Does Insomnia Cause Revenge Seeking Behavior? Using a Puzzle-Based Sleep Lab Educational Escape Room to Teach Circadian Rhythms in a Large Introductory Neuroscience Course.

Traditional large lecture classes can be passive experiences for students. Instead, imagine that several of those learners work at a sleep laboratory and admit four new patients. Within hours, the entire facility is on lockdown, and a mysterious voice on the intercom proclaims that all researchers will lose their ability to sleep within the next hour. This story is the plot of an interactive educational escape room (EER) where students work together and apply concepts related to the history of sleep research, circadian rhythms, and neurological concepts of sleep to solve puzzles. Conventionally, escape rooms are an entertainment experience that requires participants to escape a room in a limited timeframe. We have created a neuroscience EER designed to educate students about the neural basis of sleep, while providing small groups of students with an immersive and interactive experience. Students follow a specially designed digital escape room framework to review sleep pathways, researchers, and brain regions involved with sleep. Unlike conventional escape rooms that can accommodate a limited number of participants, this sleep lab EER is scalable to hundreds of students without the need for a specialized room. Puzzles are enhanced by digital technology that allows instructors to track the progress of every team and note how the entire classroom is doing. Students and teaching assistants had very positive experiences with this EER activity, reporting that the EER solidified course concepts while using creativity, collaboration, and critical thinking skills. We find that EERs are an easy, useful tool to increase engagement and boost inclusivity within large classroom settings, with potential to also be used as an assessment tool.

Sleep stability in isolated rapid eye movement sleep behavior disorder, Parkinson's disease, and dementia with Lewy bodies.

BACKGROUND: Non-REM sleep symptoms remain poorly understood in alpha-synucleinopathies. AIMS: The aims of the study were to compare sleep stability and transitions, arousals, and sleep cycle structure between isolated rapid eye movement (REM) sleep behavior disorder (iRBD), Parkinson's disease (PD), and dementia with Lewy Bodies (DLB). MATERIALS AND METHODS: Sleep transition and stability measures were assessed in one-night video-polysomnography records. Transition measures were the number of shifts between Wake and REM, Wake and NREM, and REM and NREM. Stability measures were the number of passages within the same sleep stage. We assessed arousals, the number/duration of sleep cycles (defined as a sequence of any NREM stage to REM), and the duration of N3 and REM sleep in each cycle. These variables were compared between two sets of groups (PD vs. DLB vs. iRBD and RDB+ vs. RBD-). RESULTS: We assessed 54 PD, 24 DLB, and 21 iRBD patients (54 RBD+, 22 RBD-). There were no significant differences regarding sleep stability measures. Arousal indices in N1 and N2 stages were significantly higher in PD compared with iRBD. 24% of the sample did not have any sleep cycle. PD had significantly fewer cycles than iRBD. Differences became non-significant when adjusting for medication. There was no effect of group or time of night in REM or N3 duration. There were no significant differences between RBD+ and RBD-. DISCUSSION: There were no significant differences in stability/transition measures. Arousals and disturbance in sleep cycling were higher in PD, but the difference was no longer significant after adjusting for medication. CONCLUSION: Different alpha-synucleinopathies have a similar degree of non-REM sleep instability, but medication could worsen symptoms in PD.

Chaperone Hsp70 (HSPA1) Is Involved in the Molecular Mechanisms of Sleep Cycle Integration.

The molecular mechanisms of sleep cycle integration at the beginning and the end of the inactive period are not clear. Sleep cycles with a predominance of deep slow-wave sleep (SWS) seem to be associated with accelerated protein synthesis in the brain. The inducible Hsp70 chaperone corrects protein conformational changes and has protective properties. This research explores (1) whether the Hspa1 gene encoding Hsp70 protein activates during the daily rapid-eye-movement sleep (REMS) maximum, and (2) whether a lower daily deep SWS maximum affects the Hspa1 expression level during the subsequent REMS. Combining polysomnography in male Wistar rats, RT-qPCR, and Western blotting, we reveal a three-fold Hspa1 upregulation in the nucleus reticularis pontis oralis, which regulates REMS. Hspa1 expression increases during the daily REMS maximum, 5-7 h after the natural peak of deep SWS. Using short-term selective REMS deprivation, we demonstrate that REMS rebound after deprivation exceeds the natural daily maximum, but it is not accompanied by Hspa1 upregulation. The results suggest that a high proportion of deep SWS, usually observed after sleep onset, is a necessary condition for Hspa1 upregulation during subsequent REMS. The data obtained can inform the understanding of the molecular mechanisms integrating SWS and REMS and key biological function(s) of sleep.

Immediate effects of phototherapy on sleep in very preterm neonates: an observational study.

