No Evidence for Systematic White Matter Correlates of Dyslexia: An Activation Likelihood Estimation Meta-Analysis

Abstract

Dyslexia is a prevalent neurodevelopmental disorder, characterized by reading and spelling difficulties. Beyond the behavioral and functional correlates of this condition, a growing number of studies have explored structural differences between individuals with dyslexia and typically developing individuals. To date, findings remain disparate -some studies suggest differences in fractional anisotropy (FA), an indirect measure of white matter integrity, whereas others do not identify significant disparities. Here, we synthesized the existing literature on this topic by conducting a meta-analysis of Diffusion Tensor Imaging (DTI) studies investigating white matter correlates of dyslexia via voxel-based analyses (VBA) of FA. Our results showed no reliable clusters underlying differences between dyslexics and typical individuals, after correcting for multiple comparisons (false discovery rate correction).Because group comparisons might be too coarse to yield subtle differences, we further explored differences in FA as a function of reading ability, measured on a continuous scale. Consistent with our initial findings, reading ability was not associated with reliable differences in white matter integrity. These findings nuance the current view of profound, structural differences underlying reading ability and its associated disorders, and suggest that their neural correlates might be more subtle than previously thought.

A Large-Scale Investigation of White Matter Microstructural Associations with Reading Ability

“…While our largely null results stand in opposition to previous studies reported significant FA-reading associations or group differences, a recent meta-analysis of VBA studies has suggested that these findings are not robust (Moreau et al, 2018). The present study extends this in a tract-based paradigm, using a single data set to mitigate concerns of variability from scanning protocol confounding results (Schilling et al, 2021b).…”

“…The number of participants was exceptionally large, the TOWRE is a widely used and well-established measure of single-word reading ability, and the analyses took advantage of progress in DWI analytic methods. Our largely null findings, while not consistent with several individual DTI studies of reading, are consistent with recent larger-scale meta-analyses of neuroanatomical studies of dyslexia (Moreau et al, 2018;. Without replicating individual processing pipelines, it is difficult 29 to identify precise reasons previous results were or were not consistent with this study.…”

“…We additionally looked for tract-specific differences in FA between groups of children with and without reading disabilities. Considering the limited sensitivity of group difference analyses and the meta-analysis by (Moreau et al, 2018), we did not expect to find significant FA group differences. However, with the added specificity of using tract-based ROIs and sensitivity from an individual differences approach, we hypothesized that several tracts, particularly in the left hemisphere, would exhibit positive associations between FA and reading scores.…”

“…Despite the general trend of higher FA relating to better reading and modest agreement in reading tract outcomes, a meta-analysis showed no evidence for systemic FA disruptions in dyslexia (Moreau et al, 2018). Small cohort sizes, inhomogeneous acquisition parameters, employment of different reading measures, variety of age groups, and diversity in processing and analytical methods may underlie the inconsistencies in past results (Moreau et al, 2018;Schilling et al, 2021a). To address this, we leveraged a large database, the Healthy Brain Network (Alexander et al, 2017), to investigate white matter microstructural correlates of individual differences in single-word and single-nonword aptitude in children with diverse reading abilities.…”

“…In the MCP, separate studies have paradoxically reported a higher FA in dyslexic readers compared to typically developing readers (Richards et al, 2008) as well as a positive association between FA and reading skills (Lebel et al, 2013;Travis et al, 2015). Despite the general trend of higher FA relating to better reading and modest agreement in reading tract outcomes, a meta-analysis showed no evidence for systemic FA disruptions in dyslexia (Moreau et al, 2018). Small cohort sizes, inhomogeneous acquisition parameters, employment of different reading measures, variety of age groups, and diversity in processing and analytical methods may underlie the inconsistencies in past results (Moreau et al, 2018;Schilling et al, 2021a).…”