Elsevier

Brain Research

Volume 1200, 20 March 2008, Pages 132-137
Brain Research

Research Report
Morphological features of the medial superior olive in autism

https://doi.org/10.1016/j.brainres.2008.01.009Get rights and content

Abstract

Autism is a psychosocial disorder clinically characterized by social difficulties, impairment in communication skills and repetitive behavioral patterns. Despite the increasing reported incidence of autism, the neurobiology of this disorder is poorly understood. However, researchers have uncovered numerous structural anomalies in the brainstem, cerebellum and forebrain of autistic individuals and there is substantial support for the association of hearing deficits with autism. In an effort to discover an anatomical correlate for the functional auditory deficits found in autism, we examined the SOC, a group of brainstem nuclei that function in sound source localization, in post-mortem brain tissue from autistic individuals. The neurons of the medial superior olive (MSO), an SOC nucleus, display a precise geometric organization essential for detection of timing differences between the two ears. We examined the architecture of the MSO in five autistic brains (ages 8 to 32 years) and two age-matched controls (ages 26 and 29 years) and found a significant disruption in the morphology of MSO neurons in autistic brains, involving cell body shape and orientation. The results from this study provide evidence on the cellular level that may help to explain the hearing difficulties associated with autism.

Introduction

Autism is a developmental disorder characterized by impairment of communication skills and social interaction, sensory abnormalities and a host of stereotypical behaviors (American Psychiatric Association, 1994). Recent estimates of the incidence of autism indicate that it affects approximately 1 in every 152 children (MMWR Surveillance Summary, 2007). There is ample support for neuroanatomical alterations in this disorder, including differences in neuronal packing density, reduced neuronal cell body size, less extensive dendritic arborization and in some brain regions a reduction in the amount of GABA, an inhibitory neurotransmitter (Gaffney et al., 1988, Ritvo et al., 1986, Piven et al., 1992, Palmen et al., 2004, Bauman and Kemper, 2005, Blatt, 2005). In addition, there is evidence that hearing deficiencies affect the vast majority of autistic individuals (Greenspan and Weider, 1997, Tomchek and Dunn, 2007). The auditory dysfunction observed in autism seems to affect multiple aspects of hearing, including deafness, increased thresholds to tones, intolerance for ordinary sound levels (hyperacusis) and difficulty listening in the presence of background noise (Rosenhall et al., 1999, Roper et al., 2003, Alcantara et al., 2004, Khalfa et al., 2004, Szelag et al., 2004, Kellerman et al., 2005, Lepisto et al., 2005, Teder-Salejarvi et al., 2005, Gravel et al., 2006, Tharpe et al., 2006). Moreover, results from studies examining the auditory brainstem response (ABR) from autistic individuals seem to implicate functional deficits in the lower auditory brainstem (Rosenhall et al., 2003, Tas et al., 2007, Kwon et al., 2007).

The human auditory system consists of peripherally located ear structures (pinna, tympanic membrane, ossicles), mechanoreceptive hair cells and a multitude of ascending and descending neuronal circuits within the brainstem and forebrain. The superior olivary complex (SOC) is an aggregation of auditory nuclei situated at the pons-medullary junction. The SOC is a major site of convergence of auditory information and is the first major station where information from both ears is compared. The human SOC contains eight distinct nuclei, and each of these cell groups forms a unique neuronal circuit and subserves different aspects of auditory processing (Schofield and Cant, 1991, Schofield, 2002, Kulesza, 2007). The human SOC includes two principle nuclei, the medial and lateral superior olives (MSO and LSO, respectively) that play essential roles in localization of sound sources. The human MSO consists of an elongated column of fusiform and stellate neurons that are aligned in a precise geometric pattern: the cell bodies are elongated in the coronal plane and stacked from anterior to posterior (Kulesza, 2007). Moreover, in vivo electrode recordings in cat provide evidence that the laminar organization of MSO neurons contributes to the laminar representation of sound frequencies within the nucleus (Guinan et al., 1972).

The hearing deficits identified through psychoacoustic testing and examination of the ABR in autistic individuals seem to indicate disruption of the lower auditory brainstem. Indeed, study of a single autistic brain after autopsy revealed a complete absence of the SOC (Rodier et al., 1996). Thus, the working hypothesis for this study is that the hearing deficits observed in autistic individuals are the result of a disruption of the normal cytoarchitecture in the lower auditory brainstem, namely the SOC and cochlear nucleus (CN). The goal of this study is to examine the cytoarchitecture of the human MSO in autistic brains and to compare these findings to those from control specimens. The MSO was chosen because of the important functional role it serves and its prominence within the SOC; the MSO is the largest and most densely populated nucleus in the human SOC.

Section snippets

General features

The human MSO is first recognized in the rostral medulla oblongata as a prominent column of neurons within the SOC and extends rostro-caudally nearly 6.0 mm into the mid-pons. When viewed in the transverse plane, the MSO appears as a thin stack of neurons, tilted slightly towards the midline. The MSO cell column is approximately 300 μm wide and extends from anterior to posterior approximately 1000 μm. The human MSO contains nearly equal populations of fusiform and stellate neurons and these

Discussion

Although there are reports in the literature of alterations of neuronal cell body area, number and dendritic morphology in autism, this is the first report of quantitative alterations in neuronal morphology affecting not only cell body size, but also cell body shape and orientation. We observed a disruption in the morphology of MSO neurons in each of the five autistic brains studied. In the majority of cases examined, there was a significant difference in cell body area. However, the most

Tissue sections

Histological slides from autistic and age-matched control brains were kindly loaned by the Autism Tissue Program (ATP; http://www.brainbank.org). Celloidin embedded brains were cut at a thickness of 200 μm and stained with cresyl violet. This report is based on data from five autistic cases (with no reported hearing abnormalities) and two age-matched control cases. Specimens were divided into two groups based on plane of section (since neuronal morphology varies depending on plane of section).

Acknowledgments

This work was supported in part by a grant from the Deafness Research Foundation. The authors would like to thank Dr Jerzy Weigel and the Autism Tissue Program for kindly providing the tissue and the LECOM Research Collaborative for their continued support. We would also like to thank Dr Jack Caldwell for critically reading an earlier version of this manuscript.

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