Process C (internal clock) and Process S (sleep-wake homeostasis) are the basis of sleep-wake regulation. In the last trimester of pregnancy, foetal heart rate is synchronized with the maternal circadian rhythm. At birth, this interaction fails and an ultradian rhythm appears. Light exposure is a strong factor influencing the synchronization of sleep-wake processes. However, little is known about the effects of phototherapy on the sleep rhythm of premature babies. It was hypothesized that sleep in preterm infants would not differ during phototherapy, but that a maturation effect would be seen. Sleep states were studied in 38 infants born < 32 weeks gestational age and/or < 1 500 g birth weight. Videos of 3 h were taken over the first 5 days of life. Based on breathing and movement patterns, behavioural states were defined as: awake; active sleep; or quiet sleep. Videos with and without phototherapy were compared for amounts of quiet sleep and active states (awake + active sleep). No significant association between phototherapy and amount of quiet sleep was found (P = 0.083). Analysis of videos in infants not under phototherapy revealed an increase in time spent awake with increasing gestational age. The current data suggest that the ultradian rhythm of preterm infants seems to be independent of phototherapy, supporting the notion that sleep rhythm in this population is mainly driven by their internal clock.

Blue-Enriched Morning Light as a Countermeasure to Light at the Wrong Time: Effects on Cognition, Sleepiness, Sleep, and Circadian Phase.

Light during the day and darkness at night are crucial factors for proper entrainment of the human circadian system to the solar 24-h day. However, modern life and work styles have led to much more time spent indoors, often with lower daytime and higher evening/nighttime light intensity from electrical lighting than outdoors. Whether this has long-term consequences for human health is being currently investigated. We tested if bright blue-enriched morning light over several days could counteract the detrimental effects of inadequate daytime and evening lighting. In a seminaturalistic, within-between subject study design, 18 young participants were exposed to different lighting conditions on 3 evenings (blue-enriched, bright orange, or dim light), after exposure to 2 lighting conditions (mixed blue-enriched light and control light, for 3 days each) in the mornings. Subjective sleepiness, reaction times, salivary melatonin concentrations, and nighttime sleep were assessed. Exposure to the blue-enriched morning lighting showed acute wake-promoting effects and faster reaction times than with control lighting. Some of these effects persisted until the evening, and performance improved over several days. The magnitude of circadian phase shifts induced by combinations of 3 different evening and 2 morning lighting conditions were significantly smaller with the blue-enriched morning light. During the night, participants had longer total sleep times after orange light exposure than after blue light exposure in the evening. Our results indicate that bright blue-enriched morning light stabilizes circadian phase, and it could be an effective counterstrategy for poor lighting during the day and also light exposure at the wrong time, such as in the late evening.

Time-of-night variations in the story-like organization of dream experience developed during rapid eye movement sleep.

This study aimed to investigate the cycles (2nd/4th) and duration-related (5/10 min) variations in the story-like organization of dream experience elaborated during rapid eye movement (REM) sleep. Dream reports were analysed using story grammar rules. Reports were provided by those subjects (14 of 22) capable of reporting a dream after each of the four awakenings provoked in 2 consecutive nights during REM sleep of the 2nd and 4th cycles, after periods of either 5 or 10 min, counterbalanced across the nights. Two researchers who were blind as to the sleep condition scored the dream reports independently. The values of the indicators of report length (measured as value of total word count) and of story-like organization of dream reports were matched taking time-of-night (2nd and 4th cycles) and REM duration (5 versus 10 min) as factors. Two-way analyses of variance showed that report length increased significantly in 4th-cycle REM sleep and nearly significantly for longer REM duration, whereas the number of dream-stories per report did not vary. The indices of sequential (number of statements describing the event structure developed in the story) and hierarchical (number of episodes per story) organization increased significantly only in dream-stories reported after 10 min of 4th-cycle REM sleep. These findings indicate that the characteristics of structural organization of dream-stories vary along with time of night, and suggest that the elaboration of a long and complex dream-story requires a fairly long time and the availability of a great amount of cognitive resources to maintain its continuity and coherence.

Sleep Continuity, Stability and Cyclic Organization Are Impaired in Insomniacs: A Case-Control Study.

