0302 Recovery Sleep in University Students

ABSTRACT‘How much sleep does one need?’ is a critical question that has been difficult to answer. The long history of sleep research has culminated in population‐derived normative values of 7 to 9 h of sleep per night to avoid dysfunction. Such a wide range is sufficiently large that one cannot know what is required for any given individual. ‘Sleep need’ cannot currently be directly measured, might not be represented by one number (given the multiple functions that sleep subserves), and likely varies from individual‐to‐individual and from day‐to‐day. This said, the concept should be embraced and can be considered alongside more easily operationalised and routinely measured constructs of ‘sleep opportunity’ (e.g., time in bed) and ‘sleep ability’ (i.e., the obtained sleep, such as sleep duration). Considering the dynamics of all three constructs together may drive greater understanding about sleep health, sleep insufficiency, and sleep disorder pathology. In this article, we describe a new theory called Sleep Opportunity, Need, and Ability and provide a rationale for why this theory has both theoretical and clinical value.

Extensive data implicate serotonin (5-hydroxytryptamine [5-HT]) in the regulation of sleep. Jouvet has hypothesized that 5-HT promotes wakefulness, yet is necessary for subsequent non-rapid eye movement (NREM) sleep, actions he proposes to be mediated by sleep factors. Studies in rat support this dual role for 5-HT. The objectives of this study were to (1) determine effects of serotonergic activation on sleep of mice and (2) elucidate a potential role for the cytokine interleukin-6 as a sleep factor mediating serotonergic effects on sleep. C57BL/6J and B6.129S6-II6(tm1Kopf)(interleukin-6 knockout [IL-6 KO]) mice were purchased from the Jackson Laboratory and instrumented for recording the electroencephalogram and body temperature. After recovery, separate groups of mice were injected intraperitoneally at either light or dark onset with vehicle or with the 5-HT precursor 5-hydroxytryptophan (5-HTP). Sleep-wake behavior was determined and body temperature recorded for 24 hours after injections. 5-HTP induced hypothermia in both mouse strains. When injected at dark onset, the highest dose of 5-HTP (200 mg/kg) increased NREM sleep. Light onset administration initially increased wakefulness, with increases in NREM sleep apparent only during the subsequent dark period. For most parameters, there were no differences in responses between strains. However IL-6 KO mice at some doses exhibited a greater increase in NREM sleep. 5-HTP alters sleep-wake behavior and body temperature of mice in a manner similar to that of rats. Increases in NREM sleep after 5-HTP are apparent only during the dark period, which may represent a fundamental property of the serotonergic system. These results suggest that 5-HT should not be considered either wake promoting or NREM sleep promoting. Rather, the role of 5-HT in the regulation of sleep-wake behavior must be considered within the context of the degree to which the system is activated and the time at which the activation occurs.

Environmental noise has been linked to negative health outcomes, like poor sleep, poor mental health, and cardiovascular disease, and likely accounts for more than 1 million disability-adjusted life years annually in Western Europe. Adolescence may be a particularly sensitive period for noise exposure due to an increased need for sleep, failure to meet sleep guidelines, and increased risk for first onset of some mental health disorders. However, the potential health effects of living in high-noise environments have not been studied in US adolescents, rarely in European adolescents, and mental health outcomes studied have not corresponded to diagnoses from the Diagnostic and Statistical Manual of Mental Disorders (DSM). Using a US-based nationally representative survey of urban adolescents (N = 4,508), we estimated associations of day-night average sound levels exceeding the US Environmental Protection Agency's 55 decibel limit with sleep outcomes and lifetime mental health DSM diagnoses. We implemented doubly robust targeted minimum loss-based estimation coupled with propensity score matching to account for numerous potential adolescent, household, and environmental confounders. Living in a high- versus low-noise Census block group was associated with later bedtimes on weeknights (0.48 hours, 95% confidence interval [CI] = -0.15, 1.12) and weekend nights (0.65 hours, 95% CI = 0.37, 0.93), but not with total hours slept. Associations between living in a high- versus low-noise Census block group and mental disorders were mixed, with wide CIs, and not robust to sensitivity analyses. We find evidence for an association between residence in a high-noise area and later bedtimes among urban adolescents but no consistent evidence of such an association with mental health disorders.

