Gray Matter Features of Reading Disability: A Combined Meta-Analytic and Direct Analysis Approach

Abstract

Meta-analysis of voxel-based morphometry dyslexia studies and direct analysis of 293 reading disability and control cases from 6 different research sites were performed to characterize defining gray matter features of reading disability. These analyses demonstrated consistently lower gray matter volume in left posterior superior temporal sulcus/middle temporal gyrus regions and left orbitofrontal gyrus/pars orbitalis regions. Gray matter volume within both of these regions significantly predicted individual variation in reading comprehension after correcting for multiple comparisons. These regional gray matter differences were observed across published studies and in the multi-site dataset after controlling for potential age and gender effects, and despite increased anatomical variance in the reading disability group, but were not significant after controlling for total gray matter volume. Thus, the orbitofrontal and posterior superior temporal sulcus gray matter findings are relatively reliable effects that appear to be dependent on cases with low total gray matter volume. The results are considered in the context of genetics studies linking orbitofrontal and superior temporal sulcus regions to alleles that confer risk for reading disability.

Significance Statement: Developmental reading disability limits educational, social, and professional achievement for approximately 5-15% of the U.S. population. The neuroanatomical bases for reading disability have been unclear, in part because of the heterogeneous nature of this complex disorder. A combined meta-analysis and direct data analysis of a large multi-site dataset revealed consistent left orbitofrontal and left superior temporal sulcus gray matter volume effects in reading disability compared to control cases that rise above the considerable behavioral and anatomical variance in reading disability samples. Importantly, these gray matter predictors of reading disability have been significantly associated with genetic markers that confer risk for reading disability. Thus, the results demonstrate brain regions that are consistently affected in the heterogeneous reading disability population.