Reduced White Matter Integrity of the Default Mode Network in Children with Autism Spectrum Disorder

Background: A few previous studies have suggested reduced functional connectivity within default mode network in children and adults with autism spectrum disorder (ASD), possibly related to impaired self-reference and social cognition. However, anatomical connectivity studies of the default mode network are lacking in ASD.

Objectives: To examine the white matter integrity within the default mode network in children with ASD using probabilistic white matter fiber tracking.

Methods: Diffusion tensor imaging (DTI) data of 19 children with ASD and 17 typically developing (TD) children were acquired from a 3T MRI scanner, using single-shot diffusion-weighted EPI pulse sequence with two degrees of diffusion weighting (b=0 and 2000 s/mm², 15 non-linear directions, four repetitions). Geometric distortions due to local magnetic field inhomogeneities were corrected using field maps. T1-weighted data were also acquired using spoiled gradient-recalled (SPGR) echo pulse sequence. Diffusion tensor tractography was performed using a probabilistic tracking approach from three regions of interest (ROIs) in both hemispheres, identified using Freesurfer parcellation of T1-weighted images: posterior cingulate gyrus (PCC), medial prefrontal cortex (MFC), middle temporal lobe (MTL), and inferior parietal lobe (IPL). Shared tracts for seed pairs (PCC-MFC, PCC-MTL, MFC-IPL) were obtained from single-seed tractography for each ROI and hemisphere. Fractional anisotropy (FA) was calculated to determine the white matter integrity of shared tracts.

Results: Significant group differences were detected for FA of all three region pairs in both hemispheres. No significant group differences in hemispheric asymmetry were found. In the ASD group, FA was significantly lower for the left hemisphere (lh) PCC-MFC (0.27+/-0.008 [mean+/-sem] for ASD vs. 0.29+/-0.005 for TD, p=0.04); lh PCC-MTL (0.28+/-0.007 for ASD vs. 0.30+/-0.005 for TD, p=0.03); lh MFC-IPL (0.27+/-0.007 for ASD vs. 0.29+/-0.005 for TD, p=0.05). Similar results were also found for the right hemisphere (rh): rh PCC-MFC (0.29+/-0.007 for ASD vs. 0.31+/-0.004 for TD, p=0.01); rh PCC-MTL (0.29+/-0.007 for ASD vs. 0.31+/-0.005 for TD, p=0.03); rh MFC-IPL (0.28+/-0.007 for ASD vs. 0.30+/-0.004 for TD, p=0.03).

Conclusions: These results suggest impairment of white matter tracts among regions of the default mode network in children with ASD, consistent with atypical functional connectivity of this network, as previously reported. Convergent functional and anatomical connectivity findings indicate that the default mode network may be one of (potentially many) atypically organized brain networks contributing to sociocommunicative impairments in ASD.