Enhanced human contrast sensitivity with increased stimulation of melanopsin in intrinsically photosensitive retinal ganglion cells.

The intrinsically photosensitive retinal ganglion cells (ipRGCs) are known to serve non-image-forming functions, such as photoentrainment of the circadian rhythm and pupillary light reflex. However, how they affect human spatial vision is largely unknown. The spatial contrast sensitivity function (CSF), which measures contrast sensitivity as a function of spatial frequency, was used in the current study to investigate the function of ipRGCs in pattern vision. To compare the effects of different background lights on the CSF, we utilized the silent substitution technique. We manipulated the stimulation level of melanopsin (i.e., the visual pigment of ipRGCs) from the background light while keeping the cone stimulations constant, or vice versa. We conducted four experiments to measure the CSFs at various spatial frequencies, eccentricities, and levels of background luminance. Results showed that melanopsin stimulation from the background light enhances spatial contrast sensitivity across different eccentricities and luminance levels. Our finding that melanopsin contributes to CSF, combined with the receptive field analysis, suggests a role for the magnocellular pathway and challenges the conventional view that ipRGCs are primarily responsible for non-visual functions.

Blue-light background impairs visual exogenous attention shift.

Previous research into the effects of blue light on visual-spatial attention has yielded mixed results due to a lack of properly controlling critical factors like S-cone stimulation, ipRGCs stimulation, and color. We adopted the clock paradigm and systematically manipulated these factors to see how blue light impacts the speed of exogenous and endogenous attention shifts. Experiments 1 and 2 revealed that, relative to the control light, exposure to the blue-light background decreased the speed of exogenous (but not endogenous) attention shift to external stimuli. To further clarify the contribution(s) of blue-light sensitive photoreceptors (i.e., S-cone and ipRGCs), we used a multi-primary system that could manipulate the stimulation of a single type of photoreceptor without changing the stimulation of other photoreceptors (i.e., the silent substitution method). Experiments 3 and 4 revealed that stimulation of S-cones and ipRGCs did not contribute to the impairment of exogenous attention shift. Our findings suggest that associations with blue colors, such as the concept of blue light hazard, cause exogenous attention shift impairment. Some of the previously documented blue-light effects on cognitive performances need to be reevaluated and reconsidered in light of our findings.

Relative contributions of melanopsin to brightness discrimination when hue and luminance also vary.

A large number of studies have shown the effect of melanopsin-dependent retinal ganglion cells on humans performing brightness discrimination tasks. These studies often utilized targets that only differ in their melanopsin activation levels, and not in their luminance or hue, which are both factors that make large contributions to brightness discrimination. The purpose of the present study was to evaluate the relative contribution of melanopsin activation to brightness discrimination when luminance and hue are also varying in addition to melanopsin activation. Using an apparatus consisting of three separate high luminance projectors, we were able to manipulate melanopsin-isolating stimulation, and L-, M-, and S-cone stimulation separately, thus allowing us to vary stimuli in their melanopsin activation, luminance, and hue category independently. We constructed three sets of target stimuli with three different levels of melanopsin activation (100%, 131%, and 167% relative melanopsin excitation) and five levels of luminance. We then had subjects do a two-alternative forced choice task where they compared the previously described target stimuli set to a set of four comparison stimuli that varied in their hue category but had identical luminances. We found that in our stimuli set the overall contribution of melanopsin activity to brightness discrimination was small (an average of 6% increase in likelihood to call a high melanopsin activity stimulus brighter compared to a low melanopsin activity stimulus) when luminance and hue also varied. However, a significant interaction showed that when the comparison was between stimuli differing only in melanopsin stimulation (with luminance and hue unchanged) the contribution of melanopsin to brightness judgments was about 3 times larger (an average of 18% increase in likelihood to call a high melanopsin activity stimulus brighter compared to a low melanopsin activity stimulus). This suggests that although luminance and hue have large effects on brightness discrimination such that the melanopsin contribution can become hard to detect, when there are minimal cone-dependent signals available, melanopsin can make a large contribution to brightness discrimination.

The modulation of background color on perceiving audiovisual simultaneity.

