Elsevier

NeuroImage

Volume 23, Issue 1, September 2004, Pages 364-369
NeuroImage

Superior temporal sulcus anatomical abnormalities in childhood autism: a voxel-based morphometry MRI study

https://doi.org/10.1016/j.neuroimage.2004.06.016Get rights and content

Abstract

The underlying neurobiology of autism, a severe pervasive developmental disorder, remains unknown. Few neocortical brain MRI abnormalities have been reported. Using rest functional brain imaging, two independent studies have described localized bilateral temporal hypoperfusion in children with primary autism. In order to search for convergent evidence of anatomical abnormalities in autistic children, we performed an anatomical MRI study using optimized whole-brain voxel-based morphometry (VBM). High-resolution 3-D T1-weighted MRI data sets were acquired in 21 children with primary autism (mean age 9.3 ± 2.2 years) and 12 healthy control children (mean age 10.8 ± 2.7 years). By comparing autistic children to normal children, we found bilaterally significant decreases of grey matter concentration located in superior temporal sulcus (STS) (P < 0.05 corrected, after small volume correction; SVC). Children with autism were also found to have a decrease of white matter concentration located in the right temporal pole and in cerebellum (P < 0.05, corrected) compared to normal children. These results suggest that autism is associated with bilateral anatomical abnormalities localized in the STS and are remarkably consistent with functional hypoperfusion previously reported in children with autism. The multimodal STS areas are involved in highest level of cortical integration of both sensory and limbic information. Moreover, the STS is now recognized as a key cortical area of the “social brain” and is implicated in social perceptual skills that are characteristically impaired in autism. Therefore, the convergent anatomical and functional temporal abnormalities observed in autism may be important in the understanding of brain behavior relationships in this severe developmental disorder.

Introduction

Autism is a complex, severe, and lifelong developmental disorder. Its main symptoms are social interaction and communication deficits Kanner, 1943, Rapin, 1997. Autistic children have difficulties in processing emotional expressions and have narrow interests and poor imagination (Gillberg and Coleman, 1992). Since the first description by Leo Kanner in 1943, autism has intrigued the medical and scientific world because autism associates severe cognitive–behavioral problems in the absence of marked consistent cerebral dysmorphology. Therefore, a fundamental goal of any neurobiological study of autism is a description of brain regions that are of abnormal structure or dysfunctional. Once identified and the abnormalities characterized, better strategies for early diagnosis and treatment of autism may follow.

The first MRI studies of autism were published at the end of the 1980s Courchesne et al., 1988, Gaffney et al., 1987. Since these pioneering studies, about 200 studies have appeared in the literature. Most of them have focused on specific structures such as the cerebellum, the amygdala, the hippocampus, and the corpus callosum, but subtle neocortical changes have not been systematically searched. The cerebellum is one of the most studied structures in autism since a pioneer quantitative MRI study has showed evidence of hypoplasia of the vermian lobules VI and VII in a group of autistic adults (Courchesne et al., 1988), but other groups failed to replicate these findings Piven et al., 1992, Piven et al., 1997. Some studies show increased volume of the amygdala in adults with autism (Howard et al., 2000) or in mentally retarded (MR) autistic children (Sparks et al., 2002), some have described a decreased volume in autistic adults (Aylward et al., 1999), and yet others reveal no significant abnormalities in MR or non-MR adults with autism (Haznedar et al., 2000). Likewise, to date no consistent hippocampal findings have been reported in autism. Concerning the hippocampus, some studies show no abnormalities in high-functioning and MR adults and children with autism Haznedar et al., 2000, Howard et al., 2000, Piven et al., 1998, Saitoh et al., 1995, others report decreased volume in autistic adolescent and adults (Aylward et al., 1999) or increased volumes in MR autistic children (Sparks et al., 2002). Morphometric MRI studies have reported a small corpus callosum in MR adolescent patients with autism Egaas et al., 1995, Manes et al., 1999 and in adults Hardan et al., 2000, Piven et al., 1997. Finally several groups reported an increased total brain volume in children and adults with autism Courchesne et al., 2001, Courchesne et al., 2003, Herbert et al., 2003, Piven et al., 1992, Piven et al., 1995, Piven et al., 1996, Sparks et al., 2002.

