Diffusion MRI tractography in the brain white matter. PLoS ONE 3(12): e4006. doi:10.1371/journal.pone.0004006

Autism is increasingly recognised as a disorder of abnormal connectivity patterns in the brain, particularly a decrease in the connectivity of the long distance tracts of the cortex. For example, it has been suggested that language deficits in autism could be attributed to altered connectivity between language regions in the brain, leading to poor integration of linguistic functions. Post-mortem, functional MRI and structural imaging studies support the theory of aberrant brain connectivity. One of the most powerful structural imaging methods is diffusion tensor imaging (DTI), which can be used to measure the orientation and integrity of white matter tracts.

However, a number of DTI studies investigating people with autism spectrum disorders (ASDs) have yielded inconsistent results and it has remained unclear which of the seven major long-distance tracts are involved. In a study published in Molecular Autism, Yuta Aoki from the University of Tokyo, Japan and colleagues, performed the first systematic review and meta-analysis of region-of-interest DTI studies in individuals with autism spectrum disorders (ASDs).

A comprehensive search of the literature from 1980  through to 2012 identified 25 relevant DTI studies comparing ASDs and typical development with region-of-interest methods. DTI probes white matter integrity by examining the direction of water diffusion, using measures such as fractional anisotropy and mean diffusivity. A random effects model demonstrated significant reductions in fractional anisotropy in the corpus callosum and left uncinate fasciculus, as well as significant increases in mean diffusivity in the corpus callosum and superior longitudinal fasciculus in individuals with ASDs compared with typically developing individuals.

The results of their meta-analysis strongly demonstrate that changes in white matter integrity in people with ASDs are localized to three of the seven major long distance tracts – the corpus callosum, the uncinate fasciculus and the superior longitudinal fasciculus. This further supports the hypothesis of long distance under-connectivity.

Although fractional anisotropy values generally reflect factors such as cellular membrane integrity and fiber myelination, the authors note that the abnormalities underlying the reduction in fractional anisotropy values in people with ASDs are yet to be specified. Moreover, these abnormalities may differ amongst different subpopulations and they anticipate that future work in this area will likely to account for the heterogeneities currently observed amongst people with autism.

Just like other scientific theories evolving in autism research, investigations into the under-connectivity hypothesis provide a useful means for uncovering the nature of autism, as demonstrated by studies such as that presented by Aoki and colleagues.

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