Uncovering the (un)attended: Pupil light responses index persistent biases of spatial attention in neglect.

Visuospatial neglect is a frequent and disabling disorder, mostly after stroke, that presents in impaired awareness to stimuli on one side of space. Neglect causes disability and functional dependence, even long after the injury. Improving measurements of the core attentional deficit might hold the key for better understanding of the condition and development of treatment. We present a rapid, pupillometry-based method that assesses automatic biases in (covert) attention, without requiring behavioral responses. We exploit the phenomenon that pupil light responses scale with the degree of covert attention to stimuli, and thereby reveal what draws (no) attention. Participants with left-sided neglect after right-sided lesions following stroke (n = 5), participants with hemianopia/quadrantanopia following stroke (n = 11), and controls (n = 22) were presented with two vertical bars, one of which was white and one of which was black, while fixating the center. We varied which brightness was left and right, respectively across trials. In line with the hypotheses, participants with neglect demonstrated biased pupil light responses to the brightness on the right side. Participants with hemianopia showed similar biases to intact parts of the visual field, whilst controls exhibited no bias. Together, this demonstrates that the pupil light response can reveal not only visual, but also attentional deficits. Strikingly, our pupillometry-based bias estimates were not in agreement with neuropsychological paper-and-pencil assessments conducted on the same day, but were with those administered in an earlier phase post-stroke. Potentially, we pick up on persistent biases in the covert attentional system that participants increasingly compensate for in classical neuropsychological tasks and everyday life. The here proposed method may not only find clinical application, but also advance theory and aid the development of successful restoration therapies by introducing a precise, longitudinally valid, and objective measurement that might not be affected by compensation.

Effects of Stimulus Luminance, Stimulus Color and Intra-Stimulus Color Contrast on Visual Field Mapping in Neurologically Impaired Adults Using Flicker Pupil Perimetry.

Purpose: We improve pupillary responses and diagnostic performance of flicker pupil perimetry through alterations in global and local color contrast and luminance contrast in adult patients suffering from visual field defects due to cerebral visual impairment (CVI). Methods: Two experiments were conducted on patients with CVI (Experiment 1: 19 subjects, age M and SD 57.9 ± 14.0; Experiment 2: 16 subjects, age M and SD 57.3 ± 14.7) suffering from absolute homonymous visual field (VF) defects. We altered global color contrast (stimuli consisted of white, yellow, cyan and yellow-equiluminant-to-cyan colored wedges) in Experiment 1, and we manipulated luminance and local color contrast with bright and dark yellow and multicolor wedges in a 2-by-2 design in Experiment 2. Stimuli consecutively flickered across 44 stimulus locations within the inner 60 degrees of the VF and were offset to a contrasting (opponency colored) dark background. Pupil perimetry results were compared to standard automated perimetry (SAP) to assess diagnostic accuracy. Results: A bright stimulus with global color contrast using yellow (p= 0.009) or white (p= 0.006) evoked strongest pupillary responses as opposed to stimuli containing local color contrast and lower brightness. Diagnostic accuracy, however, was similar across global color contrast conditions in Experiment 1 (p= 0.27) and decreased when local color contrast and less luminance contrast was introduced in Experiment 2 (p= 0.02). The bright yellow condition resulted in highest performance (AUC M = 0.85 ± 0.10, Mdn = 0.85). Conclusion: Pupillary responses and pupil perimetry's diagnostic accuracy both benefit from high luminance contrast and global but not local color contrast.

The Trade-Off Between Luminance and Color Contrast Assessed With Pupil Responses.

Purpose: A scene consisting of a white stimulus on a black background incorporates strong luminance contrast. When both stimulus and background receive different colors, luminance contrast decreases but color contrast increases. Here, we sought to characterize the pattern of stimulus salience across varying trade-offs of color and luminance contrasts by using the pupil light response. Methods: Three experiments were conducted with 17, 16, and 17 healthy adults. For all experiments, a flickering stimulus (2 Hz; alternating color to black) was presented superimposed on a background with a complementary color to the stimulus (i.e., opponency colors in human color perception: blue and yellow for Experiment 1, red and green for Experiment 2, and equiluminant red and green for Experiment 3). Background luminance varied between 0% and 45% to trade off luminance and color contrast with the stimulus. By comparing the locus of the optimal trade-off between color and luminance across different color axes, we explored the generality of the trade-off. Results: The strongest pupil responses were found when a substantial amount of color contrast was present (at the expense of luminance contrast). Pupil response amplitudes increased by 15% to 30% after the addition of color contrast. An optimal pupillary responsiveness was reached at a background luminance setting of 20% to 35% color contrast across several color axes. Conclusions: These findings suggest that a substantial component of pupil light responses incorporates color processing. More sensitive pupil responses and more salient stimulus designs can be achieved by adding subtle levels of color contrast between stimulus and background. Translational Relevance: More robust pupil responses will enhance tests of the visual field with pupil perimetry.

