Partial Sleep Loss Research Articles

Cumulative sleep restriction and subsequent recovery sleep: Effects on subjective sleepiness, vigilance, and executive functions

Objective: Cumulative partial sleep loss is more often practical eventually among aircrew. The sleep loss encountered on the weekdays is generally compensated by taking restorative sleep on the weekends. This study aimed to examine the subjective appreciation of sleepiness and cognitive performance pertaining to vigilance and executive functions during cumulative sleep restriction for a period of 05 days and then following 3 consecutive nights of recovery sleep. Material and Methods: In a repeated measures design, 14 healthy volunteers were longitudinally followed up twice on a day (morning and afternoon) on their subjective sleepiness (Stanford Sleepiness Scale), vigilance, and executive functions (Mackworth Clock Test and Stroop Test of Psychometric Evaluation Design for Aviators test battery, respectively) over a period of 5 days with 2 h of sleep restriction each night. These parameters were again assessed following 3 consecutive nights of restorative recovery sleep. Results: Subjective appreciation of sleepiness was significantly increased by accumulating sleep debt (F = 8.368, P < 0.001). Stroop Effect and Reaction Time did not show any significant changes; however, cumulative sleep loss significantly affected accuracy measures (F = 2.388, P = 0.04) and attention lapses (F = 2.816, P = 0.018). Following restorative sleep, the subjective sleepiness and accuracy scores did not show any significant difference from that of baseline. However, lapses continued to be significantly higher than the baseline values (P = 0.012). Conclusion: Cumulative sleep loss over a period of 5 days resulted in more sleepiness and a decrement in vigilance measures even though the executive functions remained intact. The persistence of attention lapses indicated incomplete recovery of vigilance functions following 3 days of restorative sleep.

0226 Effect of Wake Extension and Short Recovery Sleep on Objective Vigilance and Subjective Sleepiness in Young Adolescents

Abstract Introduction Adolescents routinely experience insufficient sleep. Compared to adults, less is known regarding how wake extension and recovery sleep impact objective and subjective indexes of vigilance in youth. Here we explore these questions using acute wake extension. Methods Twenty-two 10–13-year-old children (12.03±1.14 years, 12F) completed a week of actigraphy-monitored at-home sleep stabilization (9.5h TIB). Participants then slept in the laboratory with polysomnography for a baseline (BSL) opportunity of 9.5h (21:00-06:30) and returned the subsequent evening for wake extension (WE) to 02:30 and a 4h recovery sleep opportunity (02:30-06:30). Participants completed performance testing batteries including a 5-minute tablet-based visual adaptation of the psychomotor vigilance task (PVT; BrainBaseline) and introspective ratings at 20:00 and 07:30, as well as at three additional times during WE: 22:00, 00:00, and 01:30. The current analyses focused on PVT reciprocal reaction time (RRT: 1/RT) and the Stanford Sleepiness Scale (SSS) ratings. Results One-way ANOVA across WE (20:00, 22:00, 00:00, 01:30) showed a main effect of time for slower reaction times as participants remained awake (m±sd [1/s] 20:00: 2.01±0.32; 22:00: 1.84±0.33; 00:00: 1.79±0.29; 01:30: 1.71±0.34; F(3,63)=13.78, p<.05, ηp2= .40). After recovery sleep, RRTs at 07:30 (1.69±0.31) were slower than those at 07:30 after baseline sleep (1.95±0.36) (t(21)=5.46, p<.001) and did not differ from 01:30 during WE (t(21)=0.64, p=0.53), indicating persistent impairment after recovery sleep. A main effect of time during WE was also seen for the SSS (20:00: 1.77±0.69; 22:00: 3.36±1.71; 00:00: 4.14±1.21; 01:30: 5.68±1.25; F(3,63)=56.80, p<.001, ηp2= .73). Morning SSS scores were higher (sleepier) on WE (2.24±1.30) than BSL (1.71±0.90) (t(20)=2.45, p=.024). However, unlike RRTs, morning SSS scores were also significantly lower (less sleepy) at 07:30 following recovery sleep compared to 01:30 during WE (t(21)=9.80, p<.001). Conclusion Vigilance performance and sleepiness after 13.5 until 19 h awake worsened and PVT performance did not improve after 4h recovery sleep; however, perceived sleepiness after 4h recovery sleep decreased. This incongruent performance and perception confirms the vulnerability of youth to even partial sleep loss. Our next analyses will consider inattention phenotypes and recovery sleep physiology as potential moderators of these effects. Support (if any) K01MH109854, P20GM139743

