Auditory sustained potential as a biomarker of language functioning in children with autism and its implication in clinical trials

Language impairment is the most frequently reported co-occurring condition in autism; however, its neural mechanisms are not well understood. A potential neural biomarker associated with language in autism can be a 40Hz Auditory Steady-State Response (ASSR) triggered by periodic click trains which in electroencephalogram (EEG) evokes two types of responses - 40Hz steady-state gamma response (or ASSR) and sustained potential (SP). Although these responses represent low-level auditory processing, they correspond to different stages of sound perception/analysis and are essential in processing of spectrally/temporally complex sounds, including speech. However, until now there were no studies focusing on the potential of these responses to serve as objective measures in clinical trials. This open-label clinical trial evaluated the effects of the probiotic beverage supplement Bio-K+ in children with autism. Participants were assessed at three timepoints: T0 (baseline), T14 (14 weeks after treatment initiation), and T22 (8 weeks post-treatment, during the wash-out phase), including EEG 40Hz ASSR and behavioral phenotyping. First, at T0 we showed a reduction of SP amplitude in children with autism compared to typically-developing (TD) controls, and this reduction was associated with lower language skills. Second, the amplitude of SP significantly changed during the treatment period: by T14 it became similar to that of TD children. Finally, these changes in the amplitude of SP were associated with improvement in language skills. Importantly, we showed that this biomarker as well as its change was related specifically to language, but not to other behavioral measures.