New research
White Matter Compromise of Callosal and Subcortical Fiber Tracts in Children With Autism Spectrum Disorder: A Diffusion Tensor Imaging Study

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Objective

Autism spectrum disorder (ASD) is increasingly viewed as a disorder of functional networks, highlighting the importance of investigating white matter and interregional connectivity. We used diffusion tensor imaging (DTI) to examine white matter integrity for the whole brain and for corpus callosum, internal capsule, and middle cerebellar peduncle in children with ASD and typically developing (TD) children.

Method

DTI data were obtained from 26 children with ASD and 24 matched TD children. Fractional anisotropy (FA), mean diffusivity (MD), and axial and radial diffusion were calculated for the whole brain, the genu, body, and splenium of the corpus callosum, the genu and anterior and posterior limbs of the internal capsule, and the middle cerebellar peduncle.

Results

Children with ASD had reduced FA and increased radial diffusion for whole-brain white matter and all three segments of the corpus callosum and internal capsule, compared with those in TD children. Increased MD was found for the whole brain and for anterior and posterior limbs of the internal capsule. Reduced axial diffusion was found for the body of corpus callosum. Reduced FA was also found for the middle cerebellar peduncle.

Conclusions

Our findings suggest widespread white matter compromise in children with ASD. Abnormalities in the corpus callosum indicate impaired interhemispheric transfer. Results for the internal capsule and middle cerebellar peduncle add to the currently limited DTI evidence on subcortico-cortical tracts in ASD. The robust impairment found in all three segments of the internal capsule is consistent with studies documenting impairment of elementary sensorimotor function in ASD.

Section snippets

Participants

A total of 26 children with ASD (24 male and two female) and 24 TD children (23 male and one female), matched for age and nonverbal IQ were included (Table 1 and Table S1, available online). The ASD group consisted of 15 children with autistic disorder and 11 children with Asperger's disorder. Clinical diagnoses were made by an expert clinical psychologist (A.J.L.) using the Autism Diagnostic Interview–Revised (ADI-R)36 and the Autism Diagnostic Observation Schedule (ADOS).37 Children with

Results

For whole-brain white matter, FA was significantly decreased (p = .004), whereas MD and radial diffusion were significantly increased (p = .01 and .007, respectively) in the ASD group compared with the TD group. The group difference in axial diffusion did not reach significance (p = .22; Figure 2).

Pearson correlation analysis was performed to detect possible effects of age and IQ on the DTI indices. Age was negatively correlated with MD of the posterior limb of the internal capsule in both the

Discussion

Our findings add to the evidence of widespread white matter compromise in ASD, as first suggested by preliminary observations in a small-sample study by Barnea-Goraly et al.9 We observed reduced FA and increased MD and radial diffusion for whole-brain white matter in our cohort of children and adolescents with ASD, indicating loss of directional coherence of fiber bundles, reduced fiber density, and impaired myelination or axonal integrity.45, 46 In each of our ROIs, mean differences in the

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    This study was supported by National Institutes of Health grants R01-DC006155 and R01-MH081023, with additional funding from NIDCD1T32 DC007361-03 (B.K.).

    The authors express special thanks to the children and families who participated.

    Disclosure: Drs. Shukla, Müller, and Lincoln, and Mr. Keehn report no biomedical financial interests or potential conflicts of interest.

    Supplemental material cited in this article is available online.

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