An urgent proposal for the immediate use of melatonin as an adjuvant to anti- SARS-CoV-2 vaccination

Competition among pharmaceutical companies to develop safe and effective vaccines against SARS-CoV-2 is high. However, based on the prior experience with the influenza vaccine, up to 50% in lack of effectiveness would be found among healthy adults receiving effective vaccines against SARS-CoV-2. There is growing evidence that insufficient sleep may potentially be a pervasive and prominent factor accounting for this variability. Individuals experiencing total or partial sleep loss exhibit markedly reduced antigen-specific antibodies as compared to healthy sleepers. Besides, pre-vaccination sleep quality is also an important contributing factor. Several meta-analyses and expert consensus reports support the view that the chronobiotic/hypnotic properties of melatonin are useful in patients with primary sleep disorders to decrease sleep onset latency and to increase total sleep time. Hence, the prescription of melatonin for at least 2 weeks prior to vaccination can be a useful approach to improve sleep quality and to ensure that the vaccination is performed at a moment of optimal sleep conditions. Moreover, melatonin enhances the immune response to vaccines by increasing peripheral blood CD4+ T cells and IgG-expressing B cells. Administration of exogenous melatonin could increase the potency of the immune response and the duration of the immunity induced by the vaccine. Besides, melatonin could also prevent adverse effects of the vaccination due to its antioxidant and immunomodulatory properties. Therefore, the administration of melatonin from 2 weeks to at least 4 weeks after vaccination may constitute an effective means to enhance the efficacy of vaccination against SARS-CoV-2.

Partial and Total Sleep Deprivation Interferes With Neural Correlates of Consolidation of Fear Extinction Memory

BackgroundWe assessed the impact of total and partial sleep loss on neural correlates of fear conditioning, extinction learning, and extinction recall in healthy young adults. MethodsParticipants (56.3% female, age 24.8 ± 3.4 years) were randomized to a night of normal sleep (NS) (n = 48), sleep restriction (SR) (n = 53), or sleep deprivation (SD) (n = 53). All completed fear conditioning and extinction learning phases the following morning. Extinction recall was tested in the evening of the same day. Task-based contrasts were modeled at the beginning of, at the end of, and across the fear conditioning and extinction learning phases, and at the beginning of extinction recall. These contrasts were compared among the 3 groups by means of analysis of variance. Nonparametric permutation corrected analyses using a cluster-determining threshold of p < .005 and a familywise error of p < .05. ResultsAt the end of fear conditioning, NS activated medial prefrontal regions, SR activated motor areas, and participants in the SD group showed no significant activations. Across extinction learning, only NS activated both salience (fear) and extinction (regulatory) areas. For extinction recall, SD activated similar regions as NS across extinction learning, while SR activated salience and motor areas. During early fear conditioning, compared with NS, SD activated more medial prefrontal and SR activated more salience network areas. For extinction recall, NS activated more prefrontal areas and SD activated more of both salience- and extinction-related areas than SR. ConclusionsRelative to NS, SR may enhance fear-related and diminish extinction-related activity, whereas SD may delay engagement of extinction learning. Findings may have clinical implications for populations and occupations in which sleep loss is common.

