Are there shared neural correlates between dyslexia and ADHD? A meta-analysis of voxel-based morphometry studies

Abstract

Background: Dyslexia and Attention-deficit/hyperactivity disorder (ADHD) are highly comorbid neurodevelopmental disorders (estimates of 25-40% bidirectional comorbidity). Previous work has identified strong genetic and cognitive overlap between the disorders, but neural overlap is relatively unexplored. This study is a systematic meta-analysis of existing voxel-based morphometry studies to determine whether there is any overlap in the gray matter correlates of both disorders.

Methods: We conducted anatomic likelihood estimate (ALE) meta-analyses of voxel-based morphometry studies in which individuals with dyslexia (15 studies; 417 cases, 416 controls) or ADHD (22 studies; 898 cases, 763 controls) were compared to typically developing controls. We generated ALE maps for dyslexia vs. controls and ADHD vs. controls using more conservative (p < .001, k = 50) and more lenient (p < .005, k = 50) thresholds. To determine the overlap of gray matter correlates of dyslexia and ADHD, we examined the statistical conjunction between the ALE maps for dyslexia vs. controls and ADHD vs. controls (false discovery rate [FDR] p < .05, k = 50, 5000 permutations).

Results: Results showed largely distinct gray matter differences associated with dyslexia and ADHD. There was no evidence of statistically significant gray matter overlap at our conservative threshold, and only one region of overlap in the right caudate at our more lenient threshold. Reduced gray matter in the right caudate may be relevant to shared cognitive correlates in executive functioning and/or procedural learning. The more general finding of largely distinct regional differences in gray matter between dyslexia and ADHD suggests that other neuroimaging modalities may be more sensitive to overlapping neural correlates, and that current neuroimaging recruitment approaches may be hindering progress toward uncovering neural systems associated with comorbidity.

Conclusions: The current study is the first to meta-analyze overlap between gray matter differences in dyslexia and ADHD, which is a critical step toward constructing a multi-level understanding of this comorbidity that spans the genetic, neural, and cognitive levels of analysis.

Keywords: Attention-deficit/hyperactivity disorder; Caudate; Dyslexia; Meta-analysis; Voxel-based morphometry.

Fig. 1

PRISMA flow chart of literature search and screening for ADHD and dyslexia voxel-based morphometry case-control studies. From [46]. For more information, visit www.prisma-statement.org

Fig. 2

Decreased gray matter in ADHD and dyslexia. Regions of statistically significant ALE values (p_uncorrected < .001, k = 50) indicating decreased GM in ADHD vs. TD (yellow-orange) and dyslexia vs. TD (violet) are shown on the same template. FG frontal gyrus, Cb cerebellum, IFG inferior frontal gyrus, Inf inferior, MTG middle temporal gyrus, STG superior temporal gyrus, IPL inferior parietal lobule, SFG superior frontal gyrus

Fig. 3

Increased gray matter in ADHD and dyslexia. Regions of statistically significant ALE values (p_uncorrected < .001, k = 50) indicating increased GM in ADHD vs. TD (red) and dyslexia vs. TD (blue) are shown on the same template. MTG middle temporal gyrus, SMA supplementary motor area, IPL inferior parietal lobule, Cb cerebellum, STG superior temporal gyrus, med medial, mid middle, FG frontal gyrus, SFG superior frontal gyrus

Fig. 4

Conjunction of the ADHDp_uncorrected < .005, k = 50. There is visual overlap between the maps in the caudate bilaterally, left hippocampus, left cerebellum, and bilateral vmPFC. Results of the statistical conjunction analysis (FDR p < .05, k = 50) reveal overlap in the right caudate (cyan, bottom row). vmPFC ventromedial prefrontal cortex