Harmonics added to a flickering light can upset the balance between ON and OFF pathways to produce illusory colors.

The neural signals generated by the light-sensitive photoreceptors in the human eye are substantially processed and recoded in the retina before being transmitted to the brain via the optic nerve. A key aspect of this recoding is the splitting of the signals within the two major cone-driven visual pathways into distinct ON and OFF branches that transmit information about increases and decreases in the neural signal around its mean level. While this separation is clearly important physiologically, its effect on perception is unclear. We have developed a model of the ON and OFF pathways in early color processing. Using this model as a guide, we can produce imbalances in the ON and OFF pathways by changing the shapes of time-varying stimulus waveforms and thus make reliable and predictable alterations to the perceived average color of the stimulus-although the physical mean of the waveforms does not change. The key components in the model are the early half-wave rectifying synapses that split retinal photoreceptor outputs into the ON and OFF pathways and later sigmoidal nonlinearities in each pathway. The ability to systematically vary the waveforms to change a perceptual quality by changing the balance of signals between the ON and OFF visual pathways provides a powerful psychophysical tool for disentangling and investigating the neural workings of human vision.

Semantic content outweighs low-level saliency in determining children's and adults' fixation of movies.

To make sense of the visual world, we need to move our eyes to focus regions of interest on the high-resolution fovea. Eye movements, therefore, give us a way to infer mechanisms of visual processing and attention allocation. Here, we examined age-related differences in visual processing by recording eye movements from 37 children (aged 6-14years) and 10 adults while viewing three 5-min dynamic video clips taken from child-friendly movies. The data were analyzed in two complementary ways: (a) gaze based and (b) content based. First, similarity of scanpaths within and across age groups was examined using three different measures of variance (dispersion, clusters, and distance from center). Second, content-based models of fixation were compared to determine which of these provided the best account of our dynamic data. We found that the variance in eye movements decreased as a function of age, suggesting common attentional orienting. Comparison of the different models revealed that a model that relies on faces generally performed better than the other models tested, even for the youngest age group (<10years). However, the best predictor of a given participant's eye movements was the average of all other participants' eye movements both within the same age group and in different age groups. These findings have implications for understanding how children attend to visual information and highlight similarities in viewing strategies across development.

Delayed S-cone sensitivity losses following the onset of intense yellow backgrounds linked to the lifetime of a photobleaching product?

Thirty years ago, Mollon, Stockman, & Polden (1987) reported that after the onset of intense yellow 581-nm backgrounds, S-cone threshold rose unexpectedly for several seconds before recovering to the light-adapted steady-state value-an effect they called: "transient-tritanopia of the second kind" (TT2). Given that 581-nm lights have little direct effect on S-cones, TT2 must arise indirectly from the backgrounds' effects on the L- and M-cones. We attribute the phenomenon to the action of an unknown L- and M-cone photobleaching product, X, which acts at their outputs like an "equivalent" background light that then inhibits S-cones at a cone-opponent, second-site. The time-course of TT2 is similar in form to the lifetime of X in a two-stage, first-order biochemical reaction A→X→C with successive best-fitting time-constants of 3.09 ± 0.35 and 7.73 ± 0.70 s. Alternatively, with an additional slowly recovering exponential "restoring-force" with a best-fitting time-constant 23.94 ± 1.42 s, the two-stage best-fitting time-constants become 4.15 ± 0.62 and 6.79 ± 1.00 s. Because the time-constants are roughly independent of the background illumination, and thus the rate of photoisomerization, A→X is likely to be a reaction subsidiary to the retinoid cycle, perhaps acting as a buffer when the bleaching rate is too high. X seems to be logarithmically related to S-cone threshold, which may result from the logarithmic cone-opponent, second-site response compression after multiplicative first-site adaptation. The restoring-force may be the same cone-opponent force that sets the rate of S-cone recovery following the unusual threshold increase following the offset of dimmer yellow backgrounds, an effect known as "transient-tritanopia" (TT1).

Delayed cone-opponent signals in the luminance pathway.

