Seasonal Variations in Adults with and without Cataracts

Seasonal adaptation is a ubiquitous behavior seen in many species on both global hemispheres and is conveyed by changing photoperiods. In humans this seasonal adaptation is less apparent, in part because changes in daylength are masked by the use of electrical lighting at night. On the other hand, cataracts which reduce light transmission, may compound seasonal changes related to the reduced daylength of winter. To better understand the effects of different photoperiod lengths in healthy adults without and with cataracts, we tested their melanopsin-mediated light responses in summer vs. winter. Fifty-two participants (mean age 67.4 years; 30 with bilateral cataracts and 22 age-matched controls with clear lenses; pseudophakes) were tested twice, once in summer and once in winter. At each test session we assessed the electroretinogram and pupil responses during daytime and we determined melatonin suppression, subjective sleepiness and mood in response to light exposure in the evening. Circadian rest-activity cycles and sleep from activity recordings were also analyzed for both seasons. Both groups had similar visual function. There were no seasonal differences in the electroretinogram. For the pupil responses to bright blue light, the post- illumination pupil response (PIPR) was greater in winter than summer in pseudophakes, but not in cataract participants, whereas melatonin suppression to acute light exposure showed no differences between both groups and seasons. Overall, intra-daily variability of rest-activity was worse in winter but participants felt sleepier and reported worse mood at the laboratory in evening time in the summer. Those with cataracts had poorer sleep quality with lower sleep efficiency, and higher activity during sleep in winter than summer. In this study, the PIPR showed a seasonal variation in which a larger response was found during winter. This variation was only detected in participants with a clear intraocular lens. In the cataract group, visual function was not impaired yet these participants showed a lack of seasonal changes in the pupil response to blue light and poorer sleep in winter. These findings raise the question for tailored lighting conditions for cataract patients in order to counter potentially deleterious effects of living with chronically lower light exposure

The alerting effect of the wake maintenance zone during 40 hours of sleep deprivation

Under entrained conditions, the accumulation of homeostatic sleep pressure in the evening is opposed by a strong circadian arousal signal prior to the dim light melatonin onset, called the Wake Maintenance Zone (WMZ). This study aimed at investigating the impact of the WMZ on different cognitive performance tests, as well as on subjective and objective sleepiness. Twelve young male participants completed a constant routine protocol with 40 h of extended wakefulness that included two WMZs. Cognitive tests and saliva samples were assessed hourly, while the electroencephalogram (EEG) was recorded continuously. Participants improved in cognitive response inhibition during WMZ1 (13.5 h awake) and sustained attention during WMZ2 (37.5 h awake), but not in higher executive function tests. There were significant EEG power density reductions in the delta/theta frequency range during WMZ1 and in delta/theta, alpha, and sigma/beta ranges during WMZ2, with a greater change in the sigma/beta range during WMZ2 compared toWMZ1. EEG power reductions coincided during WMZ1 with stable subjective sleepiness and sustained attention. During WMZ2, EEG power reductions were more pronounced and coincided with improved sustained attention. Our results suggest the circadian arousal signal in the evening differently modulates cognitive functions and EEG power depending on the duration of prior wakefulness

Assessment of Circadian Weighted Radiance Distribution Using a Camera-Like Light Sensor

Suboptimal light distribution in a room can cause visual discomfort and glare. Next to rods and cones, perception of light is also governed by a third class of photoreceptors, important for circadian rhythm regulation and non-visual functions such as alertness, mood and hormonal secretion. These receptors show greatest sensitivity in the blue part of the visible light spectrum. In order to assess light distribution with respect to non-visual sensitivity functions, we aimed at validating a new device to create light distribution maps with a circadian weighted radiance (Lec) which accounts for this difference in sensitivity. We utilized a camera-like light sensor (CLLS) to assess the distribution of Lec. For this purpose, we equipped the device with customized filters to adapt the camera’s spectral sensitivity to circadian sensitivity, similarly, as we had previously reported for the photometric calibration with the same device [1]. After spectral calibration and circadian weighted radiance calibration, we validated the CLLS in real scenes. The results showed that circadian luminance maps of a room can be efficiently assessed in a very short time (i.e. within 100 ms) under electric lighting as well as under daylighting conditions. We also used the CLLS to compare the Lec values between two rooms, equipped with different daylighting systems such as LightLouverTM and standard venetian blinds. Our results showed different dynamics of luminance and Lec in the course of the day with highest values at noon. We also found higher luminance and Lec values in the test room with the venetian blinds, when compared to the room equipped with LightLouversTM. Taken together, the validation of circadian luminance maps under real dynamic lighting conditions offers new possibilities to integrate the CLLS into advanced (day-) light sensors systems. This would allow to instantly adapting ambient lighting conditions with respect to tailored biological user needs