Perceiving simultaneity is critical in integrating visual and auditory signals that give rise to a unified perception. We examined whether background color modulates people's perception of audiovisual simultaneity. Two hypotheses were proposed and examined: (1) the red-impairment hypothesis: visual processing speed deteriorates when viewing a red background because the magnocellular system is inhibited by red light; and (2) the blue-enhancement hypothesis: the detection of both visual and auditory signals is enhanced when viewing a blue background because it stimulates the blue-light sensitive intrinsically photosensitive retinal ganglion cells (ipRGCs), which trigger a higher alert state. Participants were exposed to different backgrounds while performing an audiovisual simultaneity judgment (SJ) task: a flash and a beep were presented at pre-designated stimulus onset asynchronies (SOAs) and participants judged whether or not the two stimuli were presented simultaneously. Experiment 1 demonstrated a shift of the point of subjective simultaneity (PSS) toward the visual-leading condition in the red compared to the blue background when the flash was presented in the periphery. In Experiment 2, the stimulation of ipRGCs was specifically manipulated to test the blue-enhancement hypothesis. The results showed no support for this hypothesis, perhaps due to top-down cortical modulations. Taken together, the shift of PSS toward the visual-leading condition in the red background was attributed to impaired visual processing speed with respect to auditory processing speed, caused by the inhibition of the magnocellular system under red light.

A quantitative analysis of the contribution of melanopsin to brightness perception.

In the retina, intrinsically photosensitive retinal ganglion cells (ipRGCs) which express photopigment melanopsin have been identified as photoreceptors which differ from cones and rods. It has been established that such melanopsin-expressing RGCs are involved in the circadian photo-entrainment and pupillary light reflexes. An additional projection from ipRGCs to the lateral geniculate nucleus has been identified, which indicates the association of ipRGCs with visual perception induced by the image-forming pathway. Reportedly, ipRGCs modulate brightness perception but quantitative analysis of brightness perception involving melanopsin and cones-based signals has not been elucidated. We conducted brightness perception experiments that involved melanopsin using a novel projector with six primary colors and formulated the results for melanopsin and cone stimuli. The white visual stimuli (5 degrees in size) that we used had a single xy-chromaticity values but melanopsin stimuli were modulated by designing different spectral distributions. Perceived brightness was measured using a magnitude estimation method at several luminance levels in the near periphery (7 degrees). Additionally, pupil diameter was measured for estimating the intensity of visual stimuli on the retina. The results showed that the perceived brightness of a white visual stimulus with different spectral distributions can be described by a summation of the nearly linear melanopsin response and the non-linear cone response with weighted coefficients, and the contribution ratio of melanopsin in brightness perception increased to 50% and more with increasing visual stimulus. These suggest that melanopsin signals play a crucial role in the estimation of the absolute intensity of the light environment by obtaining absolute brightness information even when cones are adapted by light.

Subjective time expansion with increased stimulation of intrinsically photosensitive retinal ganglion cells.

Intrinsically photosensitive retinal ganglion cells (ipRGCs) contain photoreceptors that are especially sensitive to blue light. Nevertheless, how blue light and ipRGCs affect time perception remains unsolved. We used the oddball paradigm and manipulated the background light to examine whether and how blue light and ipRGCs affect perceived duration. In the oddball paradigm, participants were asked to judge the duration of the target (oddball), compared to that of the standard, with a two alternative-forced-choice procedure. When the background light was controlled to be either blue or red in Experiment 1, results showed that blue light led to longer subjective duration compared to red light. Experiment 2 further clarified the contribution of the ipRGCs. A set of multi-primary projector system that could manipulate the ipRGC stimulation were used, while the color and luminance of the background lights were kept constant throughout. Results showed that increased stimulation of ipRGCs under metameric background expanded subjective time. These results suggest that ipRGC stimulation increases arousal/attention so as to expand subjective duration.

Influence of light exposure at nighttime on sleep development and body growth of preterm infants.

