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At least 91 records · Page 5

The effects of light on man and other mammals

The present article describes the best-studied extravisual effects of visible and ultraviolet light on humans and other mammals. It also considers the possible biological consequences to man of living in artificially lighted environments that differ significantly from the milieu in which he evolved. Cumulative evidence favors the beneficial influences of sunlight: vitamin D activation, plasma bilirubin elimination, inhibition of pineal melatonin synthesis, etc.

Wurtman, R. J.↗

Sympathetic neural control of indoleamine metabolism in the rat pineal gland

The mechanisms responsible for the acceleration in rat pineal biosynthetic activity in response to prolonged exposure to darkness or to immobilization were investigated in animals whose pineals were surgically denervated. Some animals were adrenalectomized to remove one potential source of circulating catecholamines, and some were subjected to a partial chemical sympathectomy accomplished by a series of intravenous injections of 6-hydroxydopamine. Results suggest that N-acetyltransferase (NAT) activity can be enhanced either by release of norepinephrine from sympathetic terminals within the pineal or from sympathetic nerve terminals elsewhere. The stress of immobilization stimulates the pineal by increasing circulating catecholamines. Photic control of pineal function requires intact pineal sympathetic innervation, since the onset of darkness apparently does not cause a sufficient rise in circulating catecholamines to stimulate the pineal. The present studies suggest that nonspecific stress triggers increased biosynthesis and secretion of melatonin; it is possible that this hormone may participate in mechanisms of adaptation.

Lynch, H. J.↗

Photic effects on sustained performance

Research is described which evaluates manipulating environmental light intensity as a means to attenuate fatigue. A counter balanced, within-subjects design was used to compare nine male subjects exposed to dim (100 lux) and bright (3000 lux) light conditions. Oral temperature values were greater for the bright light group over the dim light condition. Melatonin levels were suppressed by bright light treatment. Also, the frequency of eye blink rate was less for subjects during bright over dim light exposure. Light exposure was without effect on subjective fatigue. However, irrespective of light condition, significant effects on confusion, fatigue, and vigor mood dimensions were found as a result of 30 hour sleep deprivation. The findings suggest that bright lights may be used to help sustain nocturnal activity otherwise susceptible to fatigue. Such findings may have implications for the lighting arrangements on space flights during the subjective night for astronauts.

French, J.↗

Effects of light on brain and behavior

It is obvious that light entering the eye permits the sensory capacity of vision. The human species is highly dependent on visual perception of the environment and consequently, the scientific study of vision and visual mechanisms is a centuries old endeavor. Relatively new discoveries are now leading to an expanded understanding of the role of light entering the eye in addition to supporting vision, light has various nonvisual biological effects. Over the past thirty years, animal studies have shown that environmental light is the primary stimulus for regulating circadian rhythms, seasonal cycles, and neuroendocrine responses. As with all photobiological phenomena, the wavelength, intensity, timing and duration of a light stimulus is important in determining its regulatory influence on the circadian and neuroendocrine systems. Initially, the effects of light on rhythms and hormones were observed only in sub-human species. Research over the past decade, however, has confirmed that light entering the eyes of humans is a potent stimulus for controlling physiological rhythms. The aim of this paper is to examine three specific nonvisual responses in humans which are mediated by light entering the eye: light-induced melatonin suppression, light therapy for winter depression, and enhancement of nighttime performance. This will serve as a brief introduction to the growing database which demonstrates how light stimuli can influence physiology, mood and behavior in humans. Such information greatly expands our understanding of the human eye and will ultimately change our use of light in the human environment.

Brainard, George C.↗

Circadian Entrainment, Sleep-Wake Regulation and Neurobehavioral Performance During Extended Duration Space Flight

