Edward J. Silva

Amplitude Reduction and Phase Shifts of Melatonin, Cortisol and Other Circadian Rhythms after a Gradual Advance of Sleep and Light Exposure in Humans

Background The phase and amplitude of rhythms in physiology and behavior are generated by circadian oscillators and entrained to the 24-h day by exposure to the light-dark cycle and feedback from the sleep-wake cycle. The extent to which the phase and amplitude of multiple rhythms are similarly affected during altered timing of light exposure and the sleep-wake cycle has not been fully characterized. Methodology/Principal Findings We assessed the phase and amplitude of the rhythms of melatonin, core body temperature, cortisol, alertness, performance and sleep after a perturbation of entrainment by a gradual advance of the sleep-wake schedule (10 h in 5 days) and associated light-dark cycle in 14 healthy men. The light-dark cycle consisted either of moderate intensity ‘room’ light (∼90–150 lux) or moderate light supplemented with bright light (∼10,000 lux) for 5 to 8 hours following sleep. After the advance of the sleep-wake schedule in moderate light, no significant advance of the melatonin rhythm was observed whereas, after bright light supplementation the phase advance was 8.1 h (SEM 0.7 h). Individual differences in phase shifts correlated across variables. The amplitude of the melatonin rhythm assessed under constant conditions was reduced after moderate light by 54% (17–94%) and after bright light by 52% (range 12–84%), as compared to the amplitude at baseline in the presence of a sleep-wake cycle. Individual differences in amplitude reduction of the melatonin rhythm correlated with the amplitude of body temperature, cortisol and alertness. Conclusions/Significance Alterations in the timing of the sleep-wake cycle and associated bright or moderate light exposure can lead to changes in phase and reduction of circadian amplitude which are consistent across multiple variables but differ between individuals. These data have implications for our understanding of circadian organization and the negative health outcomes associated with shift-work, jet-lag and exposure to artificial light.

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 varies with circadian phase and sleep stage in older adults.

The purpose of our analysis was to determine if older adults show sleep inertia effects on performance at scheduled wake time, and whether these effects depend on circadian phase or sleep stage at awakening. Using the Digit Symbol Substitution Test, effects of sleep inertia on performance were assessed over the first 30 min after wake time on baseline days and when sleep was scheduled at different circadian phases. Mixed model analyses revealed that performance improved as time awake increased; that beginning levels of performance were poorest when wake time was scheduled to occur during the biological night; and that effects of sleep inertia on performance during the biological night were greater when awaking from non-REM (NREM) sleep than from REM sleep. Based on our current understanding of sleep inertia effects in young subjects, and previous reports that older subjects awaken at an earlier circadian phase and are more likely to have their final awakening from NREM sleep than younger adults, our findings suggest older adults may be more vulnerable to sleep inertia effects than young adults.

Effects on subjective and objective alertness and sleep in response to evening light exposure in older subjects

Evening bright light exposure is reported to ameliorate daytime sleepiness and age-related sleep complaints, and also delays the timing of circadian rhythms. We tested whether evening light exposure given to older adults with sleep-wake complaints would delay the timing of their circadian rhythms with respect to their sleep timing, thereby reducing evening sleepiness and improving subsequent sleep quality. We examined the impact of evening light exposure from two different light sources on subjective alertness, EEG activity during wakefulness, and sleep stages. Ten healthy older adults with sleep complaints (mean age=63.3 years; 6F) participated in a 13-day study. After three baseline days, circadian phase was assessed. On the evening of days 5-8 the subjects were exposed for 2h to either polychromatic blue-enriched white light or standard white fluorescent light, and on the following day circadian phase was re-assessed. Subjects were allowed to leave the laboratory during all but the two days when the circadian phase assessment took place. Evening assessments of subjective alertness, and wake and sleep EEG data were analyzed. Subjective alertness and wake EEG activity in the alpha range (9.75-11.25 Hz) were significantly higher during light exposures when compared to the pre-light exposure evening (p<0.05). The light exposures produced circadian phase shifts and significantly prolonged latency to rapid eye-movement (REM) sleep for both light groups (p<0.05). The increase in wake EEG alpha activity during the light exposures was negatively correlated with REM sleep duration (p<0.05). Evening light exposure could benefit older adults with early evening sleepiness, without negatively impacting the subsequent sleep episode.

The effects of circadian phase, time awake, and imposed sleep restriction on performing complex visual tasks: Evidence from comparative visual search

Cognitive performance not only differs between individuals, but also varies within them, influenced by factors that include sleep-wakefulness and biological time of day (circadian phase). Previous studies have shown that both factors influence accuracy rather than the speed of performing a visual search task, which can be hazardous in safety-critical tasks such as air-traffic control or baggage screening. However, prior investigations used simple, brief search tasks requiring little use of working memory. In order to study the effects of circadian phase, time awake, and chronic sleep restriction on the more realistic scenario of longer tasks requiring the sustained interaction of visual working memory and attentional control, the present study employed two comparative visual search tasks. In these tasks, participants had to detect a mismatch between two otherwise identical object distributions, with one of the tasks (mirror task) requiring an additional mental image transformation. Time awake and circadian phase both had significant influences on the speed, but not the accuracy of task performance. Over the course of three weeks of chronic sleep restriction, speed but not accuracy of task performance was impacted. The results suggest measures for safer performance of important tasks and point out the importance of minimizing the impact of circadian phase and sleep-wake history in laboratory vision experiments.