Fifty Years Exploring the Visual System.

We as a couple spent 50 years working in visual psychophysics of color vision, temporal vision, and luminance adaptation. We sought collaborations with ophthalmologists, anatomists, physiologists, physicists, and psychologists, aiming to relate visual psychophysics to the underlying physiology of the primate retina. This review describes our journey and reflections in exploring the visual system.

Flicker adaptation desensitizes the magnocellular but not the parvocellular pathway.

PURPOSE: Anatomical and physiological studies show that in primates, visual information is conveyed through two parallel pathways, including the magnocellular (MC-) and parvocellular (PC-) pathways. However, the functional separation between the two pathways remains controversial and challenging. To resolve this, we show a psychophysical approach to desensitize the inferred MC-pathway of human observers independently of the inferred PC-pathway. METHODS: The steady-pedestal and pulsed-pedestal paradigms that allow detection and discrimination to be mediated by only the inferred MC- or PC-pathway were used. Three observers (one male, aged 43 years, and two females, aged 33 and 62 years) adapted to either a steadily presented pedestal or a 2- or 10-Hz 50% contrast square-wave modulated luminance flicker. Contrast discrimination thresholds were measured following the flicker adaptation. RESULTS: Flicker adaptation reduces contrast detection and discrimination of the MC-pathway but not the PC-pathway, with larger MC losses from 10-Hz (∼ 0.28 log unit loss, P < 0.05 for all observers) than 2-Hz flicker (∼ 0.13 log unit loss, P < 0.05 for one or two observers depending on stimulus size). Further, our results show that the PC-pathway does not mediate the contrast detection threshold at the background luminance following MC-pathway desensitization. CONCLUSIONS: This study demonstrates the feasibility of independently manipulating sensitivity of the MC-pathway in human observers. Our paradigms provide powerful tools to independently investigate the perceptual functions in the MC- and PC-pathways. This could lead to a better understanding of the perceptual functions of these pathways.

Macular pigment optical density measured by heterochromatic modulation photometry.

PURPOSE: To psychophysically determine macular pigment optical density (MPOD) employing the heterochromatic modulation photometry (HMP) paradigm by estimating 460 nm absorption at central and peripheral retinal locations. METHODS: For the HMP measurements, two lights (B: 460 nm and R: 660 nm) were presented in a test field and were modulated in counterphase at medium or high frequencies. The contrasts of the two lights were varied in tandem to determine flicker detection thresholds. Detection thresholds were measured for different R:B modulation ratios. The modulation ratio with minimal sensitivity (maximal threshold) is the point of equiluminance. Measurements were performed in 25 normal subjects (11 male, 14 female; age: 30 ± 11 years, mean ± sd) using an eight channel LED stimulator with Maxwellian view optics. The results were compared with those from two published techniques - one based on heterochromatic flicker photometry (Macular Densitometer) and the other on fundus reflectometry (MPR). RESULTS: We were able to estimate MPOD with HMP using a modified theoretical model that was fitted to the HMP data. The resultant MPODHMP values correlated significantly with the MPODMPR values and with the MPODHFP values obtained at 0.25° and 0.5° retinal eccentricity. CONCLUSIONS: HMP is a flicker-based method with measurements taken at a constant mean chromaticity and luminance. The data can be well fit by a model that allows all data points to contribute to the photometric equality estimate. Therefore, we think that HMP may be a useful method for MPOD measurements, in basic and clinical vision experiments.

Differential effects of alcohol on contrast processing mediated by the magnocellular and parvocellular pathways.

This study investigated how acute alcohol intake affects contrast processing mediated by inferred magnocellular (MC) and parvocellular (PC) pathways. Achromatic contrast discrimination thresholds were measured in 16 young healthy participants using a steady-pedestal, pulsed-pedestal or pedestal-Δ-pedestal paradigm designed to favor the inferred MC or the PC pathway. Each participant completed two randomized sessions that included consumption of either 0.8 g/kg alcohol or a placebo beverage, with each session consisting of contrast discrimination measurements at baseline and at 60 min following beverage consumption. The results showed that, compared to placebo, alcohol significantly reduced MC contrast sensitivity and PC contrast gain but had no effect on PC contrast sensitivity for the majority of the participants; and did not alter MC contrast gain consistently across participants. The decrease in contrast gain in the PC pathway can be interpreted as a degradation of the postretinal signal-to-noise ratio, whereas the decrease of sensitivity in the MC pathway likely results from a change of cortical processing.

Quantal and non-quantal color matches: failure of Grassmann's laws at short wavelengths.