0312 Performance on a Cognitive Interference Task in Children After One-Night of Sleep Restriction

Abstract Introduction Short sleep contributes to attention failure in conditions such as ADHD. Whether sleep loss affects attentional processes as a task varies in cognitive interference is unclear. We used a multi-source interference task (MSIT) in a sleep restriction paradigm in children with a range of ADHD symptoms to examine how short sleep disrupts attention in these youth. Methods Thirteen children (7F, 11.7±1.28 years) with a range of ADHD symptom severity completed a repeated-measures experiment on two consecutive nights in the laboratory: baseline (BSLN; 9.5h time-in-bed) and sleep restriction (SR; 4h time-in-bed). Each morning they took part in an fMRI session including the MSIT, in which participants respond to a series of 3-digit numbers by indicating which digit is different on no-interference (e.g., 003; correct=3) or interference (e.g., 311, correct=3) trials. Performance measures were inverse reaction time (1/RT) and accuracy. A two-way within-subject ANOVA assessed performance across interference and sleep conditions respectively. Results 1/RT showed main-effects of sleep loss (BSLN vs. SR; F(1,148)=4.01;p&amp;lt;0.05;η 2=0.026) and trial type (no-interference vs. interference; F(1,148)=24.7;p&amp;lt;0.001;η 2=0.143). Responses were slower for interference (BSLN RT: 799.3ms, SR RT: 895.8ms) than no-interference (BSLN RT: 653.2ms, SR RT: 697.4ms) trials. No interaction between interference and sleep loss was found (F(1,148)=0.11;p&amp;gt;0.05;η 2=0.001). Likewise, accuracy was lower (F(1,148) = 31.1, p&amp;lt;.001;η 2=0.174) in interference trials (73.5%) than in no-interference trials (92.2%), however with no effect of sleep loss, nor an interaction of interference and sleep loss (all p’s &amp;gt; .05). Conclusion These data provide evidence that partial sleep loss disrupts attention processes in children, yet these differences do not appear to depend on cognitive interference in our sample. Future analyses will examine whether ADHD symptoms distinguish individual differences, as well as analyze fMRI data to probe neural processes underlying attention control. Support K01MH09854 (to JMS); Brown University UTRA (to GDQC).

0317 Impact of Recurrent Partial Sleep Loss Combined with Acute Exercise on Circulating and Adipose Tissue Levels of Leptin, Adiponectin and Ghrelin in Healthy Young Individuals

Abstract Introduction Chronic sleep loss and aerobic exercise have opposing effects on body weight maintenance. The effects of sleep loss on circulating levels of the orexigenic hormone ghrelin and the anorexigenic hormone leptin have been extensively studied. In contrast, how these changes interact with acute exercise, and whether these changes are reflected at the tissue level, remains poorly understood. Methods In a randomized, 2 session, crossover design, 16 normal-weight young men were studied following three nights of partial sleep deprivation (4.25 hr sleep opportunity each night) and three nights of normal sleep (8.5-h sleep opportunity), monitored in a sleep laboratory. Each condition was followed by 30 min of intense morning ergometer cycling. Plasma levels of leptin and ghrelin, as well adipose tissue mRNA levels of leptin and adiponectin, were measured before and after each exercise intervention. Results In response to acute exercise, circulating levels of both leptin (ANOVA time effect: P&amp;lt;0.001) and ghrelin (time: P&amp;lt;0.001) decreased immediately (+15 min), and remained significantly lower +30, +60 and +240 min post exercise for leptin (all P&amp;lt;0.05), and up until +30 min post exercise for ghrelin. These effects were seen regardless of sleep condition (ANOVA sleep condition: P&amp;gt;0.10). In adipose tissue, mRNA expression of leptin and adiponectin was not different between the sleep conditions (ANOVA sleep condition: P&amp;gt;0.10). In contrast, mRNA levels of leptin decreased (P=0.017), whereas adiponectin mRNA increased (P=0.010) 3.5 hours post vs. pre exercise. The decrease in leptin in response to exercise appeared to mainly occur following sleep loss (P=0.066) and not after normal sleep (P=0.38). Conclusion Our results suggest that both circulating and adipose tissue levels of appetite-regulating hormones are altered in response to acute aerobic exercise, in a manner that does not depend on prior sleep history. Whether these findings apply to older, female, or metabolically ill individuals - and whether they may differ in response to circadian misalignment, or evening exercise - remains to be established. Support The Swedish Society for Medical Research, the Swedish Society of Medicine, the Swedish Research Council and the Göran Gustafsson; Swedish Brain; Åke Wiberg and NovoNordisk Foundations.

