Concordance of White Matter and Grey Matter Abnormalities in Autism Spectrum Disorders.

Background: Over the last decade, the application of neuroimaging techniques has played an important role in increasing knowledge about structural brain organization in ASD compared to normal development. Voxel-based morphometry (VBM), a computational based technique that measures focal differences in concentrations of brain tissue, has provided new insights into the changes in brain structures associated with ASD. Various clues suggest that related neural areas may vary mutually, with morphometric changes in the same or reverse direction, due to reciprocally trophic effects mediated by direct axonal connections. Objectives: We inspected two fundamental unanswered questions in the literature on Autism Spectrum Disorders (ASD): i) Are abnormalities in white (WM) and grey matter (GM) consistent with one another? And ii) Are WM morphometric alterations consistent with alterations in the GM of areas connected by these abnormal WM bundles and vice versa? The aim of this study is to bridge this gap. Methods: After selecting voxel-based morphometry and diffusion tensor imaging studies comparing autistic and normally developing groups of subjects, we conducted an Activation Likelihood Estimation (ALE) meta-analysis to estimate consistent brain alterations in ASD. Multidimensional scaling was employed to test the similarity of the results. The ALE maps were then analyzed to identify the areas of concordance between GM and WM areas. Results: We found statistically significant topological relationships between GM and WM abnormalities in ASD. The most numerous were negative concordances, found bilaterally but with a higher prevalence in the right hemisphere. Positive concordances were found in the left hemisphere. Discordances reflected the spatial distribution of negative concordances. Thus, a different hemispheric contribution emerged, possibly related to pathogenetic factors affecting the right hemisphere during early developmental stages. Besides, WM fiber tracts linking the brain structures involved in social cognition showed abnormalities, and most of them had a negative concordance with the connected GM areas. We interpreted the results in terms of altered brain networks, and their role in the pervasive symptoms dramatically impairing communication and social skills in ASD patients. Conclusions: These results represent a new step in focusing the biological basis of the core symptoms of ASD that we have described as an altered network balance, with a different hemispheric representation, interestingly possibly related to different hemispheric development timing. A pathogenetic factor activating a genetic input could alter the balance of brain development, also involving epigenetics, possibly mediated by an inflammatory and endocrinological mechanism and widely disrupting brain connectivity, thus reflecting the pervasive symptoms dramatically damaging quality communication and social skills in the early development of ASD patients.