White matter compromise of callosal and subcortical fiber tracts in children with autism spectrum disorder: a diffusion tensor imaging study

Abstract

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.

Figure 1

Representative slices showing the region of interest (ROI) placement (rectangle box) in the genu, body and splenium of the corpus callosum (A–C), genu and anterior and posterior limbs of the internal capsule (D) and middle cerebellar peduncle (E). Note: ROIs were drawn in native space on B0 images on three representative slices that were selected to allow positioning of ROIs in the body, genu, and splenium of the callosum and genu, anterior and posterior limbs of the internal capsule in both hemispheres. Axial slices showing maximal thickness of corpus callosum (for body, genu and splenium separately) and internal capsule were identified and then ROIs were placed on three contiguous slices. For the corpus callosum, two ROIs (70μl each) were placed on each slice (reference slice and slices inferior and superior to the reference slice) for body and splenium and one for the genu. For the internal capsule, on each of the three contiguous slices (reference slice and slices inferior and superior to the reference slice), one ROI (70μl) was placed on the genu and anterior and posterior limbs of the internal capsule in each hemisphere. Left and right middle cerebellar peduncles were selected from one slice showing maximal thickness, with a volume of 158μl each. All ROI placements were confirmed by viewing them on sagittal images for any partial volume effect.

Figure 2

Fractional anisotropy (FA), mean diffusion (MD), axial and radial diffusion (mean±sem) for whole brain white matter. Note: ASD = Autism Spectrum Disorder. *p<0.05 (corr.); **p<0.005 (corr.).

Figure 3

Fractional anisotropy (FA), mean diffusion (MD), axial and radial diffusion (mean±sem) for the genu, body and splenium of the corpus callosum; anterior limb (AL), genu and posterior limb (PL) of the internal capsule bilaterally; and middle cerebellar peduncle (MCP) bilaterally. Note: ASD = Autism Spectrum Disorder. *, p<0.05 (corr.); **, p<0.005 (corr.).