Association between Quality of Sleep and its Effect on Glycemic Control in Patients with Type 2 Diabetes Mellitus- A Pilot Study

Diabetes mellitus is a common metabolic disease. Nowadays, sleep complaints are increasing day by day due to the restriction in bed time resulting in chronic partial sleep loss.(1)Type 2 diabetes mellitus accounts for 95% of all of diagnosed diabetes worldwide. Several studies have recognized sleep disorder as a novel risk factor for diabetes.(2)Sleep disorder plays a vital role in the development of diabetes via various metabolic and neuroendocrine pathways.(3) Nocturia and neuropathic pain were explained as two possible causes of decreased sleep quality.(1) People who have sleep disorder either in the quality or quantity experienced reduced insulin sensitivity, which results in elevated blood glucose that can aggravate the progress of diabetes. There are limited studies from India on the association of sleep quality and diabetes control status. In this study, we aimed to find the quality of sleep in patients with type 2 diabetes mellitus and its correlation with glycaemic control.

The impact of sleep deprivation on declarative memory.

Sleep plays a crucial role in memory stabilization and integration, yet many people obtain insufficient sleep. This review assesses what is known about the level of sleep deprivation that leads to impairments during encoding, consolidation and retrieval of declarative memories, and what can be determined about the underlying neurophysiological processes. Neuroimaging studies that deprived sleep after learning have provided some of the most compelling evidence for sleep's role in the long-term reorganization of memories in the brain (systems consolidation). However, the behavioral consequences of losing sleep after learning-shown by increased forgetting-appear to recover over time and are unaffected by more common forms of partial sleep restriction across several nights. The capacity to encode new memories is the most vulnerable to sleep loss, since long-term deficits have been observed after total and partial sleep deprivation, while retrieval mechanisms are relatively unaffected. The negative impact of sleep loss on memory has been explored extensively after a night of total sleep deprivation, but further research is needed on the consequences of partial sleep loss over many days so that impairments may be generalized to more common forms of sleep loss.

Caffeine dosing strategies to optimize alertness during sleep loss.

Sleep loss, which affects about one-third of the US population, can severely impair physical and neurobehavioural performance. Although caffeine, the most widely used stimulant in the world, can mitigate these effects, currently there are no tools to guide the timing and amount of caffeine consumption to optimize its benefits. In this work, we provide an optimization algorithm, suited for mobile computing platforms, to determine when and how much caffeine to consume, so as to safely maximize neurobehavioural performance at the desired time of the day, under any sleep-loss condition. The algorithm is based on our previously validated Unified Model of Performance, which predicts the effect of caffeine consumption on a psychomotor vigilance task. We assessed the algorithm by comparing the caffeine-dosing strategies (timing and amount) it identified with the dosing strategies used in four experimental studies, involving total and partial sleep loss. Through computer simulations, we showed that the algorithm yielded caffeine-dosing strategies that enhanced performance of the predicted psychomotor vigilance task by up to 64% while using the same total amount of caffeine as in the original studies. In addition, the algorithm identified strategies that resulted in equivalent performance to that in the experimental studies while reducing caffeine consumption by up to 65%. Our work provides the first quantitative caffeine optimization tool for designing effective strategies to maximize neurobehavioural performance and to avoid excessive caffeine consumption during any arbitrary sleep-loss condition.

