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Sleep is an active physiological state that plays a critical role in our physical and mental health and well-being. It is generated by a complex interplay between two oscillators, namely, the circadian oscillator and the sleep-wake homeostat. Sleep propensity is a function of wakefulness, that is, the longer one is awake the greater the homeostatic sleep pressure. Sleep onset occurs as a wake promoting circadian signal subsides, coinciding with an evening rise in melatonin and drop in core temperature. Light is one of the strongest time signals for the circadian oscillator. Poor sleep is a prevalent complaint today, attributable, in part, to our easy access to artificial light, especially after dusk. This non-visual effect of light is mediated by a multi-component photoreceptive system, consisting of rods, cones and melanopsin-expressing intrinsically-photosensitive retinal ganglion cells (ipRGC). Perhaps, with this available biological knowledge we can engineer artificial light to minimize its disruptive effect on sleep. We will highlight this by discussing circadian photoreception and its effect on sleep, in the blind population., (© 2020 Elsevier B.V. All rights reserved.)

Key Points: There is assumed to be a monotonic association between melatonin suppression and circadian phase resetting induced by light exposure. We tested the association between melatonin suppression and phase resetting in humans. Sixteen young healthy participants received nocturnal bright light (∼9500 lux) exposure of continuous or intermittent patterns, and different durations ranging from 12 min to 6.5 h. Intermittent exposure patterns showed significant phase shifts with disproportionately less melatonin suppression. Each and every bright light stimulus in an intermittent exposure pattern induced a similar degree of melatonin suppression, but did not appear to cause an equal magnitude of phase shift. These results suggest that phase shifts and melatonin suppression are functionally independent such that one cannot be used as a proxy measure of the other., Abstract: Continuous experimental light exposures show that, in general, the conditions that produce greater melatonin suppression also produce greater phase shift, leading to the assumption that one can be used as a proxy for the other. We tested this association in 16 healthy individuals who participated in a 9-day inpatient protocol by assessing melatonin suppression and phase resetting in response to a nocturnal light exposure (LE) of different patterns: (i) dim-light control (<3 lux; n = 6) or (ii) two 12-min intermittent bright light pulses (IBL) separated by 36 min of darkness (∼9500 lux; n = 10). We compared these results with historical data from additional LE patterns: (i) dim-light control (<3 lux; n = 11); (ii) single continuous bright light exposure of 12 min (n = 9), 1.0 h (n = 10) or 6.5 h (n = 6); or (iii) an IBL light pattern consisting of six 15-min pulses with 1.0 h dim-light recovery intervals between them during a total of 6.5 h (n = 7). All light exposure groups had significantly greater phase-delay shifts than the dim-light control condition (P < 0.0001). While a monotonic association between melatonin suppression and circadian phase shift was observed, intermittent exposure patterns showed significant phase shifts with disproportionately less melatonin suppression. Each and every IBL stimulus induced a similar degree of melatonin suppression, but did not appear to cause an equal magnitude of phase shift. These results suggest unique specificities in how light-induced phase shifts and melatonin suppression are mediated such that one cannot be used as a proxy measure of the other., (© 2018 The Authors. The Journal of Physiology © 2018 The Physiological Society.)

