A framework for predicting the non-visual effects of daylight - part I: photobiology-based model

This paper investigates the formulation of a modelling framework for the nonvisual effects of daylight, such as entrainment of the circadian system and maintenance of alertness. The body of empirical data from photobiology studies is now sufficient to start developing preliminary non-visual lighting evaluation methods for lighting design. Eventually, these non-visual effects have the potential to become a relevant quantity to consider when assessing the overall daylighting performance of a space. This paper describes the assumptions and general approach that were developed to propose a modeling framework for occupant exposure to non-visual effects of light, and presents a novel means of visualising the ‘circadian potential’ of a point in space. The proposed approach uses current outcomes of photobiology research to define – at this point static – threshold values for illumination in terms of spectrum, intensity and timing of light at the human eye. These values are then translated into goals for lighting simulation, based on vertical illuminance at the eye, that – ultimately – could become goals for building design. A new climate-based simulation model has been developed to apply these concepts to a residential environment. This will be described in Part 2 of this paper

Principles of sleep-wake regulation

The 24-hour sleep-wake cycle is generated by two oscillatory processes: an endogenous hypothalamic circadian pacemaker and a sleep- and wake-dependent homeostat. These processes combine to maintain a consolidated bout of sleep at night and relatively stable waking function across the day. They also combine to determine 'diurnal preference'-whether one is a 'lark' or an 'owl'-a reflection of the phase relationship between the circadian and homeostatic processes. These processes are affected directly by light, either through resetting of the circadian pacemaker or its direct alerting effects. Sleep deficiency and circadian disruption have been associated with a higher risk of chronic disease, although the methodology for assessing these exposures is not optimal. Both sleep and the circadian system also have myriad influences on other aspects of our physiology, behaviour, and metabolism; therefore, steps should be taken to reduce their potential confounding effects in epidemiological studies. © Oxford University Press 2018. All Rights Reserved

Non-24-hour sleep-wake rhythm disorder in sighted and blind patients

Non-24-hour sleep-wake rhythm disorder (N24SWD) is a cyclic debilitating circadian rhythm sleep disorder characterized by an inability to sleep on a 24-hour schedule. Individuals isolated from a 24-hour light-dark cycle exhibit sleep-wake cycles different from 24 hours. Relatively rare in sighted patients, it may be associated with delayed sleep-wake rhythm disorder or psychiatric disorders. It is more common in totally blind individuals owing to the lack of light information reaching the circadian pacemaker in the hypothalamus. We review the clinical characteristics of patients with N24SWD, discuss the biological mechanisms that may underlie its development, and describe treatment strategies. © 2015 Elsevier Inc

A pre-screening questionnaire to predict non-24-hour sleep-wake rhythm disorder (N24HSWD) among the blind

Study Objectives: There is currently no questionnaire-based pre-screening tool available to detect non-24-hour sleep-wake rhythm disorder (N24HSWD) among blind patients. Our goal was to develop such a tool, derived from gold standard, objective hormonal measures of circadian entrainment status, for the detection of N24HSWD among those with visual impairment. Methods: We evaluated the contribution of 40 variables in their ability to predict N24HSWD among 127 blind women, classified using urinary 6-sulfatoxymelatonin period, an objective marker of circadian entrainment status in this population. We subjected the 40 candidate predictors to 1,000 bootstrapped iterations of a logistic regression forward selection model to predict N24HSWD, with model inclusion set at the p < 0.05 level. We removed any predictors that were not selected at least 1% of the time in the 1,000 bootstrapped models and applied a second round of 1,000 bootstrapped logistic regression forward selection models to the remaining 23 candidate predictors. We included all questions that were selected at least 10% of the time in the final model. We subjected the selected predictors to a final logistic regression model to predict N24SWD over 1,000 bootstrapped models to calculate the concordance statistic and adjusted optimism of the final model. We used this information to generate a predictive model and determined the sensitivity and specificity of the model. Finally, we applied the model to a cohort of 1,262 blind women who completed the survey, but did not collect urine samples. Results: The final model consisted of eight questions. The concordance statistic, adjusted for bootstrapping, was 0.85. The positive predictive value was 88%, the negative predictive value was 79%. Applying this model to our larger dataset of women, we found that 61% of those without light perception, and 27% with some degree of light perception, would be referred for further screening for N24HSWD. Conclusions: Our model has predictive utility sufficient to serve as a pre-screening questionnaire for N24HSWD among the blind

Visual impairment and circadian rhythm sleep disorders

Many aspects of human physiology, metabolism, and behavior are dominated by 24-h circadian rhythms including the sleep-wake cycle, alertness and performance patterns, and some hormones. These rhythms are spontaneously generated by an internal circadian clock in the brain and daily light exposure to the eyes synchronizes the clock with the external environment. Most blind people with no perception of light, however, experience continual circadian desynchrony through a failure of light information to reach the circadian pacemaker, resulting in non-24-h sleep-wake disorder. Daily melatonin administration, which provides a replacement synchronizing daily �time cue,� is a promising therapeutic strategy to treat this disorder. © 2017 Elsevier Inc. All rights reserved

Unified framework to evaluate non-visual spectral effectiveness of light for human health

