Melanopsin Sensitivity in the Human Visual System

The human retina contains long [L]-wavelength, medium [M]-wavelength, and short [S]-wavelength cones, rods, and intrinsically photosensitive retinal ganglion cells expressing the blue-sensitive (λmax = ~480 nm) photopigment melanopsin. Previous animal studies have pointed to a role of melanopsin in advancing circadian phase, melatonin suppression, the pupillary light reflex (PLR), light avoidance, and brightness discrimination, often relying on genetic tools to study melanopsin in isolation in animal models. This work addresses the question of human melanopsin sensitivity and function in vivo using a spectrally tunable light source and the method of silent substitution, allowing for the selective stimulation of melanopsin in the human retina, in combination of pupillometry, psychophysics, and BOLD functional neuroimaging (fMRI). In three studies, we find (1) that the temporal transfer function of melanopsin in controlling the pupil in humans is low-pass, peaking at slow temporal frequencies (0.01 Hz), with a sharp drop off at higher frequencies (1-2 Hz); (2) that signals originating from S cones get combined in an antagonistic fashion with melanopsin signals and signals from L and M cones cones, demonstrating spectral opponency in the control of the human PLR; (3) that nominally cone-silent melanopsin-directed spectral modulations stimulate cones in the partial shadow of the retinal blood vessels (termed penumbral cones), leading to the entoptic percept of the subjective retinal vasculature; and (4) that there is no measurable signal due to melanopsin stimulation in human visual cortical areas (V1, V2/V3, MT, LOC; measured with BOLD fMRI) at temporal frequencies most relevant to spatial vision (0.5–64 Hz) while modulations directed at L+M, L–M and S photoreceptor combinations yield characteristic temporal transfer functions in these areas. This work advances to our understanding of the functional significance of melanopsin function in the human visual system, contributing to the study of human health in relation to light and color

The impact of Alzheimer’s disease risk factors on the pupillary light response

Alzheimer’s disease (AD) is the leading cause of dementia, and its prevalence is increasing and is expected to continue to increase over the next few decades. Because of this, there is an urgent requirement to determine a way to diagnose the disease, and to target interventions to delay and ideally stop the onset of symptoms, specifically those impacting cognition and daily livelihood. The pupillary light response (PLR) is controlled by the sympathetic and parasympathetic branches of the autonomic nervous system, and impairments to the pupillary light response (PLR) have been related to AD. However, most of these studies that assess the PLR occur in patients who have already been diagnosed with AD, rather than those who are at a higher risk for the disease but without a diagnosis. Determining whether the PLR is similarly impaired in subjects before an AD diagnosis is made and before cognitive symptoms of the disease begin, is an important step before using the PLR as a diagnostic tool. Specifically, identifying whether the PLR is impaired in specific at-risk groups, considering both genetic and non-genetic risk factors, is imperative. It is possible that the PLR may be impaired in association with some risk factors but not others, potentially indicating different pathways to neurodegeneration that could be distinguished using PLR. In this work, we review the most common genetic and lifestyle-based risk factors for AD and identify established relationships between these risk factors and the PLR. The evidence here shows that many AD risk factors, including traumatic brain injury, ocular and intracranial hypertension, alcohol consumption, depression, and diabetes, are directly related to changes in the PLR. Other risk factors currently lack sufficient literature to make any conclusions relating directly to the PLR but have shown links to impairments in the parasympathetic nervous system; further research should be conducted in these risk factors and their relation to the PLR

Inclusion, reporting and analysis of demographic variables in chronobiology and sleep research

Many aspects of sleep and circadian physiology are sensitive to participant-level characteristics. While recent research robustly highlights the importance of considering participant-level demographic information, the extent to which this information is consistently collected, and reported in the literature, remains unclear. This article investigates study sample characteristics within the published sleep and chronobiology research over the past 40 years. 6,777 articles were identified and a random sample of 20% was included. The reporting of sample size, age, sex, gender, ethnicity, level of education, socio-economic status, and profession of the study population was scored, and any reported aggregate summary statistics for these variables were recorded. We observed a significant upward trend in the reporting and analysis of demographic variables in sleep and chronobiology research. However, we found that while > 90% of studies reported age or sex, all other variables were reported in < 25% of cases. Reporting quality was highly variable, indicating an opportunity to standardize reporting guidelines for participant-level characteristics to facilitate Meta analyses

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

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, suggesting that attentional selection and fixation share the same spatial representation. Together with previous findings on fixational microsaccades during covert attention, our results suggest a more nuanced definition of overt vs. covert attention.Publisher PDFPeer reviewe

Report on the Workshop Use and Application of the new CIE s 026/e:2018, Metrology for ipRGC-influenced responses to light “specifying light for its eye-mediated non-visual effects in humans”

