title: Brain classification reveals the right cerebellum as the best biomarker of dyslexia.
abstract: BACKGROUND
  Developmental dyslexia is a specific cognitive disorder in reading acquisition that has genetic and neurological origins. Despite histological evidence for brain differences in dyslexia, we recently demonstrated that in large cohort of subjects, no differences between control and dyslexic readers can be found at the macroscopic level (MRI voxel), because of large variances in brain local volumes. In the present study, we aimed at finding brain areas that most discriminate dyslexic from control normal readers despite the large variance across subjects. After segmenting brain grey matter, normalizing brain size and shape and modulating the voxels' content, normal readers' brains were used to build a 'typical' brain via bootstrapped confidence intervals. Each dyslexic reader's brain was then classified independently at each voxel as being within or outside the normal range. We used this simple strategy to build a brain map showing regional percentages of differences between groups. The significance of this map was then assessed using a randomization technique.
  
  
  RESULTS
  The right cerebellar declive and the right lentiform nucleus were the two areas that significantly differed the most between groups with 100% of the dyslexic subjects (N = 38) falling outside of the control group (N = 39) 95% confidence interval boundaries. The clinical relevance of this result was assessed by inquiring cognitive brain-based differences among dyslexic brain subgroups in comparison to normal readers' performances. The strongest difference between dyslexic subgroups was observed between subjects with lower cerebellar declive (LCD) grey matter volumes than controls and subjects with higher cerebellar declive (HCD) grey matter volumes than controls. Dyslexic subjects with LCD volumes performed worse than subjects with HCD volumes in phonologically and lexicon related tasks. Furthermore, cerebellar and lentiform grey matter volumes interacted in dyslexic subjects, so that lower and higher lentiform grey matter volumes compared to controls differently modulated the phonological and lexical performances. Best performances (observed in controls) corresponded to an optimal value of grey matter and they dropped for higher or lower volumes.
  
  
  CONCLUSIONS
  These results provide evidence for the existence of various subtypes of dyslexia characterized by different brain phenotypes. In addition, behavioural analyses suggest that these brain phenotypes relate to different deficits of automatization of language-based processes such as grapheme/phoneme correspondence and/or rapid access to lexicon entries.
authors: SFC Brain Imaging Research Centre, SINAPSE Collaboration, University of Edinburgh, Edinburgh, UK. cyril.pernet@ed.ac.uk
authors: Cyril R
authors: CR
authors: Pernet
authors: Jean Baptiste
authors: JB
authors: Poline
authors: Jean François
authors: JF
authors: Demonet
authors: Guillaume A
authors: GA
authors: Rousselet
mesh_terms: D000328:Adult; D001931:Brain Mapping; D002531:Cerebellum / Q000378:metabolism*; D016001:Confidence Intervals; D004410:Dyslexia / Q000145:classification* / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D005260:Female; D007839:Functional Laterality; D006801:Humans; D021621:Imaging, Three-Dimensional / Q000379:methods; D016014:Linear Models; D008279:Magnetic Resonance Imaging; D008297:Male; D016011:Normal Distribution; D012680:Sensitivity and Specificity; D055815:Young Adult