Joseph M. Ronda

Exposure to bright light and darkness to treat physiologic maladaptation to night work.

Working at night results in a misalignment between the sleep-wake cycle and the output of the hypothalamic pacemaker that regulates the circadian rhythms of certain physiologic and behavioral variables. We evaluated whether such physiologic maladaptation to nighttime work could be prevented effectively by a treatment regimen of exposure to bright light during the night and darkness during the day. We assessed the functioning of the circadian pacemaker in five control and five treatment studies in order to assess the extent of adaptation in eight normal young men to a week of night work. In the control studies, on the sixth consecutive night of sedentary work in ordinary light (approximately 150 lux), the mean (+/- SEM) nadir of the endogenous temperature cycle continued to occur during the night (at 3:31 +/- 0:56 hours), indicating a lack of circadian adaptation to the nighttime work schedule. In contrast, the subjects in the treatment studies were exposed to bright light (7000 to 12,000 lux) at night and to nearly complete darkness during the day, and the temperature nadir shifted after four days of treatment to a significantly later, midafternoon hour (14:53 +/- 0:32; P less than 0.0001), indicating a successful circadian adaptation to daytime sleep and nighttime work. There were concomitant shifts in the 24-hour patterns of plasma cortisol concentration, urinary excretion rate, subjective assessment of alertness, and cognitive performance in the treatment studies. These shifts resulted in a significant improvement in both alertness and cognitive performance in the treatment group during the night-shift hours. We conclude that maladaptation of the human circadian system to night work, with its associated decline in alertness, performance, and quality of daytime sleep, can be treated effectively with scheduled exposure to bright light at night and darkness during the day.

Association of sleep-wake habits in older people with changes in output of circadian pacemaker

Many elderly people complain of disturbed sleep patterns but there is not evidence that the need to sleep decreases with age; it seems rather that the timing and consolidation of sleep change. We tried to find out whether there is a concurrent change in the output of the circadian pacemaker with age. The phase and amplitude of the pacemakers output were assessed by continuous measurement of the core body temperature during 40 h of sustained wakefulness under constant behavioural and environmental conditions. 27 young men (18-31 years) were compared with 21 older people (65-85 years; 11 men, 10 women); all were healthy and without sleep complaints. The mean amplitude of the endogenous circadian temperature oscillation (ECA) was 40% greater in young men than in the older group. Older men had a lower mean temperature ECA than older women. The minimum of the endogenous phase of the circadian temperature oscillation (ECP) occurred 1 h 52 min earlier in the older than in the young group. Customary bedtimes and waketimes were also earlier in the older group, as was their daily alertness peak. There was a close correlation between habitual waketime and temperature ECP in young men, which may lose precision with age, especially among women. These findings provide evidence for systematic age-related changes in the output of the human circadian pacemaker. We suggest that these changes may underlie the common complaints of sleep disturbance among elderly people. These changes could reflect the observed age-related deterioration of the hypothalamic nuclei that drive mammalian circadian rhythms.

Variation of electroencephalographic activity during non-rapid eye movement and rapid eye movement sleep with phase of circadian melatonin rhythm in humans

1 The circadian pacemaker regulates the timing, structure and consolidation of human sleep. The extent to which this pacemaker affects electroencephalographic (EEG) activity during sleep remains unclear. 2 To investigate this, a total of 1.22 million power spectra were computed from EEGs recorded in seven men (total, 146 sleep episodes; 9 h 20 min each) who participated in a one‐month‐long protocol in which the sleep–wake cycle was desynchronized from the rhythm of plasma melatonin, which is driven by the circadian pacemaker. 3 In rapid eye movement (REM) sleep a small circadian variation in EEG activity was observed. The nadir of the circadian rhythm of α‐activity (8.25–10.5 Hz) coincided with the end of the interval during which plasma melatonin values were high, i.e. close to the crest of the REM sleep rhythm. 4 In non‐REM sleep, variation in EEG activity between 0.25 and 11.5Hz was primarily dependent on prior sleep time and only slightly affected by circadian phase, such that the lowest values coincided with the phase of melatonin secretion. 5 In the frequency range of sleep spindles, high‐amplitude circadian rhythms with opposite phase positions relative to the melatonin rhythm were observed. Low‐frequency sleep spindle activity (12.25–13.0 Hz) reached its crest and high‐frequency sleep spindle activity (14.25–15.5Hz) reached its nadir when sleep coincided with the phase of melatonin secretion. 6 These data indicate that the circadian pacemaker induces changes in EEG activity during REM and non‐REM sleep. The changes in non‐REM sleep EEG spectra are dissimilar from the spectral changes induced by sleep deprivation and exhibit a close temporal association with the melatonin rhythm and the endogenous circadian phase of sleep consolidation.