The possibility of distinguishing insomniacs from good sleepers based on polysomnography (PSG) remains an open question. While these groups show modest differences in traditional PSG parameters, some studies suggest that finer measures may be more useful. Here we assess differences between good sleepers (GS), poor sleepers (PS) and insomniacs (IN) in classical PSG measures as well as in sleep continuity, stability and cyclic organization. PSG-monitored sleep (two nights) of 17 IN (diagnosed through a standard clinical interview; Pittsburgh Sleep Quality Index (PSQI) ≥ 5, Insomnia Severity Index (ISI) > 14) was compared to that of 33 GS (PSQI < 5) and 20 PS (PSQI ≥ 5, ISI ≤ 14). Compared to GS, IN were impaired in sleep macrostructure (sleep latency, sleep efficiency, WASO%) and in continuity, stability and organization, whereas PS only showed disrupted continuity and stability. Spindle parameters were comparable between IN and GS, but the former displayed enhanced power in fast frequency bands. Our findings support the hypothesis of a continuum between individuals with self-reported poor sleep and insomniacs. Further, they add to extant data on impaired sleep continuity, stability and organization in poor sleepers and elderly individuals, underlining the utility of including these measures in standard sleep assessments.

Phenotypic Interindividual Differences in the Dynamic Structure of Sleep in Healthy Young Adults.

Introduction: Evaluating the dynamic structure of sleep may yield new insights into the mechanisms underlying human sleep physiology. Methods: We analyzed data from a 12-day, 11-night, strictly controlled laboratory study with an adaptation night, 3 iterations of a baseline night followed by a recovery night after 36 h of total sleep deprivation, and a final recovery night. All sleep opportunities were 12 h in duration (22:00-10:00) and recorded with polysomnography (PSG). The PSG records were scored for the sleep stages: rapid eye movement (REM) sleep; non-REM (NREM) stage 1 sleep (S1), stage 2 sleep (S2), and slow wave sleep (SWS); and wake (W). Phenotypic interindividual differences were assessed using indices of dynamic sleep structure - specifically sleep stage transitions and sleep cycle characteristics - and intraclass correlation coefficients across nights. Results: NREM/REM sleep cycles and sleep stage transitions exhibited substantial and stable interindividual differences that were robust across baseline and recovery nights, suggesting that mechanisms underlying the dynamic structure of sleep are phenotypic. In addition, the dynamics of sleep stage transitions were found to be associated with sleep cycle characteristics, with a significant relationship between the length of sleep cycles and the degree to which S2-to-W/S1 and S2-to-SWS transitions were in equilibrium. Discussion: Our findings are consistent with a model for the underlying mechanisms that involves three subsystems - characterized by S2-to-W/S1, S2-to-SWS, and S2-to-REM transitions - with S2 playing a hub-like role. Furthermore, the balance between the two subsystems within NREM sleep (S2-to-W/S1 and S2-to-SWS) may serve as a basis for the dynamic regulation of sleep structure and may represent a novel target for interventions aiming to improve sleep.

Order matters: sleep spindles contribute to memory consolidation only when followed by rapid-eye-movement sleep.

Sleep is known to benefit memory consolidation, but little is known about the contribution of sleep stages within the sleep cycle. The sequential hypothesis proposes that memories are first replayed during nonrapid-eye-movement (NREM or N) sleep and then integrated into existing networks during rapid-eye-movement (REM or R) sleep, two successive critical steps for memory consolidation. However, it lacks experimental evidence as N always precedes R sleep in physiological conditions. We tested this sequential hypothesis in patients with central hypersomnolence disorder, including patients with narcolepsy who present the unique, anti-physiological peculiarity of frequently falling asleep in R sleep before entering N sleep. Patients performed a visual perceptual learning task before and after daytime naps stopped after one sleep cycle, starting in N or R sleep and followed by the other stage (i.e. N-R vs. R-N sleep sequence). We compared over-nap changes in performance, reflecting memory consolidation, depending on the sleep sequence during the nap. Thirty-six patients who slept for a total of 67 naps were included in the analysis. Results show that sleep spindles are associated with memory consolidation only when N is followed by R sleep, that is in physiologically ordered N-R naps, thus providing support to the sequential hypothesis in humans. In addition, we found a negative effect of rapid-eye-movements in R sleep on perceptual consolidation, highlighting the complex role of sleep stages in the balance to remember and to forget.

'SleepCycles' package for R - A free software tool for the detection of sleep cycles from sleep staging.

The detection of NREM-REM sleep cycles in human sleep data (i.e., polysomnographically assessed sleep stages) enables fine-grained analyses of ultradian variations in sleep microstructure (e.g., sleep spindles, and arousals), or other amplitude- and frequency-specific electroencephalographic features during sleep. While many laboratories have software that is used internally, reproducibility requires the availability of open-source software. Therefore, we here introduce the 'SleepCycles' package for R, an open-source software package that identifies sleep cycles and their respective (non-) rapid eye movement ([N]REM) periods from sleep staging data. Additionally, each (N)REM period is subdivided into parts of equal duration (percentiles), which may be useful for further fine-grained analyses. The detection criteria used in the package are, with some adaptations, largely based on criteria originally proposed by Feinberg and Floyd (1979). The latest version of the package can be downloaded from the Comprehensive R Archives Network (CRAN).•The package 'SleepCycles' for R allows to identify sleep cycles and their respective NREM and REM periods from sleep staging results.•Besides the cycle detection, NREM and REM periods are also split into parts of equal duration (percentiles) thereby allowing for a better temporal resolution across the night and comparisons of sleep cycles with different durations amongst different night recordings.