Comparison of unifocal, flicker, and multifocal pupil perimetry methods in healthy adults.

To this day, the most popular method of choice for testing visual field defects (VFDs) is subjective standard automated perimetry. However, a need has arisen for an objective, and less time-consuming method. Pupil perimetry (PP), which uses pupil responses to onsets of bright stimuli as indications of visual sensitivity, fulfills these requirements. It is currently unclear which PP method most accurately detects VFDs. Hence, the purpose of this study is to compare three PP methods for measuring pupil responsiveness. Unifocal (UPP), flicker (FPP), and multifocal PP (MPP) were compared by monocularly testing the inner 60 degrees of vision at 44 wedge-shaped locations. The visual field (VF) sensitivity of 18 healthy adult participants (mean age and SD 23.7 ± 3.0 years) was assessed, each under three different artificially simulated scotomas for approximately 4.5 minutes each (i.e. stimulus was not or only partially present) conditions: quadrantanopia, a 20-, and 10-degree diameter scotoma. Stimuli that were fully present on the screen evoked strongest, partially present stimuli evoked weaker, and absent stimuli evoked the weakest pupil responses in all methods. However, the pupil responses in FPP showed stronger discriminative power for present versus absent trials (median d-prime = 6.26 ± 2.49, area under the curve [AUC] = 1.0 ± 0) and MPP performed better for fully present versus partially present trials (median d-prime = 1.19 ± 0.62, AUC = 0.80 ± 0.11). We conducted the first in-depth comparison of three PP methods. Gaze-contingent FPP had best discriminative power for large (absolute) scotomas, whereas MPP performed slightly better with small (relative) scotomas.

Maintaining fixation by children in a virtual reality version of pupil perimetry.

The assessment of the visual field in young children continues to be a challenge. Children often do not sit still, fail to fixate stimuli for longer durations, and have limited verbal capacity to report visibility. Therefore, we introduced a head-mounted VR display with gazecontingent flicker pupil perimetry (VRgcFPP). We presented large flickering patches at different eccentricities and angles in the periphery to evoke pupillary oscillations, and three fixation stimulus conditions to determine best practices for optimal fixation and pupil response quality. A total of twenty children (3-11y) passively fixated a dot, counted the repeated appearance of an animated character (counting task), and watched an animated movie in separate trials of 80s each (20 patch locations, 4s per location). The results showed that gaze precision and accuracy did not differ significantly across the fixation conditions but pupil amplitudes were strongest for the dot and count task. The VR set-up appears to be an ideal apparatus for children to allow free range of movement, an engaging visual task, and reliable eye measurements. We recommend the use of the fixation counting task for pupil perimetry because children enjoyed it the most and it achieved strongest pupil responses.

Blind spot and visual field anisotropy detection with flicker pupil perimetry across brightness and task variations.

The pupil can be used as an objective measure for testing sensitivities across the visual field (pupil perimetry; PP). The recently developed gaze-contingent flicker PP (gcFPP) is a promising novel form of PP, with improved sensitivity due to retinotopically stable and repeated flickering stimulations, in a short time span. As a diagnostic tool gcFPP has not yet been benchmarked in healthy individuals. The main aims of the current study were to investigate whether gcFPP has the sensitivity to detect the blind spot, and upper versus lower visual field differences that were found before in previous studies. An additional aim was to test for the effects of attentional requirements and background luminance. A total of thirty individuals were tested with gcFPP across two separate experiments. The results showed that pupil oscillation amplitudes were smaller for stimuli presented inside as compared to outside the blind spot. Amplitudes also decreased as a function of eccentricity (i.e., distance to fixation) and were larger for upper as compared to lower visual fields. We measured the strongest and most sensitive pupil responses to stimuli presented on dark- and mid-gray backgrounds, and when observers covertly focused their attention to the flickering stimulus. GcFPP thus evokes pupil responses that are sensitive enough to detect local, and global differences in pupil sensitivity. The findings further encourage (1) the use of a gray background to prevent straylight without affecting gcFPPs sensitivity and (2) the use of an attention task to enhance pupil sensitivity.

Lessons Learned from 23 Years of Experience in Testing Visual Fields of Neurologically Impaired Children.

We sought to investigate the reliability of standard conventional perimetry (SCP) in neurologically impaired (NI) children using the examiner-based assessment of reliability scoring system and to determine the difference in time to diagnosis of a visual field defect between SCP and a behavioural visual field (BVF) test. Patient records of 115 NI children were retrospectively analysed. The full field peritest (FFP) had best reliability with 44% 'good' scores versus 22% for Goldmann perimetry (p < .001). The mean age of NI children able to perform SCP was 8.3 years versus 4.6 years for the BVF test (p < .001). Use of the BVF test may significantly reduce time to diagnosis.