Cone signals in the luminance or achromatic pathway were investigated by measuring how the perceptual timing of M- or L-cone-detected flicker depended on temporal frequency and chromatic adaptation. Relative timings were measured, as a function of temporal frequency, by superimposing M- or L-cone-isolating flicker on "equichromatic" flicker (flicker of the same wavelength as the background) and asking observers to vary contrast and phase to cancel the perception of flicker. Measurements were made in four observers on up to 35 different backgrounds varying in wavelength and radiance. Observers showed substantial perceptual delays or advances of L- and M-cone flicker that varied systematically with cone class, background wavelength, and radiance. Delays were largest for M-cone-isolating flicker. Although complex, the results can be characterised by a surprisingly simple model in which the representations of L- and M-cone flicker are comprised not only of a fast copy of the flicker signal, but also of a slow copy that is delayed by roughly 30 ms and varies in strength and sign with both background wavelength and radiance. The delays, which are too large to be due to selective cone adaptation by the chromatic backgrounds, must arise postreceptorally. Clear evidence for the slow signals can also be found in physiological measurements of horizontal and magnocellular ganglion cells, thus placing the origin of the slow signals in the retina-most likely in an extended horizontal cell network. Luminance-equated stimuli chosen to isolate chromatic channels may inadvertently generate slow signals in the luminance channel.

Linear-nonlinear models of the red-green chromatic pathway.

The mean hue of flickering waveforms comprising only the first two harmonics depends on their temporal alignment. We evaluate explanatory models of this hue-shift effect using previous data obtained using L- and M-cone-isolating stimuli together with chromatic sensitivity and hue discrimination data. The key questions concerned what type of nonlinearity produced the hue shifts, and where the nonlinearities lay with respect to the early band-pass and late low-pass temporal filters in the chromatic pathways. We developed two plausible models: (a) a slew-rate limited nonlinearity that follows both early and late filters, and (b) a half-wave rectifying nonlinearity-consistent with the splitting of the visual input into ON- and OFF-channels-that lies between the early and late filters followed by a compressive nonlinearity that lies after the late filter.

Hue shifts produced by temporal asymmetries in chromatic signals depend on the alignment of the first and second harmonics.

When M- or L-cone-isolating sawtooth waveforms flicker at frequencies between 4 and 13.3 Hz, there is a mean hue shift in the direction of the shallower sawtooth slope. Here, we investigate how this shift depends on the alignment of the first and second harmonics of sawtooth-like waveforms. Below 4 Hz, observers can follow hue variations caused by both harmonics, and reliably match reddish and greenish excursions. At higher frequencies, however, the hue variations appear as chromatic flicker superimposed on a steady light, the mean hue of which varies with second-harmonic alignment. Observers can match this mean hue against a variable-duty-cycle rectangular waveform and, separately, set the alignment at which the mean hue flips between reddish and greenish. The maximum hue shifts were approximately frequency independent and occurred when the peaks or troughs of the first and second harmonics roughly aligned at the visual input-consistent with the hue shift's being caused by an early instantaneous nonlinearity that saturates larger hue excursions. These predictions, however, ignore phase delays introduced within the chromatic pathway between its input and the nonlinearity that produces the hue shifts. If the nonlinearity follows the substantial filtering implied by the chromatic temporal contrast-sensitivity function, phase delays will alter the alignment of the first and second harmonics such that at the nonlinearity, the waveforms that produce the maximum hue shifts might well be those with the largest differences in rising and falling slopes-consistent with the hue shift's being caused by a central nonlinearity that limits the rate of hue change.

Hue shifts produced by temporal asymmetries in chromatic signals.