Previous studies have demonstrated that a light-dark cycle has promoted better sleep development and weight gain in preterm infants than constant light or constant darkness. However, it was unknown whether brief light exposure at night for medical treatment and nursing care would compromise the benefits brought about by such a light-dark cycle. To examine such possibility, we developed a special red LED light with a wavelength of >675 nm which preterm infants cannot perceive. Preterm infants born at <36 weeks' gestational age were randomly assigned for periodic exposure to either white or red LED light at night in a light-dark cycle after transfer from the Neonatal Intensive Care Unit to the Growing Care Unit, used for supporting infants as they mature. Activity, nighttime crying and body weight were continuously monitored from enrolment until discharge. No significant difference in rest-activity patterns, nighttime crying, or weight gain was observed between control and experimental groups. The data indicate that nursing care conducted at 3 to 4-hour intervals exposing infants to light for <15 minutes does not prevent the infants from developing circadian rest-activity patterns, or proper body growth as long as the infants are exposed to regular light-dark cycles.

Clinical evaluation of the Shin-Nippon SRW-5000 autorefractor in adults: an update.

PURPOSE: The Shin-Nippon SRW-5000 is an open view autorefractor that superseded the Canon R-1 autorefractor in the mid-1990 s and has been used widely in optometry and vision science laboratories. It has been used to measure refractive error, accommodation responses both statically and dynamically, off-axis refractive error, and adapted to measure pupil size. This paper presents an overview of the original 2001 clinical evaluation of the SRW-5000 in adults (Mallen et al., Ophthal Physiol Opt 2001; 21: 101) and provides an update on the use and modification of the instrument since the original publication. RECENT FINDINGS: The SRW-5000 instrument, and the family of devices which followed, have shown excellent validity, repeatability, and utility in clinical and research settings. The instruments have also shown great potential for increased research functionality following a number of modifications. SUMMARY: The SRW-5000 and its derivatives have been, and continue to be, of significant importance in our drive to understand myopia progression, myopia control techniques, and oculomotor function in human vision.

Association between melanopsin gene polymorphism (I394T) and pupillary light reflex is dependent on light wavelength.

BACKGROUND: Our aim was to determine the association between melanopsin gene polymorphism and pupillary light reflex under diverse photic conditions, including different intensities and wavelengths. METHODS: A total of 195 visually corrected subjects volunteered for investigation of the melanopsin gene of single nucleotide polymorphism (SNP) of rs1079610 (I394T). The genotype groups were TT (n = 126), TC (n = 55), and CC (n = 8), and 75 of the subjects, including subjects with TT (n = 34), TC (n = 33), and CC (n = 8) participated in our experiment. Three monochromatic lights with peak wavelengths of 465 nm (blue), 536 nm (green), and 632 nm (red) were prepared, and each light was projected to the subjects with five intensities, 12, 13, 14, 14.5 and 15 log photons/(cm2 s), for one minute. The pupil size of the left eye was measured under each light condition after a 1-minute adaptation. RESULTS: The pupils of the TC + CC genotypes (n = 38) were significantly smaller than those of the TT genotype (n = 31) under a blue (463 nm) light condition with 15 log photons/(cm2 s) (P < 0.05). In contrast, there were no significant differences under green (536 nm) and red (632 nm) light conditions. Conversely, relative pupil constrictions of the TC + CC genotypes were greater than those of the TT genotype under both blue and green conditions with high intensities (14.5 and 15 log photons/(cm2 s)). In contrast, there were no significant differences between genotype groups in pupil size and relative pupilloconstriction under the red light conditions. CONCLUSIONS: Our findings suggest that the melanopsin gene polymorphism (I394T) functionally interacts with pupillary light reflex, depending on light intensity and, particularly, wavelength, and that under a light condition fulfilling both high intensity and short wavelength, the pupillary light response of subjects with the C allele (TC + CC) is more sensitive to light than that of subjects with the TT genotype.

Melanopsin gene polymorphism I394T is associated with pupillary light responses in a dose-dependent manner.

