Manuel Spitschan

Opponent melanopsin and S-cone signals in the human pupillary light response

Significance Our eyes sense bright light using cones (L, M, and S) and recently discovered melanopsin-containing ganglion cells. Both S cones and melanopsin respond to blueish (short-wavelength) light. How does melanopsin interact with the cones in visual function? We measured the response of the human pupil to isolated stimulation of the different photoreceptors. Our work reveals a curious, opponent response to blue light in the otherwise familiar pupillary light response. Increased stimulation of S cones can cause the pupil to dilate, but this effect is usually masked by a stronger and opposite response from melanopsin-containing cells. Our results have clinical importance because the sensing of blue light is known to be related to seasonal depression, sleep, and pain from bright light. In the human, cone photoreceptors (L, M, and S) and the melanopsin-containing, intrinsically photosensitive retinal ganglion cells (ipRGCs) are active at daytime light intensities. Signals from cones are combined both additively and in opposition to create the perception of overall light and color. Similar mechanisms seem to be at work in the control of the pupil’s response to light. Uncharacterized however, is the relative contribution of melanopsin and S cones, with their overlapping, short-wavelength spectral sensitivities. We measured the response of the human pupil to the separate stimulation of the cones and melanopsin at a range of temporal frequencies under photopic conditions. The S-cone and melanopsin photoreceptor channels were found to be low-pass, in contrast to a band-pass response of the pupil to L- and M-cone signals. An examination of the phase relationships of the evoked responses revealed that melanopsin signals add with signals from L and M cones but are opposed by signals from S cones in control of the pupil. The opposition of the S cones is revealed in a seemingly paradoxical dilation of the pupil to greater S-cone photon capture. This surprising result is explained by the neurophysiological properties of ipRGCs found in animal studies.

Variation of outdoor illumination as a function of solar elevation and light pollution.

The illumination of the environment undergoes both intensity and spectral changes during the 24 h cycle of a day. Daylight spectral power distributions are well described by low-dimensional models such as the CIE (Commission Internationale de l’Éclairage) daylight model, but the performance of this model in non-daylight regimes is not characterised. We measured downwelling spectral irradiance across multiple days in two locations in North America: One rural location (Cherry Springs State Park, PA) with minimal anthropogenic light sources, and one city location (Philadelphia, PA). We characterise the spectral, intensity and colour changes and extend the existing CIE model for daylight to capture twilight components and the spectrum of the night sky.

Human Visual Cortex Responses to Rapid Cone and Melanopsin-Directed Flicker.

Signals from cones are recombined in postreceptoral channels [luminance, L + M; red-green, L − M; blue-yellow, S − (L + M)]. The melanopsin-containing retinal ganglion cells are also active at daytime light levels and recent psychophysical results suggest that melanopsin contributes to conscious vision in humans. Here, we measured BOLD fMRI responses to spectral modulations that separately targeted the postreceptoral cone channels and melanopsin. Responses to spatially uniform (27.5° field size, central 5° obscured) flicker at 0.5, 1, 2, 4, 8, 16, 32, and 64 Hz were recorded from areas V1, V2/V3, motion-sensitive area MT, and the lateral occipital complex. In V1 and V2/V3, higher temporal sensitivity was observed to L + M + S (16 Hz) compared with L − M flicker (8 Hz), consistent with psychophysical findings. Area MT was most sensitive to rapid (32 Hz) flicker of either L + M + S or L − M. We found S cone responses only in areas V1 and V2/V3 (peak frequency: 4–8 Hz). In addition, we studied an L + M modulation and found responses that were effectively identical at all temporal frequencies to those recorded for the L + M + S modulation. Finally, we measured the cortical response to melanopsin-directed flicker and compared this response with control modulations that addressed stimulus imprecision and the possibility of stimulation of cones in the shadow of retinal blood vessels (penumbral cones). For our stimulus conditions, melanopsin flicker did not elicit a cortical response exceeding that of the control modulations. We note that failure to control for penumbral cone stimulation could be mistaken for a melanopsin response. SIGNIFICANCE STATEMENT The retina contains cone photoreceptors and ganglion cells that contain the photopigment melanopsin. Cones provide brightness and color signals to visual cortex. Melanopsin influences circadian rhythm and the pupil, but its contribution to cortex and perception is less clear. We measured the response of human visual cortex with fMRI using spectral modulations tailored to stimulate the cones and melanopsin separately. We found that cortical responses to cone signals vary systematically across visual areas. Differences in temporal sensitivity for achromatic, red-green, and blue-yellow stimuli generally reflect the known perceptual properties of vision. We found that melanopsin signals do not produce a measurable response in visual cortex at temporal frequencies between 0.5 and 64 Hz at daytime light levels.