Sleep restriction progress to cardiac autonomic imbalance

Previous studies have shown that night shift work is thought to be a risk factor for cardiovascular disease and inadequate sleep is a common feature of night shift work. Since it’s more difficult to maintain adequate sleep duration among night watchmen during their working schedule, hence the purpose of our present study was to investigate whether mental stress or fatigue over restricted sleep period in night shift, affects HRV, in order to elucidate on cardiac autonomic modulation among nigh watchmen. With the purpose of this, autonomic activity determined from the levels of the heart rate variability (HRV), and also measured, body mass index (BMI), body fat percentage from skin fold thickness (biceps, triceps, and sub-scapular, supra-iliac) among normal sleep watchmen) (n=28) and restricted sleep watchmen (n=28) at first (1st) day, fourth (4th) day and seventh (7th) day of restricted sleep period. We observed that among restricted sleep individuals, sleepiness was significant increase at 4th day and 7th day when compare to normal sleep individuals, and, there was significant increase in, mean NN, VLF, LF, LF(nu), LF/HF AND significant decrease in SDNN, RMSSD, TSP, HF, and HF(nu) at 4th and 7th day of restricted sleep period. In addition to, this variable was more significant increase on 7th day, when compare with 4th day. As well as there was significant negative correlation between LF(nu) and HF(nu) at subsequent 4th day [r (48)=−0.84; P=0.01] and 7th day[r (48)=−0.95; P=0.01] of restricted sleep period. However we didn’t observe any significant variation in BMI, and body fat percentage among restricted sleep individuals when compare to normal sleep individuals with in this restricted sleep periods. Hence we concluded that partial sleep loss may cause autonomic imbalance represented by increased sympathetic and decreased parasympathetic activity; as revealed by altered HRV indices observed in this study.

0071 ROLE OF SLEEP RESTRICTION IN ADIPOCYTE INSULIN SENSITIVITY DURING AN INTRAVENOUS GLUCOSE TOLERANCE TEST IN HEALTHY ADULT MEN

Sleep restriction, or chronic partial sleep loss, increases obesity and diabetes risk by disrupting glucose metabolism and reducing whole-body insulin sensitivity without a compensatory increase in insulin secretion. Healthy adipocytes suppress hormone sensitive lipase (HSL) activity in response to insulin, which severely limits non-esterified fatty acid (NEFA) release. Elevated overnight NEFA levels are correlated with the reduction in insulin sensitivity that occurs in sleep restriction. Additionally, subcutaneous adipose biopsies from sleep-restricted subjects have reduced pAKT, evidence that sleep restriction decreases insulin sensitivity in adipocytes. The objective of this pilot study was to extend previous findings of the effects of sleep restriction on plasma glucose to mechanistic shifts within adipocyte metabolism. Subjects (20–35 y/o) were enrolled in an 11-day in-lab protocol; light exposure, activity, temperature, and diet were carefully controlled. An intravenous glucose tolerance test (IVGTT) was performed at three time points: after three nights of baseline sleep (10 hrs/night), after five nights of sleep restriction (5 hrs/night), and after two nights of recovery sleep (10 hrs/night). NEFA were quantified (Wako Diagnostics) and parameters describing NEFA kinetics (i.e. rate of NEFA production, utilization, suppression threshold) in the Boston and Moate minimal model were calculated using WinSAAM Compartmental Modeling software. Five subjects completed the sleep restriction protocol; one did not complete IVGTT procedures for safety reasons. Preliminary results from four subjects show the fractional rate of NEFA utilization was increased by 0.024 [0.009, 0.039] min-1 in the restricted condition (p=0.008). Restriction also increased the modifier of the inhibitory effect of remote glucose on NEFA production by 4.3 fold [1.2, 15.9] from baseline (p=0.04). Sleep restriction induces symmetrical changes in both glucose and lipid markers of insulin sensitivity in vivo. Preliminary evidence indicates that NEFA rate of utilization is increased in response to sleep restriction. In the context of whole-body metabolism, this indicates a shift in Randle cycle fuel selection by metabolic tissues. Additionally, a greater concentration of glucose was required to initiate NEFA suppression, evidence that sleep restriction functionally impairs HSL activity. UL1TR000127 (Chang PI) T32GM108563 (to KMN; Korzick PI).

Absorbed in sleep: Dissociative absorption as a predictor of sleepiness following sleep deprivation in two high-functioning samples.

