Assessment of novel binocular colour, motion and contrast tests in glaucoma

The effects of glaucoma on binocular visual sensitivity for the detection of various stimulus attributes are investigated at the fovea and in four paracentral retinal regions. The study employed a number of visual stimuli designed to isolate the processing of various stimulus attributes. We measured absolute contrast detection thresholds and functional contrast sensitivity by using Landolt ring stimuli. This psychophysical Landolt C-based contrast test of detection and gap discrimination allowed us to test parafoveally at 6 ° from fixation and foveally by employing interleaved testing locations. First-order motion perception was examined by using moving stimuli embedded in static luminance contrast noise. Red/green (RG) and yellow/blue (YB) colour thresholds were measured with the Colour Assessment and Diagnosis (CAD) test, which utilises random dynamic luminance contrast noise (± 45 %) to ensure that only colour and not luminance signals are available for target detection. Subjects were normal controls (n = 65) and glaucoma patients with binocular visual field defects (n = 15) classified based on their Humphrey Field Analyzer mean deviation (MD) scores. The impairment of visual function varied depending on the stimulus attribute and location tested. Progression of loss was noted for all tests as the degree of glaucoma increased. For subjects with mild glaucoma (MD −0.01 dB to −6.00 dB) significantly more data points fell outside the normal age-representative range for RG colour thresholds than for any other visual test, followed by motion thresholds. This was particularly the case for the parafoveal data compared with the foveal data. Thus, a multifaceted measure of binocular visual performance, incorporating RG colour and motion test at multiple locations, might provide a better index for comparison with quality of life measures in glaucoma

Exploring Eye Movements in Patients with Glaucoma When Viewing a Driving Scene

Background: Glaucoma is a progressive eye disease and a leading cause of visual disability. Automated assessment of the visual field determines the different stages in the disease process: it would be desirable to link these measurements taken in the clinic with patient's actual function, or establish if patients compensate for their restricted field of view when performing everyday tasks. Hence, this study investigated eye movements in glaucomatous patients when viewing driving scenes in a hazard perception test (HPT). Methodology/Principal Findings: The HPT is a component of the UK driving licence test consisting of a series of short film clips of various traffic scenes viewed from the driver's perspective each containing hazardous situations that require the camera car to change direction or slow down. Data from nine glaucomatous patients with binocular visual field defects and ten age-matched control subjects were considered (all experienced drivers). Each subject viewed 26 different films with eye movements simultaneously monitored by an eye tracker. Computer software was purpose written to pre-process the data, co-register it to the film clips and to quantify eye movements and point-of-regard (using a dynamic bivariate contour ellipse analysis). On average, and across all HPT films, patients exhibited different eye movement characteristics to controls making, for example, significantly more saccades (P<0.001; 95% confidence interval for mean increase: 9.2 to 22.4%). Whilst the average region of ‘point-of-regard’ of the patients did not differ significantly from the controls, there were revealing cases where patients failed to see a hazard in relation to their binocular visual field defect. Conclusions/Significance: Characteristics of eye movement patterns in patients with bilateral glaucoma can differ significantly from age-matched controls when viewing a traffic scene. Further studies of eye movements made by glaucomatous patients could provide useful information about the definition of the visual field component required for fitness to drive

Relationship Between Flicker Modulation Sensitivity and Retinal Ganglion Cell Related Layer Thicknesses

Purpose: Early detection of structural changes in retinal ganglion cells (RGCs) and corresponding changes in visual function is important in early degenerative diseases of the retina, but the sensitivity of both measurements is limited by the inherent variability in healthy subjects. This study investigates the relationships between RGC-related layer thicknesses and foveal and parafoveal flicker modulation sensitivity (FMS) across photopic and mesopic light levels in healthy subjects. Methods: Photopic and mesopic FMS was measured in 56 young adults, at the point of fixation and at an eccentricity of 5 degrees, in each of the four quadrants. Spectral-domain optical coherence tomography (SD-OCT) was used to measure retinal thicknesses. Relationships between foveal and parafoveal FMS and the retinal thickness in the corresponding region were examined after adjusting for confounding variables. Results: Total macular and inner retinal layer (IRL) thicknesses in the parafoveal ring were significant predictors of photopic (P = 0.034) and mesopic (P = 0.034) parafoveal FMS, respectively. The superior peripapillary retinal nerve fiber layer (pRNFL) thickness was a contributing factor to the inferior parafoveal FMS (photopic: P = 0.006 and mesopic: P = 0.021) and the inferior pRNFL thickness was also a contributing factor to the superior parafoveal FMS (photopic: P < 0.001 and mesopic: P = 0.015). Conclusions: The pRNFL thicknesses predict parafoveal FMS for both mesopic and photopic conditions in healthy eyes. Translational Relevance: The measurement of rapid flicker sensitivity in the parafoveal retina together with the pRNFL thickness profiles measured before the onset of disease, may provide a more sensitive biomarker for detecting loss of sensitivity caused by the earliest neurodegenerative changes in the eyes

