Structural white matter deficits in high-functioning individuals with autistic spectrum disorder: A voxel-based investigation Neuroimage

Department of Radiology, University of Aberdeen, Aberdeen, UK.
NeuroImage (Impact Factor: 6.36). 02/2005; 24(2):455-61. DOI: 10.1016/j.neuroimage.2004.08.049
Source: PubMed


A number of imaging and neuropathological studies have reported structural abnormalities in white matter areas such as the corpus callosum in autism spectrum disorder (ASD). Differences in both global brain volume and the size of specific neural structures have been reported. In order to expand these previously reported findings and to describe more precisely the nature of such structural changes, we performed a voxel-based morphometric whole brain analysis, using a group-specific template, in male adolescents with ASD. Fifteen individuals with normal intelligence and ASD, and a group of 16 controls, matched for age, sex, and IQ, were investigated. High-resolution T1-weighted 3D data sets were acquired and analysed. Local white matter volume deficits were found in the corpus callosum, particularly in the anterior splenium and isthmus, and right hemisphere. White matter volume deficits were also found in the left middle temporal, right middle frontal, and left superior frontal gyri. No significant areas of increased white matter volume were found. Our findings support the hypothesis that reduced white matter volume in the corpus callosum and right hemisphere may play a role in the pathophysiology of ASD.

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    • "Early MRI studies of autism found significant reductions in the corpus callosum, particularly among posterior regions, in children and adults with autistic disorder relative to control subjects (Egaas et al., 1995; Piven et al., 1997; Manes et al., 1999). More recent work using higher resolution imaging protocols have identified similar reductions in corpus callosum size in adults (Freitag et al., 2009) and both children and adults (Waiter et al., 2005; Just et al., 2007; Hardan et al., 2009; Keary et al., 2009) with ASD. A meta-analysis of this work indicates that decreased corpus callosum size associated with ASD is observed in terms of total corpus callosum area as well as most subdivisions (Frazier and Hardan, 2009). "
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    ABSTRACT: Numerous brain imaging studies indicate that the corpus callosum is smaller in older children and adults with autism spectrum disorder. However, there are no published studies examining the morphological development of this connective pathway in infants at-risk for the disorder. Magnetic resonance imaging data were collected from 270 infants at high familial risk for autism spectrum disorder and 108 low-risk controls at 6, 12 and 24 months of age, with 83% of infants contributing two or more data points. Fifty-seven children met criteria for ASD based on clinical-best estimate diagnosis at age 2 years. Corpora callosa were measured for area, length and thickness by automated segmentation. We found significantly increased corpus callosum area and thickness in children with autism spectrum disorder starting at 6 months of age. These differences were particularly robust in the anterior corpus callosum at the 6 and 12 month time points. Regression analysis indicated that radial diffusivity in this region, measured by diffusion tensor imaging, inversely predicted thickness. Measures of area and thickness in the first year of life were correlated with repetitive behaviours at age 2 years. In contrast to work from older children and adults, our findings suggest that the corpus callosum may be larger in infants who go on to develop autism spectrum disorder. This result was apparent with or without adjustment for total brain volume. Although we did not see a significant interaction between group and age, cross-sectional data indicated that area and thickness differences diminish by age 2 years. Regression data incorporating diffusion tensor imaging suggest that microstructural properties of callosal white matter, which includes myelination and axon composition, may explain group differences in morphology.
    Brain 05/2015; 138(Pt 7). DOI:10.1093/brain/awv118 · 9.20 Impact Factor
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    • "Among WM tracts, the corpus callosum (CC) has been reported to be one of the most commonly affected WM tracts in patients with ASD (Aoki et al. 2013). Structural magnetic resonance imaging (MRI) studies have found a significant reduction in volume of the total CC (Hardan et al. 2009b; Keary et al. 2009), rostrum (Keary et al. 2009), genu (Keary et al. 2009; Vidal et al. 2006), body (Hardan et al. 2009b; Keary et al. 2009), isthmus (Freitag et al. 2009; Waiter et al. 2005) and splenium (Hardan et al. 2009b; Vidal et al. 2006; Waiter et al. 2005) in patients with ASD compared to healthy controls. In addition, a reduced FA and AD, and an increased RD of the total CC and its subdivisions in patients with ASD have been reported using several DTI techniques, such as voxel-based morphometry (VBM) (Barnea-Goraly et al. 2004), tractbased spatial statistics (TBSS) (Bakhtiari et al. 2012), and region-of-interest (ROI) analyses (Shukla et al. 2010). "
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    ABSTRACT: In addition to social and communicative deficits, many studies have reported motor deficits in autism spectrum disorder (ASD). This study investigated the macro and microstructural properties of the corpus callosum (CC) of 18 children with ASD and 12 typically developing controls using diffusion tensor imaging tractography. We aimed to explore whether abnormalities of the CC were related to motor deficits, as well as social and communication deficits in children with ASD. The ASD group displayed abnormal macro and microstructure of the total CC and its subdivisions and its structural properties were related to socio-communicative deficits, but not to motor deficits in ASD. These findings advance our understanding of the contributions of the CC to ASD symptoms.
    Journal of Autism and Developmental Disorders 03/2014; 44(9). DOI:10.1007/s10803-014-2096-8 · 3.06 Impact Factor
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    • "Following this initial acceleration, growth rates decline significantly causing an apparent normalization of brain volume by adolescence and early adulthood (Courchesne et al., 2001, Courchesne et al., 2004; Waiter et al., 2005). This relative decrease is most marked in the white matter in that children with autism experience only a 10% increase in cerebral white matter between the ages of 3 and 12 years (Courchesne et al., 2001). "
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    ABSTRACT: Current theories concerning the cause of autism spectrum disorders (ASDs) have converged on the concept of abnormal development of brain connectivity. This concept is supported by accumulating evidence from functional imaging, diffusion tensor imaging, and high definition fiber tracking studies which suggest altered microstructure in the axonal tracts connecting cortical areas may underly many of the cognitive manifestations of ASD. Additionally, large-scale genomic studies implicate numerous gene candidates known or suspected to mediate neuritic outgrowth and axonal guidance in fetal and perinatal life. Neuropathological observations in postmortem ASD brain samples further support this model and include subtle disturbances of cortical lamination and subcortical axonal morphology. Of note is the relatively common finding of poor differentiation of the gray-white junction associated with an excess superficial white matter or "interstitial" neurons (INs). INs are thought to be remnants of the fetal subplate, a transient structure which plays a key role in the guidance and morphogenesis of thalamocortical and cortico-cortical connections and the organization of cortical columnar architecture. While not discounting the importance of synaptic dysfunction in the etiology of ASD, this paper will briefly review the cortical abnormalities and genetic evidence supporting a model of dysregulated axonal growth and guidance as key developmental processes underlying the clinical manifestations of ASD.
    Frontiers in Human Neuroscience 10/2013; 7:671. DOI:10.3389/fnhum.2013.00671 · 3.63 Impact Factor
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