Circadian rhythms, sleep, and performance in space.

Maintaining optimal alertness and neurobehavioral functioning during space operations is critical to enable the National Aeronautics and Space Administration's (NASA's) vision "to extend humanity's reach to the Moon, Mars and beyond" to become a reality. Field data have demonstrated that sleep times and performance of crewmembers can be compromised by extended duty days, irregular work schedules, high workload, and varying environmental factors. This paper documents evidence of significant sleep loss and disruption of circadian rhythms in astronauts and associated performance decrements during several space missions, which demonstrates the need to develop effective countermeasures. Both sleep and circadian disruptions have been identified in the Behavioral Health and Performance (BH&P) area and the Advanced Human Support Technology (AHST) area of NASA's Bioastronautics Critical Path Roadmap. Such disruptions could have serious consequences on the effectiveness, health, and safety of astronaut crews, thus reducing the safety margin and increasing the chances of an accident or incident. These decrements oftentimes can be difficult to detect and counter effectively in restrictive operational environments. NASA is focusing research on the development of optimal sleep/wake schedules and countermeasure timing and application to help mitigate the cumulative effects of sleep and circadian disruption and enhance operational performance. Investing research in humans is one of NASA's building blocks that will allow for both short- and long-duration space missions and help NASA in developing approaches to manage and overcome the human limitations of space travel. In addition to reviewing the current state of knowledge concerning sleep and circadian disruptions during space operations, this paper provides an overview of NASA's broad research goals. Also, NASA-funded research, designed to evaluate the relationships between sleep quality, circadian rhythm stability, and performance proficiency in both ground-based simulations and space mission studies, as described in the 2003 NASA Task Book, will be reviewed.

Chronic centrifugation (hypergravity) disrupts the circadian system of the rat.

The present study was conducted to evaluate the response of rat deep body temperature (DBT) and gross locomotor activity (LMA) circadian rhythms to acute hypergravity onset and adaptation to chronic (14 day) hypergravity exposure over three gravity intensities (1.25, 1.5, and 2 G). Centrifugation of unanesthetized naive animals resulted in a dramatic acute decrease in DBT (-1.45, -2.40, and -3.09 degrees C for the 1.25, 1.5, and 2.0 G groups, respectively). LMA was suppressed for the duration of centrifugation (vs. control period); the percent decrease for each group on days 12-14, respectively, was 1.0 G, -15.2%, P = not significant; 1.25 G, -26.9%, P < 0.02; 1.5 G, -44.5%, P < 0.01; and 2.0 G, -63.1%, P < 0.002. The time required for DBT and LMA circadian rhythmic adaptation and stabilization to hypergravity onset increased from 1.25 to 2.0 G in all circadian metrics except daily means. Periodicity analysis detected the phenomenon of circadian rhythm splitting, which has not been reported previously in response to chronic hypergravity exposure. Our analysis documents the disruptive and dose-dependent effects of hypergravity on circadian rhythmicity and the time course of adaptation to 14-day chronic centrifugation exposure.

Effects of gravitational and optical stimulation on the perception of target elevation.

To examine the combined effects of gravitational and optical stimulation on perceived target elevation, we independently altered gravitational-inertial force and both the orientation and the structure of a background visual array. While being exposed to 1.0, 1.5, or 2.0 Gz in the human centrifuge at NASA Ames Research Center, observers attempted to set a target to the apparent horizon. The target was viewed against the far wall of a box that was pitched at various angles. The box was brightly illuminated, had only its interior edges dimly illuminated, or was kept dark. Observers lowered their target settings as Gz was increased; this effect was weakened when the box was illuminated. Also, when the box was visible, settings were displaced in the same direction as that in which the box was pitched. We attribute our results to the combined influence of otolith-oculomotor mechanisms that underlie the elevator illusion and visual-oculomotor mechanisms (optostatic responses) that underlie the perceptual effects of viewing pitched visual arrays.

Effects of Command and Control Vehicle (C2V) operational environment on soldier health and performance.

The purpose of this project was to use NASA technology to assist the US Army in the assessment of motion sickness incidences and effects on soldier performance and mood states within the Command and Control Vehicle (C2V). Specific objectives were (1) to determine if there was a significant difference between three internal configurations of the C2V and/or between seats within these vehicles; (2) to determine if there was a significant difference between the park, move, or short-halt field conditions; and (3) to validate a method of converging indicators developed by NASA to assess environmental impact of long duration spaceflight on crewmembers, using a large sample of subjects under ground-based operational conditions.

