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This article makes a case for examining dying person's visions during wakefulness and their dreams during sleep as separate and unique phenomena. The reason being that the mode of experience, for example, being visited by a deceased loved one while awake and conscious vs having a deceased loved one appear in a dream while asleep, may have a different impact on the dying person. A better understanding of the content and impact of waking visions and sleeping dreams, respectively, may be beneficial to both dying persons and their families., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objectives: Many sleep-wake behaviors have been associated with cognition. We examined a panel of sleep-wake/activity characteristics to determine which are most robustly related to having low cognitive performance in midlife. Secondarily, we evaluate the predictive utility of sleep-wake measures to screen for low cognitive performance., Methods: The outcome was low cognitive performance defined as being >1 standard deviation below average age/sex/education internally normalized composite cognitive performance levels assessed in the Hispanic Community Health Study/Study of Latinos. Analyses included 1006 individuals who had sufficient sleep-wake measurements about 2years later (mean age=54.9, standard deviation= 5.1; 68.82% female). We evaluated associations of 31 sleep-wake variables with low cognitive performance using separate logistic regressions., Results: In individual models, the strongest sleep-wake correlates of low cognitive performance were measures of weaker and unstable 24-hour rhythms; greater 24-hour fragmentation; longer time-in-bed; and lower rhythm amplitude. One standard deviation worse on these sleep-wake factors was associated with ∼20%-30% greater odds of having low cognitive performance. In an internally cross-validated prediction model, the independent correlates of low cognitive performance were: lower Sleep Regularity Index scores; lower pseudo-F statistics (modellability of 24-hour rhythms); lower activity rhythm amplitude; and greater time in bed. Area under the curve was low/moderate (64%) indicating poor predictive utility., Conclusion: The strongest sleep-wake behavioral correlates of low cognitive performance were measures of longer time-in-bed and irregular/weak rhythms. These sleep-wake assessments were not useful to identify previous low cognitive performance. Given their potential modifiability, experimental trials could test if targeting midlife time-in-bed and/or irregular rhythms influences cognition., (Copyright © 2024 National Sleep Foundation. Published by Elsevier Inc. All rights reserved.)

Sleep is a vital restorative process that has occupied our curiosity for millennia. Despite our longstanding research efforts, the biology of sleep and its connection to mental states remains enigmatic. Unsurprisingly, sleep and wakefulness, the fundamental processes between which our mental states oscillate, are inseparable from our physical and mental health. Thus, clinical consideration of sleep impairments warrants a transdiagnostic approach whilst appropriately acknowledging that certain individual disorders (e.g. depression, schizophrenia) may have somewhat distinct sleep disturbances. Moreover, our knowledge of the anatomy and physiology of sleep regulation-albeit limited-forms the foundation for current treatments for sleep difficulties. This pictorial article overviews the core concepts and future of sleep neuroscience and mental state biology for trainees and practitioners in psychiatry and related professions., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Sleep disruption is a frequent problem of advancing age, often accompanied by low-grade chronic central and peripheral inflammation. We examined whether chronic neuroinflammation in the preoptic and basal forebrain area (POA-BF), a critical sleep-wake regulatory structure, contributes to this disruption. We developed a targeted viral vector designed to overexpress tumor necrosis factor-alpha (TNFα), specifically in astrocytes (AAV5-GFAP-TNFα-mCherry), and injected it into the POA of young mice to induce heightened neuroinflammation within the POA-BF. Compared to the control (treated with AAV5-GFAP-mCherry), mice with astrocytic TNFα overproduction within the POA-BF exhibited signs of increased microglia activation, indicating a heightened local inflammatory milieu. These mice also exhibited aging-like changes in sleep-wake organization and physical performance, including (a) impaired sleep-wake functions characterized by disruptions in sleep and waking during light and dark phases, respectively, and a reduced ability to compensate for sleep loss; (b) dysfunctional VLPO sleep-active neurons, indicated by fewer neurons expressing c-fos after suvorexant-induced sleep; and (c) compromised physical performance as demonstrated by a decline in grip strength. These findings suggest that inflammation-induced dysfunction of sleep- and wake-regulatory mechanisms within the POA-BF may be a critical component of sleep-wake disturbances in aging., Competing Interests: The authors declare no conflicts of interest.