Recommendations for daytime, evening, and nighttime indoor light exposure to best support physiology, sleep, and wakefulness in healthy adults

Ocular light exposure has important influences on human health and well-being through modulation of circadian rhythms and sleep, as well as neuroendocrine and cognitive functions. Prevailing patterns of light exposure do not optimally engage these actions for many individuals, but advances in our understanding of the underpinning mechanisms and emerging lighting technologies now present opportunities to adjust lighting to promote optimal physical and mental health and performance. A newly developed, international standard provides a SI-compliant way of quantifying the influence of light on the intrinsically photosensitive, melanopsin-expressing, retinal neurons that mediate these effects. The present report provides recommendations for lighting, based on an expert scientific consensus and expressed in an easily measured quantity (melanopic equivalent daylight illuminance (melaponic EDI)) defined within this standard. The recommendations are supported by detailed analysis of the sensitivity of human circadian, neuroendocrine, and alerting responses to ocular light and provide a straightforward framework to inform lighting design and practice

Circadian and homeostatic sleep regulation in humans : effects of age and monochromatic light

The first part of this thesis deals with age-related modifications in the circadian and homeostatic sleep regulation, whereas in the second part, the effects of an evening exposure to monochromatic light on subsequent sleep architecture and sleep electroencephalographic power spectra are described. Age and sleep Sleep in humans undergoes several age-related changes, resulting in less consolidated sleep, reduced slow wave sleep, advanced sleep-wake timing and shorter nocturnal sleep episodes. The first aim of this thesis was to gain comprehensive information about the influence of age on circadian and homeostatic aspects of sleep regulation. We compared the sleep electroencephalogram (EEG) of healthy young with older volunteers under high and low sleep pressure conditions. The study design consisted of two different protocols, both started with a baseline and ended up with a recovery night. The 40-h episode between these two nights comprised either an episode of total sleep deprivation (SD; high sleep pressure) or 10 sleep/wake cycles with 75 min of sleep followed by 150 min of wakefulness (low sleep pressure). The recovery nights served to investigate the age-related influence during enhanced and reduced sleep pressure conditions. The sleep episodes during the nap protocol allowed comparing circadian modulation of sleep characteristics between young and older subjects. The response to high sleep pressure (i.e. after 40 hours of sleep deprivation) revealed a significantly attenuated frontal predominance of spectral EEG delta power in the sleep EEG of older participants, most pronounced at the beginning of the night (Chapter 2). In addition, the dissipation of homeostatic sleep pressure, as indexed by EEG delta power density, was shallower in the older than in the young group. This implies either an age-related weaker homeostatic response to sleep deprivation, predominantly in frontal brain areas, and/or altered cortical functions with an agerelated higher vulnerability to sleep deprivation. Under low sleep pressure (i.e. after multiple naps), older participants exhibited an attenuated occipital decline in delta frequencies in the all-night EEG during recovery sleep. This arose from an altered time course of EEG delta power density. The reduction of EEG delta activity after sleep satiation was similar in both age groups during the first sleep cycle. However, the EEG delta decrease to low sleep pressure was not longer present during the second sleep cycle in the older study group compared with the young (Chapter 4). During the 40-h nap protocol (Chapter 3), we have quantitative evidence for a weaker circadian arousal signal in the older volunteers. This is reflected in higher subjective sleepiness levels during the late afternoon and evening (‘wake maintenance zone’), with more sleep in the elderly during the naps at this time of day (Chapter 3). The day-night differences in the EEG lower alpha and spindle range were less pronounced in the older group. Furthermore, the amplitude of the circadian modulation of REM sleep was attenuated in the elderly and the nocturnal melatonin secretion was significantly reduced. Taken together, our study revealed different responses to high and low sleep pressure, as assessed by the sleep EEG, subjective sleepiness levels and melatonin secretion, in older subjects when compared to the younger group. These results emphasize both the attenuation of circadian amplitude and alterations in homeostatic sleep regulation with age. We also gained insight into age-related differences in responsiveness of regional and time-dependent aspects of sleep. These age-related modifications are not uniformly spread over the brain and thus are likely to reflect differences in recovery or reactivation processes during sleep. Light and sleep Beside rods and cones, there is an additional so-called non-image-forming visual system (NIF) in the human retinal ganglion cells, with highest sensitivity in the ‘blue’ portion of visible light. The NIF is mediated by the photopigment melanopsin and projects to the circadian pacemaker, located in the suprachiasmatic nuclei (SCN). With efferents from the SCN to sleep- and wake-promoting brain regions, the NIF influences the circadian regulation of sleep and wakefulness. We compared sleep architecture and EEG spectra in young healthy men after evening exposure to two different wavelengths of light (blue; 460 nm vs. green; 550 nm) or no light. The time course of EEG slow-wave activity (SWA; 0.75-4.5 Hz) after blue light was altered, with slightly lower SWA during the first and significantly higher SWA during the third sleep cycle in parietal and occipital brain regions. These findings could be interpreted either as the immediate induction of a circadian phase delay, or that the acute alerting effects of blue light continue into the sleep episode and are followed by an intra-sleep SWA rebound. Concomitantly, shorter REM sleep cycles after blue light exposure were observed during these two cycles. Our results show that the effects of light on human physiology including sleep not only depend on the duration and intensity of light but also on its wavelength, and thus further emphasize the critical role of the NIF in the regulation of sleep and circadian rhythms

