Eating during the biological night is associated with nausea.

OBJECTIVES: This study assessed whether there was a time-of-day effect on nausea reports in participants during studies employing circadian protocols. METHODS: Visual-analog-scales of nausea ratings were recorded from 34 participants (18-70years; 18 women) during forced desynchrony studies, where meals were scheduled at different circadian phases. Subjective nausea reports from a further 81 participants (18-35years; 36 women) were recorded during constant routine studies, where they ate identical isocaloric hourly snacks for 36-40 hours. RESULTS: Feelings of nausea varied by circadian phase in the forced desynchrony studies, peaking during the biological night. Nausea during the constant routine was reported by 27% of participants, commencing 2.9 ± 5.2 hours after the midpoint of usual sleep timing, but was never reported to start in the evening (4-9 PM). CONCLUSIONS: Nausea occurred more often during the biological night and early morning hours. This timing is relevant to overnight and early morning shift workers and suggests that a strategy to counteract that is to pay careful attention to meal timing.

Circadian protein expression patterns in healthy young adults.

OBJECTIVES: To explore how the blood plasma proteome fluctuates across the 24-hour day and identify a subset of proteins that show endogenous circadian rhythmicity. METHODS: Plasma samples from 17 healthy adults were collected hourly under controlled conditions designed to unmask endogenous circadian rhythmicity; in a subset of 8 participants, we also collected samples across a day on a typical sleep-wake schedule. A total of 6916 proteins were analyzed from each sample using the SomaScan aptamer-based multiplexed platform. We used differential rhythmicity analysis based on a cosinor model with mixed effects to identify a subset of proteins that showed circadian rhythmicity in their abundance. RESULTS: One thousand and sixty-three (15%) proteins exhibited significant daily rhythmicity. Of those, 431 (6.2%) proteins displayed consistent endogenous circadian rhythms on both a sleep-wake schedule and under controlled conditions: it included both known and novel proteins. When models were fitted with two harmonics, an additional 259 (3.7%) proteins exhibited significant endogenous circadian rhythmicity, indicating that some rhythmic proteins cannot be solely captured by a simple sinusoidal model. Overall, we found that the largest number of proteins had their peak levels in the late afternoon/evening, with another smaller group peaking in the early morning. CONCLUSIONS: This study reveals that hundreds of plasma proteins exhibit endogenous circadian rhythmicity in humans. Future analyses will likely reveal novel physiological pathways regulated by circadian clocks and pave the way for improved diagnosis and treatment for patients with circadian disorders and other pathologies. It will also advance efforts to include knowledge about time-of-day, thereby incorporating circadian medicine into personalized medicine.

Association of cortical arousals with sleep-disordered breathing events.

STUDY OBJECTIVES: The American Academy of Sleep Medicine recommends scoring hypopneas in adults when there is a ≥ 3% oxygen desaturation or when the event is associated with an arousal. However, there is no rule regarding the duration of the interval between the event termination and the associated arousal. The purpose of this study is to explore the timing between arousals and sleep-disordered breathing (SDB) events. METHODS: We analyzed cortical arousals (> 1.6 million) and SDB events (> 350,000 apneas and > 1.9 million hypopneas) from 11,400 manually scored polysomnography recordings. Only arousals that started within ±30 seconds from the end of SDB events were included. We used the 2 local minimums on either side of the arousal distribution as the start/end times for the distribution and to define which arousals are associated with SDB events. Finally, we calculated arousal probability near the end of SDB events. RESULTS: Cortical arousals with start times that fell within the 2 minimums were considered to be associated with SDB events. Using this definition, we found that 90% of apnea-associated arousals started no earlier than 4 seconds before and no later than 9 seconds after the end of apneas. Similarly, 90% of hypopnea-associated arousals started no earlier than 6 seconds before and no later than 14 seconds after the end of hypopneas, with the peak of the distribution coinciding with event end time. Arousal probability was highest during the first 10 seconds after the end of the event and was higher for longer events. CONCLUSIONS: Our results suggest that 90% of SDB-associated arousals start no earlier than 6 seconds before and no later than 14 seconds after the end of the respiratory events. CITATION: Zitting K-M, Lockyer BJ, Azarbarzin A, et al. Association of cortical arousals with sleep-disordered breathing events. J Clin Sleep Med. 2023;19(5):899-912.