Recently, quantitative structural imaging studies have benefited greatly from both new technologies for data acquisition and new approaches to image analysis. In addition, these newer methods are more adequate for the study of complex and subtle neocortical abnormalities, and some very recent results are very promising. Using a parametric mesh-based analytic technique to create a three-dimensional model of the cerebral cortex and using detailed maps of 22 major sulci in stereotaxic space, Levitt et al. (2003) showed significant differences in cortical sulcal patterns in children with autism localized mainly in the frontal and temporal sulci.

In the functional domain, most brain imaging studies in autism were performed with activation paradigms (for a review, see Cody et al., 2002) but few studies were performed at rest. Recently, two independent high-resolution PET and SPECT studies have described localized bilateral temporal hypoperfusion in children with primary autism. These rest functional abnormalities were centered in the superior temporal sulcus (STS) and superior temporal gyrus (STG) Ohnishi et al., 2000, Zilbovicius et al., 2000.

In order to search for convergent evidence of temporal anatomical abnormalities in autistic children, we performed an anatomical MRI study using whole-brain voxel-based morphometry. In contrast to techniques relying on inspection and manual demarcation of structures, VBM is unbiased toward particular regions. All of the stages of image processing are automated and the software is widely available (SPM99, Wellcome Department of Imaging Neuroscience, London, UK, http://www.fil.ion.ucl.ac.uk/spm/). It enables detection of subtle changes between two groups. A pioneering study in high-functioning adults with autism (Asperger's syndrome) using VBM was published in 1999 by Abell et al. (1999) showing frontotemporal grey matter abnormalities. Since this publication, VBM has benefited from substantial improvements. Therefore, we used the optimized VBM method (Good et al., 2001) to examine possible localized abnormalities in grey and white matter concentration in children with primary autism. On the basis of previous functional data Ohnishi et al., 2000, Zilbovicius et al., 2000, we predicted that MRI abnormalities may be localized in the temporal lobes.

Section snippets

Subjects

Twenty-one children with a primary autistic disorder, of which 16 were boys, were selected among patients attending pediatric psychiatry outpatient units. They were aged from 7 to 15 years (mean age 9.3 ± 2.2 years). All children met the DSM-IV diagnosis criteria for autistic disorder. The Autism Diagnostic Interview—Revised (ADI-R) was performed in 18 autistic children and confirmed the diagnosis (Table 1) (Lord et al., 1994). The 21 autistic children were also evaluated with the Behavior

Visual inspection of the MRI

Clinical review of anatomical MRI was performed by two pediatric neuroradiologists (NB and FB), and no abnormality was found in both autistic and healthy children.

Grey matter abnormalities

By comparing the autistic group to normals, the exploratory analysis (P < 0.001, uncorrected for multiple comparisons, Z score > 3.15) revealed significant decrease in grey matter concentration only in the temporal lobes bilaterally. No abnormality was found outside the temporal lobes. The grey matter decrease was precisely located on

Discussion

Using anatomical MRI and optimized voxel-based morphometry, we found bilateral grey matter decrease localized in the superior temporal lobes in children with primary autism. Moreover, the temporal superior sulcal grey matter abnormalities observed in children with autism are entirely consistent with previously rest functional brain imaging data obtained in autism (Zilbovicius et al., 2000). Fig. 2 shows that the grey matter decrease (Fig. 2a) we report in children with autism is almost

Acknowledgements

Supported by Programme Hospitalier de Recherche Clinique-Ministère de la Santé (France), France-Télecom Foundation, and France Foundation.

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