Short-term memory, alertness and performance: a reappraisal of their relationship to body temperature

SUMMARY  Previous studies have led to the beliefs: (1) that short‐term memory is best during the night when the body temperature is at its nadir, and (2) that the circadian rhythms of short‐term memory and subjective alertness are driven by oscillators independent from each other and from the body temperature cycle. Unfortunately, these conclusions, which would have major implications for understanding the organization of the human circadian timing system, are largely based on field and laboratory studies, which in many cases sampled data infrequently and/or limited data collection to normal waking hours. In order to investigate these points further, we have monitored behavioural variables in two different protocols under controlled laboratory conditions: (1) during a period of 36–60 h of sustained wakefulness; and (2) during forced desynchrony between the body temperature and sleep/wake cycles, allowing testing of non‐sleep‐deprived subjects at all circadian phases. Contrary to earlier findings, we report here that the circadian rhythm of short‐term memory varies in parallel with the circadian rhythms of subjective alertness, calculation performance, and core body temperature under both these experimental conditions. These results challenge the notion that short‐term memory is inversely linked to the body temperature cycle and suggest that the human circadian pacemaker, which drives the body temperature cycle, is the primary determinant of endogenous circadian variations in subjective alertness and calculation performance as well as in the immediate recall of meaningful material.

Sleep and Wakefulness Out of Phase with Internal Biological Time Impairs Learning in Humans

Sleepwake homeostatic and internal circadian timedependent brain processes interact to regulate human brain function so that alert wakefulness is promoted during the daytime and consolidated sleep is promoted at nighttime. The consequence of chronically altering the normal relationship between these processes for human brain function is largely unknown. We tested cognitive and vigilance performance while subjects lived in the laboratory for over a month. The subjects lived on either 24.0- or 24.6-hr day lengths. Half of the subjects tested maintained a normal relationship between sleepwakefulness and internal circadian time (synchronized group), whereas the other half did not (nonsynchronized group). Levels of the sleep-promoting hormone melatonin were high during scheduled sleep in the synchronized group, whereas melatonin levels were high during scheduled wakefulness in the nonsynchronized group. Failure to adapt to the scheduled day length was dependent upon individual differences in intrinsic circadian period. Total sleep time was reduced, sleep latency and Rapid Eye Movement (REM) latency were shortened, and wakefulness after sleep onset was increased in the nonsynchronized group. Cognitive performance improved (i.e., learning) in the synchronized group, whereas learning was significantly impaired in the nonsynchronized group. Attention progressively declined in both groups, suggesting that 8 hr of scheduled sleep per night is insufficient to maintain brain vigilance even when sleep occurs at an appropriate biological time. Our results establish that proper alignment between sleepwakefulness and internal circadian time is crucial for enhancement of cognitive performance. In addition, our results demonstrate that exposure to dim light (~25 lx) is sufficient to expand the range of entrainment in humans.

A role for non-rapid-eye-movement sleep homeostasis in perceptual learning.