In recent years, a labile sleep-wake cycle has been implicated as a cause for dissociative experiences, and studies show that dissociation is elevated following sleep deprivation. Dissociative individuals may find it harder to regulate sleepiness in the face of sleep disruption. Although there is significant variability in reactions to sleep deprivation, research on trait predictors is scarce. The present study examined the ability of trait dissociation to prospectively predict sleepiness following sleep loss and recovery sleep. Two high-functioning samples, namely, Remotely Piloted Aircraft officers (N=29) and Air Force jet pilots (N=57) completed state and trait questionnaires assessing sleep and dissociation before and after full or partial sleep loss. Dissociative absorption was a consistent predictor of an increase in sleepiness following sleep loss and following recovery sleep, controlling for baseline sleepiness levels. We discuss the findings in light of a difficulty to regulate and monitor consciousness states.

The effects of sleep restriction and sleep deprivation in producing false memories

False memory has been claimed to be the result of an associative process of generalisation, as well as to be representative of memory errors. These can occur at any stage of memory encoding, consolidation, or retrieval, albeit through varied mechanisms. The aim of this paper is to experimentally determine: (i) if cognitive dysfunction brought about by sleep loss at the time of stimulus encoding can influence false memory production; and (ii) whether this relationship holds across sensory modalities. Subjects undertook both the Deese-Roedigger-McDermott (DRM) false memory task and a visual task designed to produce false memories. Performance was measured while subjects were well-rested (9h Time in Bed or TIB), and then again when subjects were either sleep restricted (4h TIB for 4 nights) or sleep deprived (30h total SD). Results indicate (1) that partial and total sleep loss produced equivalent effects in terms of false and veridical verbal memory, (2) that subjects performed worse after sleep loss (regardless of whether this was partial or total sleep loss) on cued recognition-based false and veridical verbal memory tasks, and that sleep loss interfered with subjects’ ability to recall veridical, but not false memories under free recall conditions, and (3) that there were no effects of sleep loss on a visual false memory task. This is argued to represent the dysfunction and slow repair of an online verbal associative process in the brain following inadequate sleep.

Associations between Sleep Duration and Indicators of Cardiometabolic Disease in Canadian Children and Adolescents: Analyses of the 2007-2009 Canadian Health Measures Survey.

Indicators of cardiometabolic disease-including obesity, hyperinsulinemia, and dyslipidemia-are associated with an increased risk of cardiovascular disease and type 2 diabetes. Rates of obesity and type 2 diabetes in Canadian children and adolescents have increased rapidly in recent years; research exploring modifiable risk factors is critical. Experimental and epidemiological research demonstrates that partial sleep loss is linked with deteriorations in indicators of cardiometabolic health. The objectives of this study are (1) to examine associations between short sleep duration and indicators of cardiometabolic disease in Canadian children and adolescents and (2) to identify determinants of short sleep duration in this population. Logistic regression models were developed to examine associations between sleep duration and indicators of cardiometabolic disease and to identify predictors of short sleep duration. Compared with longer sleepers, children and adolescents with short sleep duration had greater odds of being overweight or obese. Sex- and age-stratified analyses indicated that short sleep duration was linked with greater odds of overweight/obesity in boys and adolescents only. Short sleepers did not have greater odds of having hyperinsulinemia, low HDL cholesterol, or high triglycerides. Age was a strong predictor of inadequate sleep duration. Future studies should include longitudinal designs that address whether short sleep duration in boys and in adolescents contributes directly to the development of overweight and obesity.

Effects of partial sleep deprivation on slow waves during non-rapid eye movement sleep: A high density EEG investigation

ObjectiveChanges in slow waves during non-rapid eye movement (NREM) sleep in response to acute total sleep deprivation are well-established measures of sleep homeostasis. This investigation utilized high-density electroencephalography (hdEEG) to examine topographic changes in slow waves during repeated partial sleep deprivation. MethodsTwenty-four participants underwent a 6-day sleep restriction protocol. Spectral and period-amplitude analyses of sleep hdEEG data were used to examine changes in slow wave energy, count, amplitude, and slope relative to baseline. ResultsChanges in slow wave energy were dependent on the quantity of NREM sleep utilized for analysis, with widespread increases during sleep restriction and recovery when comparing data from the first portion of the sleep period, but restricted to recovery sleep if the entire sleep episode was considered. Period-amplitude analysis was less dependent on the quantity of NREM sleep utilized, and demonstrated topographic changes in the count, amplitude, and distribution of slow waves, with frontal increases in slow wave amplitude, numbers of high-amplitude waves, and amplitude/slopes of low amplitude waves resulting from partial sleep deprivation. ConclusionsTopographic changes in slow waves occur across the course of partial sleep restriction and recovery. SignificanceThese results demonstrate a homeostatic response to partial sleep loss in humans.