Previous studies of color matching found that Grassmann's laws are not obeyed in the short-wavelength region when the method of maximum saturation matching is compared with Maxwell matching. The first experiment evaluated whether the discrepancy might be due to a discrimination matching range asymmetry around either the saturated or desaturated matches and concluded that asymmetry is not the dominant factor. The second and third experiments were designed to evaluate postreceptoral mechanisms. The results pointed to the conjunction of three factors as being the principal cause of the failures of Grassmann's laws: the spatial inhomogeneity of the macular pigment distribution, the spatially dissimilar L/M-and S-cone distributions, and a change in the weightings of postreceptoral mechanisms mediating S-cone chromatic and L/M-cone luminance discriminations.

Functional loss in the magnocellular and parvocellular pathways in patients with optic neuritis.

PURPOSE: To evaluate contrast threshold and contrast gain in patients with optic neuritis under conditions designed to favor mediation by either the inferred magnocellular (MC) or parvocellular (PC) pathway. METHODS: Achromatic and chromatic contrast discrimination was measured in 11 patients with unilateral or bilateral optic neuritis and in 18 age-matched controls with normal vision, using achromatic steady- and pulsed-pedestal paradigms to bias performance toward the MC or PC pathway, respectively. In addition, L-M chromatic discrimination at equiluminance was evaluated using the steady-pedestal paradigm. A physiologically plausible model could describe the data with parameters accounting for contrast gain and contrast sensitivity in the inferred MC or PC pathway. The fitted parameters from the eye affected by optic neuritis were compared with those from the normal eye using generalized estimation equation (GEE) models that can account for within-subject correlations. RESULTS: Compared with normal eyes, the affected eyes had significantly higher saturation parameters when measured with both the achromatic pulsed-pedestal paradigm (GEE: ß [SE] = 0.35 [0.06]; P < 0.001) and the chromatic discrimination paradigm (ß [SE] = 0.18 [0.08]; P = 0.015), suggesting that contrast gain in the inferred PC pathway is reduced; the affected eyes also had reduced absolute sensitivity in the inferred MC pathway measured with the achromatic steady-pedestal paradigm (ß [SE] = 0.12 [0.04]; P = 0.005). CONCLUSIONS: Optic neuritis produced large sensitivity losses mediated by the MC pathway and contrast gain losses in the inferred PC pathway. A clinical framework is presented for interpreting contrast sensitivity and gain loss to chromatic and achromatic stimuli in terms of retinal and postretinogeniculate loci contributions to detection and discrimination.

Review: steady and pulsed pedestals, the how and why of post-receptoral pathway separation.

In the mid-1990s, the Pokorny and Smith research group began a series of psychophysical experiments with the aim of separately measuring magnocellular (MC)- and parvocellular (PC)-pathway mediated achromatic contrast discrimination. Three paradigms provide complementary information: The pulsed-pedestal paradigm reveals PC contrast gain, the steady-pedestal paradigm reveals steady-state MC-pathway sensitivity, and the pedestal-Δ-pedestal paradigm reveals MC contrast gain. Further studies investigated the temporal and spatial summation properties of the underlying mechanisms and extended the work to include measures of spatial resolution, chromatic contrast discrimination, the detection and identification of stimulus polarity, and the inferred retinal mechanisms mediating illusory distortions. Other laboratories have also applied the methods to the study of normal and clinically impaired vision. This review describes the pedestal methodologies, how they relate to physiology, and how they have been and should be employed.

Isolated mesopic rod and cone electroretinograms realized with a four-primary method.

The purpose of this study was to evaluate the feasibility of measuring rod and cone electroretinograms (ERGs) at a single mesopic adaptation level. To accomplish this, a four-primary photostimulator was implemented using a commercially available ERG system (Diagnosys ColorDome) to generate three types of stimuli that temporally modulated rods alone, cones alone, and rods and cones simultaneously. For each stimulus type, ERGs were recorded as a function of temporal frequency (2, 4, 8, or 16 Hz) and mesopic light levels (0.02, 0.16, or 1.26 cd/m(2)) in normal observers and patients with retinitis pigmentosa (RP) or cone-rod degeneration. The normal observers ERG waveforms showed a clear periodic pattern, mirroring the sinusoidal stimuli. At all light levels, rod responses were always higher than cone responses for temporal frequencies between 2 and 8 Hz, suggesting that rods dominated the responses. Cone responses were minimal at the lowest light level and increased with increases in light level. The amplitude of the response to the combined stimuli was intermediate between that of the isolated cone and the isolated rod stimuli for all light levels. Good receptoral isolation was confirmed by the results showing (1) minimal or no rod ERGs but recordable cone ERGs in the patients and (2) high correlation between the ERG amplitudes obtained from the four-primary method and those from the ISCEV standard clinical protocol in normal observers.

