13q32.1 as a candidate region for physiological anisocoria

ABSTRACT Background. Physiological anisocoria is an asymmetry of pupil size in the absence of pathology. Methods. Images of the pupils under standard illumination were collected in the course of a whole-genome association study of a range of visual functions in 1060 healthy adults. DNA for each participant was extracted from saliva samples. Results. We found no relationship between anisocoria and the difference in refraction between the eyes, nor between anisocoria and difference in acuity. There was a small but significant relationship with lightness of the iris, in that the eye with the smaller pupil was associated with the lighter iris. There was a strong association between anisocoria and a local region of chromosome 13 (13q32.1), a region lying between the genes GPR180 and SOX21. The strongest association was with the single nucleotide polymorphism rs9524583. Conclusion. The very specific region associated with anisocoria is one where microdeletions (or microduplications) are known to lead to abnormal development of pupil dilator muscle and hence to the autosomal dominant condition of microcoria. It is possible that alterations at 13q32.1 act by altering the expression of SOX21, which encodes a nuclear transcription factor.Gatsby Charitable Foundation Gonville and Caius Colleg

Cortical hyperexcitability and sensitivity to discomfort glare

AbstractIt is well established that there are two main aspects to glare, the visual impairment and the discomfort, known as disability and discomfort glare, respectively. In contrast to the case of disability glare we understand very little about the underlying mechanisms or physiology of discomfort glare. This study attempts to elucidate the neural mechanisms involved using fMRI and glare sources with controlled levels of retinal illuminance. Prior to carrying out the fMRI experiment, we determined each participant's discomfort glare threshold. The participants were then divided into two groups of equal size based on their ranked sensitivity to discomfort glare, a low and high sensitivity group. In the fMRI experiment each participant was presented with three levels of glare intensity whilst simultaneously required to carry out a simple behavioral task. We compared BOLD responses between the two groups and found that the group more sensitive to glare had an increased response that was localized at three discrete, bilateral cortical locations: one in the cunei, one in the lingual gyri and one in the superior parietal lobules. This increased response was present for all light levels tested, whether or not they were intense enough to cause discomfort glare. Based on the results, we present the case that discomfort glare may be a response to hyperexcitability or saturation of visual neurons

The Oxytocin Receptor Gene ( OXTR) and Face Recognition.

A recent study has linked individual differences in face recognition to rs237887, a single-nucleotide polymorphism (SNP) of the oxytocin receptor gene ( OXTR; Skuse et al., 2014). In that study, participants were assessed using the Warrington Recognition Memory Test for Faces, but performance on Warrington's test has been shown not to rely purely on face recognition processes. We administered the widely used Cambridge Face Memory Test-a purer test of face recognition-to 370 participants. Performance was not significantly associated with rs237887, with 16 other SNPs of OXTR that we genotyped, or with a further 75 imputed SNPs. We also administered three other tests of face processing (the Mooney Face Test, the Glasgow Face Matching Test, and the Composite Face Test), but performance was never significantly associated with rs237887 or with any of the other genotyped or imputed SNPs, after corrections for multiple testing. In addition, we found no associations between OXTR and Autism-Spectrum Quotient scores.This work was supported by Gatsby Charitable Foundation Grant GAT2903

An online version of the Mooney Face Test: phenotypic and genetic associations.

The Mooney Face Test is a widely used test of face perception, but was originally designed to be administered by personal interview. We have developed a three-alternative forced-choice version for online testing. We tested 397 healthy adults between the ages of 18 and 42 (M=24 years). There was a wide range of performance (64-100% correct; M=89.6%). We observed a significant sex difference favoring males (.31 standard deviation; p =.004). In addition, independently of sex, higher 2D:4D digit ratios were significantly associated with higher scores (ρ=.14, p=.006). A genome-wide association study (GWAS) for a subset of 370 participants identified an association between Mooney performance and a polymorphism in the RAPGEF5 gene (rs1522280; p=9.68×10(-8)). This association survives a permutation test (p=.031).This is the author's accepted manuscript. The final version of this paper is published by Elsevier in Neuropsychologia here: http://www.sciencedirect.com/science/article/pii/S0028393214002747

General and specific factors in the processing of faces.

