How reliable are gray matter disruptions in specific reading disability across multiple countries and languages? Insights from a large-scale voxel-based morphometry study.

The neural basis of specific reading disability (SRD) remains only partly understood. A dozen studies have used voxel-based morphometry (VBM) to investigate gray matter volume (GMV) differences between SRD and control children, however, recent meta-analyses suggest that few regions are consistent across studies. We used data collected across three countries (France, Poland, and Germany) with the aim of both increasing sample size (236 SRD and controls) to obtain a clearer picture of group differences, and of further assessing the consistency of the findings across languages. VBM analysis reveals a significant group difference in a single cluster in the left thalamus. Furthermore, we observe correlations between reading accuracy and GMV in the left supramarginal gyrus and in the left cerebellum, in controls only. Most strikingly, we fail to replicate all the group differences in GMV reported in previous studies, despite the superior statistical power. The main limitation of this study is the heterogeneity of the sample drawn from different countries (i.e., speaking languages with varying orthographic transparencies) and selected based on different assessment batteries. Nevertheless, analyses within each country support the conclusions of the cross-linguistic analysis. Explanations for the discrepancy between the present and previous studies may include: (1) the limited suitability of VBM to reveal the subtle brain disruptions underlying SRD; (2) insufficient correction for multiple statistical tests and flexibility in data analysis, and (3) publication bias in favor of positive results. Thus the study echoes widespread concerns about the risk of false-positive results inherent to small-scale VBM studies.