Objectives: This study investigated oral behaviors in various temporomandibular disorder (TMD) subtypes, assessing their frequency, extent, and associations with both jaw functional status and psychological distress., Materials and Methods: Anonymized data from consecutive "initial-visit" TMD patients at a university-affiliated oral medicine clinic were obtained. Alongside demographic information, patients completed various questionnaires including the Diagnostic Criteria for TMD (DC/TMD) Symptom Questionnaire, Oral Behavior Checklist (OBC), Jaw Functional Limitation Scale-20 (JFLS-20), Patient Health Questionnaire-9 (PHQ-9), and General Anxiety Disorder Scale-7 (GAD-7). Patients underwent a protocolized clinical examination and received diagnoses of pain-related (PT), intra-articular (IT), or combined (CT) TMD using the DC/TMD diagnostic algorithms. Data were evaluated with Chi-square/non-parametric tests and logistic regression analyses (α = 0.05)., Results: The study comprised 700 patients (mean age 37.4 ± 15.7 years), with 12.6%, 15.1%, and 72.3% diagnosed with PT, IT, and CT, respectively. For all TMD subtypes, oral activities during sleep were more prevalent than those during wakefulness. While variations in total/subscale OBC scores were insignificant, substantial differences were observed in global/subscale JFLS (PT, CT > IT), depression (PT, CT > IT), and anxiety (CT > IT) scores. Near-moderate correlations (r s  = 0,36-0.39) were discerned between overall/waking-state non-functional oral behaviors and depression/anxiety. Multivariate analysis indicated that the odds of different TMD subtypes were influenced by sex, age, and jaw functional status., Conclusions: For all TMD patients, sleep-related oral activities were more commonly reported than waking-state activities. Factors such as sex, age, and jaw functional limitation are associated with the likelihood of different TMD subtypes., Statement of Clinical Relevance: Oral behaviors, in themselves, do not predict distinct TMD subtypes, in contrast to factors such as sex, age, and jaw functional status., (© 2024. The Author(s).)

