Reading the dyslexic brain: multiple dysfunctional routes revealed by a new meta-analysis of PET and fMRI activation studies

Abstract

Developmental dyslexia has been the focus of much functional anatomical research. The main trust of this work is that typical developmental dyslexics have a dysfunction of the phonological and orthography to phonology conversion systems, in which the left occipito-temporal cortex has a crucial role. It remains to be seen whether there is a systematic co-occurrence of dysfunctional patterns of different functional systems perhaps converging on the same brain regions associated with the reading deficit. Such evidence would be relevant for theories like, for example, the magnocellular/attentional or the motor/cerebellar ones, which postulate a more basic and anatomically distributed disorder in dyslexia. We addressed this issue with a meta-analysis of all the imaging literature published until September 2013 using a combination of hierarchical clustering and activation likelihood estimation methods. The clustering analysis on 2360 peaks identified 193 clusters, 92 of which proved spatially significant. Following binomial tests on the clusters, we found left hemispheric network specific for normal controls (i.e., of reduced involvement in dyslexics) including the left inferior frontal, premotor, supramarginal cortices and the left infero-temporal and fusiform regions: these were preferentially associated with reading and the visual-to-phonology processes. There was also a more dorsal left fronto-parietal network: these clusters included peaks from tasks involving phonological manipulation, but also motoric or visuo-spatial perception/attention. No cluster was identified in area V5 for no task, nor cerebellar clusters showed a reduced association with dyslexics. We conclude that the examined literature demonstrates a specific lack of activation of the left occipito-temporal cortex in dyslexia particularly for reading and reading-like behaviors and for visuo-phonological tasks. Additional deficits of motor and attentional systems relevant for reading may be associated with altered functionality of dorsal left fronto-parietal cortex.

Keywords: ALE; PET; developmental dyslexia; fMRI; hierarchical clustering; meta-analysis.

Figure 1

Peaks of reduced activations in dyslexia for all tasks that involved reading (circles in red), for visual or auditory phonological tasks (circles in blue and in green, respectively) and for non-linguistic tasks (circles in yellow). (A) Show the highly replicated reduction of dyslexics at the level of the left ventral occipito-temporal peaks reported in literature. In (B) all the peaks of reduced activations observed in dyslexics during reading tasks included in our meta-analysis are reported. Finally, in (C) all the peaks of reduced activations observed in dyslexics during reading, phonological and non-linguistic tasks included in our meta-analysis are reported.

Figure 2

A schematic flowchart diagram showing the procedure by which data are selected, clusters are estimated, tested and classified using HC and ALE.

Figure 3

Clusters identified with HC (A), clusters identified using ALE approach (B) and the final data-set of clusters, identified in both HC and ALE meta-analyses and considered for post-hoc statistical analyses (C).

Figure 4

Distribution of group-related clusters that showed a spatial congruence in the HC and ALE procedures. The red dots represent the control-related clusters that fell in reading and phonological specific activations in Danelli et al. (2013), the blue dots represent the control-related clusters that were not observed in Danelli et al. (2013) and the green dots represent the control-related clusters fell in visual motion and motoric activations in Danelli et al. (2013). The right yellow dots represent the control-related cluster identified by the meta-analysis restricted to the non-reading-like tasks. Finally, dyslexic-related clusters are reported in cyan.

Figure 5

Clusters that showed a significant group-by-task and group-by-age interaction effect. For each clusters a histogram describe the peak distribution across group/conditions.

Figure 6

Overlap of raw data, group-related clusters and the MT/V5 region of interest extracted from activations reported by Eden et al. (1996) in normal controls.

Figure 7

Cerebellar clusters identified in both HC and ALE meta-analyses. In none of these there was a significant association with normal controls.