BACKGROUND: Melanopsin-containing intrinsically photosensitive retinal ganglion cells (ipRGCs) play an important role in non-image forming responses to light, such as circadian photoentrainment, light-induced melatonin suppression, and pupillary light response. Although it is known that there are some single nucleotide polymorphisms (SNPs) in the melanopsin (OPN4) gene in humans, the associations of the SNPs with non-image forming responses to light remains unclear. In the present study, we examined the associations of melanopsin gene polymorphisms with pupillary light response. METHODS: Japanese university students (mean age: 21.0 ± 1.7 years) with the genotypes of TT (n = 38), TC (n = 28) and CC (n = 7) at rs1079610 (I394T) located in the coding region participated in the present study. They were matched by age and sex ratio. Dark-adapted pupil size (<1 lx) was first measured. Then steady-state pupil size was measured during exposure to five lighting conditions (10 lx, 100 lx, 1000 lx, 3000 lx, 6000 lx in the vertical direction at eye level). RESULTS: Significant interaction between the genotype of I394T (TT versus TC+CC) and luminance levels was found in pupil size. Under high illuminance levels (1000 lx, 3000 lx and 6000 lx), pupil sizes in subjects with the C allele were significantly smaller than those in subjects with the TT genotype. On the other hand, pupil size in subjects with the C allele under low illuminance (<1 lx) was significantly larger than that in subjects with the TT genotype. Percentages of pupil constriction under high illuminance levels were significantly greater in subjects with the C allele than in subjects with the TT genotype. CONCLUSIONS: Human melanopsin gene polymorphism I394T interacted with irradiance in association with pupil size. This is the first evidence suggesting a functional connection between melanopsin gene polymorphism and pupillary light response as an index of non-image forming response to light.

Melanopsin-based brightness discrimination in mice and humans.

Photoreception in the mammalian retina is not restricted to rods and cones but extends to a small number of intrinsically photoreceptive retinal ganglion cells (ipRGCs), expressing the photopigment melanopsin. ipRGCs are known to support various accessory visual functions including circadian photoentrainment and pupillary reflexes. However, despite anatomical and physiological evidence that they contribute to the thalamocortical visual projection, no aspect of visual discrimination has been shown to rely upon ipRGCs. Based on their currently known roles, we hypothesized that ipRGCs may contribute to distinguishing brightness. This percept is related to an object's luminance-a photometric measure of light intensity relevant for cone photoreceptors. However, the perceived brightness of different sources is not always predicted by their respective luminance. Here, we used parallel behavioral and electrophysiological experiments to first show that melanopsin contributes to brightness discrimination in both retinally degenerate and fully sighted mice. We continued to use comparable paradigms in psychophysical experiments to provide evidence for a similar role in healthy human subjects. These data represent the first direct evidence that an aspect of visual discrimination in normally sighted subjects can be supported by inner retinal photoreceptors.

Delayed response of human melanopsin retinal ganglion cells on the pupillary light reflex.

PURPOSE: A recent study has shown that retinal ganglion cells containing the photopigment melanopsin, which are intrinsically photosensitive in primates, project to the pupillary control centre in the pretectum. The aim of this study was to investigate how melanopsin retinal ganglion cells (mRGCs) contribute to the pupillary pathway. METHODS: We designed and built a novel multi-primary stimulation system to control stimulation of the three cone types and mRGCs independently in the human eye. We measured the latency and amplitude of transient pupillary responses to three types of test stimuli modulating excitations of mRGCs and cones (mRGC, luminance and the light flux stimuli). RESULTS: It was found that the transient pupillary response to mRGC stimuli has a longer latency than that to luminance and the light flux stimuli when an onset of sinusoidal stimulus was used. CONCLUSIONS: The results indicate that we successfully demonstrated the pupillary response to mRGCs under conditions where mRGCs are isolated in humans. Furthermore, the data confirm that the delayed response disappeared when the stimulus is presented as a square-wave pulse and not weighted by a sinusoid. The similarity of time courses for the earlier phase of pupillary responses to all stimuli suggested that these transient pupillary responses were driven by a single mechanism, which is perhaps associated with cone-mediated signals.

Nonlinear two-stage model for color discrimination.

We modified a two-stage model for color discrimination proposed in a previous study [Color Res. Appl.25, 105 (2000)]; in order to extend the model to wider conditions, we considered the conditions with luminance modulations in addition to color modulations. Using the modified model, we successfully predicted color discrimination data with test color changes along both the chromatic and luminance axes under a variety of background colors. Both qualitative and quantitative assessments in modeling showed that nonlinearity is required in both the cone and the cone-opponent stages to interpret adaptation effects of both color and luminance on color discrimination. This fact suggests that the nonlinear properties at each stage have different roles in color perception.

The ERG responses to light stimuli of melanopsin-expressing retinal ganglion cells that are independent of rods and cones.