Observers viewed M- or L-cone-isolating stimuli and compared slowly-on and slowly-off sawtooth waveforms of the same mean chromaticity and luminance. Between 6 and 13 Hz, the mean hue of slowly-on L-cone and slowly-off M-cone sawtooth flicker appeared redder, and the mean hue of slowly-off L-cone and slowly-on M-cone sawtooth stimuli appeared greener-despite all the waveforms' having the same mean, near-yellow-appearing chromaticity. We measured the effect of the modulation depth and the slope of the sawtooth on the mean hue shifts as a function of temporal frequency. The results are complex but show that discriminability depended mainly on the second harmonic of the waveforms. We considered several models with combinations of linear and nonlinear stages. First, we considered models in which a nonlinear stage limits the rate of change of hue and restricts the steep slope of the sawtooth waveform more than its shallow slope, thus shifting the mean hue in the direction of the shallower slope (such a nonlinearity is also known as a slew-rate limit). Second, we considered saturation models in which the nonlinear stage compresses hue signals and thus shifts the mean of asymmetrical waveforms with or without differentiation before the nonlinearity. Overall, our modeling and results suggest that the hue shift occurs at some nonlinear mechanism in the chromatic pathway; and that, in terms of the Fourier components of the various waveforms, the effect of the nonlinearity depends crucially on the timing of the second harmonic relative to the first.

Multiple-stage ambiguity in motion perception reveals global computation of local motion directions.

The motion of a 1D image feature, such as a line, seen through a small aperture, or the small receptive field of a neural motion sensor, is underconstrained, and it is not possible to derive the true motion direction from a single local measurement. This is referred to as the aperture problem. How the visual system solves the aperture problem is a fundamental question in visual motion research. In the estimation of motion vectors through integration of ambiguous local motion measurements at different positions, conventional theories assume that the object motion is a rigid translation, with motion signals sharing a common motion vector within the spatial region over which the aperture problem is solved. However, this strategy fails for global rotation. Here we show that the human visual system can estimate global rotation directly through spatial pooling of locally ambiguous measurements, without an intervening step that computes local motion vectors. We designed a novel ambiguous global flow stimulus, which is globally as well as locally ambiguous. The global ambiguity implies that the stimulus is simultaneously consistent with both a global rigid translation and an infinite number of global rigid rotations. By the standard view, the motion should always be seen as a global translation, but it appears to shift from translation to rotation as observers shift fixation. This finding indicates that the visual system can estimate local vectors using a global rotation constraint, and suggests that local motion ambiguity may not be resolved until consistencies with multiple global motion patterns are assessed.

Formulae for generating standard and individual human cone spectral sensitivities.

Normal color perception is complicated. But at its initial stage it is relatively simple, since at photopic levels it depends on the activations of just three photoreceptor types: the long- (L-), middle- (M-) and short- (S-) wavelength-sensitive cones. Knowledge of how each type responds to different wavelengths-the three cone spectral sensitivities-can be used to model human color vision and in practical applications to specify color and predict color matches. The CIE has sanctioned the cone spectral sensitivity estimates of Stockman and Sharpe (Stockman and Sharpe, 2000, Vision Res) and their associated measures of luminous efficiency as "physiologically-relevant" standards for color vision (CIE, 2006; 2015). These LMS cone spectral sensitivities are specified at 5- and 1-nm steps for mean "standard" observers with normal cone photopigments and average ocular transparencies, both of which can vary in the population. Here, we provide formulae for the three cone spectral sensitivities as well as for macular and lens pigment density spectra, all as continuous functions of wavelength from 360 to 850 nm. These functions reproduce the tabulated discrete CIE LMS cone spectral sensitivities for 2-deg and 10-deg with little error in both linear and logarithmic units. Furthermore, these formulae allow the easy computation of non-standard cone spectral sensitivities (and other color matching functions) with individual differences in macular, lens and photopigment optical densities, and with spectrally shifted hybrid or polymorphic L- and M-cone photopigments appropriate for either normal or red-green color vision deficient observers.

A reinterpretation of critical flicker-frequency (CFF) data reveals key details about light adaptation and normal and abnormal visual processing.