Desynchronizing the sleep---wake cycle from circadian timing to assess their separate contributions to physiology and behaviour and to estimate intrinsic circadian period.

Circadian clocks drive cyclic variations in many aspects of physiology, but some daily variations are evoked by periodic changes in the environment or sleep-wake state and associated behaviors, such as changes in posture, light levels, fasting or eating, rest or activity and social interactions; thus, it is often important to quantify the relative contributions of these factors. Yet, circadian rhythms and these evoked effects cannot be separated under typical 24-h day conditions, because circadian phase and the length of time awake or asleep co-vary. Nathaniel Kleitman's forced desynchrony (FD) protocol was designed to assess endogenous circadian rhythmicity and to separate circadian from evoked components of daily rhythms in multiple parameters. Under FD protocol conditions, light intensity is kept low to minimize its impact on the circadian pacemaker, and participants have sleep-wake state and associated behaviors scheduled to an imposed non-24-h cycle. The period of this imposed cycle, Τ, is chosen so that the circadian pacemaker cannot entrain to it and therefore continues to oscillate at its intrinsic period (τ, ~24.15 h), ensuring circadian components are separated from evoked components of daily rhythms. Here we provide detailed instructions and troubleshooting techniques on how to design, implement and analyze the data from an FD protocol. We provide two procedures: one with general guidance for designing an FD study and another with more precise instructions for replicating one of our previous FD studies. We discuss estimating circadian parameters and quantifying the separate contributions of circadian rhythmicity and the sleep-wake cycle, including statistical analysis procedures and an R package for conducting the non-orthogonal spectral analysis method that enables an accurate estimation of period, amplitude and phase.

Increased sleep duration and delayed sleep timing during the COVID-19 pandemic.

Many studies have examined how the 2019 Coronavirus Disease (COVID-19) has impacted sleep health. Early evidence suggests that lockdown policies worldwide have led to changes in sleep timing, duration, and quality; however, few studies have attempted to look at the longer-term effects across multiple countries in a large data set. This study uses self-reported data from 64,858 users of the Sleep As Android smartphone application from around the world over a 24-month period in 2019 to 2020. We found a significant but modest increase in time in bed (TIB), as well as a significant delay in sleep timing that was especially prominent on weekdays. While this effect persisted throughout the year, differences in sleep timing were more widespread and pronounced in the earlier months of the pandemic. We observed a small overall increase in TIB when comparing 2020 to 2019, but these changes depended on location and time of year, suggesting that sleep duration may have more closely tracked the progression of the pandemic in each country. Our findings suggest that pandemic-induced changes in lifestyle, such as remote work and lockdown policies, may have facilitated later sleep timing but that these changes may diminish as restrictions are lifted.

Impact of chronic sleep restriction on sleep continuity, sleep structure, and neurobehavioral performance.

Chronic sleep restriction (CSR) has been associated with adverse effects including cognitive impairment and increased risk of diabetes and cardiovascular disease. Yet, sleep restriction therapy is an essential component of most behavioral treatments for insomnia. Moreover, little is known about the impact of CSR on sleep continuity and structure in healthy people whose need for sleep is satiated. We investigated the impact of CSR on sleep continuity and structure in nine healthy participants. They had 4 nights of sleep extension, 2 nights of post-extension sleep, 21 nights of CSR (5/5.6-hour time-in-bed), and 9 nights of recovery sleep. Compared to postextension sleep, during CSR sleep duration was reduced by 95.4 ±â€…21.2 min per night, Slow-Wave Activity was significantly increased, and sleep was more consolidated. During recovery, sleep duration was increased by 103.3 ±â€…23.8 min compared to CSR, and the CSR-induced increase in Slow-Wave Activity persisted, particularly after the 5-hour exposure. Yet, we found that sustained vigilant attention was not fully recovered even after nine nights of recovery sleep. Our results suggest that CSR improves traditional metrics of sleep quality and may have a persistent impact on sleep depth, which is consistent with the reported benefits on sleep continuity and structure of sleep restriction therapy. However, these improvements in traditional metrics of sleep quality were associated with deterioration rather than improvement in neurobehavioral performance, demonstrating that sleep duration should be included in assessments of sleep quality. These results have implications for the long-term use of sleep restriction in the behavioral treatment of insomnia. Clinical Trial Registration: Impact of Chronic Circadian Disruption vs. Chronic Sleep Restriction on Metabolism (https://clinicaltrials.gov/ct2/show/; #NCT02171273).