The discovery of a novel non-rod, non-cone photoreceptor in the mammalian eye that mediates a range of 'non-visual' responses to light has required reexamination of how lighting needs for human health are characterised and evaluated. Existing literature provides useful information about how to quantify non-visual spectral sensitivities to light but the optimal approach is far from decided. As more is learned about the underlying biology, new approaches will continue to be published. What is currently lacking is a flexible framework to describe the non-visual spectral effectiveness of light using a common language. Without a unified description of quantities and units, much of the value of scientific publications can be lost. In this paper, we review the existing approaches by categorising the proposed quantities depending on their application. Based on this review, a unified framework is provided for use in evaluating and reporting the spectral effectiveness of light for human health. The unified framework will provide greater flexibility to model the non-visual responses to light and is adaptable to a wide range of lighting solutions of interest to researchers, designers and developers. A new visualisation tool, the SpeKtro dashboard, is available to explore the unified framework online at spektro.epfl.ch. © Chartered Institution of Building Services Engineers

Prediction of Cognitive Performance and Subjective Sleepiness Using a Model of Arousal Dynamics

A model of arousal dynamics is applied to predict objective performance and subjective sleepiness measures, including lapses and reaction time on a visual Performance Vigilance Test (vPVT), performance on a mathematical addition task (ADD), and the Karolinska Sleepiness Scale (KSS). The arousal dynamics model is comprised of a physiologically based flip-flop switch between the wake- and sleep-active neuronal populations and a dynamic circadian oscillator, thus allowing prediction of sleep propensity. Published group-level experimental constant routine (CR) and forced desynchrony (FD) data are used to calibrate the model to predict performance and sleepiness. Only the studies using dim light (<15 lux) during alertness measurements and controlling for sleep and entrainment before the start of the protocol are selected for modeling. This is done to avoid the direct alerting effects of light and effects of prior sleep debt and circadian misalignment on the data. The results show that linear combination of circadian and homeostatic drives is sufficient to predict dynamics of a variety of sleepiness and performance measures during CR and FD protocols, with sleep-wake cycles ranging from 20 to 42.85 h and a 2:1 wake-to-sleep ratio. New metrics relating model outputs to performance and sleepiness data are developed and tested against group average outcomes from 7 (vPVT lapses), 5 (ADD), and 8 (KSS) experimental protocols, showing good quantitative and qualitative agreement with the data (root mean squared error of 0.38, 0.19, and 0.35, respectively). The weights of the homeostatic and circadian effects are found to be different between the measures, with KSS having stronger homeostatic influence compared with the objective measures of performance. Using FD data in addition to CR data allows us to challenge the model in conditions of both acute sleep deprivation and structured circadian misalignment, ensuring that the role of the circadian and homeostatic drives in performance is properly captured. © 2018, © 2018 The Author(s)

Suppression of Melatonin Secretion in Totally Visually Blind People by Ocular Exposure to White Light: Clinical Characteristics

Purpose: Although most totally visually blind individuals exhibit nonentrained circadian rhythms due to an inability of light to entrain the circadian pacemaker, a small proportion retain photic circadian entrainment, melatonin suppression, and other nonimage-forming responses to light. It is thought that these responses to light persist because of the survival of melanospin-containing intrinsically photosensitive retinal ganglion cells (ipRGCs), which project primarily to the circadian pacemaker and are functionally distinct from the rod and cone photoreceptors that mediate vision. We aimed to assess the integrity of nonimage-forming photoreception in totally visually blind patients with a range of ocular disorders. Design: Within-subject, dark-controlled design. Participants: A total of 18 totally visually blind individuals (7 females; mean age ± standard deviation = 49.8±11.0 years) with various causes of blindness, including 3 bilaterally enucleated controls. Methods: Melatonin concentrations were compared during exposure to a 6.5-hour bright white light (�7000 lux) with melatonin concentrations measured 24 hours earlier at the corresponding clock times under dim-light (4 lux) conditions. Main Outcome Measures: Area under the curve (AUC) for melatonin concentration. Results: Melatonin concentrations were significantly suppressed (defined as �33% suppression) during the bright-light condition compared with the dim-light condition in 5 of 15 participants with eyes (retinitis pigmentosa, n = 2; retinopathy of prematurity [ROP], n = 2; bilateral retinal detachments, n = 1). Melatonin concentrations remained unchanged in response to light in the remaining 10 participants with eyes (ROP, n = 3; optic neuritis/neuropathy, n = 2; retinopathy unknown, n = 2; congenital glaucoma, n = 1; congenital rubella syndrome, n = 1; measles retinopathy, n = 1) and in all 3 bilaterally enucleated participants. Conclusions: These data confirm that light-induced suppression of melatonin remains functionally intact in a minority of totally visually blind individuals with eyes. None of the bilaterally enucleated individuals or those with phthisis bulbi was responsive to light; of the remainder, half were responsive to light. Although inner retinal damage is associated with a high likelihood that nonimage-forming photoreception is absent, the impact of outer retinal damage is more ambiguous, and therefore the assessment of the presence, attenuation, or absence of nonimage-forming light responses in totally blind patients requires careful individual confirmation and cannot simply be assumed from the type of blindness. © 2018 American Academy of Ophthalmolog