Long-duration manned space flight requires crew members to maintain a high level of cognitive performance and vigilance while operating and monitoring sophisticated instrumentation. However, the reduction in the strength of environmental synchronizers in the space environment leads to misalignment of circadian phase among crew members, coupled with restricted time available to sleep, results in sleep deprivation and consequent deterioration of neurobehavioral function. Crew members are provided, and presently use, long-acting benzodiazepine hypnotics on board the current, relatively brief space shuttle missions to counteract such sleep disruption, a situation that is only likely to worsen during extended duration missions. Given the known carry-over effects of such compounds on daytime performance, together with the reduction in emergency readiness associated with their use at night, NASA has recognized the need to develop effective but safe countermeasures to allow crew members to obtain an adequate amount of sleep. Over the past eight years, we have successfully implemented a new technology for shuttle crew members involving bright light exposure during the pre-launch period to facilitate adaptation of the circadian timing system to the inversions of the sleep-wake schedule often required during dual shift missions. However for long duration space station missions it will be necessary to develop effective and attainable countermeasures that can be used chronically to optimize circadian entrainment. Our current research effort is to study the effects of light-dark cycles with reduced zeitgeber strength, such as are anticipated during long-duration space flight, on the entrainment of the endogenous circadian timing system and to study the effects of a countermeasure that consists of scheduled brief exposures to bright light on the human circadian timing system. The proposed studies are designed to address the following Specific Aims: (1) test the hypothesis that synchronization of the human circadian pacemaker will be disturbed in men and women by the reduction in LD cycle strength. (2) test the hypothesis that this disturbed circadian synchronization will result in the secretion of the sleep-promoting hormone melatonin during the waking day, disturbed sleep, reduced growth hormone secretion, and impaired performance and daytime alertness; (3) as a countermeasure, test the hypothesis that brief daily exposures to bright light (10,000 lux) will reestablish normal entrained circadian phase, resulting in improved sleep consolidation, normalized sleep structure and endogenous growth hormone secretion and enhanced daytime performance. To date, we have carried out twelve experiments to address Hypotheses I and 2 and data analyses are in progress. The results of the current research may have important implications for the treatment of circadian rhythm sleep disorders, such as delayed sleep phase syndrome and shift-work dyssomnia, which are anticipated to have a high incidence and prevalence during extended duration space flight such as planned for the International Space Station and manned missions to Mars.

Czeisler, Charles A.↗

Light-Emitting Diodes (LED) for Primary Animal Habitat Lighting in Highly Controlled Environments

Significant alterations in Biological Clock responses have been reported following sidereal time changes (e.g., Jet-lag), and exposure to microgravity (e.g., daytime sleepiness). Additionally, light reduces circulating melatonin (spectral specificity greatest between 450-500 nm). It was hypothesized that LEDs can replace the current light sources used in zero gravity and terrestrial research laboratories because of their small size, low mass, low energy consumption and long functional life. This report evaluates the capacity of LEDs to entrain the circadian system of rats as judged by measurement of overt behavioral circadian rhythms (activity, feeding, drinking). These data were collected in highly controlled environments similar to the shuttle Animal Enclosure Modules. Two groups were compared: control - animals exposed to standard cool-white fluorescent lights, and test - animals exposed to LEDs with a spectral power distribution matching the fluorescent lights. Gross locomotor activity, feeding and drinking frequencies were continuously monitored and stored at 10 minute intervals. Animals were exposed to the following photoperiods: 28 days of 12L:12D, 19 days of 24L:0D and 16 days of 12L:12D. Light intensities tested varied between 0.1 to 100 lux. Rats received food and water ad libitum, and temperature and humidity were controlled throughout the study. The general health status of all rats was acceptable for each day of this study. No incidents of aggressive behavior were observed. Growth, locomotor activity, food and water consumption were comparable for all groups of animals, i.e, the circadian characteristics of the animals under these conditions were comparable. These results indicate that LED arrays are as effective in maintaining circadian rhythm stability as the commonly used cool-white fluorescent light sources. LEDs with their flexible spectrum, low energy requirements and minimal heat production have advantages for some chronopharmacology studies and for microgravity animal habitats.

