Cerebellar morphology in developmental dyslexia

Recent evidence has suggested cerebellar anomalies in developmental dyslexia. Therefore, we investigated cerebellar morphology in subjects with documented reading disabilities. We obtained T1-weighted magnetic resonance images in the coronal and sagittal planes from 11 males with prior histories of developmental dyslexia, and nine similarly-aged male controls. Proton magnetic resonance spectra (TE=136 ms, TR=2.4 s) were obtained bilaterally in the cerebellum. Phonological decoding skill was measured using non-word reading. Handedness was assessed using both the Annett questionnaire of hand preference and Annett’s peg moving task. Cerebellar symmetry was observed in the dyslexics but there was significant asymmetry (right grey matter>left grey matter) in controls. The interpretation of these results depended whether a motor- or questionnaire-based method was used to determine handedness. The degree of cerebellar symmetry was correlated with the severity of dyslexics’ phonological decoding deficit. Those with more symmetric cerebella made more errors on a nonsense word reading measure of phonological decoding ability. Left cerebellar metabolite ratios were shown to correlate significantly with the degree of cerebellar asymmetry (P<0.05) in controls. This relationship was absent in developmental dyslexics. Cerebellar morphology reflects the higher degree of symmetry found previously in the temporal and parietal cortex of dyslexics. The relationship of cerebellar asymmetry to phonological decoding ability and handedness, together with our previous finding of altered metabolite ratios in the cerebellum of dyslexics, lead us to suggest that there are alterations in the neurological organisation of the cerebellum which relate to phonological decoding skills, in addition to motor skills and handedness.

Fourth-root summation of contrast over area:no end in sight when spatially inhomogeneous sensitivity is compensated by a witch's hat

Measurements of area summation for luminance-modulated stimuli are typically confounded by variations in sensitivity across the retina. Recently we conducted a detailed analysis of sensitivity across the visual field (Baldwin et al, 2012) and found it to be well-described by a bilinear “witch’s hat” function: sensitivity declines rapidly over the first 8 cycles or so, more gently thereafter. Here we multiplied luminance-modulated stimuli (4 c/deg gratings and “Swiss cheeses”) by the inverse of the witch’s hat function to compensate for the inhomogeneity. This revealed summation functions that were straight lines (on double log axes) with a slope of -1/4 extending to ≥33 cycles, demonstrating fourth-root summation of contrast over a wider area than has previously been reported for the central retina. Fourth-root summation is typically attributed to probability summation, but recent studies have rejected that interpretation in favour of a noisy energy model that performs local square-law transduction of the signal, adds noise at each location of the target and then sums over signal area. Modelling shows our results to be consistent with a wide field application of such a contrast integrator. We reject a probability summation model, a quadratic model and a matched template model of our results under the assumptions of signal detection theory. We also reject the high threshold theory of contrast detection under the assumption of probability summation over area.

Genome-wide association analysis identifies novel loci for chronotype in 100,420 individuals from the UK Biobank

Our sleep timing preference, or chronotype, is a manifestation of our internal biological clock. Variation in chronotype has been linked to sleep disorders, cognitive and physical performance, and chronic disease. Here we perform a genome-wide association study of self-reported chronotype within the UK Biobank cohort (n=100,420). We identify 12 new genetic loci that implicate known components of the circadian clock machinery and point to previously unstudied genetic variants and candidate genes that might modulate core circadian rhythms or light-sensing pathways. Pathway analyses highlight central nervous and ocular systems and fear-response-related processes. Genetic correlation analysis suggests chronotype shares underlying genetic pathways with schizophrenia, educational attainment and possibly BMI. Further, Mendelian randomization suggests that evening chronotype relates to higher educational attainment. These results not only expand our knowledge of the circadian system in humans but also expose the influence of circadian characteristics over human health and life-history variables such as educational attainment.