Effects of thermoregulation on human sleep patterns: A mathematical model of sleep-wake cycles with REM-NREM subcircuit

In this paper we construct a mathematical model of human sleep/wake regulation with thermoregulation and temperature e ects. Simulations of this model show features previously presented in experimental data such as elongation of duration and number of REM bouts across the night as well as the appearance of awakenings due to deviations in body temperature from thermoneutrality. This model helps to demonstrate the importance of temperature in the sleep cycle. Further modi cations of the model to include more temperature e ects on other aspects of sleep regulation such as sleep and REM latency are discussedPostprint (author's final draft

Evening use of light-emitting eReaders negatively affects sleep, circadian timing, and next-morning alertness

In the past 50 y, there has been a decline in average sleep duration and quality, with adverse consequences on general health. A representative survey of 1,508 American adults recently revealed that 90% of Americans used some type of electronics at least a few nights per week within 1 h before bedtime. Mounting evidence from countries around the world shows the negative impact of such technology use on sleep. This negative impact on sleep may be due to the short-wavelength–enriched light emitted by these electronic devices, given that artificial-light exposure has been shown experimentally to produce alerting effects, suppress melatonin, and phase-shift the biological clock. A few reports have shown that these devices suppress melatonin levels, but little is known about the effects on circadian phase or the following sleep episode, exposing a substantial gap in our knowledge of how this increasingly popular technology affects sleep. Here we compare the biological effects of reading an electronic book on a light-emitting device (LE-eBook) with reading a printed book in the hours before bedtime. Participants reading an LE-eBook took longer to fall asleep and had reduced evening sleepiness, reduced melatonin secretion, later timing of their circadian clock, and reduced next-morning alertness than when reading a printed book. These results demonstrate that evening exposure to an LE-eBook phase-delays the circadian clock, acutely suppresses melatonin, and has important implications for understanding the impact of such technologies on sleep, performance, health, and safety

Suppression of Melatonin Secretion in Totally Visually Blind People by Ocular Exposure to White Light: Clinical Characteristics

Purpose: Although most totally visually blind individuals exhibit nonentrained circadian rhythms due to an inability of light to entrain the circadian pacemaker, a small proportion retain photic circadian entrainment, melatonin suppression, and other nonimage-forming responses to light. It is thought that these responses to light persist because of the survival of melanospin-containing intrinsically photosensitive retinal ganglion cells (ipRGCs), which project primarily to the circadian pacemaker and are functionally distinct from the rod and cone photoreceptors that mediate vision. We aimed to assess the integrity of nonimage-forming photoreception in totally visually blind patients with a range of ocular disorders. Design: Within-subject, dark-controlled design. Participants: A total of 18 totally visually blind individuals (7 females; mean age ± standard deviation = 49.8±11.0 years) with various causes of blindness, including 3 bilaterally enucleated controls. Methods: Melatonin concentrations were compared during exposure to a 6.5-hour bright white light (�7000 lux) with melatonin concentrations measured 24 hours earlier at the corresponding clock times under dim-light (4 lux) conditions. Main Outcome Measures: Area under the curve (AUC) for melatonin concentration. Results: Melatonin concentrations were significantly suppressed (defined as �33% suppression) during the bright-light condition compared with the dim-light condition in 5 of 15 participants with eyes (retinitis pigmentosa, n = 2; retinopathy of prematurity [ROP], n = 2; bilateral retinal detachments, n = 1). Melatonin concentrations remained unchanged in response to light in the remaining 10 participants with eyes (ROP, n = 3; optic neuritis/neuropathy, n = 2; retinopathy unknown, n = 2; congenital glaucoma, n = 1; congenital rubella syndrome, n = 1; measles retinopathy, n = 1) and in all 3 bilaterally enucleated participants. Conclusions: These data confirm that light-induced suppression of melatonin remains functionally intact in a minority of totally visually blind individuals with eyes. None of the bilaterally enucleated individuals or those with phthisis bulbi was responsive to light; of the remainder, half were responsive to light. Although inner retinal damage is associated with a high likelihood that nonimage-forming photoreception is absent, the impact of outer retinal damage is more ambiguous, and therefore the assessment of the presence, attenuation, or absence of nonimage-forming light responses in totally blind patients requires careful individual confirmation and cannot simply be assumed from the type of blindness. © 2018 American Academy of Ophthalmolog

Distinct Non-Additive Effects of Acute and Chronic Sleep Loss and Circadian Phase on Inadvertent Attentional Failures