Rod and cone contrast gains derived from reaction time distribution modeling.

Contrast gain reflects the rapidity of response amplitude increase with increase in stimulus contrast. In physiology, contrast gain can be measured directly as the initial slope of cell contrast response function. In psychophysics, contrast gain estimation is not straightforward. Further, rod and cone contrast gains have not been measured psychophysically at mesopic light levels where both rods and cones are active, due to the difficulty in producing stimuli that excite rods and cones separately at the same adaptation level. Here, we estimated rod and contrast gains by fitting reaction time distributions measured at a light level in which rods alone (scotopic), rods and cones (mesopic), or cones alone (photopic) mediate vision. The reaction time distributions were modeled by two different strategies, a simplified diffusion model that assumes a stochastic accumulation process and a model we developed that begins with sensory input based on early visual processing impulse response functions and assumes the reaction time variability originates in the response criterion. Estimates of contrast gain from both models were comparable and consistent with primate physiology measurements.

S-cone discrimination for stimuli with spatial and temporal chromatic contrast.

In the natural environment, color discriminations are made within a rich context of spatial and temporal variation. In classical laboratory methods for studying chromatic discrimination, there is typically a border between the test and adapting fields that introduces a spatial chromatic contrast signal. Typically, the roles of spatial and temporal contrast on chromatic discrimination are not assessed in the laboratory approach. In this study, S-cone discrimination was measured using stimulus paradigms that controlled the level of spatio-temporal S-cone contrast between the tests and adapting fields. The results indicate that S-cone discrimination of chromaticity differences between a pedestal and adapting surround is equivalent for stimuli containing spatial, temporal or spatial-and-temporal chromatic contrast between the test field and the surround. For a stimulus condition that did not contain spatial or temporal contrast, the visual system adapted to the pedestal instead of the surround. The data are interpreted in terms of a model consistent with primate koniocellular pathway physiology. The paradigms provide an approach for studying the effects of spatial and temporal contrast on discrimination in natural scenes.

Chromatic discrimination in the presence of incremental and decremental rod pedestals.

Signals from rods can alter chromatic discrimination. Here, chromatic discrimination ellipses were determined in the presence of rod incremental and decremental pedestals at mesopic light levels. The data were represented in a relative cone Troland space, normalized by discrimination thresholds measured along the cardinal axes without a rod pedestal. In the quadrant of cone space where L-cone relative to M-cone excitation increased, and S-cone excitation decreased, rod incremental pedestals degraded chromatic discrimination, and rod decremental pedestals improved chromatic discrimination. Discrimination in the other three quadrants of cone space was unaffected by the incremental or decremental rod pedestals. A second experiment measured chromatic discrimination under conditions where cone pedestals were matched to the appearances of the incremental and decremental rod pedestals. Based on the matching pedestal data, discrimination then could be measured independently along the cardinal axes using either chromatic [L/(L + M); S/(L + M)] or luminance (L + M) pedestal components. The discrimination data altered by the rod pedestals were similar to chromatic cone pedestals for L/M increment discrimination, but similar to luminance cone pedestals for S decrement discrimination. The results indicated that the rod and cone signals combined differently in determining chromatic discrimination for different post-receptoral pathways.

The color of night: surface color categorization by color defective observers under dim illuminations.

People with normal trichromatic color vision experience variegated hue percepts under dim illuminations where only rod photoreceptors mediate vision. Here, hue perceptions were determined for persons with congenital color vision deficiencies over a wide range of light levels, including very low light levels where rods alone mediate vision. Deuteranomalous trichromats, deuteranopes and protanopes served as observers. The appearances of 24 paper color samples from the OSA Uniform Color Scales were gauged under successively dimmer illuminations from 10 to 0.0003 Lux (1.0 to -3.5 log Lux). Triads of samples were chosen representing each of eight basic color categories; "red," "pink," "orange," "yellow," "green," "blue," "purple," and "gray." Samples within each triad varied in lightness. Observers sorted samples into groups that they could categorize with specific color names. Above -0.5 log Lux, the dichromatic and anomalous trichromatic observers sorted the samples into the original representative color groups, with some exceptions. At light levels where rods alone mediate vision, the color names assigned by the deuteranomalous trichromats were similar to the color names used by color normals; higher scotopic reflectance samples were classified as blue-green-grey and lower reflectance samples as red-orange. Color names reported by the dichromats at the dimmest light levels had extensive overlap in their sample scotopic lightness distributions. Dichromats did not assign scotopic color names based on the sample scotopic lightness, as did deuteranomalous trichromats and colour-normals. We reasoned that the reduction in color gamut that a dichromat experiences at photopic light levels leads to a limited association of rod color perception with objects differing in scotopic reflectance.