Chronic circadian disruption on a high-fat diet impairs glucose tolerance.

BACKGROUND: Nearly 14% of Americans experience chronic circadian disruption due to shift work, increasing their risk of obesity, diabetes, and other cardiometabolic disorders. These disorders are also exacerbated by modern eating habits such as frequent snacking and consumption of high-fat foods. METHODS: We investigated the effects of recurrent circadian disruption (RCD) on glucose metabolism in C57BL/6 mice and in human participants exposed to non-24-h light-dark (LD) schedules vs. those on standard 24-h LD schedules. These LD schedules were designed to induce circadian misalignment between behaviors including rest/activity and fasting/eating with the output of the near-24-h central circadian pacemaker, while minimizing sleep loss, and were maintained for 12 weeks in mice and 3 weeks in humans. We examined interactions of these circadian-disrupted schedules compared to control 24-h schedules with a lower-fat diet (LFD, 13% in mouse and 25-27% in humans) and high-fat diet (HFD, 45% in mouse and 45-50% in humans). We also used young vs. older mice to determine whether they would respond differently to RCD. RESULTS: When combined with a HFD, we found that RCD caused significant weight gain in mice and increased body fat in humans, and significantly impaired glucose tolerance and insulin sensitivity in both mice and humans, but this did not occur when RCD was combined with a LFD. This effect was similar in both young and older mice. CONCLUSION: These results in both humans and a model organism indicate that circadian disruption has an adverse effect on metabolism among individuals eating a high-fat Western-style diet, even in the absence of significant sleep loss, and suggest that reducing dietary fat may protect against the metabolic consequences of a lifestyle (such as shift work) that involves chronic circadian disruption.

Human thermal perception and time of day: A review.

The circadian clock regulates diurnal variations in autonomic thermoregulatory processes such as core body temperature in humans. Thus, we might expect that similar daily fluctuations also characterize human thermal perception, the ultimate role of which is to drive thermoregulatory behaviors. In this paper, we explore this question by reviewing experimental and observational thermal comfort investigations which include the "time of day" variable. We found only 21 studies considering this factor, and not always as their primary analysis. Due to the paucity of studies and the lack of a specific focus on time-of-day effects, the results are difficult to compare and appear on the whole contradictory. However, we observe a tendency for individuals to prefer higher ambient temperatures in the early evening as compared to the rest of the day, a result in line with the physiological decrease of the core body temperature over the evening. By drawing from literature on the physiology of thermoregulation and circadian rhythms, we outline some potential explanations for the inconsistencies observed in the findings, including a potential major bias due to the intensity and spectrum of the selected light conditions, and provide recommendations for conducting future target studies in highly-controlled laboratory conditions. Such studies are strongly encouraged as confirmed variations of human thermal perceptions over the day would have enormous impact on building operations, thus on energy consumption and occupant comfort. List of abbreviations: TSV: Thermal Sensation Vote; TCV: Thermal Comfort Vote; Tpref: Preferred Temperature; TA: Indoor Air Temperature; RH: Indoor Relative Humidity; Tskin: Skin Temperature; Tty: Tympanic Temperature; Tre: Rectal Temperature; Toral: Oral Temperature.

Chronic Sleep Restriction While Minimizing Circadian Disruption Does Not Adversely Affect Glucose Tolerance.