Our ability to see flicker has an upper frequency limit above which flicker is invisible, known as the "critical flicker frequency" (CFF), that typically grows with light intensity (I). The relation between CFF and I, the focus of nearly 200 years of research, is roughly logarithmic, i.e., CFF âˆ log(I)-a relation called the Ferry-Porter law. However, why this law should occur, and how it relates to the underlying physiology, have never been adequately explained. Over the past two decades we have measured CFF in normal observers and in patients with retinal gene defects. Here, we reanalyse and model our data and historical CFF data. Remarkably, CFF-versus-I functions measured under a wide range of conditions in patients and in normal observers all have broadly similar shapes when plotted in double-logarithmic coordinates, i.e., log (CFF)-versus-log(I). Thus, the entire dataset can be characterised by horizontal and vertical logarithmic shifts of a fixed-shape template. Shape invariance can be predicted by a simple model of visual processing built from a sequence of low-pass filters, subtractive feedforward stages and gain adjustment (Rider, Henning & Stockman, 2019). It depends primarily on the numbers of visual processing stages that approach their power-law region at a given intensity and a frequency-independent gain reduction at higher light levels. Counter-intuitively, the CFF-versus-I relation depends primarily on the gain of the visual response rather than its speed-a conclusion that changes our understanding and interpretation of human flicker perception. The Ferry-Porter "law" is merely an approximation of the shape-invariant template.

Clinical vision and molecular loss: Integrating visual psychophysics with molecular genetics reveals key details of normal and abnormal visual processing.

Over the past two decades we have developed techniques and models to investigate the ways in which known molecular defects affect visual performance. Because molecular defects in retinal signalling invariably alter the speed of visual processing, our strategy has been to measure the resulting changes in flicker sensitivity. Flicker measurements provide not only straightforward clinical assessments of visual performance but also reveal fundamental details about the functioning of both abnormal and normal visual systems. Here, we bring together our past measurements of patients with pathogenic variants in the GNAT2, RGS9, GUCA1A, RPE65, OPA1, KCNV2 and NR2E3 genes and analyse the results using a standard model of visual processing. The model treats flicker sensitivity as the result of the actions of a sequence of simple processing steps, one or more of which is altered by the genetic defect. Our analyses show that most defects slow down the visual response directly, but some speed it up. Crucially, however, other steps in the processing sequence can make compensatory adjustments to offset the abnormality. For example, if the abnormal step slows down the visual response, another step is likely to speed up or attenuate the response to rebalance system performance. Such compensatory adjustments are probably made by steps in the sequence that usually adapt to changing light levels. Our techniques and modelling also allow us to tease apart stationary and progressive effects, and the localised molecular losses help us to unravel and characterise individual steps in the normal and abnormal processing sequences.

Motion-induced position shifts in global dynamic Gabor arrays.

Objects in motion appear shifted in space. For global motion stimuli we can ask whether the shift depends on the local or global motion. We constructed arrays of randomly oriented Gaussian enveloped drifting sine gratings (dynamic Gabors) whose speed was set such that the normal component of motion was consistent with a single global velocity. The array appears shifted in space in the direction of the global motion. The size of the shift is the same as for arrays of uniformly oriented dynamic Gabors that are moving in the same direction at the same global speed. Arrays made up of vertically oriented gratings whose speeds were set to the horizontal component of the random array elements were shifted less far. This shows that motion-induced position shifts of coherently moving surface patches are generated after the completion of the global motion computation.

Light adaptation controls visual sensitivity by adjusting the speed and gain of the response to light.