Slow-wave activity (SWA; EEG power density in the 0.75–4.5 Hz range) in non-rapid-eye-movement (NREM) sleep is the primary marker of sleep homeostasis and thought to reflect sleep need. But it is unknown whether the generation of SWA itself serves a fundamental function. Previously, SWA has been implicated in brain plasticity and learning, yet the evidence for a causal role remains correlative. Here, we used acoustic slow-wave suppression to test whether overnight improvement in visual texture discrimination, a form of perceptual learning, directly depends on SWA during sleep. Two groups of subjects were trained on a texture discrimination task (TDT) after baseline sleep, and were tested 24 h later, after a 4 h experimental (EX) sleep episode (with or without SWA suppression), and again after a night of recovery sleep. In the suppression group, SWA during EX sleep was reduced by 30% compared with the control group, whereas total sleep time and REM sleep were not affected. Texture discrimination improved after EX sleep in the control group but not in the suppression group. Moreover, overnight improvement in TDT performance correlated with EEG power density during NREM sleep in the frequency range of SWA (maximum r = 0.75 at 0.75–1.0 Hz) over brain areas involved in TDT learning. We conclude that SWA is an important determinant of sleep-dependent gains in perceptual performance, a finding that directly implicates processes of sleep homeostasis in learning.

Comparison of subjective and objective assessments of sleep in healthy older subjects without sleep complaints

Older adults have reduced sleep quality compared with younger adults when sleeping at habitual times and greater sleep disruption when their sleep is at adverse times. The purpose of this analysis was to investigate how subjective measures of sleep relate to objectively recorded sleep in older subjects scheduled to sleep at all times of day. We analyzed data from 24 healthy older (55–74 years) subjects who took part in a 32‐day inpatient study where polysomnography was recorded each night and subjective sleep was assessed after each scheduled wake time. The study included baseline nights and a forced desynchrony (FD) protocol when the subjects lived on a 20‐h rest activity schedule. Our postsleep questionnaire both included quantitative and qualitative questions about the prior sleep. Under baseline and FD conditions, objective and subjective sleep latency were correlated, subjective sleep duration was related to slow‐wave sleep and wake after sleep onset, subjective sleep quality was related to stage 1 and 2 sleep, and sleepiness and refreshment at wake time were related to duration of premature awakening. During FD, most measures of objective and subjective sleep varied with circadian phase and many additional correlations between objective and subjective sleep were present. Our findings show that when sleeping at habitual times, these healthy older subjects did not perceive their generally poor sleep quality, but under FD conditions where sleep quality changed from day‐to‐day their subjective sleep ratings were more associated with their objective sleep.

Sleep inertia, sleep homeostatic and circadian influences on higher-order cognitive functions

Sleep inertia, sleep homeostatic and circadian processes modulate cognition, including reaction time, memory, mood and alertness. How these processes influence higher‐order cognitive functions is not well known. Six participants completed a 73‐day‐long study that included two 14‐day‐long 28‐h forced desynchrony protocols to examine separate and interacting influences of sleep inertia, sleep homeostasis and circadian phase on higher‐order cognitive functions of inhibitory control and selective visual attention. Cognitive performance for most measures was impaired immediately after scheduled awakening and improved during the first ~2–4 h of wakefulness (decreasing sleep inertia); worsened thereafter until scheduled bedtime (increasing sleep homeostasis); and was worst at ~60° and best at ~240° (circadian modulation, with worst and best phases corresponding to ~09:00 and ~21:00 hours, respectively, in individuals with a habitual wake time of 07:00 hours). The relative influences of sleep inertia, sleep homeostasis and circadian phase depended on the specific higher‐order cognitive function task examined. Inhibitory control appeared to be modulated most strongly by circadian phase, whereas selective visual attention for a spatial‐configuration search task was modulated most strongly by sleep inertia. These findings demonstrate that some higher‐order cognitive processes are differentially sensitive to different sleep–wake regulatory processes. Differential modulation of cognitive functions by different sleep–wake regulatory processes has important implications for understanding mechanisms contributing to performance impairments during adverse circadian phases, sleep deprivation and/or upon awakening from sleep.