Selective Stimulation of Penumbral Cones Reveals Perception in the Shadow of Retinal Blood Vessels

In 1819, Johann Purkinje described how a moving light source that displaces the shadow of the retinal blood vessels to adjacent cones can produce the entopic percept of a branching tree. Here, we describe a novel method for producing a similar percept. We used a device that mixes 56 narrowband primaries under computer control, in conjunction with the method of silent substitution, to present observers with a spectral modulation that selectively targeted penumbral cones in the shadow of the retinal blood vessels. Such a modulation elicits a clear Purkinje-tree percept. We show that the percept is specific to penumbral L and M cone stimulation and is not produced by selective penumbral S cone stimulation. The Purkinje-tree percept was strongest at 16 Hz and fell off at lower (8 Hz) and higher (32 Hz) temporal frequencies. Selective stimulation of open-field cones that are not in shadow, with penumbral cones silenced, also produced the percept, but it was not seen when penumbral and open-field cones were modulated together. This indicates the need for spatial contrast between penumbral and open-field cones to create the Purkinje-tree percept. Our observation provides a new means for studying the response of retinally stabilized images and demonstrates that penumbral cones can support spatial vision. Further, the result illustrates a way in which silent substitution techniques can fail to be silent. We show that inadvertent penumbral cone stimulation can accompany melanopsin-directed modulations that are designed only to silence open-field cones. This in turn can result in visual responses that might be mistaken as melanopsin-driven.

Chromatic clocks: Color opponency in non-image-forming visual function.

HighlightsAs the Earth rotates around it’s own axis, the light environment changes in a predictable fashion in terms of both intensity and spectral composition (color).To synchronize their physiology and behavior to the 24 h cycle, organisms use intensity and color information encoded by their non‐image‐forming visual systems.Spectral shifts during twilight shifts can be encoded by a color‐opponent sensory system for non‐image‐forming (NIF) visual functions including circadian phase shifting and melatonin suppression. Abstract During dusk and dawn, the ambient illumination undergoes drastic changes in irradiance (or intensity) and spectrum (or color). While the former is a well‐studied factor in synchronizing behavior and physiology to the earth’s 24‐h rotation, color sensitivity in the regulation of circadian rhythms has not been systematically studied. Drawing on the concept of color opponency, a well‐known property of image‐forming vision in many vertebrates (including humans), we consider how the spectral shifts during twilight are encoded by a color‐opponent sensory system for non‐image‐forming (NIF) visual functions, including phase shifting and melatonin suppression. We review electrophysiological evidence for color sensitivity in the pineal/parietal organs of fish, amphibians and reptiles, color coding in neurons in the circadian pacemaker in mice as well as sporadic evidence for color sensitivity in NIF visual functions in birds and mammals. Together, these studies suggest that color opponency may be an important modulator of light‐driven physiological and behavioral responses.

The human visual cortex response to melanopsin-directed stimulation is accompanied by a distinct perceptual experience.