Wearable sleep-tracking technology is of growing use in the sleep and circadian fields, including for applications across other disciplines, inclusive of a variety of disease states. Patients increasingly present sleep data derived from their wearable devices to their providers and the ever-increasing availability of commercial devices and new-generation research/clinical tools has led to the wide adoption of wearables in research, which has become even more relevant given the discontinuation of the Philips Respironics Actiwatch. Standards for evaluating the performance of wearable sleep-tracking devices have been introduced and the available evidence suggests that consumer-grade devices exceed the performance of traditional actigraphy in assessing sleep as defined by polysomnogram. However, clear limitations exist, for example, the misclassification of wakefulness during the sleep period, problems with sleep tracking outside of the main sleep bout or nighttime period, artifacts, and unclear translation of performance to individuals with certain characteristics or comorbidities. This is of particular relevance when person-specific factors (like skin color or obesity) negatively impact sensor performance with the potential downstream impact of augmenting already existing healthcare disparities. However, wearable sleep-tracking technology holds great promise for our field, given features distinct from traditional actigraphy such as measurement of autonomic parameters, estimation of circadian features, and the potential to integrate other self-reported, objective, and passively recorded health indicators. Scientists face numerous decision points and barriers when incorporating traditional actigraphy, consumer-grade multi-sensor devices, or contemporary research/clinical-grade sleep trackers into their research. Considerations include wearable device capabilities and performance, target population and goals of the study, wearable device outputs and availability of raw and aggregate data, and data extraction, processing, and analysis. Given the difficulties in the implementation and utilization of wearable sleep-tracking technology in real-world research and clinical settings, the following State of the Science review requested by the Sleep Research Society aims to address the following questions. What data can wearable sleep-tracking devices provide? How accurate are these data? What should be taken into account when incorporating wearable sleep-tracking devices into research? These outstanding questions and surrounding considerations motivated this work, outlining practical recommendations for using wearable technology in sleep and circadian research., (© The Author(s) 2023. Published by Oxford University Press on behalf of Sleep Research Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Sleep deprivation enhances risk for serious injury and fatality on the roads and in workplaces. To facilitate future management of these risks through advanced detection, we developed and validated a metabolomic biomarker of sleep deprivation in healthy, young participants, across three experiments. Bi-hourly plasma samples from 2 × 40-hour extended wake protocols (for train/test models) and 1 × 40-hour protocol with an 8-hour overnight sleep interval were analyzed by untargeted liquid chromatography-mass spectrometry. Using a knowledge-based machine learning approach, five consistently important variables were used to build predictive models. Sleep deprivation (24 to 38 hours awake) was predicted accurately in classification models [versus well-rested (0 to 16 hours)] (accuracy = 94.7%/AUC 99.2%, 79.3%/AUC 89.1%) and to a lesser extent in regression ( R = 86.1 and 47.8%) models for within- and between-participant models, respectively. Metabolites were identified for replicability/future deployment. This approach for detecting acute sleep deprivation offers potential to reduce accidents through "fitness for duty" or "post-accident analysis" assessments.2 = 86.1 and 47.8%) models for within- and between-participant models, respectively. Metabolites were identified for replicability/future deployment. This approach for detecting acute sleep deprivation offers potential to reduce accidents through "fitness for duty" or "post-accident analysis" assessments.

The sleep-wake cycle is determined by circadian and sleep homeostatic processes. However, the molecular impact of these processes and their interaction in different brain cell populations are unknown. To fill this gap, we profiled the single-cell transcriptome of adult Drosophila brains across the sleep-wake cycle and four circadian times. We show cell type-specific transcriptomic changes, with glia displaying the largest variation. Glia are also among the few cell types whose gene expression correlates with both sleep homeostat and circadian clock. The sleep-wake cycle and sleep drive level affect the expression of clock gene regulators in glia, and disrupting clock genes specifically in glia impairs homeostatic sleep rebound after sleep deprivation. These findings provide a comprehensive view of the effects of sleep homeostatic and circadian processes on distinct cell types in an entire animal brain and reveal glia as an interaction site of these two processes to determine sleep-wake dynamics., (© 2024. The Author(s).)

Objectives: Facial recognition is one of the key functions of the human brain, and linking a face to a name is critical in many social and occupational settings. This study assessed circadian- and wake-dependent effects on face-name recognition in healthy adults., Methods: Thirteen healthy adults (20-70years; 7 F) were studied in a 39-day inpatient protocol that included 3weeks of 28 hours forced desynchrony with sleep restriction (6.5:21.5 hours sleep:wake). Starting 3 hours after scheduled wake, 6 novel face-name pairs were presented every 4 waking hours; recognition was tested 2 hours later. Performance data were averaged across ∼4 hours circadian phase or time-awake bins., Results: Face-name recognition deteriorated with increased time awake (p < .0001) and exhibited significant circadian variation (p < .0001), with worst performance shortly after the core temperature nadir. There was a significant interaction between sex and circadian phase (p = .0177), with women performing significantly better than men at all circadian phases except 60° and 120°. Women exhibited a significantly higher amplitude than men during the third week of forced desynchrony (p < .01)., Conclusions: Like many other aspects of neurobehavioral performance, recalling face-name associations is impacted by both duration of time awake and circadian phase. These results have implications for face recognition testing in medical contexts, such as in testing for dementia, because performance may be impacted by sleep deficiency and the time of testing., (Copyright © 2024 National Sleep Foundation. Published by Elsevier Inc. All rights reserved.)