Effect of monocular sensitivity on binocular summation of luminance-modulated flicker

Binocular summation of luminance contrast signals in the spatial domain has been investigated in many studies, but less attention has been paid to the analogous interactions in the temporal domain. The present study determined the impact of monocular sensitivity on the binocular detection of luminance-modulated flickering stimuli. Binocular summation ratios (BSRs) were determined in 13 visually-normal adults for a range of monocular flicker modulation thresholds (FMTs), generated by changing stimulus size (7'- 60') and luminance (mesopic and photopic). Monocular and binocular FMTs were measured at the point of regard and in each of the four quadrants at 5° eccentricity for each target size and luminance using the Flicker-Plus test. Monocular and binocular FMT's increased with decreasing target size for all retinal locations (p0.12). The results demonstrate that the visual system successfully summates inputs from the two eyes to enhance flicker detection, independent of their absolute monocular detection thresholds. These findings may serve as a predictive baseline for further experiments designed to determine how other stimulus properties and interocular differences in monocular thresholds may affect the binocular perception of flicker

Pupillary Responses to Static Images of Men and Women: A Possible Measure of Sexual Interest?

The pupil dilates to images that are arousing. In Experiment 1, we examined if the pupil’s response to brief presentations (2,000 ms) of static images could be used to identify individuals’ sexual orientation. Participants were grouped according to their self-reported gender and sexual orientation (male heterosexual, N = 20; male bisexual, N = 13; male homosexual, N = 19; female heterosexual, N = 28; female bisexual, N = 21; female homosexual, N = 17). Pupil size was monitored to images of men in seminude poses, women in seminude poses, or neutral images. Every group showed the same pattern of responses, with the greatest dilation to male images, then female images, and least dilation to the neutral images. Experiment 2 used more tightly controlled stimuli and tested at two different image durations (150 and 3,000 ms). Both heterosexual men (N = 18) and women (N = 20) showed greater pupil dilation to images of nude men than to nude women. However, in Experiment 3, where we reduced the erotic content by using images of clothed models, both heterosexual men and women showed greater pupil dilation to images of women. The results showed that while the pupil does dilate strongly to sexual imagery, its response to these brief static images does not correspond to a person’s sexual orientation in a simple manne

Visually Driven Activation in Macaque Areas V2 and V3 without Input from the Primary Visual Cortex

Creating focal lesions in primary visual cortex (V1) provides an opportunity to study the role of extra-geniculo-striate pathways for activating extrastriate visual cortex. Previous studies have shown that more than 95% of neurons in macaque area V2 and V3 stop firing after reversibly cooling V1 [1], [2], [3]. However, no studies on long term recovery in areas V2, V3 following permanent V1 lesions have been reported in the macaque. Here we use macaque fMRI to study area V2, V3 activity patterns from 1 to 22 months after lesioning area V1. We find that visually driven BOLD responses persist inside the V1-lesion projection zones (LPZ) of areas V2 and V3, but are reduced in strength by ∼70%, on average, compared to pre-lesion levels. Monitoring the LPZ activity over time starting one month following the V1 lesion did not reveal systematic changes in BOLD signal amplitude. Surprisingly, the retinotopic organization inside the LPZ of areas V2, V3 remained similar to that of the non-lesioned hemisphere, suggesting that LPZ activation in V2, V3 is not the result of input arising from nearby (non-lesioned) V1 cortex. Electrophysiology recordings of multi-unit activity corroborated the BOLD observations: visually driven multi-unit responses could be elicited inside the V2 LPZ, even when the visual stimulus was entirely contained within the scotoma induced by the V1 lesion. Restricting the stimulus to the intact visual hemi-field produced no significant BOLD modulation inside the V2, V3 LPZs. We conclude that the observed activity patterns are largely mediated by parallel, V1-bypassing, subcortical pathways that can activate areas V2 and V3 in the absence of V1 input. Such pathways may contribute to the behavioral phenomenon of blindsight