Promethazine as a motion sickness treatment: impact on human performance and mood states.

PURPOSE: Intramuscular (i.m.) injections of promethazine in 25 mg or 50 mg dosages are commonly used to treat space motion sickness in astronauts. The present study examined the effects of i.m. injections of promethazine on performance, mood states, and motion sickness in humans. METHODS: Subjects were 12 men, mean age 36 + 3.1, who participated in 1 training day and 3 treatment conditions: a 25-mg injection of promethazine, a 50-mg injection of promethazine, and a placebo injection of sterile saline. Each condition, scheduled at 7-d intervals, required an 8-10-h day in which subjects were tested on 12 performance tasks, and were given a rotating chair motion sickness test. On the training day subjects were trained on each task to establish stability and proficiency. Treatment conditions were counterbalanced and a double-blind procedure was used to administer the medication or placebo. RESULTS: Statistically significant decrements in performance were observed for both dosages of promethazine as compared with the placebo. Performance decrements were associated with mean blood alcohol dose equivalency levels of 0.085% for 25 mg and 0.137% for 50 mg doses. Mood scale results showed significant changes in individual subjective experiences with maximum deterioration in the arousal state and fatigue level. Only the 25-mg dosage significantly increased motion sickness tolerance when compared with the placebo. CONCLUSIONS: These data suggest that effective doses of promethazine currently used to counteract motion sickness in astronauts may significantly impair task components of their operational performance.

Reduction of the elevator illusion from continued hypergravity exposure and visual error-corrective feedback.

Ten subjects served as their own controls in two conditions of continuous, centrifugally produced hypergravity (+2 Gz) and a 1-G control condition. Before and after exposure, open-loop measures were obtained of (1) motor control, (2) visual localization, and (3) hand-eye coordination. During exposure in the visual feedback/hypergravity condition, subjects received terminal visual error-corrective feedback from their target pointing, and in the no-visual feedback/hypergravity condition they pointed open loop. As expected, the motor control measures for both experimental conditions revealed very short lived underreaching (the muscle-loading effect) at the outset of hypergravity and an equally transient negative aftereffect on returning to 1 G. The substantial (approximately 17 degrees) initial elevator illusion experienced in both hypergravity conditions declined over the course of the exposure period, whether or not visual feedback was provided. This effect was tentatively attributed to habituation of the otoliths. Visual feedback produced a smaller additional decrement and a postexposure negative after-effect, possible evidence for visual recalibration. Surprisingly, the target-pointing error made during hypergravity in the no-visual-feedback condition was substantially less than that predicted by subjects' elevator illusion. This finding calls into question the neural outflow model as a complete explanation of this illusion.

Performance and mood-state parameters during 30-day 6 degrees head-down bed rest with exercise training.

The study was designed to determine if performance and mood impairments occur in bed-rested subjects, and if different exercise-training regimens modify or prevent them. Eighteen normal, healthy men were divided on the basis of age, peak oxygen uptake, and maximal isometric knee extension strength into three similar groups: no exercise (NOE), isotonic exercise (ITE), and isokinetic exercise (IKE). A 15-min battery of 10 performance tests and 8 mood and 2 sleep scales were administered daily during ambulatory control, 30 d of absolute bed rest (BR), and 4 d of ambulatory recovery. Performance test proficiency increased (p < 0.05) for all three groups during BR in 7 of 10 tests and there were no consistent significant differences between the three groups. However, during BR, the ITE group was distinguished from the other groups by a decline (p < 0.05) in the activation mood dimension and in two of its constituent scales (motivation and concentration), and by improvement (p < 0.05) in the trouble-falling-asleep and psychological-tension scales. Since few deleterious changes in performance and mood occurred in the three groups and did not exceed baseline ambulatory levels, we conclude that mood and performance did not deteriorate in response to prolonged BR and were not altered by exercise training. However, the decline in activation mood scales in the ITE group may reflect overtraining or excess total workload in this group.

Cerebral blood flow velocity in humans exposed to 24 h of head-down tilt.