To characterize sleep duration, timing and continuity measures in pregnancy and their association with key demographic variables. Multisite prospective cohort study. Women enrolled in the nuMoM2b study (nulliparous women with a singleton gestation) were recruited at the second study visit (16-21 weeks of gestation) to participate in the Sleep Duration and Continuity substudy. Women <18 years of age or with pregestational diabetes or chronic hypertension were excluded from participation. Women wore a wrist activity monitor and completed a sleep log for 7 consecutive days. Time in bed, sleep duration, fragmentation index, sleep efficiency, wake after sleep onset, and sleep midpoint were averaged across valid primary sleep periods for each participant. Valid data were available from 782 women with mean age of 27.3 (5.5) years. Median sleep duration was 7.4 hours. Approximately 27.9% of women had a sleep duration of <7 hours; 2.6% had a sleep duration of >9 hours. In multivariable models including age, race/ethnicity, body mass index, insurance status, and recent smoking history, sleep duration was significantly associated with race/ethnicity and insurance status, while time in bed was only associated with insurance status. Sleep continuity measures and sleep midpoint were significantly associated with all covariates in the model, with the exception of age for fragmentation index and smoking for wake after sleep onset. Our results demonstrate the relationship between sleep and important demographic characteristics during pregnancy.

Sleep is important for processing memories and emotions. It is widely assumed that during sleep, particularly during slow-wave sleep (SWS), newly acquired memory traces are spontaneously reactivated, thereby supporting their consolidation and stabilization. Beyond memory traces, the Memories-of-Sleep (MemoSleep-) Hypothesis suggests that cognitive concepts are also reactivated during sleep. The repeated reactivations of these concepts potentially influence sleep quality by either impairing or improving sleep, depending on the particular content of these concepts. However, it remains unclear whether memory reactivations occur primarily during SWS or whether the non-rapid eye movement (NREM) sleep stage N2 is also involved. Additionally, the exact nature of sleep disturbances induced by unfamiliar environments, particularly over non-consecutive nights, has not yet been fully characterized and explained by the MemoSleep-Hypothesis. Finally, the influence of emotions on sleep within the context of the MemoSleep-Hypothesis remains to be clarified. This dissertation addresses these research gaps through three independent sleep studies. The first study investigated the contribution of memory reactivation during NREM sleep stage N2 compared to SWS. However, no significant difference was found between words that were externally reactivated during N2 and those reactivated during SWS. Moreover, there was no overall memory benefit from targeted memory reactivation (TMR) during sleep. The second study examined sleep disturbances during the first night in an unfamiliar environment, known as the First-Night Effect (FNE), as an example of the reactivation of stressful mental concepts during sleep. The results show that an FNE exists also in non-consecutive nights and even occurs in familiar environments. However, prior familiarization with the recording equipment was found to attenuate the FNE. The third study explored, for the first time, whether musical chords associated with varying emotional ratings can elicit different brain responses during sleep. The results confirmed that the sleeping brain is capable of differentially processing specific musical chords. The results of this dissertation challenge the specific role of SWS in memory reactivation during sleep. Additionally, they demonstrate that unfamiliar sleep environments generally impact sleep quality, however, a habituation occurs even over non-consecutive nights. Finally, these findings pave the way for novel approaches to using emotion-associated musical stimuli to influence activated mental concepts during sleep, providing new knowledge and a foundation for further refinements and future research directions within the framework of the MemoSleep-Hypothesis.

Sleep-wake behavior and responses to sleep deprivation of mice lacking both interleukin-1β receptor 1 and tumor necrosis factor-α receptor 1

Effects of traumatic brain injury (TBI) on hypocretin neurons and sleep of mice

IntroductionDuring sleep periods, most mammals alternate multiple times between rapid-eye-movement (REM) sleep and non-REM (NREM) sleep. A common theory proposes that these transitions are governed by an “hourglass-like” homeostatic need to enter REM sleep that accumulates during the inter-REM interval and partially discharges during REM sleep. However, markers or mechanisms for REM homeostatic pressure remain undetermined. Recently, an analysis of sleep in mice demonstrated that the cumulative distribution function (CDF) of the amount of NREM sleep between REM bouts correlates with REM bout duration, suggesting that time in NREM sleep influences REM sleep need. Here, we build on those results and construct a predictive measure for the propensity to enter REM sleep as a function of time in NREM sleep since the previous REM episode.MethodsThe REM propensity measure is precisely defined as the probability to enter REM sleep before the accumulation of an additional pre-specified amount of NREM sleep.ResultsAnalyzing spontaneous sleep in mice, we find that, as NREM sleep accumulates between REM bouts, the REM propensity exhibits a peak value and then decays to zero with further NREM accumulation. We show that the REM propensity at REM onset predicts features of the subsequent REM bout under certain conditions. Specifically, during the light phase and for REM propensities occurring before the peak in propensity, the REM propensity at REM onset is correlated with REM bout duration, and with the probability of the occurrence of a short REM cycle called a sequential REM cycle. Further, we also find that proportionally more REM sleep occurs during sequential REM cycles, supporting a correlation between high values of our REM propensity measure and high REM sleep need.DiscussionThese results support the theory that a homeostatic need to enter REM sleep accrues during NREM sleep, but only for a limited range of NREM sleep accumulation.