BACKGROUND. In humans, a single light exposure of 12 minutes and multiple-millisecond light exposures can shift the phase of the circadian pacemaker. We investigated the response of the human circadian pacemaker to a single 15-second or 2-minute light pulse administered during the biological night. METHODS. Twenty-six healthy individuals participated in a 9-day inpatient protocol that included assessment of dim light melatonin onset time (DLMO time) before and after exposure to a single 15-second ( n = 8) or 2-minute ( n = 12) pulse of bright light (9,500 lux; 4,100 K fluorescent) or control background dim light (<3 lux; n = 6). Phase shifts were calculated as the difference in clock time between the two phase estimates. RESULTS. Both 15-second and 2-minute exposures induced phase delay shifts [median (± SD)] of -34.8 ± 47.2 minutes and -45.4 ± 28.4 minutes, respectively, that were significantly ( P = 0.04) greater than the control condition (advance shift: +22.3 ± 51.3 minutes) but were not significantly different from each other. Comparisons with historic data collected under the same conditions confirmed a nonlinear relationship between exposure duration and the magnitude of phase shift. CONCLUSIONS. Our results underscore the exquisite sensitivity of the human pacemaker to even short-duration single exposures to light. These findings may have real-world implications for circadian disruption induced by exposure to brief light stimuli at night. TRIAL REGISTRATION. The study was registered as a clinical trial on www.clinicaltrials.org, NCT #01330992. FUNDING. Funding for this study was provided by NSBRI HFP02802 and NIH P01-AG09975, R01-HL114088 (EBK), RC2-HL101340-0 (EBK, SWL, SAR, REK), K02-HD045459 (EBK), K24-HL105664 (EBK), T32-HL07901 (MSH, SAR), HL094654 (CAC), and AG044416 (JFD). The project described was supported by NIH grant 1UL1 TR001102-01, 8UL1TR000170-05, UL1 RR 025758, Harvard Clinical and Translational Science Center, from the National Center for Advancing Translational Science., Competing Interests: Conflict of interest: Possible conflicts of interest for all authors are disclosed in the online supplement (https://doi.org/10.1172/jci.insight.89494DS1).

The transition from sleep to wakefulness entails a temporary period of reduced alertness and impaired performance known as sleep inertia. The extent to which its severity varies with task and cognitive processes remains unclear. We examined sleep inertia in alertness, attention, working memory and cognitive throughput with the Karolinska Sleepiness Scale (KSS), the Psychomotor Vigilance Task (PVT), n-back and add tasks, respectively. The tasks were administered 2 hours before bedtime and at regular intervals for four hours, starting immediately after awakening in the morning, in eleven participants, in a four-way cross-over laboratory design. We also investigated whether exposure to Blue-Enhanced or Bright Blue-Enhanced white light would reduce sleep inertia. Alertness and all cognitive processes were impaired immediately upon awakening (p<0.01). However, alertness and sustained attention were more affected than cognitive throughput and working memory. Moreover, speed was more affected than accuracy of responses. The light conditions had no differential effect on performance except in the 3-back task (p<0.01), where response times (RT) at the end of four hours in the two Blue-Enhanced white light conditions were faster (200 ms) than at wake time. We conclude that the effect of sleep inertia varies with cognitive domain and that it's spectral/intensity response to light is different from that of sleepiness. That is, just increasing blue-wavelength in light may not be sufficient to reduce sleep inertia. These findings have implications for critical professions like medicine, law-enforcement etc., in which, personnel routinely wake up from night-time sleep to respond to emergency situations.

Light exposure in the early night induces phase delays of the circadian rhythm in melatonin in humans. Previous studies have investigated the effect of timing, intensity, wavelength, history and pattern of light stimuli on the human circadian timing system. We present results from a study of the duration–response relationship to phase-delaying bright light. Thirty-nine young healthy participants (16 female; 22.18±3.62 years) completed a 9-day inpatient study. Following three baseline days, participants underwent an initial circadian phase assessment procedure in dim light (<3 lux), and were then randomized for exposure to a bright light pulse (∼10,000 lux) of 0.2 h, 1.0 h, 2.5 h or 4.0 h duration during a 4.5 h controlled-posture episode centred in a 16 h wake episode. After another 8 h sleep episode, participants completed a second circadian phase assessment. Phase shifts were calculated from the difference in the clock time of the dim light melatonin onset (DLMO) between the initial and final phase assessments. Exposure to varying durations of bright light reset the circadian pacemaker in a dose-dependent, non-linear manner. Per minute of exposure, the 0.2 h duration was over 5 times more effective at phase delaying the circadian pacemaker (1.07±0.36 h) as compared with the 4.0 h duration (2.65±0.24 h). Acute melatonin suppression and subjective sleepiness also had a dose-dependent response to light exposure duration. These results provide strong evidence for a non-linear resetting response of the human circadian pacemaker to light duration.