Daylight – visual comfort and non-visual functions

Within the last decades it became evident that light through the eyes is essential for both visual and non-visual functions. One of the most important non-visual functions of light is the daily entrainment of the circadian clock by environmental light conditions. As most people spent the majority of their time inside of buildings, room light quality defines not only vision related properties but also many physiological and behavioral functions. This is true for acute light responses but also for circadian (and probably even longer lasting) light effects. Another emerging question is to what extent visual and non-visual functions might be associated with each other. We tested whether visual comfort is associated with subjective alertness, mood and physical wellbeing. By comparing these effects under two different office lighting conditions in healthy young subjects during daytime, we found that associations of visual comfort with alertness, mood and wellbeing were not only dependent on the light condition but also on the time of day. We also found repercussions of different light conditions during the afternoon on cognitive performance in the evening. We conclude that for optimized environmental light conditions visual and non-visual human aspects of light need further to be integrated into architectural and building science

Überblick dynamische Beleuchtung - Chronobiologische Beurteilung der Beleuchtungssituation

Aperçu de l'éclairage dynamique Evaluation chronobiologique de la situation d'éclairage On sait bien que la qualité d'une situation d'éclairage dépend de la puissance d'éclairage. Mais le fait que la composition spectrale de la lumière joue également un rôle est moins connu. Le spectre lumineux influence, outre les fonctions visuelles de sécurité et de communication, également des fonctions non visuelles, comme par exemple la performance cognitive, et il exerce une influence sur la santé. C'est un domaine avec un vaste potentiel, au sujet duquel quelques questions n'ont pas encore trouvé de réponses