The mechanisms by which melanopsin-expressing retinal ganglion cells (mRGCs) regulate circadian rhythms in humans have not been established. To understand mRGC characteristics and their role independent of effects due to the rods and cones, mRGC responses should be induced or measured independent of cone and rod responses. In the present study, we obtained results from light stimuli which differentially induce only the mRGC response by using a receptor-silent substitution technique. The mRGCs responded linearly to contrast changes of light stimuli, whereas they showed complicated responses to frequency changes with regard to the latency of response time. These results suggest that mRGC behavior is not a simple response to the various frequencies found in solar light but may be related to intrinsic neural circuits with feedback connections in the mRGC pathway. The results in this study also demonstrated that the test stimuli affected only the mRGC response and that this could be successfully detected by using the electroretinogram (ERG).

Contribution of human melanopsin retinal ganglion cells to steady-state pupil responses.

The recent discovery of melanopsin-containing retinal ganglion cells (mRGCs) has led to a fundamental reassessment of non-image forming processing, such as circadian photoentrainment and the pupillary light reflex. In the conventional view of retinal physiology, rods and cones were assumed to be the only photoreceptors in the eye and were, therefore, considered responsible for non-image processing. However, signals from mRGCs contribute to this non-image forming processing along with cone-mediated luminance signals; although both signals contribute, it is unclear how these signals are summed. We designed and built a novel multi-primary stimulation system to stimulate mRGCs independently of other photoreceptors using a silent-substitution technique within a bright steady background. The system allows direct measurements of pupillary functions for mRGCs and cones. We observed a significant change in steady-state pupil diameter when we varied the excitation of mRGC alone, with no change in luminance and colour. Furthermore, the change in pupil diameter induced by mRGCs was larger than that induced by a variation in luminance alone: that is, for a bright steady background, the mRGC signals contribute to the pupillary pathway by a factor of three times more than the L- and M-cone signals.

Two distinct cone-opponent processes in the L+M luminance pathway.

We measured phase shifts between Long-wavelength cone (L-cone) and Middle-wavelength cone (M-cone) signals as well as sensitivity in the luminance pathway either following a cone-silent substitution of colored background or on a steady colored background. In background substitution, the phase shifts between L- and M-cone signals varied only slightly depending on the substituted color, whereas marked elevation of the threshold following the substitution of colored background was found. In contrast, the phase shifts, as well as threshold, varied largely, depending on the background color in the steady background. These facts suggest that suppression by the cone-opponent process for background color substitution is different from the one for a steady colored background.

Pupil response to color signals in cone-contrast space.

PURPOSE: It is widely accepted that pupil responses to visual stimuli are determined by the ambient illuminance, and recently it has been shown that changes in stimulus color also contributes to a pupillary control mechanism. However, the role of pupillary responses to chromatic stimuli is not clear. The aim of this study was to investigate how color and luminance signals contribute to the pupillary control mechanism. METHODS: We measured pupillary iso-response contours in M-and L-cone contrast space. The iso-response contours in cone-contrast space have been determined to examine what mechanisms contribute to the pupillary pathway. The shapes of the iso-response contour change when different mechanisms determine the response. RESULTS: It was shown that for all subjects, the pupillary iso-response contours form an ellipse with positive slope in cone-contrast space, indicating that the sensitivities to the chromatic stimuli are higher than those for the luminance stimuli. The pupil responds maximally to a grating that has a stronger L-cone modulation than the red-green isoluminant grating. CONCLUSIONS: The sensitivity of the chromatic pathway, in terms of pupillary response, is three times larger than that of the luminance pathway, a property that might have utility in clinical applications.

Similarities between visual processing of shear and uniform motion.

A number of papers have claimed that at moderate to high contrasts, sensitivity is higher for shear motion than for uniform motion. We show in a 2 x 2AFC task, designed to minimize any potential artefacts due to criterion level or response bias, that sensitivities are essentially equal for shear and uniform motion under general conditions. It has also been claimed that position tracking enhances sensitivity for shear motion. We added moving sinusoidal gratings to stationary sinusoidal gratings of the same spatial frequency and orientation, to create stimuli in which position changes and motion energy have opposite directions, to show that shear and uniform motion are both subserved by motion-energy mechanisms at speeds above 2.0 deg/s and by position tracking at slower speeds.