Significance Melanopsin-containing retinal cells detect bright light and contribute to reflex visual responses such as pupil constriction. Their role in conscious, cortical vision is less understood. Using functional MRI to measure brain activity, we find that melanopsin-directed stimulation reaches the visual cortex in people. Such stimulation also produces a distinct perceptual experience. Our results have clinical importance as melanopsin function may contribute to the discomfort that some people experience from bright light. The photopigment melanopsin supports reflexive visual functions in people, such as pupil constriction and circadian photoentrainment. What contribution melanopsin makes to conscious visual perception is less studied. We devised a stimulus that targeted melanopsin separately from the cones using pulsed (3-s) spectral modulations around a photopic background. Pupillometry confirmed that the melanopsin stimulus evokes a response different from that produced by cone stimulation. In each of four subjects, a functional MRI response in area V1 was found. This response scaled with melanopic contrast and was not easily explained by imprecision in the silencing of the cones. Twenty additional subjects then observed melanopsin pulses and provided a structured rating of the perceptual experience. Melanopsin stimulation was described as an unpleasant, blurry, minimal brightening that quickly faded. We conclude that isolated stimulation of melanopsin is likely associated with a response within the cortical visual pathway and with an evoked conscious percept.

Vision: Melanopsin as a Raumgeber

Two new studies show that neural systems receiving inputs from the melanopsin-containing retinal ganglion cells encode spatial information and therefore see the world in more detail than previously thought.

Eye fixation during multiple object attention is based on a representation of discrete spatial foci

We often look at and attend to several objects at once. How the brain determines where to point our eyes when we do this is poorly understood. Here we devised a novel paradigm to discriminate between different models of spatial selection guiding fixation. In contrast to standard static attentional tasks where the eye remains fixed at a predefined location, observers selected their own preferred fixation position while they tracked static targets that were arranged in specific geometric configurations and which changed identity over time. Fixations were best predicted by a representation of discrete spatial foci, not a polygonal grouping, simple 2-foci division of attention or a circular spotlight. Moreover, attentional performance was incompatible with serial selection. Together with previous studies, our findings are compatible with a view that attentional selection and fixation rely on shared spatial representations and suggest a more nuanced definition of overt vs. covert attention.We often look at and attend to several objects at once. How the brain determines where to point our eyes when we do this is poorly understood. Here we devised a novel paradigm to discriminate between different models of spatial selection guiding fixation. In contrast to standard static attentional tasks where the eye remains fixed at a predefined location, observers selected their own preferred fixation position while they tracked static targets that were arranged in specific geometric configurations and which changed identity over time. Fixations were best predicted by a representation of discrete spatial foci, not a polygonal grouping, simple 2-foci division of attention or a circular spotlight. Moreover, attentional performance was incompatible with serial selection. Together with previous studies, our findings are compatible with a view that attentional selection and fixation rely on shared spatial representations and suggest a more nuanced definition of overt vs. covert attention.

Ocular fixations are consistent with the endogenous selection of multiple discrete spatial foci of attention

Humans have the capacity to selectively attend to more than one item in the visual field. Whether this is accomplished by a single scalable attentional window, grouping targets into a virtual polygon, serial monitoring of targets, or divided multiple foci of attention has remained a controversy. Recent neurophysiological results have demonstrated divided focus of attention in humans and monkeys (Neibergall et al., 2011; Stoermer et al., 2013), but evidence for endogenously selected multi-focal attention that can differentiate between various mechanisms has been elusive. One strategy is to exploit the close linkage between ocular fixations and spatial selection (Goffart, Hafed & Krauzlis, 2012; Fehd & Seiffert, 2008). We used a novel attentional task paradigm where subjects selectively attended multiple static target locations while ignoring distractor locations within a geometric array. The arrays consisted of letters that rapidly changed identity at a rate of 5 or 10 Hertz. The subjects task was to detect the occurence of probe numeral that was briefly displayed (single frame) at one of the target locations. Importantly, in contrast to standard attentional tasks, subjects were free to select their own preferred fixation position. We found that the mean preferred fixation positions were close to the centroid defined over a group of discrete circular windows encompassing target locations only, consistent with divided multi-focal attention. Fixation positions were not consistent with selection based on a single attentional window or a virtual polygon defined by target locations. Moreover, analysis of differences in the detectability of probes in configurations with 3 or 5 target items were incompatible with serial covert monitoring of targets. Our results are consistent with the view that ocular fixation represents the equilibrium point of the spatial distribution of discrete multiple foci of attention and suggest a more nuanced definition of covert versus overt attention. Meeting abstract presented at VSS 2015.