This study investigates cerebral blood flow (CBF) velocity in humans before, during, and after 24 h of 6 degree head-down tilt (HDT), which is a currently accepted experimental model to simulate microgravity. CBF velocity was measured by use of the transcranial Doppler technique in the right middle cerebral artery of eight healthy male subjects. Mean CBF velocity increased from the pre-HDT upright seated baseline value of 55.5 +/- 3.7 (SE) cm/s to 61.5 +/- 3.3 cm/s at 0.5 h of HDT (P < 0.05), reached a peak value of 63.2 +/- 4.1 cm/s at 3 h of HDT, and remained significantly above the pre-HDT baseline for > or = 6 h of HDT. During upright seated recovery (1-5 h post-HDT), mean CBF velocity decreased to 87% of the pre-HDT baseline value (P < 0.05). Mean CBF velocity correlated well with calculated intracranial arterial pressure (IAP) (r = 0.54, P < 0.001). As analyzed by linear regression, mean CBF velocity = 29.6 + 0.32IAP. These results suggest that HDT increases CBF velocity by increasing IAP during several hours after the onset of microgravity. Importantly, the decrease in CBF velocity after HDT may be responsible, in part, for the increased risk of syncope observed in subjects after prolonged bed rest and also in astronauts returning to Earth.

New findings regarding light intensity and its effects as a zeitgeber in the Sprague-Dawley rat.

Circadian rhythmicities are oscillations of physiological cycles designed to create temporal organization. Circadian rhythms ensure that physiological mechanisms are expressed in proper relationship to each other and the 24 hour day. Light is the main zeitgeber ("time giver") for biological clocks. The daily variations in light intensity from dawn to dusk, and seasonally due to the rotation of the earth, act upon organisms to give them photoperiodic information. This entrainment allows them to vary biologically to prepare for reproduction, hibernation, migration and the daily adaptations necessary for survival. In most mammals, the suprachiasmatic nucleus of the anterior hypothalamus has been implicated as the central diving mechanism of circadian rhythmicity. The photic input from the retina, via the retino-hypothalamic tract, and modulation from the pineal gland help regulate the clock. In this study we investigated the effects of low light intensity on the circadian system of the Sprague-Dawley rat. A series of light intensity experiments were conducted to determine if a light level of 0.1 Lux will maintain entrained circadian rhythms of feeding, drinking, and locomotor activity.

Circadian rhythms and athletic performance.

Daily or circadian rhythmical oscillations occur in several physiological and behavioral functions that contribute to athletic performance. These functions include resting levels of sensory motor, perceptual, and cognitive performance and several neuromuscular, behavioral, cardiovascular, and metabolic variables. In addition, circadian rhythms have been reported in many indices of aerobic capacity, in certain physiological variables at different exercise levels, and, in a few studies, in actual athletic performance proficiency. Circadian rhythmicity in components of athletic performance can be modulated by workload, psychological stressors, motivation, "morningness/eveningness" differences, social interaction, lighting, sleep disturbances, the "postlunch dip" phenomenon, altitude, dietary constituents, gender, and age. These rhythms can significantly influence performance depending upon the time of day at which the athletic endeavor takes place. Disturbance of circadian rhythmicity resulting from transmeridian flight across several time zones can result in fatigue, malaise, sleep disturbance, gastrointestinal problems, and performance deterioration in susceptible individuals (circadian dysrhythmia or "jet-lag"). Factors influencing the degree of impairment and duration of readaptation include direction of flight, rhythm synchronizer intensity, dietary constituents and timing of meals, and individual factors such as morningness/eveningness, personality traits, and motivation. It is the intent of the authors to increase awareness of circadian rhythmic influences upon physiology and performance and to provide a scientific data base for the human circadian system so that coaches and athletes can make reasonable decisions to reduce the negative impact of jet-lag and facilitate readaptation following transmeridian travel.

A review of human physiological and performance changes associated with desynchronosis of biological rhythms.