Sequential processing in vision: The interaction of sensitivity regulation and temporal dynamics.

The goal of this work was to describe the interaction of sensitivity regulation and temporal dynamics through the primate retina. A linear systems model was used to describe the temporal amplitude sensitivity at different retinal illuminances. Predictions for the primate H1 horizontal cell were taken as the starting point. The H1 model incorporated an early time-dependent stage of sensitivity regulation by the cones. It was adjusted to reduce the effects of gap junction input and then applied as input to a model describing temporal amplitude sensitivity of Parvocellular and Magnocellular pathway retinal ganglion cells. The ganglion cell model incorporated center-surround subtraction. The H1 based model required little modification to describe the Parvocellular data. The Magnocellular data required a further time-dependent stage of sensitivity regulation that resulted in Weber's Law. Psychophysical data reflect the sensitivity regulation of the retinal ganglion cell pathways but show a decline in temporal resolution that is most pronounced for the post-retinal processing of Parvocellular signals.

Rod contributions to color perception: linear with rod contrast.

At mesopic light levels, an incremental change in rod activation causes changes in color appearance. In this study, we investigated how rod mediated changes in color perception varied as a function of the magnitude of the rod contrast. Rod-mediated changes in color appearance were assessed by matching them with cone-mediated color changes. A two-channel four-primary colorimeter allowed independent control of the rods and each of the L-, M- and S-cone photoreceptor types. At all light levels, rod contributions to inferred PC, KC and MC pathway mediated vision were linearly related to the rod incremental contrast. This linear relationship could be described by a model based on primate ganglion cell responses with the assumption that rod signals were conveyed via rod-cone gap junctions at mesopic light levels.

Rod-cone interactions and the temporal impulse response of the cone pathway.

Dark-adapted rods suppress cone-mediated flicker detection. This study evaluates the effect that rod activity has on cone temporal processing by investigating whether rod mediated suppression changes the cone pathway impulse response function, regardless of the form of the temporal signal. Stimuli were generated with a 2-channel photostimulator that has four primaries for the central field and four primaries for the surround. Cone pathway temporal impulse response functions were derived from temporal contrast sensitivity data with periodic stimuli, and from two-pulse discrimination data in which pairs of briefly pulsed stimuli were presented successively at a series of stimulus onset asynchronies. Dark-adapted rods altered the amplitude and timing of cone pathway temporal impulse response functions, irrespective of whether they were derived from measurements with temporally periodic stimuli or in a brief presentation temporal resolution task with pulsed stimuli. Rod-cone interactions are a fundamental operation in visual temporal processing under mesopic light levels, acting to decrease the temporal bandwidth of the visual system.

Chromatic adaptation in red-green cone-opponent retinal ganglion cells of the macaque.

The degree of chromatic adaptation of midget ganglion cells of the parvocellular (PC) pathway was studied by measuring long-(L) to middle-wavelength (M) cone weighting at different mean chromaticities in the mid-photopic range. Cone weighting was measured using a protocol involving changing the relative phase of modulated lights, which provided an estimate independent of the level of maintained activity. The degree of adaptation at 2500 td was found to be less than complete (i.e., sub-Weberian), with the M- and L-cone contributions having slopes averaging 0.89 rather than 1.0. This is broadly consistent with the degree of light adaptation present in this cell class. The changes in maintained activity following a step change in chromaticity took tens of seconds to return toward a baseline level, but changes in cone weighting appeared much faster.

Anisometropic amblyopia: spatial contrast sensitivity deficits in inferred magnocellular and parvocellular vision.

