White and Grey Matter Abnormalities and Cognitive Functioning in Autism Spectrum Disorders
Atypical brain growth in ASD has been linked to functional underconnectivity and the autism phenotype. Imaging research indicates that white matter abnormalities in autism spectrum disorder (ASD) affect long-distance neural connections and entire neural networks, mostly those of higher-order functioning. More studies are needed to better define the characteristics of the neural abnormalities and their association with cognitive deficits in ASD.
We planned to examine neuroanatomical differences between ASD adolescents and typical controls and wanted to probe whether the neuroanatomical differences in ASD are associated with cognitive functioning.
We used structural magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) to compare the neuroanatomy of 20 adolescents with ASD and 10 typical controls. We applied Voxel Based Morphometry (VBM) for a between-group comparison of the local concentration of grey and white matter, Tensor Based Morphometry (TBM) to detect group-related differences in the shape of brain regions, and DTI to quantify and compare differences in white matter (WM) microstructure. Cognitive function was measured by using the Peabody Picture Vocabulary Test Third Edition (PPVT-III).
The ASD group showed a significantly lower grey matter concentration (GMC) in inferior portions of the left frontal lobe, most notably the operculum, which includes Brodmann area 44 (Broca’s), the right superior temporal gyrus, responsible for auditory and language processing, and the left anterior cingulate, a processing switchboard implicated in learning and problem solving. The ASD group showed a significantly higher white matter concentration (WMC) in the upper portions of the frontal lobe on both sides and the middle temporal and superior temporal gyrus on the right. Activity across the frontotemporal network has been shown to be desynchronized in ASD. Significantly lower WMC was found in the mid portions of the right frontal lobe, the left cingulate gyrus, and the right postcentral gyrus, which receives the bulk of thalamocortical projections from sensory input fields.
Group-related shape differences detected significant shrinkage and expansionin the ASD group in regions that are in over-projection with the uncinate fasciculus, which connects parts of the limbic system of the temporal lobe to parts of the frontal lobe, and a significant shrinkage along the inferior temporal gyrus and the fusiform gyrus on the left side, an area implicated in face and word recognition.
PVVT-III as independent variable
We used the percentile scores from the PPVT-III instead of group designation and found a negative correlation between low scores and significantly increased GMC in the parahippocampal gyrus, along with an increased WMC and increased fractional anisotropy (FA) in the temporal lobe. In the lower scoring subjects, several regions with increased WM density were found along the uncinate fasciculus and the left and right arcuate fasciculus, which connects Broca’s with Wernicke’s.
Our results point to significant disturbances in major neural pathways in ASD. Most interestingly, our study indicates that the neurological profile of high functioning ASD subjects lies on a continuum with typically developing controls rather than clustering with that of ASD subjects with more severe cognitive impairments.