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.
    Full-text · Article · May 2015 · Brain
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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.
    Full-text · Article · Mar 2014 · Journal of Autism and Developmental Disorders
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    • "Concerning investigations with VBM, there is a trend towards increased gray 203 matter volumes in adolescents with autism compared to healthy individuals, par- 204 ticularly affecting frontal and temporal lobes (Waiter et al. 2004; Hazlett et al. 205 2006; Bonilha et al. 2008), together with a reduction of the white matter volumes 206 (Chung et al. 2004; Waiter et al. 2005; Bonilha et al. 2008; Jou et al. 2011) mainly 207 involving the corpus callosum and the medial frontal lobes. Other areas of 208 decreased white matter size included internal capsule, superior longitudinal fascic- 209 ulus, corona radiata, and temporal and parietal regions (Waiter et al. 2005; Bonilha 210 et al. 2008), although not in all studies (Hazlett et al. 2006). "
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    ABSTRACT: This chapter is focused on the developmental trajectory of the white matter in autism. The most recent results of volumetric and diffusivity studies are reported and widely described by subdividing them according to different age ranges. The first part is dedicated to the early childhood, and data presented showed an altered trajectory of brain growth in the first years of life that results in bigger brain volumes in children with autism at 2 or 3 years of life. During childhood, multiple alterations of both volumetric and diffusivity indexes are reported, in a widespread network involving fronto-temporoparietal regions. In the last part, the outcomes of such altered white matter maturation are analyzed, reporting studies on adolescence and adulthood. Results showed persistent alterations in the frontal and temporal white matter and in the corpus callosum. All together these evidences support the view that brain alterations in autism cannot be attributed to a focal dysfunction but have to be considered as a widespread alteration of brain maturation, particularly as a disorder of white matter connectivity.
    Full-text · Chapter · Jan 2014
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