The pineal hormone melatonin is a popular treatment for sleep and circadian rhythm disruption. Melatonin administered at optimal times of the day for treatment often results in a prolonged melatonin profile. In photoperiodic (day length-dependent) species, changes in melatonin profile duration influence the timing of seasonal rhythms. We investigated the effects of an artificially prolonged melatonin profile on endogenous melatonin and cortisol rhythms, wrist actigraphy, and reproductive hormones in humans. Eight healthy men took part in this double-blind, crossover study. Surge/sustained release melatonin (1.5 mg) or placebo was administered for 8 d at the beginning of a 16-h sleep opportunity (1600 h to 0800 h) in dim light. Compared with placebo, melatonin administration advanced the timing of endogenous melatonin and cortisol rhythms. Activity was reduced in the first half and increased in the second half of the sleep opportunity with melatonin; however, total activity during the sleep opportunities and wake episodes was not affected. Melatonin treatment did not affect the endogenous melatonin profile duration, pituitary/gonadal hormone levels (24-h), or sleepiness and mood levels on the subsequent day. In the short term, suitably timed sustained-release melatonin phase-shifts circadian rhythms and redistributes activity during a 16-h sleep opportunity, with no evidence of changes in the duration of endogenous melatonin secretion or pituitary/gonadal hormones.

To determine whether variation in sleep duration reflects variation in sleep need or self-imposed sleep restriction. After habitual bedrest duration of participants was assessed during a 2-week outpatient protocol, volunteers were scheduled to sleep according to this schedule for 1 week prior to and the first night after admission to a general clinical research center. The inpatient protocol included multiple sleep latency testing on the second day and sleep recordings during a bedrest extension protocol that included 16 hours of sleep opportunity (12 hours at night and 4 hours at midday) for 3 consecutive days. Outpatient monitoring followed by inpatient assessment of sleep. Seventeen healthy volunteers (10 women) aged 18-32 years without clinical sleep disorders. Extension of sleep opportunity. The habitual bedrest duration varied from 6.1 to 10.3 hours. Individuals with shorter habitual bedrest duration fell asleep more quickly and frequently during the multiple sleep latency test than did those with longer habitual bedrest duration. On the first day of extended sleep opportunity, the total sleep time of all individuals was greater than their habitual bedrest duration; the average increase in total sleep time was 4.9 hours (P = 0.001). The increase in total sleep time declined across the 3 day bedrest-extension protocol (P = 0.003 for trend). During the third day of increased sleep opportunity, the total sleep time was negatively associated with habitual bedrest duration (P = 0.005); individuals with shorter habitual bedrest duration continued to sleep more than those with longer habitual bedrest duration. Those individuals with shorter habitual sleep durations carry a higher sleep debt than do those with longer habitual sleep duration. Interindividual variation in sleep duration may primarily reflect variation in self-selected sleep restriction or wake extension.

Caffeine During Sleep Deprivation: Sleep Tendency and Dynamics of Recovery Sleep in Rats

Introduction Characterizing habitual sleep patterns in children and adolescents is challenging due to the well-documented variability inherent in standard assessment methods, which often yield poor to moderate internal consistency. This quality control study aimed to evaluate the internal consistency of habitual sleep assessment methods (questionnaire, sleep diary, and accelerometry) using data from the Interacting Mechanisms of SLeep and Endurance Exercise in Pediatrics (iSLEEP) study, an ancillary project of the UCI pediatric Molecular Transducers of Physical Activity Consortium (MoTrPAC). Additionally, it examined whether incorporating sleep/wake pattern parameters into sleep continuity measures improve internal consistency. Methods Seventy-seven healthy children and adolescents (Mage=15.0±2.3 years, 62.3%f) completed the iSLEEP MoTrPAC ancillary study including questionnaire [School Sleep Habit Survey (SSHS)] and 7-14 days of accelerometry (Actiwatch) with daily sleep diaries. Sleep continuity variables [i.e., sleep onset/offset times, midsleep time, total sleep time (TST), and sleep efficiency (SE)], were derived from SSHS, diary, and accelerometry (using standardized scoring approaches that include the diary). Behavioral sleep/wake patterns were estimated using UP/DOWN times/slopes, deriving from Shape Language Modeling (SLM) using minute-by-minute activity counts. Internal consistency (Cronbach’s alpha) and reliability coefficients were computed. Factor analyses identified latent structures which were correlated between measurement approaches, and the contribution of sleep/wake pattern correlation metrics to traditional sleep continuity measures from accelerometry was evaluated. Results Sleep continuity measures from diaries (α=0.63) and accelerometry (α=0.65) demonstrated similar moderate internal consistency, while questionnaire showed expected poor consistency (α=0.21). Behavioral sleep/wake pattern variables (UP/DOWN times/slopes) showed good and acceptable internal consistency (α=0.78). Factor analyses identified two key components solutions for sleep continuity measures in diaries and accelerometry: Factor 1: sleep timing (onset, offset, midsleep; p’s&amp;lt; 0.001) and Factor 2: TST and SE (p’s&amp;lt; 0.001). Factors were significantly correlated between the measurement approaches (timing factor, r=0.87; TST/SE factor, r=0.50, p’s&amp;lt; 0.001). Integrating behavioral sleep/wake pattern variables with the traditional accelerometry-derived sleep continuity measures resulted in strong internal consistency (α=0.83). Conclusion Diary and accelerometry exhibited comparable internal structure and validity of habitual sleep pattern characterization in children and adolescents. Incorporating behavioral sleep/wake activity patterns alongside traditional sleep continuity measures enhances validity measures. Support (if any) Support: R01 HL153807, U01 AR071158, PERC Systems Biology Program.