In December 2018, the international standard CIE S 026/E:2018 “CIE System for Metrology of Optical Radiation for ipRGC-Influenced Responses to Light” (doi.org/10.25039/S026.2018) was published. This standard defines spectral sensitivity functions, quantities and metrics to describe the ability of optical radiation to stimulate each of the five retinal photoreceptor classes that can contribute, via the melanopsin-containing intrinsically-photosensitive retinal ganglion cells (ipRGCs), to the retinally mediated non-visual effects of light in humans. This one-hour workshop started with four 10 minute presentations about the standard, followed by a general discussion and questions. The four presentations focused on the following topics:1) Introduction to CIE S 026 and its quantities (Luc Schlangen)2) Demonstration of toolkit (in preparation) to calculate CIE S 026 quantities (Presented by Luc Schlangen on behalf of Luke Price)3) Accounting for field of view (David Sliney)4) ipRGCs and pupil response (Manuel Spitschan

The impact of Alzheimer's disease risk factors on the pupillary light response

Alzheimer’s disease (AD) is the leading cause of dementia, and its prevalence is increasing and is expected to continue to increase over the next few decades. Because of this, there is an urgent requirement to determine a way to diagnose the disease, and to target interventions to delay and ideally stop the onset of symptoms, specifically those impacting cognition and daily livelihood. The pupillary light response (PLR) is controlled by the sympathetic and parasympathetic branches of the autonomic nervous system, and impairments to the pupillary light response (PLR) have been related to AD. However, most of these studies that assess the PLR occur in patients who have already been diagnosed with AD, rather than those who are at a higher risk for the disease but without a diagnosis. Determining whether the PLR is similarly impaired in subjects before an AD diagnosis is made and before cognitive symptoms of the disease begin, is an important step before using the PLR as a diagnostic tool. Specifically, identifying whether the PLR is impaired in specific at-risk groups, considering both genetic and non-genetic risk factors, is imperative. It is possible that the PLR may be impaired in association with some risk factors but not others, potentially indicating different pathways to neurodegeneration that could be distinguished using PLR. In this work, we review the most common genetic and lifestyle-based risk factors for AD and identify established relationships between these risk factors and the PLR. The evidence here shows that many AD risk factors, including traumatic brain injury, ocular and intracranial hypertension, alcohol consumption, depression, and diabetes, are directly related to changes in the PLR. Other risk factors currently lack sufficient literature to make any conclusions relating directly to the PLR but have shown links to impairments in the parasympathetic nervous system; further research should be conducted in these risk factors and their relation to the PLR

Demonstrating a multi-primary high dynamic range display system for vision experiments.

We describe the design, construction, calibration, and characterization of a multi-primary high dynamic range (MPHDR) display system for use in vision research. The MPHDR display is the first system to our knowledge to allowfor spatially controllable, high dynamic range stimulus generation using multiple primaries.We demonstrate the high luminance, high dynamic range, and wide color gamut output of the MPHDR display. During characterization, the MPHDR display achieved a maximum luminance of 3200 cd=m2, a maximum contrast range of 3; 240; 000 V 1, and an expanded color gamut tailored to dedicated vision research tasks that spans beyond traditional sRGB displays. We discuss how the MPHDR display could be optimized for psychophysical experiments with photoreceptor isolating stimuli achieved through the method of silent substitution. We present an example case of a range of metameric pairs of melanopsin isolating stimuli across different luminance levels, from an available melanopsin contrast of117%at 75 cd=m2 to a melanopsin contrast of23%at 2000 cd=m2

Power Analysis for Human Melatonin Suppression Experiments

In humans, the nocturnal secretion of melatonin by the pineal gland is suppressed by ocular exposure to light. In the laboratory, melatonin suppression is a biomarker for this neuroendocrine pathway. Recent work has found that individuals differ substantially in their melatonin-suppressive response to light, with the most sensitive individuals being up to 60 times more sensitive than the least sensitive individuals. Planning experiments with melatonin suppression as an outcome needs to incorporate these individual differences, particularly in common resource-limited scenarios where running within-subjects studies at multiple light levels is costly and resource-intensive and may not be feasible with respect to participant compliance. Here, we present a novel framework for virtual laboratory melatonin suppression experiments, incorporating a Bayesian statistical model. We provide a Shiny web app for power analyses that allows users to modify various experimental parameters (sample size, individual-level heterogeneity, statistical significance threshold, light levels), and simulate a systematic shift in sensitivity (e.g., due to a pharmacological or other intervention). Our framework helps experimenters to design compelling and robust studies, offering novel insights into the underlying biological variability in melatonin suppression relevant for practical applications