Pharmacotherapy of Schizophrenic Patients: Preponderance of Off-Label Drug Use

Multiple drug class combinations are often prescribed for the treatment of schizophrenia, although antipsychotic monotherapy reflects FDA labeling and scientific justification for combinations is highly variable. This study was performed to gain current data regarding drug treatment of schizophrenia as practiced in the community and to assess the frequencies of off-label drug class combinations. 200 DSM IV-diagnosed schizophrenic patients recruited from community treatment sources participated in this cross-sectional study of community based schizophrenic patients. Drug class categories include First and Second Generation Antipsychotic drugs (FGA and SGA, respectively), mood stabilizers, antidepressants and anti-anxiety drugs. 25.5% of patients received antipsychotic monotherapy; 70% of patients received an antipsychotic and another drug class. A total of 42.5% of patients received more than one antipsychotic drug. The most common drug class combination was antipsychotic and a mood stabilizer. Stepwise linear discriminant function analysis identified the diagnosis of schizoaffective schizophrenia, history of having physically hurt someone and high scores on the General Portion of the PANSS rating scale predicted the combined use of an antipsychotic drug and a mood stabilizer. “Real world” pharmacotherapy of schizophrenia has developed its own established practice that is predominantly off-label and may have outstripped current data support. The economic implications for public sector payers are substantial as well as for the revenue of the pharmaceutical industry, whose promotion of off-label drug use is an increasingly problematic. These data are consistent with the recognition of the therapeutic limitations of both first and second generation antipsychotic drugs

Abnormal social reward processing in autism as indexed by pupillary responses to happy faces

Background: Individuals with Autism Spectrum Disorders (ASD) typically show impaired eye contact during social interactions. From a young age, they look less at faces than typically developing (TD) children and tend to avoid direct gaze. However, the reason for this behavior remains controversial; ASD children might avoid eye contact because they perceive the eyes as aversive or because they do not find social engagement through mutual gaze rewarding. Methods: We monitored pupillary diameter as a measure of autonomic response in children with ASD (n = 20, mean age = 12.4) and TD controls (n = 18, mean age = 13.7) while they looked at faces displaying different emotions. Each face displayed happy, fearful, angry or neutral emotions with the gaze either directed to or averted from the subjects. Results: Overall, children with ASD and TD controls showed similar pupillary responses; however, they differed significantly in their sensitivity to gaze direction for happy faces. Specifically, pupillary diameter increased among TD children when viewing happy faces with direct gaze as compared to those with averted gaze, whereas children with ASD did not show such sensitivity to gaze direction. We found no group differences in fixation that could explain the differential pupillary responses. There was no effect of gaze direction on pupil diameter for negative affect or neutral faces among either the TD or ASD group. Conclusions: We interpret the increased pupillary diameter to happy faces with direct gaze in TD children to reflect the intrinsic reward value of a smiling face looking directly at an individual. The lack of this effect in children with ASD is consistent with the hypothesis that individuals with ASD may have reduced sensitivity to the reward value of social stimuli

Pupillary Stroop effects

We recorded the pupil diameters of participants performing the words’ color-naming Stroop task (i.e., naming the color of a word that names a color). Non-color words were used as baseline to firmly establish the effects of semantic relatedness induced by color word distractors. We replicated the classic Stroop effects of color congruency and color incongruency with pupillary diameter recordings: relative to non-color words, pupil diameters increased for color distractors that differed from color responses, while they reduced for color distractors that were identical to color responses. Analyses of the time courses of pupil responses revealed further differences between color-congruent and color-incongruent distractors, with the latter inducing a steep increase of pupil size and the former a relatively lower increase. Consistent with previous findings that have demonstrated that pupil size increases as task demands rise, the present results indicate that pupillometry is a robust measure of Stroop interference, and it represents a valuable addition to the cognitive scientist’s toolbox