Comparison of sustained attention assessed by auditory and visual psychomotor vigilance tasks prior to and during sleep deprivation

To date, no detailed examination of the pattern of change in reaction time performance for different sensory modalities has been conducted across the circadian cycle during sleep deprivation. Therefore, we compared sustained auditory and visual attention performance during 40 h of sleep deprivation assessing multiple metrics of auditory and visual psychomotor vigilance tasks (PVT). Forty healthy participants (14 women) aged 30.8 ± 8.6 years were studied. Subjects were scheduled for an ∼8 h sleep schedule at home prior to three–six laboratory baseline days with an 8 h sleep schedule followed by 40 h sleep deprivation. Visual and auditory PVTs were 10 min in duration, and were administered every 2 h during sleep deprivation. Data were analysed with mixed‐model anova. Sleep deprivation and circadian phase increased response time, lapses, anticipations, standard deviation of response times and time on task decrements for visual and auditory PVTs. In general, auditory vigilance was faster and less variable than visual vigilance, with larger differences between auditory and visual PVT during sleep deprivation versus baseline. Failures to respond to stimuli within 10 s were four times more likely to occur to visual versus auditory stimuli. Our findings highlight that lapses during sleep deprivation are more than just long responses due to eye closure or visual distraction. Furthermore, our findings imply that the general pattern of change in attention during sleep deprivation (e.g. circadian variation, response slowing, lapsing and anticipations, time on task decrements and state instability) is similar among sensory–motor behavioral response modalities.

Prevalence of sleep deficiency and use of hypnotic drugs in astronauts before, during, and after spaceflight: an observational study

BACKGROUND Sleep deprivation and fatigue are common subjective complaints among astronauts. Previous studies of sleep and hypnotic drug use in space have been limited to post-flight subjective survey data or in-flight objective data collection from a small number of crew members. We aimed to characterise representative sleep patterns of astronauts on both short-duration and long-duration spaceflight missions. METHODS For this observational study, we recruited crew members assigned to Space Transportation System shuttle flights with in-flight experiments between July 12, 2001, and July 21, 2011, or assigned to International Space Station (ISS) expeditions between Sept 18, 2006, and March 16, 2011. We assessed sleep-wake timing objectively via wrist actigraphy, and subjective sleep characteristics and hypnotic drug use via daily logs, in-flight and during Earth-based data-collection intervals: for 2 weeks scheduled about 3 months before launch, 11 days before launch until launch day, and for 7 days upon return to Earth. FINDINGS We collected data from 64 astronauts on 80 space shuttle missions (26 flights, 1063 in-flight days) and 21 astronauts on 13 ISS missions (3248 in-flight days), with ground-based data from all astronauts (4014 days). Crew members attempted and obtained significantly less sleep per night as estimated by actigraphy during space shuttle missions (7·35 h [SD 0·47] attempted, 5·96 h [0·56] obtained), in the 11 days before spaceflight (7·35 h [0·51], 6·04 h [0·72]), and about 3 months before spaceflight (7·40 h [0·59], 6·29 h [0·67]) compared with the first week post-mission (8·01 h [0·78], 6·74 h [0·91]; p<0·0001 for both measures). Crew members on ISS missions obtained significantly less sleep during spaceflight (6·09 h [0·67]), in the 11 days before spaceflight (5·86 h [0·94]), and during the 2-week interval scheduled about 3 months before spaceflight (6·41 h [SD 0·65]) compared with in the first week post-mission (6·95 h [1·04]; p<0·0001). 61 (78%) of 78 shuttle-mission crew members reported taking a dose of sleep-promoting drug on 500 (52%) of 963 nights; 12 (75%) of 16 ISS crew members reported using sleep-promoting drugs. INTERPRETATION Sleep deficiency in astronauts was prevalent not only during space shuttle and ISS missions, but also throughout a 3 month preflight training interval. Despite chronic sleep curtailment, use of sleep-promoting drugs was pervasive during spaceflight. Because chronic sleep loss leads to performance decrements, our findings emphasise the need for development of effective countermeasures to promote sleep. FUNDING The National Aeronautics and Space Administration.