This review discusses the effects, in the aerospace environment, of alterations in approximately 24-h periodicities (circadian rhythms) upon physiological and psychological functions and possible therapies for desynchronosis induced by such alterations. The consequences of circadian rhythm alteration resulting from shift work, transmeridian flight, or altered day lengths are known as desynchronosis, dysrhythmia, dyschrony, jet lag, or jet syndrome. Considerable attention is focused on the ability to operate jet aircraft and manned space vehicles. The importance of environmental cues, such as light-dark cycles, which influence physiological and psychological rhythms is discussed. A section on mathematical models is presented to enable selection and verification of appropriate preventive and corrective measures and to better understand the problem of dysrhythmia.

Relations between visceral and behavioral function in men at bedrest.

Multiple physiological measurements as well as a self-assessment of arousal was made in eight men on the first, third, and fifth days of bedrest. On the third day, additional measurements of performance on memory and dexterity tasks were made. Univariate analysis did not reveal any physiological variable to either predict subsequent performance well or to co-vary acutely with it; however, self-rating scores did prove to be useful predictors of subsequent performance. Principal components analysis suggested an "alertness" factor comprised of physiological measures as well as self-ratings which helped in predicting better performance. Although the individual patterns of correlations between variable on each of the three test days was variable, even more variability between subjects was found on the performance testing day. We believe this effect of behavioral activation may be due to the injection of common, slow temporal trends into many of the different data sets.

Quantitation of desynchronosis.

In order to find ways of preventing or correcting the effects of desynchronosis, it is necessary to know the physiological mechanisms that are affected and to quantitatively determine their rate of recovery following a time-zone change. To best accomplish this, it is necessary not only to establish the rates of change brought about in performance and physiological systems during actual flight experiments, but to complement these observations with ground-based simulation experiments. A mathematical model was developed to quantitatively describe desynchronosis and was applied to data obtained from ground-based photoperiod shift studies using monkeys. An initial steady state, Vc, and a final steady state, Vs are postulated. The measured data vector, Vt, initially equals Vc, and finally equals Vs. The difference vector, Vts, with components A(t) and B(t), defined as the dot product and cross product of vectors Vt and Vs, is termed the desynchronosis vector. The trajectory of A(t) with time is given by: A(t) = A - e (alpha + betat), where A is the asymptote denoting complete resynchronization, alpha is proportional to the total desynchronosis on day O, and beta is the rate of resynchronization. The number of cycles required to achieve a 95% recovery, t95, is computed. This model has been applied to body temperature (BT) data from a monkey subjected to a 180 degrees phase-shift by alternating the photoperiod. The BT rhythm was initially stable and a 180 degrees reversal of phase with the new environment was eventually achieved. Estimated rephasal times were: 37% in 2.6 days; 50% in 5.6 days, and 95% in 8.4 days. Similar rates of internal and external resynchronization have been obtained from human photoperiod shift, ground-based experiments. Estimated rephasal time for BT rhythms with HR rhythms to the new photoperiod (t95) is 4.9 days.

Mechanisms of action of light on circadian rhythms in the monkey.

Light is considered by many investigators to be the primary Zeitgeber for most physiologic rhythms. In order to study the effects on biorhythms of changing photoperiods and to provide information on the nature of the wave forms and the mechanisms of entrainment, unrestrained male monkeys (Cebus albifrons, Macaca nemestrina) were maintained in a sound-proofed environmental chamber. The Cebus was initially maintained on a 12L:12D schedule; it was subjected to a 180 degrees phase shift for 14 days, then returned to the original photoperiod. In two experiments (24 days; 27 days each) the same monkey was again maintained on a 12L:12D schedule which was gradually altered to a constant light environment. Deep body temperature (DBT) data were obtained with miniature radiotransmitters. Locomotor activity (LMA) was measured by strain gauges. Under the 12L:12D regimens the Macaca DBT cycles were uniform as to phase and wave form for over 60 weeks. These wave forms were analyzed by the use of periodogram and correlogram analyses and by fitting to the Volterra Integro-Differential Equation. Phase angle relationships between Zeitgeber and physiologic parameters were characterized. After the photoperiod phase shift the DBT cycle rephased in about 9 days. During the rephasing process the wave form changed. The shapes of the wave forms of DBT and activity were maintained with increasing light until an 18L:6D photoperiod was reached. The rhythms were entrained to the onset of darkness rather than lights on. Major and minor periods of LMA were detected. Hysteresis diagrams showed that DBT led the onset of major LA by 6 hr and the end of major activity by 2 hr.