Insufficient sleep, which has been shown to adversely affect metabolism, is generally associated with prolonged exposure to artificial light at night, a known circadian disruptor. There is growing evidence suggesting that circadian disruption adversely affects metabolism, yet few studies have attempted to evaluate the adverse metabolic effects of insufficient sleep while controlling for circadian disruption. We assessed postprandial glucose and insulin responses to a standard breakfast meal in healthy adults (n = 9) who underwent 3 weeks of chronic sleep restriction (CSR) in a 37-day inpatient study while minimizing circadian disruption by maintaining the same duration of light exposure each study day. We compared these results to findings from an earlier inpatient study which used a forced desynchrony (FD) protocol to assess the influence of 3 weeks of CSR combined with recurrent circadian disruption (RCD) on glycemic control in healthy adults (n = 21). CSR combined with RCD resulted in significantly elevated postprandial plasma glucose levels (p < 0.0001), while CSR with minimized circadian disruption had no adverse glycemic effects after 3 weeks of exposure (EXP). These results suggest that one mechanism by which sleep restriction impacts metabolism may be via concurrent circadian disruption.

Google Trends reveals increases in internet searches for insomnia during the 2019 coronavirus disease (COVID-19) global pandemic.

STUDY OBJECTIVES: The 2019 coronavirus disease (COVID-19) has become a global health and economic crisis. Recent evidence from small samples suggest that it has increased mood and sleep disturbances, including insomnia, around the world. This study aimed to estimate the effect of COVID-19 on insomnia levels worldwide and in the United States during the acute phase of the pandemic. METHODS: We analyzed search query data recorded between January 2004 and May 2020 from Google Trends and Google Keyword Planner for the search term "insomnia". RESULTS: The number of search queries for insomnia has increased over the past decade and is greater than the number of search queries for other major sleep disorders. The COVID-19 pandemic increased search queries for insomnia both worldwide and in the United States, with the number in the United States increasing by 58% during the first 5 months of 2020 compared with the same months from the previous 3 years. There is a robust diurnal pattern in insomnia search queries in the United States, with the number of queries peaking around 3 am and the overall pattern remaining stable during the pandemic. CONCLUSIONS: These results highlight the impact the COVID-19 pandemic has had on sleep health and the urgent need for making effective interventions accessible. Future studies will be needed to determine whether the increase in insomnia symptoms will persist and lead to higher rates of chronic insomnia in the population.

Fasting blood triglycerides vary with circadian phase in both young and older people.

Daily rhythms in several physiological processes are important for cardiometabolic health. The lipid panel is used clinically to assess cardiovascular disease risk, but previous attempts to demonstrate circadian variation in lipids have failed to uncouple the endogenous circadian rhythm from the effects of meals and wake duration. Changes in basal lipid levels and dampening of circadian rhythms have been reported with aging, but it is unknown whether aging is also associated with changes in the rhythmic variation of lipids. We measured fasting lipid panels (triglycerides, total cholesterol, high-density lipoprotein, and low-density lipoprotein) in blood at wake time in 21 healthy adults using a specialized laboratory protocol that uncouples sleep-wake and activity-related effects from the endogenous circadian rhythm. Young and older adults exhibited endogenous circadian variations in fasting triglycerides, with both groups peaking in the early biological morning. Young adults also exhibited significant circadian rhythmicity in total cholesterol and low-density lipoprotein, while older adults did not exhibit circadian rhythmicity in any other lipids. These results reveal that triglyceride metabolism may be regulated by the central circadian pacemaker. Moreover, our findings may have clinical implications in assessing cardiovascular risk in shift workers and younger adults, since routine measurement of morning/fasting lipids may not fully and reliably assess triglyceride- and other lipid-related biomarkers of cardiovascular disease risk in these groups.

Human Resting Energy Expenditure Varies with Circadian Phase.

There is emerging evidence that circadian misalignment may alter energy expenditure, leading to obesity risk among those with irregular schedules [1-5]. It has been reported that energy expenditure is affected by the timing of sleep, exercise, and meals [6]. However, it is unclear whether the circadian system also modulates energy expenditure, independent of behavioral state and food intake. Here, we used a forced desynchrony protocol to examine whether fasted resting energy expenditure (REE) varies with circadian phase in seven participants. This protocol allowed us to uncouple sleep-wake and activity-related effects from the endogenous circadian rhythm, demonstrating that REE varies by circadian phase. REE is lowest at circadian phase ∼0°, corresponding to the endogenous core body temperature (CBT) nadir in the late biological night, and highest at circadian phase ∼180° in the biological afternoon and evening. Furthermore, we found that respiratory quotient (RQ), reflecting macronutrient utilization, also varies by circadian phase. RQ is lowest at circadian phase ∼240° and highest at circadian phase ∼60°, which corresponds to biological morning. This is the first characterization of a circadian profile in fasted resting energy expenditure and fasted respiratory quotient (with rhythmic profiles in both carbohydrate and lipid oxidation), decoupled from effects of activity, sleep-wake cycle, and diet in humans. The rhythm in energy expenditure and macronutrient metabolism may contribute to greater weight gain in shift workers and others with irregular schedules.

