Cerebellar morphology in developmental dyslexia
Introduction
Developmental dyslexia is now well established as a disorder of neurobiological origin. Documented abnormalitites include visual [8], [34], [53] and auditory processing deficits [35], [54], [59], probable altered lateral cerebral asymmetry [29], [32], [47] histological and biochemical cerebral abnormalities [20], [42], [45] and altered patterns of cerebral activation on particular visual, auditory and verbal tasks [9], [13], [40], [44], [46], [49].
Evidence has emerged to implicate the cerebellum in some aspects of dyslexic dysfunction. Indirect evidence includes the presence of “soft cerebellar signs”, delayed motor milestones such as crawling, walking and learning to ride a bicycle and a characteristic clumsiness [14], [15], [16], [38]. Evidence directly indicating cerebellar involvement has also emerged. We have previously shown biochemical abnormalities in the right cerebellum of people with developmental dyslexia compared to control subjects and also differences in the right side of dyslexic cerebellum compared to the left side [42]. The right cerebellum has also been shown to display a functional deficit, exhibiting decreased blood flow in response to both learned and novel motor tasks [37]. Blamire et al. [5] have shown biochemical abnormalities similar to those seen in humans with dyslexia [42] in the cerebella of mice injected with sera from mothers who have two or more dyslexic offspring, and have shown that the degree of severity of the biochemical abnormality correlates significantly with motor performance in these mice.
Morphological examination of the brains of those with dyslexia has typically been confined to the cerebral cortex, mostly focussing on the planum temporale [36]. These studies have yielded contradictory findings (e.g. [20], [26], [27], [32], [52]) and may have been confounded by the method employed and how handedness was assessed (reviewed in [3], [28]). Galaburda et al. [20] analysed brains from persons with dyslexia post-mortem. These brains showed symmetry in the planum temporale (a temporal lobe language area), an effect that was argued to result from enlarged right hemisphere areas rather than a relative decrease on the left side. The cortical symmetry was later interpreted as a difference (increase) in the numbers of right hemisphere neurons [17], a potential consequence of altered neuronal migration patterns and/or a decreased rate of neuronal “pruning” in development. Patterns of neuronal migration may be abnormal in dyslexics [20] and our own magnetic resonance spectroscopy (MRS) studies have provided data consistent with different patterns of relative cell distribution in the right temporo-parietal lobe compared with the left, a histological/biochemical asymmetry which is not present in control subjects [42].
Little is known about the morphology/asymmetry of the cerebellum in developmental dyslexia so, given our findings of anomalous cerebellar biochemistry in dyslexia, it was of interest to determine whether cerebellar morphology in dyslexia reflects anomalous patterns already reported in the cortex. Therefore, we quantified cerebellar asymmetry by the comparison of relative amounts of tissue on the left and right sides of the cerebellum as well as relative amounts of grey and white matter on each side using subjects from our recent MRS study.
Section snippets
Subjects
Twenty adult male volunteers, aged 20–41 years, participated with informed consent. Nine were normal readers and 11 had prior histories of developmental dyslexia. These men were recruited for an investigation into possible alterations in brain biochemistry in developmental dyslexia as detailed previously [42]. The study was approved by the Central Oxford Research Ethics Committee.
All the individuals with dyslexia had been formally diagnosed by educational psychologists as reading disabled,
Between group differences in cerebellar asymmetry
The ratio of left grey matter to right grey matter was greater in the cerebella of those with dyslexia than in the controls (P=0.068, Mann–Whitney U-test, the medians were 0.89 for controls and 0.99 for dyslexic group). Inspection of relative volumes revealed that this was due to a significant left/right asymmetry present in controls (left grey/total volume median=0.35 versus right grey/total volume median=0.39 in controls, P=0.05, Wilcoxon signed rank test) which was absent in dyslexics (0.38
Cerebellar asymmetry
Clear morphometric differences in the ratios of the left and right cerebellar hemispheres, specifically in the grey matter, were found between the dyslexics and the controls. Dyslexics were found to have symmetric cerebellar grey matter whereas the controls had greater asymmetry (right>left). Such differences can be interpreted as a trend toward increased symmetry of the hemispheres in the dyslexic group compared to the control group. In the control group, left hemisphere volumes were smaller
Conclusion
The relationship of cerebellar asymmetry to word reading skill and handedness, together with our previous finding of altered metabolite ratios in the cerebellum of dyslexics leads us to suggest that there are metabolic and morphological alterations in the cerebellum which relate to reading skills, in addition to motor skills and handedness.
Acknowledgements
This work was supported by the Medical Research Council of Great Britain and the Australian National Health and Medical Research Council. Individuals were also supported by the NHMRC (RD Wright Fellowship, CR) and the Faculty of Medicine and the Prince of Wales Medical Research Institute, UNSW (JH).
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