The Effects of Sleep Continuity Disruption on Positive Mood and Sleep Architecture in Healthy Adults.

The purpose of this study was to test an experimental model of the effects of sleep continuity disturbance on sleep architecture and positive mood in order to better understand the mechanisms linking insomnia and depression. Participants were randomized to receive 3 consecutive nights of sleep continuity disruption via forced nocturnal awakenings (FA, n = 21), or one of two control conditions: restricted sleep opportunity (RSO, n = 17) or uninterrupted sleep (US, n = 24). The study was set in an inpatient clinical research suite. Healthy, good-sleeping men and women were included. Polysomnography was used to measure sleep architecture, and mood was assessed via self-report each day. Compared to restricted sleep opportunity controls, forced awakenings subjects had significantly less slow wave sleep (P < 0.05) after the first night of sleep deprivation, and significantly lower positive mood (P < 0.05) after the second night of sleep deprivation. The differential change in slow wave sleep statistically mediated the observed group differences in positive mood (P = 0.002). To our knowledge, this is the first human experimental study to demonstrate that, despite comparable reductions in total sleep time, partial sleep loss from sleep continuity disruption is more detrimental to positive mood than partial sleep loss from delaying bedtime, even when controlling for concomitant increases in negative mood. With these findings, we provide temporal evidence in support of a putative biologic mechanism (slow wave sleep deficit) that could help explain the strong comorbidity between insomnia and depression.

A single night of partial sleep loss impairs fasting insulin sensitivity but does not affect cephalic phase insulin release in young men.

The present study sought to investigate whether a single night of partial sleep deprivation (PSD) would alter fasting insulin sensitivity and cephalic phase insulin release (CPIR) in humans. A rise in circulating insulin in response to food-related sensory stimulation may prepare tissues to break down ingested glucose, e.g. by stimulating rate-limiting glycolytic enzymes. In addition, given insulin's anorexigenic properties once it reaches the brain, the CPIR may serve as an early peripheral satiety signal. Against this background, in the present study 16 men participated in two separate sessions: one night of PSD (4.25 h sleep) versus one night of full sleep (8.5 h sleep). In the morning following each sleep condition, subjects' oral cavities were rinsed with a 1-molar sucrose solution for 45 s, preceded and followed by blood sampling for repeated determination of plasma glucose and serum insulin concentrations (-3, +3, +5, +7, +10 and +20 min). Our main result was that PSD, compared with full sleep, was associated with significantly higher peripheral insulin resistance, as indicated by a higher fasting homeostasis model assessment of insulin resistance index (+16%, P = 0.025). In contrast, no CPIR was observed in any of the two sleep conditions. Our findings indicate that a single night of PSD is already sufficient to impair fasting insulin sensitivity in healthy men. In contrast, brief oral cavity rinsing with sucrose solution did not change serum insulin concentrations, suggesting that a blunted CPIR is an unlikely mechanism through which acute sleep loss causes metabolic perturbations during morning hours in humans.

Sleep deprivation and divergent toll-like receptor-4 activation of cellular inflammation in aging.