Introduction : In modern societies, many humans are exposed to a combination of acute and chronic sleep loss and circadian misalignment. We previously reported non-additive effects of these three factors on performance measures derived from the psychomotor vigilance task [Cohen et al., Sci Transl Med, 2010]. Here we tested whether this result were specific to this task or whether it reflects a more fundamental principle of sleep-wake regulation by quantifying the impact of these three factors on the occurrence of spontaneous attentional failures (AF) derived from continuous electro-oculographic (EOG) recordings in that same study. Methods : Nine volunteers (age 21-34 years, 4F) completed a three-week forced desynchrony protocol consisting of 12 consecutive 42.85-h sleep-wake cycles with 32.85 h of scheduled wakefulness and 10 h of scheduled sleep (sleep:wake ratio of 1:3.3). Over three weeks, the protocol therefore induced an increasing chronic sleep loss while allowing extended wake and sleep episodes to occur at all circadian phases. Continuous EOG recordings were obtained. AF were quantified as number of 30-s epochs with visually scored slow eye movements per hour of wakefulness. Data were analyzed by time since scheduled wake onset in 4.1-h bins (acute sleep loss), study week (chronic sleep loss), and circadian phase derived from plasma melatonin. Results : During the first 8.2 h of a wake episode, the number of AF (nAF) was low (< 1/h), irrespective of study week. Across the subsequent wake bins, nAF increased steadily, with the rate of increase being higher in weeks 2 and 3 compared to week 1 (mixed ANOVA, Week x Wake bin, p=0.001). At the end of the wake episode, nAF was 2.0±0.4/h (±SEM), 3.8±0.5/h, and 3.0±0.8/h in weeks 1, 2, and 3, respectively (effect of Week in final wake bin, p<0.0001). Moreover, the effects of acute and chronic sleep loss on nAF were magnified during the biological night (Phase x Wake bin, Phase x Week, both p<0.0002). Conclusion: A single episode of extended recovery sleep can temporarily–i.e., for the first few hours of subsequent wakefulness–restore to baseline levels attentional impairment associated with chronic sleep loss. Chronic sleep loss speeds up the accumulation of inadvertent AF during a wake episode. Thus, acute and chronic sleep loss in combination with circadian phase should be considered as distinct factors that interact in a non-additive way to affect waking function

Direct Effects of Light on Alertness, Vigilance, and the Waking Electroencephalogram in Humans Depend on Prior Light History

Study Objectives: Light can induce an acute alerting response in humans; however, it is unknown whether the magnitude of this response is simply a function of the absolute illuminance of the light itself, or whether it depends on illuminance history preceding the stimulus. Here, we compared the effects of illuminance history on the alerting response to a subsequent light stimulus. Design: A randomized, crossover design was used to compare the effect of two illuminance histories (1 lux vs. 90 lux) on the alerting response to a 6.5-h 90-lux light stimulus during the biological night. Setting: Intensive Physiologic Monitoring Unit, Brigham and Women’s Hospital, Boston, MA. Participants: Fourteen healthy young adults (6 F; 23.5 ± 2.9 years). Interventions: Participants were administered two 6.5-h light exposures (LE) of 90 lux during the biological night. For 3 days prior to each LE, participants were exposed to either 1 lux or 90 lux during the wake episode. Measurements and Results: The alerting response to light was assessed using subjective sleepiness ratings, lapses of attention, and reaction times as measured with an auditory psychomotor vigilance task, as well as power density in the delta/theta range of the waking EEG. The alerting response to light was greater and lasted longer when the LE followed exposure to 1 lux compared to 90 lux light. Conclusion: The magnitude and duration of the alerting effect of light at night depends on the illuminance history and appears to be subject to sensitization and adaptation

Characterizing the temporal Dynamics of Melatonin and Cortisol Changes in Response to Nocturnal Light Exposure

We studied the dynamics of melatonin suppression and changes in cortisol levels in humans in response to light exposure at night using high-frequency blood sampling. Twenty-one young healthy participants were randomized to receive either intermittent bright (~9,500 lux) light (IBL), continuous bright light (CBL) or continuous dim (~1 lux) light (VDL) for 6.5 h during the biological night (n = 7 per condition). Melatonin suppression occurred rapidly within the first 5 min and continued until the end of each IBL stimuli (t1/2 = ~13 min). Melatonin recovery occurred more slowly between IBL stimuli (half-maximal recovery rate of ~46 min). Mean melatonin suppression (~40%) and recovery (~50%) were similar across IBL stimuli. Suppression dynamics under CBL were also rapid (t1/2 = ~18 min), with no recovery until the light exposure ended. There was a significant linear increase of cortisol levels between the start and end of each IBL stimulus. Under CBL conditions cortisol showed trimodal changes with an initial linear activating phase, followed by an exponential inhibitory phase, and a final exponential recovery phase. These results show that light exposure at night affects circadian driven hormones differently and that outcomes are influenced by the duration and pattern of light exposure. © 2019, The Author(s)

Self-reported drowsiness and safety outcomes while driving after an extended duration work shift in trainee physicians

Study Objectives: Extended duration (�24 hours) work shifts (EDWSs) are associated with increased risk of motor vehicle crashes, and awareness of any impairment has important implications on legal accountability for any adverse driving outcome. The extent to which adverse driving events were preceded by predrive self-reported sleepiness was evaluated in medical residents after an EDWS. Methods: Sixteen resident physicians (10 females; 29.2 ± 2.0 years) working EDWS were monitored when driving on their commute to and from the hospital (438 drives). Sleep and work hours were obtained from daily logs, and adverse driving outcomes were captured from a driving log completed at the end of each drive. Self-reported sleepiness (Karolinska Sleepiness Scale; KSS) and objective drowsiness were captured using a time-stamped, hand-held device and infra-red reflectance oculography. Results: Self-reported sleepiness and objective indices of drowsiness were positively correlated, and both were elevated following EDWSs. Compared with the commute to work, EDWSs were associated with more than double the self-reported adverse outcomes when driving home, significantly higher than drives to or from the day shift at comparable times of day. EDWSs more than tripled the odds of reporting sleep-related, inattentive, hazardous, or violation-driving events. The number and type of adverse event was predicted by the predrive KSS level and in a dose-dependent manner. Conclusions: Driving after an EDWS puts resident physicians/drivers and other road users at avoidable and unnecessary risk. Demonstrating self-reported sleepiness at the beginning of the drive is associated with adverse outcomes has serious implications on the legal accountability for driving when drowsy. © Sleep Research Society 2017