Alterations in Frontal Lobe Tracts and Corpus Callosum in Young Children with Autism Spectrum Disorder

Background:

It has been suggested that autism spectrum disorder (ASD) may be a disorder of brain networks, rather than associated with dysfunction in discrete brain regions and a number of studies have found abnormalities in the brain white matter, particularly in frontal lobe and corpus callosum.

Objectives:

In the present study, we used magnetic resonance diffusion tensor imaging (DTI) to investigate the major association tracts of the frontal lobe and the corpus callosum in young children with ASD.

Methods:

Thirty-five children with ASD (mean age: 5.1 years; range: 2.3-8.8 years, 30 males and 5 females) and 16 typically developing children (mean age: 5.5 years; range: 2.5-8.6 months, 12 males and 4 females), underwent neuropsychological evaluation and DTI. The uncinate fasciculus (UF), inferior fronto-occipital fasciculus (IFO), arcuate fasciculus (AF), cingulum (Cg), and corpus callosum (CC) were isolated using DTI tractography and fractional anisotropy (FA), apparent diffusion coefficient (ADC), mean fiber length, mean fiber volume and mean fiber density were calculated for each fiber tract. In order to independently confirm the results (FA, ADC) obtained by tractography, we also performed tract based spatial statistics (TBSS), an automated, operator-independent voxel-wise analysis, of brain white matter.

Results:

Right UF (p=0.02), bilateral IFO (p=0.04 for both left and right), left AF (p=0.01), right Cg (p=0.04) and CC (p=0.03) had significantly decreased FA in ASD group compared to controls. Right AF was found to have significantly increased diffusivity (ADC) in ASD group compared to controls (p=0.04). TBSS analysis also revealed that the voxels in the regions of bilateral UF, IFO, AF, right Cg and CC had significantly different FA between the two groups (reduced FA in ASD group). Left UF showed shorter fiber length (p=0.008), while right UF had significantly longer fiber length (p=0.04), increased fiber volume (p=0.01) and higher fiber density (p=0.006) in ASD group compared to controls. There was also a reversed pattern of asymmetry in average fiber length (p=0.001) and fiber density (p=0.006) of the UF in the ASD group compared to controls: average fiber length and fiber density of the right UF was higher than those of the left UF in the ASD group, whereas this pattern was opposite in controls. CC, in ASD group, had significantly longer fiber length (p=0.008) with higher fiber density (p=0.009). Left Cg was also found to have significantly higher fiber density in the ASD group (p=0.02). There was also difference in the fiber length distribution of right UF and right AF between the two groups. Whereas, both right UF and right AF had bi-modal distribution of fiber length in controls, the right UF had a significantly larger second peak (fiber distribution skewed to the right; p=0.009) and the right AF was uni-modal and sharper (right skewed; p=0.03) in the ASD group, indicating more longer fibers in these tracts.

Conclusions:

We found qualitative and quantitative abnormalities in frontal lobe white matter tracts and corpus callosum in young children with ASD, which may indicate developmental dysregulation of neuronal connectivity.