Evidence for Brainstem Contributions to Autism Spectrum Disorders.

Brittany G. Travers,Olga I. Dadalko

doi:10.3389/fnint.2018.00047

Abstract

Autism spectrum disorder (ASD) is a neurodevelopmental condition that affects one in 59 children in the United States. Although there is a mounting body of knowledge of cortical and cerebellar contributions to ASD, our knowledge about the early developing brainstem in ASD is only beginning to accumulate. Understanding how brainstem neurotransmission is implicated in ASD is important because many of this condition’s sensory and motor symptoms are consistent with brainstem pathology. Therefore, the purpose of this review was to integrate epidemiological, behavioral, histological, neuroimaging, and animal evidence of brainstem contributions to ASD. Because ASD is a neurodevelopmental condition, we examined the available data through a lens of hierarchical brain development. The review of the literature suggests that developmental alterations of the brainstem could have potential cascading effects on cortical and cerebellar formation, ultimately leading to ASD symptoms. This view is supported by human epidemiology findings and data from animal models of ASD, showing that perturbed development of the brainstem substructures, particularly during the peak formation of the brainstem’s monoaminergic centers, may relate to ASD or ASD-like behaviors. Furthermore, we review evidence from human histology, psychophysiology, and neuroimaging suggesting that brainstem development and maturation may be atypical in ASD and may be related to key ASD symptoms, such as atypical sensorimotor features and social responsiveness. From this review there emerges the need of future research to validate early detection of the brainstem-based somatosensory and psychophysiological behaviors that emerge in infancy, and to examine the brainstem across the life span, while accounting for age. In all, there is preliminary evidence for brainstem involvement in ASD, but a better understanding of the brainstem’s role would likely pave the way for earlier diagnosis and treatment of ASD.

Highlights

Autism spectrum disorder (ASD) is a lifelong condition affecting one in 59 children (Baio et al, 2018)
The brainstem hypothesis of ASD was first proposed in the 1960s by pioneering researcher, Dr Bernard Rimland and initiated scientific inquiry into the brain basis of ASD
When shifting the focus from the core to the cooccurring features of ASD such as sensorimotor challenges or psychophysiological atypicalities, it becomes clear that abnormal brainstem neurotransmission contributes to ASD symptoms

Summary

Introduction

Autism spectrum disorder (ASD) is a lifelong condition affecting one in 59 children (Baio et al, 2018). This condition is clinically heterogeneous and has neurodevelopmental origin (Inui et al, 2017; Piven et al, 2017; Shen and Piven, 2017). The brainstem was at the center of the first brain-based hypothesis of ASD, which theorized that this early-developing neural structure was responsible for the behavioral features of autism (Rimland, 1964). ASD symptomatology was ascribed to the hypoplasia of the brainstem’s pons, supporting the neurodevelopmental model of autism and the critical role of the brainstem in ASD behaviors (Inui et al, 2017)

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Conclusion