Bayesian Model Search for Nonstationary Periodic Time Series.

We propose a novel Bayesian methodology for analyzing nonstationary time series that exhibit oscillatory behavior. We approximate the time series using a piecewise oscillatory model with unknown periodicities, where our goal is to estimate the change-points while simultaneously identifying the potentially changing periodicities in the data. Our proposed methodology is based on a trans-dimensional Markov chain Monte Carlo algorithm that simultaneously updates the change-points and the periodicities relevant to any segment between them. We show that the proposed methodology successfully identifies time changing oscillatory behavior in two applications which are relevant to e-Health and sleep research, namely the occurrence of ultradian oscillations in human skin temperature during the time of night rest, and the detection of instances of sleep apnea in plethysmographic respiratory traces. Supplementary materials for this article are available online.

Dynamics and Ultradian Structure of Human Sleep in Real Life.

The temporal dynamics that characterize sleep are difficult to capture outside the sleep laboratory. Therefore, longitudinal studies and big-data approaches assessing sleep dynamics are lacking. Here, we present the first large-scale analysis of human sleep dynamics in real life by making use of longitudinal wrist movement recordings of >16,000 sleep bouts from 573 subjects. Through non-linear conversion of locomotor activity to "Locomotor Inactivity During Sleep" (LIDS), movement patterns are exposed that directly reflect ultradian sleep cycles and replicate the dynamics of laboratory sleep parameters. Our current analyses indicate no sex differences in LIDS-derived sleep dynamics, whereas especially age but also shift work have pronounced effects, specifically on decline rates and ultradian amplitude. In contrast, ultradian period and phase emerged as remarkably stable across the tested variables. Our approach and results provide the necessary quantitative sleep phenotypes for large field studies and outcome assessments in clinical trials.

Age-Related Differences in Sleep Architecture and Electroencephalogram in Adolescents in the National Consortium on Alcohol and Neurodevelopment in Adolescence Sample.

STUDY OBJECTIVES: To investigate age-related differences in polysomnographic and sleep electroencephalographic (EEG) measures, considering sex, pubertal stage, ethnicity, and scalp topography in a large group of adolescents in the National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA). METHODS: Following an adaptation/clinical screening night, 141 healthy adolescents (12-21 y, 64 girls) had polysomnographic recordings, from which sleep staging and EEG measures were derived. The setting was the SRI International Human Sleep Laboratory and University of Pittsburgh Pediatric Sleep Laboratory. RESULTS: Older age was associated with a lower percentage of N3 sleep, accompanied by higher percentages of N2, N1, and rapid eye movement (REM) sleep. Older boys compared with younger boys had more frequent awakenings and wakefulness after sleep onset, effects that were absent in girls. Delta (0.3-4 Hz) EEG power in nonrapid eye movement NREM sleep was lower in older than younger adolescents at all electrode sites, with steeper slopes of decline over the occipital scalp. EEG power in higher frequency bands was also lower in older adolescents than younger adolescents, with equal effects across electrodes. Percent delta power in the first NREM period was similar across age. African Americans had lower EEG power across frequency bands (delta to sigma) compared with Caucasians. Finally, replacing age with pubertal status in the models showed similar relationships. CONCLUSIONS: Substantial differences in sleep architecture and EEG were evident across adolescence in this large group, with sex modifying some relationships. Establishment and follow-up of this cohort allows the investigation of sleep EEG-brain structural relationships and the effect of behaviors, such as alcohol and substance use, on sleep EEG maturation.

Change of mood during sleep and REM sleep variables.

Polysomnography was performed during two consecutive nights in 23 patients with major depression. After every final awakening patients estimated the change of their mood from evening to morning: 1. Mood worse in the morning than in the evening; 2. Mood does not change; 3. Mood better in the morning. When mood was estimated as being better in the morning (20% of all nights), eye movement density in REM sleep increased from the first to the fourth cycle. In all other nights eye movement density was slightly higher in the first than in subsequent cycles. Mood improvement correlated positively with eye movement density in the fourth cycle and negatively with REM sleep duration in the first cycle. Eye movement density in the first cycle correlated positively with the subjective estimation of sleep latency. A possible functional difference between initial and final REM sleep periods is proposed.