Winget, C. M.↗

A Gravity-Responsive Time-Keeping Protein of the Plant and Animal Cell Surface

The hypothesis under investigation was that a ubiquinol (NADH) oxidase protein of the cell surface with protein disulfide-thiol interchange activity (= NOX protein) is a plant and animal time-keeping ultradian (period of less than 24 h) driver of both cell enlargement and the biological clock that responds to gravity. Despite considerable work in a large number of laboratories spanning several decades, this is, to my knowledge, our work is the first demonstration of a time-keeping biochemical reaction that is both gravity-responsive and growth-related and that has been shown to determine circadian periodicity. As such, the NOX protein may represent both the long-sought biological gravity receptor and the core oscillator of the cellular biological clock. Completed studies have resulted in 12 publications and two issued NASA-owned patents of the clock activity. The gravity response and autoentrainment were characterized in cultured mammalian cells and in two plant systems together with entrainment by light and small molecules (melatonin). The molecular basis of the oscillatory behavior was investigated using spectroscopic methods (Fourier transform infrared and circular dichroism) and high resolution electron microscopy. We have also applied these findings to an understanding of the response to hypergravity. Statistical methods for analysis of time series phenomena were developed (Foster et al., 2003).

Morre, D. James↗

Hormonal changes during 17 days of head-down bed-rest

We investigated in six men the impact of 17 days of head-down bed rest (HDBR) on the daily rhythms of the hormones involved in hydroelectrolytic regulation. This HDBR study was designed to mimic a real space flight. Urine samples were collected at each voiding before, during and after HDBR. Urinary excretion of Growth Hormone (GH), Cortisol, 6 Sulfatoxymelatonin, Normetadrenaline (NMN) and Metadrenaline (NM) was determined. A decrease in urinary cortisol excretion during the night of HDBR was noted. For GH, a rhythm was found before and during HDBR. The rhythm of melatonin, evaluated with the urine excretion of 6 Sulfatoxymelatonin (aMT6S), the main hepatic metabolite, persisted throughout the experiment without any modification to the level of phase. A decrease during the night was noted for normetadrenaline urinary derivates, but only during the HDBR.

Non-NASA Center↗

Integration of human sleep-wake regulation and circadian rhythmicity

The human sleep-wake cycle is generated by a circadian process, originating from the suprachiasmatic nuclei, in interaction with a separate oscillatory process: the sleep homeostat. The sleep-wake cycle is normally timed to occur at a specific phase relative to the external cycle of light-dark exposure. It is also timed at a specific phase relative to internal circadian rhythms, such as the pineal melatonin rhythm, the circadian sleep-wake propensity rhythm, and the rhythm of responsiveness of the circadian pacemaker to light. Variations in these internal and external phase relationships, such as those that occur in blindness, aging, morning and evening, and advanced and delayed sleep-phase syndrome, lead to sleep disruptions and complaints. Changes in ocular circadian photoreception, interindividual variation in the near-24-h intrinsic period of the circadian pacemaker, and sleep homeostasis can contribute to variations in external and internal phase. Recent findings on the physiological and molecular-genetic correlates of circadian sleep disorders suggest that the timing of the sleep-wake cycle and circadian rhythms is closely integrated but is, in part, regulated differentially.

Review↗

Sleep, performance, circadian rhythms, and light-dark cycles during two space shuttle flights

Sleep, circadian rhythm, and neurobehavioral performance measures were obtained in five astronauts before, during, and after 16-day or 10-day space missions. In space, scheduled rest-activity cycles were 20-35 min shorter than 24 h. Light-dark cycles were highly variable on the flight deck, and daytime illuminances in other compartments of the spacecraft were very low (5.0-79.4 lx). In space, the amplitude of the body temperature rhythm was reduced and the circadian rhythm of urinary cortisol appeared misaligned relative to the imposed non-24-h sleep-wake schedule. Neurobehavioral performance decrements were observed. Sleep duration, assessed by questionnaires and actigraphy, was only approximately 6.5 h/day. Subjective sleep quality diminished. Polysomnography revealed more wakefulness and less slow-wave sleep during the final third of sleep episodes. Administration of melatonin (0.3 mg) on alternate nights did not improve sleep. After return to earth, rapid eye movement (REM) sleep was markedly increased. Crewmembers on these flights experienced circadian rhythm disturbances, sleep loss, decrements in neurobehavioral performance, and postflight changes in REM sleep.