Sleep disturbance and aging are associated with increases in inflammation, as well as increased risk of infectious disease. However, there is limited understanding of the role of sleep loss on age-related differences in immune responses. This study examines the effects of sleep deprivation on toll-like receptor activation of monocytic inflammation in younger compared to older adults. Community-dwelling adults (n = 70) who were categorized as younger (25-39 y old, n = 21) and older (60-84 y old, n = 49) participants, underwent a sleep laboratory-based experimental partial sleep deprivation (PSD) protocol including adaptation, an uninterrupted night of sleep, sleep deprivation (sleep restricted to 03:00-07:00), and recovery. Blood samples were obtained each morning to measure toll-like receptor-4 activation of monocyte intracellular production of the inflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). Partial sleep deprivation induced a significant increase in the production of IL-6 and/or TNF-α that persisted after a night of recovery sleep (F(2,121.2) = 3.8, P < 0.05). Age moderated the effects of sleep loss, such that younger adults had an increase in inflammatory cytokine production that was not present in older adults (F(2,121.2) = 4.0, P < 0.05). Older adults exhibit reduced toll-like receptor 4 stimulated cellular inflammation that, unlike in younger adults, is not activated after a night of partial sleep loss. Whereas sleep loss increases cellular inflammation in younger adults and may contribute to inflammatory disorders, blunted toll-like receptor activation in older adults may increase the risk of infectious disease seen with aging.

Role of orexin in respiratory and sleep homeostasis during upper airway obstruction in rats.

Chronic upper airway obstruction (UAO) elicits a cascade of complex endocrine derangements that affect growth, sleep, and energy metabolism. We hypothesized that elevated hypothalamic orexin has a role in maintaining ventilation during UAO, while at the same time altering sleep-wake activity and energy metabolism. Here, we sought to explore the UAO-induced changes in hypothalamic orexin and their role in sleep-wake balance, respiratory activity, and energy metabolism. The tracheae of 22-day-old Sprague-Dawley rats were surgically narrowed; UAO and sham-operated control animals were monitored for 7 weeks. We measured food intake, body weight, temperature, locomotion, and sleep-wake activity. Magnetic resonance imaging was used to quantify subcutaneous and visceral fat tissue volumes. In week 7, the rats were sacrificed and levels of hypothalamic orexin, serum leptin, and corticosterone were determined. The effect of dual orexin receptor antagonist (almorexant 300 mg/kg) on sleep and respiration was also explored. UAO increased hypothalamic orexin mRNA and protein content by 64% and 65%, respectively. UAO led to 30% chronic sleep loss, excessive active phase sleepiness, decreased body temperature, increased food intake, reduction of abdominal and subcutaneous fat tissue volume, and growth retardation. Administration of almorexant normalized sleep but induced severe breathing difficulties in UAO rats, while it had no effect on sleep or on breathing of control animals. In upper airway obstruction animals, enhanced orexin secretion, while crucially important for respiratory homeostasis maintenance, is also responsible for chronic partial sleep loss, as well as considerable impairment of energy metabolism and growth.

Sleep Loss and the Inflammatory Response in Mice Under Chronic Environmental Circadian Disruption

Shift work and trans-time zone travel lead to insufficient sleep and numerous pathologies. Here, we examined sleep/wake dynamics during chronic exposure to environmental circadian disruption (ECD), and if chronic partial sleep loss associated with ECD influences the induction of shift-related inflammatory disorder. Sleep and wakefulness were telemetrically recorded across three months of ECD, in which the dark-phase of a light-dark cycle was advanced weekly by 6 h. A three month regimen of ECD caused a temporary reorganization of sleep (NREM and REM) and wake processes across each week, resulting in an approximately 10% net loss of sleep each week relative to baseline levels. A separate group of mice were subjected to ECD or a regimen of imposed wakefulness (IW) aimed to mimic sleep amounts under ECD for one month. Fos-immunoreactivity (IR) was quantified in sleep-wake regulatory areas: the nucleus accumbens (NAc), basal forebrain (BF), and medial preoptic area (MnPO). To assess the inflammatory response, trunk blood was treated with lipopolysaccharide (LPS) and subsequent release of IL-6 was measured. Fos-IR was greatest in the NAc, BF, and MnPO of mice subjected to IW. The inflammatory response to LPS was elevated in mice subjected to ECD, but not mice subjected to IW. Thus, the net sleep loss that occurs under ECD is not associated with a pathological immune response.