The prevalence of hazardous incidents induced by attentional impairment during night work and ensuing commute times is attributable to circadian misalignment and increased sleep pressure. In a 10-day shift work simulation protocol (4 day shifts and 3 night shifts), the efficacies of 2 countermeasures against nighttime (2300 to 0700 h) attentional impairment were compared: (1) Morning Sleep (0800 to 1600 h; n = 18) in conjunction with a phase-delaying light exposure (2300 to 0300 h), and (2) Evening Sleep (1400 to 2200 h; n = 17) in conjunction with a phase-advancing light exposure (0300 to 0700 h). Analysis of the dim light salivary melatonin onset indicated a modest but significant circadian realignment in both sleep groups (evening sleep: 2.27 +/- 0.6 h phase advance, p < 0.01; morning sleep: 4.98 +/- 0.43 h phase delay, p < 0.01). Daytime sleep efficiency and total sleep time did not differ between them or from their respective baseline sleep (2200 to 0600 h; p > 0.05). However, on the final night shift, the evening sleep subjects had 37% fewer episodes of attentional impairment (long response times: 22 +/- 4 vs. 35 +/- 4; p = 0.02) and quicker responses (p < 0.01) on the Psychomotor Vigilance Task than their morning sleep counterparts. Their response speed recovered to near daytime levels (p = 0.47), whereas those of the morning sleep subjects continued to be slower than their daytime levels (p = 0.008). It is concluded that partial circadian realignment to night work in combination with reduced homeostatic pressure contributed to the greater efficacy of a schedule of Evening Sleep with a phase-advancing light exposure as a countermeasure against attentional impairment, over a schedule of Morning Sleep with a phase-delaying light exposure. These results have important implications for managing patients with shift work disorder.

Shift work results in a misalignment between circadian timing and the sleep/wake schedule, leading to irregular and poor quality sleep. Inconsistent input from the daily light cycle further interferes with circadian entrainment. It has been hypothesized that scheduling the sleep/dark cycle on the night shift could aid in promoting adaptation to night shift work by facilitating appropriate phase shifts. In a simulated shift-work study, we compared the ability of two sleep/dark schedules to shift circadian phase. Our results indicate that scheduled sleep/darkness can aid in adaptation to night shift work by inducing both advance and delay phase shifts, depending on the timing of the sleep schedule, although the size of the phase shifts are not sufficient to produce complete adaptation to the night shift. These results have applications to night shift workers, particularly in occupations in which alterations in the timing of light exposure cannot be achieved during working hours.

Timing of the human sleep-wake cycle is determined by social constraints, biological processes (sleep homeostasis and circadian rhythmicity) and environmental factors, particularly natural and electrical light exposure. To what extent seasonal changes in the light-dark cycle affect sleep timing and how this varies between weekdays and weekends has not been firmly established. We examined sleep and activity patterns during weekdays and weekends in late autumn (standard time, ST) and late spring (daylight saving time, DST), and expressed their timing in relation to three environmental reference points: clock-time, solar noon (SN) which occurs one clock hour later during DST than ST, and the midpoint of accumulated light exposure (50% LE). Observed sleep timing data were compared to simulated data from a mathematical model for the effects of light on the circadian and homeostatic regulation of sleep. A total of 715 days of sleep timing and light exposure were recorded in 19 undergraduates in a repeated-measures observational study. During each three-week assessment, light and activity were monitored, and self-reported bed and wake times were collected. Light exposure was higher in spring than in autumn. 50% LE did not vary across season, but occurred later on weekends compared to weekdays. Relative to clock-time, bedtime, wake-time, mid-sleep, and midpoint of activity were later on weekends but did not differ across seasons. Relative to SN, sleep and activity measures were earlier in spring than in autumn. Relative to 50% LE, only wake-time and mid-sleep were later on weekends, with no seasonal differences. Individual differences in mid-sleep did not correlate with SN but correlated with 50% LE. Individuals with different habitual bedtimes responded similarly to seasonal changes. Model simulations showed that light exposure patterns are sufficient to explain sleep timing in spring but less so in autumn. The findings indicate that during autumn and spring, the timing of sleep associates with actual light exposure rather than sun time as indexed by SN. [ABSTRACT FROM AUTHOR]