Young adults are more vulnerable to chronic sleep deficiency and recurrent circadian disruption than older adults.

More than a third of US adults report fewer than 6 hours of sleep a night, making chronic sleep restriction a growing public health concern. Sleep curtailment is associated with an increase in industrial accidents, motor vehicle accidents, medical and other occupational errors. Young adults are more vulnerable to acute sleep deprivation than older adults, but less is known about how young vs. older adults respond to the more commonly experienced chronic sleep restriction. To test the hypothesis that young adults are more vulnerable to chronic sleep loss than older adults, we compared data from young and older adults who underwent three weeks of chronic sleep restriction (equivalent to 5.6 hours/24 hours) combined with recurrent circadian disruption in an experiment that enabled us to separate the influences of the sleep-wake homeostatic process, the circadian timing system, and the chronic sleep deficit. We found that while young and older adults reported similar levels of subjective sleepiness, objective measures of sleepiness revealed that young adults were more vulnerable and had more attentional failures than the older adults. These results have important public health implications, particularly related to prevention of sleep-related motor vehicle crashes in young drivers. Further research is needed to understand the neurobiological basis of these age-related differences.

Aging and Circadian Rhythms.

Aging is associated with numerous changes, including changes in sleep timing, duration, and quality. The circadian timing system interacts with a sleep-wake homeostatic system to regulate human sleep, including sleep timing and structure. This article reviews key features of the human circadian timing system, age-related changes in the circadian timing system, and how those changes may contribute to the observed alterations in sleep.

A new face of sleep: The impact of post-learning sleep on recognition memory for face-name associations.

Sleep has been demonstrated to improve consolidation of many types of new memories. However, few prior studies have examined how sleep impacts learning of face-name associations. The recognition of a new face along with the associated name is an important human cognitive skill. Here we investigated whether post-presentation sleep impacts recognition memory of new face-name associations in healthy adults. Fourteen participants were tested twice. Each time, they were presented 20 photos of faces with a corresponding name. Twelve hours later, they were shown each face twice, once with the correct and once with an incorrect name, and asked if each face-name combination was correct and to rate their confidence. In one condition the 12-h interval between presentation and recall included an 8-h nighttime sleep opportunity ("Sleep"), while in the other condition they remained awake ("Wake"). There were more correct and highly confident correct responses when the interval between presentation and recall included a sleep opportunity, although improvement between the "Wake" and "Sleep" conditions was not related to duration of sleep or any sleep stage. These data suggest that a nighttime sleep opportunity improves the ability to correctly recognize face-name associations. Further studies investigating the mechanism of this improvement are important, as this finding has implications for individuals with sleep disturbances and/or memory impairments.

The Case for Addressing Operator Fatigue.

Sleep deficiency, which can be caused by acute sleep deprivation, chronic insufficient sleep, untreated sleep disorders, disruption of circadian timing, and other factors, is endemic in the U.S., including among professional and non-professional drivers and operators. Vigilance and attention are critical for safe transportation operations, but fatigue and sleepiness compromise vigilance and attention by slowing reaction times and impairing judgment and decision-making abilities. Research studies, polls, and accident investigations indicate that many Americans drive a motor vehicle or operate an aircraft, train or marine vessel while drowsy, putting themselves and others at risk for error and accident. In this chapter, we will outline some of the factors that contribute to sleepiness, present evidence from laboratory and field studies demonstrating how sleepiness impacts transportation safety, review how sleepiness is measured in laboratory and field settings, describe what is known about interventions for sleepiness in transportation settings, and summarize what we believe are important gaps in our knowledge of sleepiness and transportation safety.