Non-NASA Center↗

Circadian and sleep-dependent regulation of hormone release in humans

Daily oscillations characterize the release of nearly every hormone. The circadian pacemaker, located in the suprachiasmatic nucleus of the hypothalamus, generates circadian, approximately 24-hour rhythms in many physiologic functions. However, the observed hormonal oscillations do not simply reflect the output of this internal clock. Instead, daily hormonal profiles are the product of a complex interaction between the output of the circadian pacemaker, periodic changes in behavior, light exposure, neuroendocrine feedback mechanisms, gender, age, and the timing of sleep and wakefulness. The interaction of these factors can affect hormonal secretory pulse frequency and amplitude, with each endocrine system differentially affected by these factors. This chapter examines recent advances in understanding the effects on endocrine rhythms of a number of these factors. Sleep exerts a profound effect on endocrine secretion. Sleep is a dynamic process that is characterized by periodic changes in electrophysiologic activity. These electrophysiologic changes, which are used to mark the state and depth of sleep, are associated with periodic, short-term variations in hormonal levels. The secretion of hormones such as renin and human growth hormone are strongly influenced by sleep or wake state, while melatonin and cortisol levels are relatively unaffected by sleep or wake state. In addition, sleep is associated with changes in posture, behavior, and light exposure, each of which is known to affect endocrine secretion. Furthermore, the tight concordance of habitual sleep and wake times with certain circadian phases has made it difficult to distinguish sleep and circadian effects on these hormones. Specific protocols, designed to extract circadian and sleep information semi-independently, have been developed and have yielded important insights into the effects of these regulatory processes. These results may help to account for changes in endocrine rhythms observed in circadian rhythm sleep disorders, including the dyssomnia of shift work and visual impairment. Yet to be fully investigated are the interactions of these factors with age and gender. Characterization of the factors governing hormone secretion is critical to understanding the temporal regulation of endocrine systems and presents many exciting areas for future research.

Non-NASA Center↗

Stability, precision, and near-24-hour period of the human circadian pacemaker

Regulation of circadian period in humans was thought to differ from that of other species, with the period of the activity rhythm reported to range from 13 to 65 hours (median 25.2 hours) and the period of the body temperature rhythm reported to average 25 hours in adulthood, and to shorten with age. However, those observations were based on studies of humans exposed to light levels sufficient to confound circadian period estimation. Precise estimation of the periods of the endogenous circadian rhythms of melatonin, core body temperature, and cortisol in healthy young and older individuals living in carefully controlled lighting conditions has now revealed that the intrinsic period of the human circadian pacemaker averages 24.18 hours in both age groups, with a tight distribution consistent with other species. These findings have important implications for understanding the pathophysiology of disrupted sleep in older people.

NASA Discipline Regulatory Physiology↗

Stabilized NADH as a Countermeasure for Jet Lag

Current remedies for jet lag (phototherapy, melatonin, stimulant, and sedative medications) are limited in efficacy and practicality. The efficacy of a stabilized, sublingual form of reduced nicotin amide adenine dinucleotide (NADH, ENADAlert, Menuco Corp.) as a countermeasure for jet lag was examined. Because NADH increases cellular production of ATP and facilitates dopamine synthesis, it may counteract the effects of jet lag on cognitive functioning and sleepiness. Thirty-five healthy, employed subjects participated in this double-blind, placebo-controlled study. Training and baseline testing were conducted on the West Coast before subjects flew overnight to the East Coast, where they would experience a 3-hour time difference. Upon arrival, individuals were randomly assigned to receive either 20 mg of sublingual stabilized ADH (n=18) or identical placebo tablets (n=17). All participants completed computer-administered tests (including CogScreen7) to assess changes in cognitive functioning, mood, and sleepiness in the morning and afternoon. Jet lag resulted in increased sleepiness for over half the participants and deterioration of cognitive functioning for approximately one third. The morning following the flight, subjects experienced lapses of attention in addition to disruptions in working memory, divided attention, and visual perceptual speed. Individuals who received NADH performed significantly better on 5 of 8 cognitive and psychomotor test measures (P less than or equal to 0.5) and showed a trend for better performance on the other three measures (P less than or equal to .l0). Subjects also reported less sleepiness compared with those who received placebo. No adverse effects were observed with NADH treatment. Stabilized NADH significantly reduced jet lag-induced disruptions of cognitive functioning, was easily administered, and was found to have no adverse side effects.

