可能存在自上而下的听觉反馈缺陷，这可能是可遗传的神经生理标志物。