The range of c. 1012 ambient light levels to which we can be exposed massively exceeds the <103 response range of neurons in the visual system, but we can see well in dim starlight and bright sunlight. This remarkable ability is achieved largely by a speeding up of the visual response as light levels increase, causing characteristic changes in our sensitivity to different rates of flicker. Here, we account for over 65 years of flicker-sensitivity measurements with an elegantly-simple, physiologically-relevant model built from first-order low-pass filters and subtractive inhibition. There are only two intensity-dependent model parameters: one adjusts the speed of the visual response by shortening the time constants of some of the filters in the direct cascade as well as those in the inhibitory stages; the other parameter adjusts the overall gain at higher light levels. After reviewing the physiological literature, we associate the variable gain and three of the variable-speed filters with biochemical processes in cone photoreceptors, and a further variable-speed filter with processes in ganglion cells. The variable-speed but fixed-strength subtractive inhibition is most likely associated with lateral connections in the retina. Additional fixed-speed filters may be more central. The model can explain the important characteristics of human flicker-sensitivity including the approximate dependences of low-frequency sensitivity on contrast (Weber's law) and of high-frequency sensitivity on amplitude ("high-frequency linearity"), the exponential loss of high-frequency sensitivity with increasing frequency, and the logarithmic increase in temporal acuity with light level (Ferry-Porter law). In the time-domain, the model can account for several characteristics of flash sensitivity including changes in contrast sensitivity with light level (de Vries-Rose and Weber's laws) and changes in temporal summation (Bloch's law). The new model provides fundamental insights into the workings of the visual system and gives a simple account of many visual phenomena.

The Pattern of Retinal Ganglion Cell Loss in OPA1-Related Autosomal Dominant Optic Atrophy Inferred From Temporal, Spatial, and Chromatic Sensitivity Losses.

Purpose: Progressive retinal ganglion cell (RGC) loss is the pathological hallmark of autosomal dominant optic atrophy (DOA) caused by pathogenic OPA1 mutations. The aim of this study was to conduct an in-depth psychophysical study of the visual losses in DOA and to infer any selective vulnerability of visual pathways subserved by different RGC subtypes. Methods: We recruited 25 patients carrying pathogenic OPA1 mutations and age-matched healthy individuals. Spatial contrast sensitivity functions (SCSFs) and chromatic contrast sensitivity were quantified, the latter using the Cambridge Colour Test. In 11 patients, long (L) and short (S) wavelength-sensitive cone temporal acuities were measured as a function of target illuminance, and L-cone temporal contrast sensitivity (TCSF) as a function of temporal frequency. Results: Spatial contrast sensitivity functions were abnormal, with the loss of sensitivity increasing with spatial frequency. Further, the highest L-cone temporal acuity fell on average by 10 Hz and the TCSFs by 0.66 log10 unit. Chromatic thresholds along the protan, deutan, and tritan axes were 8, 9, and 14 times higher than normal, respectively, with losses increasing with age and S-cone temporal acuity showing the most significant age-related decline. Conclusions: Losses of midget parvocellular, parasol magnocellular, and bistratified koniocellular RGCs could account for the losses of high spatial frequency sensitivity and protan and deutan sensitivities, high temporal frequency sensitivity, and S-cone temporal and tritan sensitivities, respectively. The S-cone-related losses showed a significant deterioration with increasing patient age and could therefore prove useful biomarkers of disease progression in DOA.

Psychophysical measures of visual function and everyday perceptual experience in a case of congenital stationary night blindness.

An appreciation of the relation between laboratory measures of visual deficit and everyday perceptual experience is fundamental to understanding the impact of a visual condition on patients and so to a fuller characterization of the disorder. This study aims to understand better the interpretative processes by which modified sensory information is perceived by a patient with congenital stationary night blindness and the adaptive strategies that are devised to deal with their measurable visual loss. Psychophysical measurements of temporal resolution, spectral sensitivity, and color discrimination were conducted on a 78-year-old male patient with the condition, who was also interviewed at length about the ways in which his diagnosis affected his daily life. Narrative analysis was employed to identify the relation between his subjective perceptual experiences and functional deficits in identifiable components of the visual system. Psychophysical measurements indicated a complete lack of rod perception and substantially reduced cone sensitivity. Two particular effects of this visual loss emerged during interviews: 1) the development of navigational techniques that relied on light reflections and point sources of light and 2) a reluctance to disclose the extent of visual loss and resulting lifelong psychosocial consequences. This study demonstrates the valuable complementary role that rich descriptive patient testimony can play, in conjunction with laboratory and clinical measurements, in more fully characterizing a disorder and in reaching a more complete understanding of the experience of vision loss. It also evidences the particular suitability of filmmaking techniques as a means of accessing and communicating subjective patient experience.