Gary Bargary

Do different 'magnocellular tasks' probe the same neural substrate?

The sensory abnormalities associated with disorders such as dyslexia, autism and schizophrenia have often been attributed to a generalized deficit in the visual magnocellular–dorsal stream and its auditory homologue. To probe magnocellular function, various psychophysical tasks are often employed that require the processing of rapidly changing stimuli. But is performance on these several tasks supported by a common substrate? To answer this question, we tested a cohort of 1060 individuals on four ‘magnocellular tasks’: detection of low-spatial-frequency gratings reversing in contrast at a high temporal frequency (so-called frequency-doubled gratings); detection of pulsed low-spatial-frequency gratings on a steady luminance pedestal; detection of coherent motion; and auditory discrimination of temporal order. Although all tasks showed test–retest reliability, only one pair shared more than 4 per cent of variance. Correlations within the set of ‘magnocellular tasks’ were similar to the correlations between those tasks and a ‘non-magnocellular task’, and there was little consistency between ‘magnocellular deficit’ groups comprising individuals with the lowest sensitivity for each task. Our results suggest that different ‘magnocellular tasks’ reflect different sources of variance, and thus are not general measures of ‘magnocellular function’.

A population study of binocular function

As part of a genome-wide association study (GWAS) of perceptual traits in healthy adults, we measured stereo acuity, the duration of alternative percepts in binocular rivalry and the extent of dichoptic masking in 1060 participants. We present the distributions of the measures, the correlations between measures, and their relationships to other psychophysical traits. We report sex differences, and correlations with age, interpupillary distance, eye dominance, phorias, visual acuity and personality. The GWAS, using data from 988 participants, yielded one genetic association that passed a permutation test for significance: The variant rs1022907 in the gene VTI1A was associated with self-reported ability to see autostereograms. We list a number of other suggestive genetic associations (p<10(-5)).

Variants in the 1q21 risk region are associated with a visual endophenotype of autism and schizophrenia

Deficits in sensitivity to visual stimuli of low spatial frequency and high temporal frequency (so‐called frequency‐doubled gratings) have been demonstrated both in schizophrenia and in autism spectrum disorder (ASD). Such basic perceptual functions are ideal candidates for molecular genetic study, because the underlying neural mechanisms are well characterized; but they have sometimes been overlooked in favor of cognitive and neurophysiological endophenotypes, for which neural substrates are often unknown. Here, we report a genome‐wide association study of a basic visual endophenotype associated with psychological disorder. Sensitivity to frequency‐doubled gratings was measured in 1060 healthy young adults, and analyzed for association with genotype using linear regression at 642 758 single nucleotide polymorphism (SNP) markers. A significant association (P = 7.9 × 10−9) was found with the SNP marker rs1797052, situated in the 5′‐untranslated region of PDZK1; each additional copy of the minor allele was associated with an increase in sensitivity equivalent to more than half a standard deviation. A permutation procedure, which accounts for multiple testing, showed that the association was significant at the α = 0.005 level. The region on chromosome 1q21.1 surrounding PDZK1 is an established susceptibility locus both for schizophrenia and for ASD, mirroring the common association of the visual endophenotype with the two disorders. PDZK1 interacts with N‐methyl‐d‐aspartate receptors and neuroligins, which have been implicated in the etiologies of schizophrenia and ASD. These findings suggest that perceptual abnormalities observed in two different disorders may be linked by common genetic elements.

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).

Individual differences in human eye movements: An oculomotor signature?

ABSTRACT Human eye movements are stereotyped and repeatable, but how specific to a normal individual are the quantitative properties of his or her eye movements? We recorded saccades, anti‐saccades and smooth‐pursuit eye movements in a sample of over 1000 healthy young adults. A randomly selected subsample (10%) of participants were re‐tested on a second occasion after a median interval of 18.8 days, allowing us to estimate reliabilities. Each of several derived measures, including latencies, accuracies, velocities, and left‐right asymmetries, proved to be very reliable. We give normative means and distributions for each measure and describe the pattern of correlations amongst them. We identify several measures that exhibit significant sex differences. The profile of our oculomotor measures for an individual constitutes a personal oculomotor signature that distinguishes that individual from most other members of the sample of 1000.

General and specific factors in the processing of faces

ABSTRACT 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.

Cortical hyperexcitability and sensitivity to discomfort glare.

It 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 participants 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.

Suggestive association with ocular phoria at chromosome 6p22

PURPOSE We conducted a genome-wide association study to identify genetic factors that contribute to the etiology of heterophoria. METHODS We measured near and far vertical and horizontal phorias in 988 healthy adults aged 16 to 40 using the Keystone telebinocular with plates 5218 and 5219. We regressed degree of phoria against genotype at 642758 genetic loci. To control for false positives, we applied the conservative genome-wide permutation test to our data. RESULTS A locus at 6p22.2 was found to be associated with the degree of near horizontal phoria (P = 2.3 × 10(-8)). The P value resulting from a genome-wide permutation test was 0.014. CONCLUSIONS The strongest association signal arose from an intronic region of the gene ALDH5A1, which encodes the mitochondrial enzyme succinic semialdehyde dehydrogenase (SSADH), an enzyme involved in γ-aminobutyric acid metabolism. Succinic semialdehyde dehydrogenase deficiency, resulting from mutations of ALDH5A1, causes a variety of neural and behavioral abnormalities, including strabismus. Variation in ALDH5A1 is likely to contribute to degree of horizontal phoria.

Mechanisms for discomfort glare in central vision

PURPOSE The presence of a bright light source in the visual field can generate visual discomfort. Based on empirical observations we can predict to a reasonable degree of accuracy how uncomfortable a given lighting installation is likely to be; yet very little is known about the mechanism or physiological underpinnings that lead to visual discomfort. This study attempts to elucidate some of the underlying mechanisms by controlling the amount of light reaching the retina and by varying photometric properties of the glare source. METHODS The participants were required to view a source of light presented against a simulated residential street background in the form of uniform flashes of light of varying intensity. Discomfort-glare thresholds were estimated using a staircase procedure; the dependent variable was retinal illuminance. The size of the glare source and the luminance of the surrounding background were varied systematically. RESULTS Across glare-source sizes or background luminances the discomfort-glare threshold varied less in terms of retinal illuminance than it did in terms of pupil-plane illuminance or light flux. A two-stage model based on saturation of photoreceptors followed by summation of an edge response signal that defines the edges of the glare-source accurately predicted the data. CONCLUSIONS Discomfort glare in central vision is more closely associated with the spatial properties of the glare source, such as contrast-defined edges, than the overall amount of light entering the eye. The results suggest that discomfort glare in lighting installations could be reduced while maintaining adequate illuminance levels by an appropriate choice of illuminant source size.