The ability to recognize faces varies considerably between individuals, but does performance co-vary for tests of different aspects of face processing? For 397 participants (of whom the majority were university students) we obtained scores on the Mooney Face Test, Glasgow Face Matching Test (GFMT), Cambridge Face Memory Test (CFMT) and Composite Face Test. Overall performance was significantly correlated for each pair of tests, and we suggest the term f for the factor underlying this pattern of positive correlations. However, there were large variations in the amount of variance shared by individual tests: The GFMT and CFMT are strongly related, whereas the GFMT and the Mooney test tap largely independent abilities. We do not replicate a frequently reported relationship between holistic processing (from the Composite test) and face recognition (from the CFMT)-indeed, holistic processing does not correlate with any of our tests. We report associations of performance with digit ratio and autism-spectrum quotient (AQ), and from our genome-wide association study we include a list of suggestive genetic associations with performance on the four face tests, as well as with f.Gatsby Charitable Foundation (Grant ID: GAT2903

The oxytocin receptor gene OXTR is not associated with face recognition

A recent study has linked individual differences in face recognition to rs237887, a single-nucleotide polymorphism (SNP) of the oxytocin receptor gene (OXTR; Skuse et al., 2014). In that study, participants were assessed using the Warrington Recognition Memory Test for Faces, but performance on Warrington’s test has been shown not to rely purely on face recognition processes. We administered the widely used Cambridge Face Memory Test—a purer test of face recognition—to 370 participants. Performance was not significantly associated with rs237887, with 16 other SNPs of OXTR that we genotyped, or with a further 75 imputed SNPs. We also administered three other tests of face processing (the Mooney Face Test, the Glasgow Face Matching Test, and the Composite Face Test), but performance was never significantly associated with rs237887 or with any of the other genotyped or imputed SNPs, after corrections for multiple testing. In addition, we found no associations between OXTR and Autism-Spectrum Quotient scores

Understanding disability glare: light scatter and retinal illuminance as predictors of sensitivity to contrast

The presence of a bright light in the visual field has two main effects on the retinal image: reduced contrast and increased retinal illuminance due to scattered light; the latter can, under some conditions, lead to an improvement in retinal sensitivity. The combined effect remains poorly understood, particularly at low light levels. A psychophysical flicker-cancellation test was used to measure the amount and angular distribution of scattered light in the eye for 40 observers. Contrast thresholds were measured using a functional contrast sensitivity test. Pupil-plane glare-source illuminances (i.e. 0, 1.35, 19.21 lm/m2), eccentricities (5°, 10°, 15°), and background luminances (1, 2.6, 26 cd/m2) were investigated. Visual performance was better than predicted, based on loss of retinal image contrast caused by scattered light, particularly in the mesopic range. Prediction accuracy improved significantly when the expected increase in retinal sensitivity in the presence of scattered light was also incorporated in the model

Elucidating multisensory interactions in synaesthesia

THESIS 8617This work examines synaesthesia; a neurodevelopmental phenomenon widely believed to be the result of aberrant cross-talk from one cortical area to another. A number of behavioural measures were used to assess the nature of the aberrant crosstalk in synaesthesia. Also, \u27normal\u27 cross-talk between the senses was examined to gain insight into the mechanisms which enable cross-talk or multisensory interactions between the senses

Evidence for an association between a pH-dependent potassium channel, TWIK-1, and the accuracy of smooth pursuit eye movements.

PURPOSE. Within the healthy population there is a large variation in the ability to perform smooth pursuit eye movements. Our purpose was to investigate the genetic and physiological bases for this variation. METHODS. We carried out a whole-genome association study, recording smooth pursuit movements for 1040 healthy volunteers by infra-red oculography. The primary phenotypic measure was root mean square error (RMSE) of eye position relative to target position. Secondary measures were: pursuit gain; frequency of catch-up saccades; frequency of anticipatory saccades. 10% of participants, chosen randomly, were tested twice, giving estimates of test-retest reliability. RESULTS. No significant association was found with three genes previously identified as candidate genes for variation in smooth pursuit: DRD3, COMT, NRG1. A strong association (p = 3.55 x 10 11) was found between RMSE and chromosomal region 1q42.2. The most strongly associated marker (rs701232) lies in an intron of KCNK1, which encodes a two-pore-domain potassium ion channel TWIK 1 (or K2P1) that affects cell excitability. Each additional copy of the A allele decreased RMSE by 0.29 standard deviation. When a psychophysical test of visually perceived motion was used as a covariate in the regression analysis, the association with rs701232 did not weaken (p = 5.38 x 10 12). CONCLUSION. Variation in the sequence or the expression of the pH-dependent ion channel TWIK-1 is a likely source of variance in smooth pursuit. The variance associated with TWIK-1 appears not to arise from sensory mechanisms, since the use of a perceptual covariate left the association intact.Gatsby Charitable Foundatio