Kay, Gary G.↗

Prescribed Travel Schedules for Fatigue Management

The NASA Fatigue Management Team is developing recommendations for managing fatigue during travel and for shift work operations, as Clinical Practice Guidelines for the Management of Circadian Desynchrony in ISS Operations. The Guidelines provide the International Space Station (ISS ) flight surgeons and other operational clinicians with evidence-based recommendations for mitigating fatigue and other factors related to sleep loss and circadian desynchronization. As much international travel is involved both before and after flight, the guidelines provide recommendations for: pre-flight training, in-flight operations, and post-flight rehabilitation. The objective of is to standardize the process by which care is provided to crewmembers, ground controllers, and other support personnel such as trainers, when overseas travel or schedule shifting is required. Proper scheduling of countermeasures - light, darkness, melatonin, diet, exercise, and medications - is the cornerstone for facilitating circadian adaptation, improving sleep, enhancing alertness, and optimizing performance. The Guidelines provide, among other things, prescribed travel schedules that outline the specific implementation of these mitigation strategies. Each travel schedule offers evidence based protocols for properly using the NASA identified countermeasures for fatigue. This presentation will describe the travel implementation schedules and how these can be used to alleviate the effects of jet lag and/or schedule shifts.

Whitmire, Alexandra↗

Validating and Verifying Biomathematical Models of Human Fatigue

Airline pilots experience acute and chronic sleep deprivation, sleep inertia, and circadian desynchrony due to the need to schedule flight operations around the clock. This sleep loss and circadian desynchrony gives rise to cognitive impairments, reduced vigilance and inconsistent performance. Several biomathematical models, based principally on patterns observed in circadian rhythms and homeostatic drive, have been developed to predict a pilots levels of fatigue or alertness. These models allow for the Federal Aviation Administration (FAA) and commercial airlines to make decisions about pilot capabilities and flight schedules. Although these models have been validated in a laboratory setting, they have not been thoroughly tested in operational environments where uncontrolled factors, such as environmental sleep disrupters, caffeine use and napping, may impact actual pilot alertness and performance. We will compare the predictions of three prominent biomathematical fatigue models (McCauley Model, Harvard Model, and the privately-sold SAFTE-FAST Model) to actual measures of alertness and performance. We collected sleep logs, movement and light recordings, psychomotor vigilance task (PVT), and urinary melatonin (a marker of circadian phase) from 44 pilots in a short-haul commercial airline over one month. We will statistically compare with the model predictions to lapses on the PVT and circadian phase. We will calculate the sensitivity and specificity of each model prediction under different scheduling conditions. Our findings will aid operational decision-makers in determining the reliability of each model under real-world scheduling situations.

fatigue↗

Fatigue Monitoring in Scheduled Airline Operations

Reporting and monitoring are important facets of a comprehensive Fatigue Risk Management System. As part of efforts to reduce fatigue risks, we partnered with an international airline to study 44 (4 Female) volunteer pilots over a 4 week period that included baseline earlymiddaylate flight days and rest days off. All study procedures were approved by an IRB and participants provided written informed consent prior to beginning the study. Reduced sleep duration was associated with both early and late duties. Performance was influenced by duty timing, time of day and time awake. TLX ratings were highest for mental and effort demands, while ATC and weather were the most identified hassle factors. Melatonin analysis revealed individual variations in circadian shift over the study period. The study results highlight the value of FRMS monitoring in airline operations. Ongoing crew education should emphasize individual variation and effective mitigation strategies. Further study could focus on workload and time of day scheduling factors.

sleep loss↗

Abstract: Orion Lighting Workaround for Maintaining Crew Circadian Entrainment

Introduction. Light is the major environmental time cue of our endogenous circadian pacemaker. Suboptimal crew circadian entrainment (CCE) is common and associated with acute and chronic medical symptoms. Additionally, fatigue from suboptimal CCE promotes problematic use of sleep medications. The Orion Cabin Lighting System (OCLS) consists of monochromatic light-emitting diode (LED) lamps. However, light is a powerful suppressor of melatonin and it is a disruptor of CCE if used at incorrect times. A commercial off the shelf (COTS) dynamic lighting system (COTS-DLS) is a potential workaround for maintaining CCE.

Matthew Lindsey↗