PURPOSE: To measure achromatic spatial contrast sensitivity in patients with anisometropic amblyopia under conditions favoring inferred parvocellular (PC) or magnocellular (MC) pathway mediation. METHODS: Fourteen anisometropic amblyopes (VA amblyopic eye 6/12 or lower; better eye greater than 6/7.5) and 10 age-matched, nonamplyopic controls (VA 6/6) participated. Foveal spatial contrast sensitivity was measured using localized, spatially narrow band targets (0.25-8.0 cpd) presented in the center of a steady pedestal (favoring MC detection) or a pulsed pedestal (favoring PC detection) that was set within a uniform surround. RESULTS: Spatial contrast sensitivity functions were bandpass for the steady-pedestal and lowpass for the pulsed-pedestal. Under steady-pedestal adaptation, the amblyopes showed reduced spatial contrast sensitivity at intermediate frequencies (1-2 cpd), consistent with MC sensitivity loss. For the pulsed-pedestal condition, a generalized loss of sensitivity was observed across all spatial frequencies (0.5-4 cpd), consistent with PC sensitivity loss. The magnitudes of inferred MC and PC loss were similar. In the steady- and pulsed-pedestal paradigms, results for the better eye of greater than 75% of the amblyopes were normal or near normal at low and intermediate spatial frequencies. CONCLUSIONS: Anisometropic amblyopia produces spatial contrast sensitivity losses in inferred PC- and MC-mediated vision, suggesting there may be anomalous processing of MC and PC signals in higher visual areas, including those with orientation and spatial frequency selective cells in the visual cortex. With spatially localized stimuli and a paradigm designed to distinguish between MC and PC vision under conditions that differ only in the interstimulus adaptation, the better eye of the amblyopes was normal or near normal.

Linking impulse response functions to reaction time: rod and cone reaction time data and a computational model.

Reaction times for incremental and decremental stimuli were measured at five suprathreshold contrasts for six retinal illuminance levels where rods alone (0.002-0.2 Trolands), rods and cones (2-20 Trolands) or cones alone (200 Trolands) mediated detection. A 4-primary photostimulator allowed independent control of rod or cone excitations. This is the first report of reaction times to isolated rod or cone stimuli at mesopic light levels under the same adaptation conditions. The main findings are: (1) For rods, responses to decrements were faster than increments, but cone reaction times were closely similar. (2) At light levels where both systems were functional, rod reaction times were approximately 20 ms longer. The data were fitted with a computational model that incorporates rod and cone impulse response functions and a stimulus-dependent neural sensory component that triggers a motor response. Rod and cone impulse response functions were derived from published psychophysical two-pulse threshold data and temporal modulation transfer functions. The model fits were accomplished with a limited number of free parameters: two global parameters to estimate the irreducible minimum reaction time for each receptor type, and one local parameter for each reaction time versus contrast function. This is the first model to provide a neural basis for the variation in reaction time with retinal illuminance, stimulus contrast, stimulus polarity, and receptor class modulated.

Human and macaque pupil responses driven by melanopsin-containing retinal ganglion cells.

Melanopsin, a novel photopigment, has recently been localized to a population of retinal ganglion cells that display inherent photosensitivity. During continuous light and following light offset, primates are known to exhibit sustained pupilloconstriction responses that resemble closely the photoresponses of intrinsically-photoreceptive ganglion cells. We report that, in the behaving macaque, following pharmacological blockade of conventional photoreceptor signals, significant pupillary responses persist during continuous light and following light offset. These pupil responses display the unique spectral tuning, slow kinetics, and irradiance coding of the sustained, melanopsin-derived ganglion cell photoresponses. We extended our observations to humans by using the sustained pupil response following light offset to document the contribution of these novel ganglion cells to human pupillary responses. Our results indicate that the intrinsic photoresponses of intrinsically-photoreceptive retinal ganglion cells play an important role in the pupillary light reflex and are primarily responsible for the sustained pupilloconstriction that occurs following light offset.

Threshold units: a correct metric for reaction time?

PURPOSE: To compare reaction time (RT) to rod incremental and decremental stimuli expressed in physical contrast units or psychophysical threshold units. METHODS: Rod contrast detection thresholds and suprathreshold RTs were measured for Rapid-On and Rapid-Off ramp stimuli. RESULTS: Threshold sensitivity to Rapid-Off stimuli was higher than to Rapid-On stimuli. Suprathreshold RTs specified in Weber contrast for Rapid-Off stimuli were shorter than for Rapid-On stimuli. Reaction time data expressed in multiples of threshold reversed the outcomes: Reaction times for Rapid-On stimuli were shorter than those for Rapid-Off stimuli. The use of alternative contrast metrics also failed to equate RTs. CONCLUSIONS: A case is made that the interpretation of RT data may be confounded when expressed in threshold units. Stimulus energy or contrast is the only metric common to the response characteristics of the cells underlying speeded responses. The use of threshold metrics for RT can confuse the interpretation of an underlying physiological process.