Do night naps impact driving performance and daytime recovery sleep?

Introduction Circadian phase and homeostatic sleep drive affect selective visual attention during sleep inertia (SI), a period of cognitive performance decrement upon awakening that dissipates with time. This study examined the combined effects of circadian misalignment and sleep restriction on visual search performance during SI. Methods Twenty adults (mean±standard deviation [SD] age 25.7±4.2 years; 12M, 8F) completed a 39-day protocol. Prior to a 4-day in-laboratory visit, participants maintained habitual 8h sleep schedules for 2 weeks at home. In-laboratory sleep opportunities (1 per day) were timed to induce varying levels of both circadian misalignment and sleep restriction: 8h on night 1, 3h on night 2, and 3h on mornings 3 and 4. After 3 days of recovery sleep at home (unscheduled), participants repeated the entire protocol. SI was assessed with the Serial Visual Search Task, a measure of selective visual attention, ~ 1, 16, and 31 min after electroencephalogram (EEG) verified awakening following each 3h sleep opportunity. The task required participants to determine whether a target was present or absent among nontarget distractors. Outcomes included median reaction times (RT) and number of missed targets. Sleep opportunities with ≥4.5 min of EEG-verified wakefulness in the 30 min prior to scheduled awakening were excluded from analysis. Data were analyzed with mixed-model ANOVA. Results Mean±SD average amount of wakefulness in the 30 min and 10 min prior to SI testing was 1.2±0.11 and 0.43±0.06 minutes, respectively. Following all sleep opportunities, median RT for overall correct responses and for correct response to target absent trials improved with time since awakening (all p&amp;lt;0.05). In contrast, median RT for correct responses to target present trials improved and number of missed targets worsened with time since awakening following the morning 3 sleep opportunity only (all p&amp;lt;0.05). Conclusion Reaction speed was impaired during SI regardless of circadian timing or level of homeostatic sleep drive, whereas missing targets appears to be dependent upon circadian phase and the level of homeostatic sleep debt. These findings have important implications for military and first responders. Support (If Any) Office of Naval Research MURI N00014-15-1-2809; NIH TR001082; Undergraduate Research Opportunities Grant, University of Colorado Boulder.

The ventral subiculum regulates emotion, stress responses, and spatial and social cognition. In our previous studies, we have demonstrated anxiety- and depression-like symptoms, deficits in spatial and social cognition in ventral subicular lesioned (VSL) rats, and restoration of affective and cognitive behaviors following photoperiod manipulation (short photoperiod regime, SPR; 6:18 LD cycle). In the present study, we have studied the impact of VSL on sleep-wake behavioral patterns and the effect of SPR on sleep-wakefulness behavior. Adult male Wistar rats subjected to VSL demonstrated decreased wake duration and enhanced total sleep time due to increased non-rapid eye movement sleep (NREMS) and rapid eye movement sleep (REMS). Power spectral analysis indicated increased delta activity during NREMS and decreased sigma band power during all vigilance states. Light is one of the strongest entrainers of the circadian rhythm, and its manipulation may have various physiological and functional consequences. We investigated the effect of 21-day exposure to SPR on sleep-wakefulness (S-W) behavior in VSL rats. We observed that SPR exposure restored S-W behavior in VSL rats, resulting in an increase in wake duration and a significant increase in theta power during wake and REMS. This study highlights the crucial role of the ventral subiculum in maintaining normal sleep-wakefulness patterns and highlights the effectiveness of photoperiod manipulation as a non-pharmacological treatment for reversing sleep disturbances reported in mood and neuropsychiatric disorders like Alzheimer's disease, bipolar disorder, and major depressive disorder, which also involve alterations in circadian rhythm.