Physiological reviewAlerting effects of light☆
Introduction
The definition of light in current encyclopedias is predominantly limited to its physical explanation as the visible part of the electromagnetic spectrum. However, precisely speaking, our eyes cannot see a spectrum, it is rather the photoreceptors, i.e., rods and cones in the eyes which collect, decipher and transpose the emission or reflectance of electromagnetic waves in a specific range or photons into meaningful visual signals in our brain. However, light serves for much more than just vision in humans. Sunlight acts via the skin for the synthesis of vitamin D or to reduce serum bilirubin in neonatal jaundice. Some totally blind people even show physiological responses to light stimuli without consciously seeing them. Seen in a historical context, light in old Egypt had such a central role that Egyptian theology under the reign of Akhenaten has been designated as the “theology of light” by Egyptologists.1 As a consequence, night and darkness were negatively characterized as times without sunlight during which humans and animals remain in their homes as dead until the sun rises again. According to Akhenaten, light makes life possible while darkness symbolizes death. It was maybe also the “theological aspect” of light in the following millennia which precluded its scientific investigation in humans.
It is only two decades since the entraining and phase-shifting capacity of light on human circadian rhythms was discovered. It has been the primary research focus since. Relatively little attention has been paid to other effects of light on the human brain, such as its alerting properties. As of 1995, only a handful of studies had directly or indirectly examined the immediate activating effects of light on alertness, performance and/or mood.2, 3 This has recently changed since Berson et al.4 detected a novel, third type of photoreceptor in the retina of mammals. This novel photoreceptor cell type, an intrinsic photosensitive retinal ganglion cell, is considered to play a crucial role in many of the non-visual biological effects of light also in humans. The existence of such a photoreceptor can explain why pupil constriction, melatonin suppression and circadian entrainment are still possible in rodless–coneless transgenic mice.5, 6 Similarly, studies in humans have indicated that partial or complete loss of the visual system still allows for normal melatonin suppression and circadian phase shifting.7, 8 Recent studies have shown that transfecting non-photosensitive cells with the melanopsin gene confers light sensitivity to these cells, which provides compelling evidence for melanopsin being the functional photopigment of the photosensitive retinal ganglion cells.9, 10, 11 Phylogenetically, melanopsin resembles invertebrate opsins more closely than it does other mammalian opsins (e.g., rhodopsin, cone opsins), indicating that it may have evolved before the vertebrates.12 Studies of melanopsin-knockout mice, however, demonstrate that although melanopsin plays an integral role in circadian phototransduction, it is not essential for non-visual ocular-mediated responses.13, 14, 15
The photosensitive ganglion cells have their own neural connections to the suprachiasmatic nuclei (SCN), the site of the principal mammalian pacemaker.16 Moreover, they also have direct and indirect (via the SCN) projections to brain areas implicated in the regulation of arousal.16 The spectral sensitivity of melanopsin ganglion cells is different from that of the classical photoreceptors.12, 17 This allows designing human study protocols in which the non-visual effects of light at specific wavelengths (i.e., monochromatic light) can be tested and deriving conclusions about a possible involvement of the new photoreceptors in the alerting response to light.
In the following review, studies on human alerting responses to light and their sequelae (e.g., melatonin, cortisol, core body temperature (CBT), circadian gene expression) will be summarized and discussed within the framework of current concepts of neuroanatomical and neurophysiological findings from animal studies and neural circuitries involved in the regulation of sleep/wake states. A brief outlook of possible clinical and non-clinical applications of lights’ alerting properties will be given, with considering its involvement in the design of more effective lighting at home and in the workplace.
Section snippets
Measures of alertness
In healthy people, alertness or sleepiness can be reliably measured by simply asking them or by subjective rating scales. The precise meaning of the terms sleepiness, alertness, fatigue or tiredness may differ between languages and situations (e.g., real life on shift work or constant routine conditions in a sleep laboratory). In general, in the studies on alerting effects of light, standardized fatigue or sleepiness scales have been used, which allow for a good comparison between experiments.
Circadian rhythmicity of alertness
From early on, alertness has been related to time of day. Kleitman already noticed that the diurnal modulation of alertness shows a close temporal association with the circadian rhythm of core body temperature with its maximum in the evening and nadir in the early morning.20 More recently, the contribution of circadian rhythmicity to alterations in subjective alertness has been quantified in forced desynchrony protocols.21, 22, 23 These protocols revealed that the contribution of the circadian
Timing
Most studies on the alerting properties of light have been conducted during the nighttime hours (e.g., during simulated night shift work in the laboratory or under field conditions). This makes sense from a circadian perspective since the circadian drive for sleep is maximal during the night between 2 and 6 a.m., and the homeostatic drive for sleep usually rises when exceeding 16 h of prior wakefulness (i.e., elevated sleep pressure). Although different light intensities and light exposure
Dose
In early studies looking at the alerting properties of light, relatively high irradiances (i.e., 1000 lx or more) of white polychromatic light were used.31, 35, 36, 46, 47, 48, 49, 50 This was because the first demonstration of a physiological effect of light was Lewy's discovery in 1980 that at least 1000 lx of white light was required to suppress melatonin in healthy humans.51 This finding led to the assumption that, in contrast to animals, humans require much higher light irradiances to
Wavelength
The relationship between the wavelength of light and its alerting response has been investigated in four studies so far.60, 61, 62, 63 All of them reported superiority of short wavelength light (470 nm and lower). We compared a 2-h evening exposure to monochromatic light of two different wavelengths (460 and 550 nm) at very low intensities (photopic range: 5.0 lx for 460 nm and 68.1 lx for 550 nm) in non-pupil dilated subjects.60 Although the subjects’ pupils during the blue (460 nm) light treatment
Clinical and non-clinical application
Light is the first choice to treat winter depression.85 Seasonal Affective Disorder (SAD) is a form of depression in which symptoms typically recur every year during the shorter days of autumn and winter and remit during the longer days of spring and summer. Symptoms include low mood, reduced interest, decreased concentration, low energy, and fatigue. Other clusters of symptoms are often present, including an increased need for sleep, increased appetite and carbohydrate craving with resultant
Conclusions
The alerting action of light in humans has received little attention so far. Since the discovery of the non-image forming photoreceptor system and its connection to neural circuits implicated with alertness regulation, the investigation of the alerting properties of light in humans has just started. Recent studies confirm the potential role the non-image forming system has for alertness. This may lead to new approaches to prevent and treat undesirable sleepiness and performance decrements
Acknowledgments
I thank Prof. Anna Wirz-Justice, Dr. Gilles Vandewalle, Silvia Frey and Jakub Späti for helpful comments on an earlier version of the manuscript. Research of CC cited in this paper was supported by grants from by the NASA Cooperative Agreement NCC 9-58 with the National Space Biomedical Research Institute, by the Velux Foundation Switzerland, by Swiss National Science Foundation Grants (# 823A-046640, START # 3130-054991.98 and #3100-055385.98) the Daimler-Benz-Foundation (CLOCKWORK) and by the
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Cited by (0)
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Dedicated to Anna Wirz-Justice in recognition of her contributions to the field made during her career at the Psychiatric University Clinics Basel.
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The most important references are denoted by an asterisk.