Studies on chronobiological aspects of non-visual light effects in humans

Die in dieser Habilitationsschrift präsentierten chronobiologischen Untersuchungen zu nicht-visuellen Lichtwirkungen zeigen qualitative Unterschiede derselben in Abhängigkeit von Alter, Lang- und Kurzzeitadaptation. Weiter wurde mittels chromatischer Pupillometrie untersucht, inwieweit sich der Pupillenreflex auf Licht dazu eignet, bei Gesunden und Patienten mit einer Sehbeeinträchtigung als Marker für melanopsinabhängige Funktionen eingesetzt zu werden. Ein wesentlicher Beitrag der vorgestellten Arbeiten liegt im Aufzeigen konkreter Bedeutungen der 'prior light history'. Unter diesem Begriff verstehen wir die direkten und indirekten Nachwirkungen einer Lichtexposition beim Menschen, beispielsweise die Auswirkungen auf die kognitive Leistung am Abend entsprechend den Lichtbedingungen am Nachmittag oder die größere Wachheit am Abend als Folge wiederholter Lichtexpositionen mit hellerer Beleuchtung an den vorausgehenden Abenden. Im Ultrakurzzeitbereich wiesen wir mittels der evozierten Potentiale im EEG nach, dass je nach spektraler Zusammensetzung der Lichtstimuli eine unterschiedliche neuronale Aktivierung stattfand. Dies könnte für Situationen, in welchen sehr schnelle Reaktionen erforderlich sind, von Bedeutung sein. In diesem interdisziplinären und teilweise neuen Forschungsfeld sind noch viele spannende Fragen unbeantwortet. Wie wirkt sich beispielsweise eine längerfristig (zu) schwache Beleuchtung tagsüber auf unsere Leistungsfähigkeit und Gesundheit aus? Die behandelte Thematik betrifft sowohl die Grundlagenforschung wie auch die praktische Anwendung und wird uns in den nächsten Jahren sicherlich noch stark beschäftigen und beeinflussen. Die in zwei der eigenen Arbeiten vorgestellte Entwicklung und Validierung der chromatischen Pupillometrie und deren Einsatz für chronobiologische Fragestellungen könnten in Zukunft dazu beitragen, die Entwicklung maßgeschneiderter (Beleuchtungs-) Bedingungen für verschiedene Populationen und Patienten weiter voranzutreiben.The chronobiological studies presented in this habilitation show qualitative differences in the non-visual effects of light depending on age, short and long term adaptation. Chromatic pupillometry was used to ask to what extent the pupillary reflex to light could be used in healthy subjects and patients with visual impairments as a marker for melanopsin-dependent functions. A major contribution of the work presented here is the demonstration of specific meanings of 'prior light history'. This term comprises the direct and indirect after-effects of light exposure in humans, such as the effects on cognitive performance in the evening dependent on precedent lighting conditions in the afternoon; or the greater alertness at night as a result of repeated light exposures with brighter lighting on the previous evenings. We demonstrated by means of very fast responses to different light stimuli in the evoked potentials of the EEG that different spectral compositions of light stimuli resulted in different neural activations. This could be of importance in situations which require very fast reaction times. In this interdisciplinary and partly new research field many exciting questions still remain unanswered. For example, what are the long-term consequences of (too) dim lighting conditions during daytime on our performance and health? This topic relates both to basic research as well as to practical applications, and there is certainly more work to do with strong impact on both fields. Two of the presented studies aimed to develop and validate chromatic pupillometry and its use for chronobiological questions. This method could foster the development of customized (lighting) conditions for different populations and patients

Evening exposure to blue light stimulates the expression of the clock gene PER2 in humans

We developed a non-invasive method to measure and quantify human circadian PER2 gene expression in oral mucosa samples and show that this gene oscillates in a circadian (= about a day) fashion. We also have the first evidence that induction of human PER2 expression is stimulated by exposing subjects to 2 h of light in the evening. This increase in PER2 expression was statistically significant in comparison to a non-light control condition only after light at 460 nm (blue) but not after light exposure at 550 nm (green). Our results indicate that the non-image-forming visual system is involved in human circadian gene expression. The demonstration of a functional circadian machinery in human buccal samples and its response to light opens the door for investigation of human circadian rhythms at the gene level and their associated disorders

The relevance of daylight for humans

Daylight is ubiquitous and is crucial for mammalian vision as well as for non-visual input to the brain via the intrinsically photosensitive retinal ganglion cells (ipRGCs) that express the photopigment melanopsin. The ipRGCs project to the circadian clock in the suprachiasmatic nuclei and thereby ensure entrainment to the 24-hour day-night cycle, and changes in daylength trigger the appropriate seasonal behaviours. The ipRGCs also project to the perihabenular nucleus and surrounding brain regions that modulate mood, stress and learning in animals and humans. Given that light has strong direct effects on mood, cognition, alertness, performance, and sleep, light can be considered a “drug” to treat many clinical conditions. Light therapy is already well established for winter and other depressions and circadian sleep disorders. Beyond visual and non-visual effects via the retina, daylight contributes to prevent myopia in the young by its impact on eye development, and is important for Vitamin D synthesis and bone health via the skin. The sun is the most powerful light source and, dependent on dose, its ultraviolet radiance is toxic for living organisms and can be used as a disinfectant. Most research involves laboratory-based electric light, without the dynamic and spectral changes that daylight undergoes moment by moment. There is a gap between the importance of daylight for human beings and the amount of research being done on this subject. Daylight is taken for granted as an environmental factor, to be enjoyed or avoided, according to conditions. More daylight awareness in architecture and urban design beyond aesthetic values and visual comfort may lead to higher quality work and living environments. Although we do not yet have a factual basis for the assumption that natural daylight is overall “better” than electric light, the environmental debate mandates serious consideration of sunlight not just for solar power but also as biologically necessary for sustainable and healthy living