Dysfunction of the Auditory Brainstem as a Neurophysiology Subtype of Autism Spectrum Disorder.

Jierong Chen,Xuejun Kong,Zhen Wei,Binguang Liu,Ziwen Peng,Guobin Wan,Chun Liang,Minshi Huang,Jimin Guo

doi:10.3389/fnins.2021.637079

Abstract

Autism spectrum disorder (ASD) is very heterogeneous, particularly in language. Studies have suggested that language impairment is linked to auditory-brainstem dysfunction in ASD. However, not all ASD children have these deficits, which suggests potential subtypes of ASD. We classified ASD children into two subtypes according to their speech-evoked auditory brainstem response (speech-ABR) and explored the neural substrates for possible subtypes. Twenty-nine children with ASD and 25 typically developing (TD) peers were enrolled to undergo speech-ABR testing and structural magnetic resonance imaging (sMRI). There were significant differences between the ASD group and TD group in surface area, cortical volume and cortical thickness. According to speech-ABR results, ASD participants were divided into the ASD-typical (ASD-T) group and ASD-atypical (ASD-A) group. Compared with the ASD-T group, the ASD-A group had a lower score in language of the Gesell Developmental Diagnosis Scale (GDDS), increased left rostral middle frontal gyrus (lRMFG) area and decreased local gyrification index of the right superior temporal gyrus. GDDS-language and surface area of lRMFG were correlated to the wave-A amplitude in ASD. Surface area of lRMFG had an indirect effect on language performance via alteration of the wave-V amplitude. Thus, cortical deficits may impair language ability in children with ASD by causing subcortical dysfunction at preschool age. These evidences support dysfunction of the auditory brainstem as a potential subtype of ASD. Besides, this subtype-based method may be useful for various clinical applications.

Highlights

Autism spectrum disorder (ASD) is a neurodevelopmental disorder involving deficits in social communication and restricted and repetitive behaviors, with an onset prior to 3 years of age (American Psychiatric Association, 2013)
Mediation Effect According to the result of correlation analyses, we further explored whether the auditory brainstem function moderated the relationship between the brain structure and language ability of all ASD participants controlled for age and sex
Our study indicated that the speech-auditory brainstem response (ABR) could be a clinical-assessment tool to predict the language ability of ASD children at preschool age

Summary

INTRODUCTION

Autism spectrum disorder (ASD) is a neurodevelopmental disorder involving deficits in social communication and restricted and repetitive behaviors, with an onset prior to 3 years of age (American Psychiatric Association, 2013). Not all ASD children have subcortical auditory deficits (Russo et al, 2010a), and the exact percentage needs to be obtained by large-sample studies These findings suggest there are potential auditory subcortical processing-related subtypes of ASD children linked to language impairment. Numerous studies have found abnormalities in the cortex and subcortex levels of ASD cases, and these abnormalities have been related to language impairment (Brambilla et al, 2003; Bauman and Kemper, 2005). Taken together, those findings suggest the possibility of interactions among the cortex, subcortex, and language in ASD children, but little empirical evidence is available. We hypothesized that: (i) two distinct subtypes in a population of ASD cases aged 3–6 years would have significant differences in language scores; (ii) there would be significant differences in brain structure among ASD subtypes and typically developing (TD) children; and (iii) structural differences of ASD subgroups would interact with the function of the subcortex and language in ASD children (hypothesized model see Supplementary Figure 1)

Ethical Approval of the Study Protocol

Participants

RESULTS

DISCUSSION

CONCLUSION

ETHICS STATEMENT