Functional connectivity (FC) during sleep has been shown to break down as non-rapid eye movement (NREM) sleep deepens before returning to a state closer to wakefulness during rapid eye movement (REM) sleep. However, the specific spatial and temporal signatures of these fluctuations in connectivity patterns remain poorly understood. This study aimed to investigate how frequency-dependent network-level FC fluctuates during nocturnal sleep in healthy young adults using high-density electroencephalography (hdEEG). Specifically, we examined source-localized FC in resting-state networks during NREM2, NREM3 and REM sleep (sleep stages scored using a semi-automatic procedure) in the first three sleep cycles of 29 participants. Our results showed that FC within and between all resting-state networks decreased from NREM2 to NREM3 sleep in multiple frequency bands and all sleep cycles. The data also highlighted a complex modulation of connectivity patterns during the transition to REM sleep whereby delta and sigma bands hosted a persistence of the connectivity breakdown in all networks. In contrast, a reconnection occurred in the default mode and the attentional networks in frequency bands characterizing their organization during wake (i.e., alpha and beta bands, respectively). Finally, all network pairs (except the visual network) showed higher gamma-band FC during REM sleep in cycle three compared to earlier sleep cycles. Altogether, our results unravel the spatial and temporal characteristics of the well-known breakdown in connectivity observed as NREM sleep deepens. They also illustrate a complex pattern of connectivity during REM sleep that is consistent with network- and frequency-specific breakdown and reconnection processes., (© 2023 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Fatigue risk in humans has few biomathematical models, and existing biomathematical models have many shortcomings. We developed a biomathematical model of fatigue risk based on the concept of energy to quantify human alertness from the perspective of energy and used alertness to characterise human psychological fatigue risk. The model allows mathematical modelling of activity processes that concern sleep intensity and quality and distinguishes between intrinsic exertion in the waking state and workload exertion in the workload state. This alertness and fatigue risk biomathematical model predicts changes in human alertness and fatigue risk indices at any point in the day. We applied numerical simulation and model analysis to five cases to validate the potential value of the alertness energy fatigue risk biomathematical model. Practitioner summary: To overcome the shortcomings of current biomathematical models that evaluate fatigue risk, this study developed a biomathematical model of fatigue risk based on the concept of energy to quantify human alertness from the perspective of energy and used alertness to characterise human fatigue risk. Abbreviations : S: The sleep homeostatic process; C: The circadian process; SAFTE: The sleep activity fatigue and task effectiveness model; FAID: The fatigue audit interdyne model; EEG: Electroencephalogram.

Objectives: Prior studies have documented the existence of sleep disparities between social groups and have proposed possible reasons for these gaps. To extend these empirical findings, the current study elucidates whether and how intersections between sociocultural identities shape the lived experience and management of sleep and sheds light on the social factors that explain within-group heterogeneity., Methods: This article draws on semi-structured interviews with 66 employed Israelis, aged 40-60, conducted between February 2020 and February 2022. Participants were selected using a non-probability purposeful sampling design that sought to include individuals with a wide range of sociodemographic backgrounds in terms of gender, ethnonationality, socioeconomic status, religion, and religiosity as well as the quality of sleep., Results: The analysis shows that intersections of gender, socioeconomic status, ethnonationality, religion, and religiosity prompt qualitatively different understandings, experiences, and management of sleep, in a way that affects both sleep opportunity and sleep ability., Conclusions: This study contributes to the scholarly understanding of the social determinants of sleep by highlighting the significance of the intersections of sociocultural identities for sleep health and implementing a nuanced socioecological approach to understanding within-group variability. The results call for the design of tailored interventions that consider the sociocultural context., Competing Interests: Declaration of conflicts of interest The author declares that she has no competing interests., (Copyright © 2023 National Sleep Foundation. Published by Elsevier Inc. All rights reserved.)

Vigilance is highly sensitive to the time-of-day effect and goes through the daytime trough during the period of the post-noon dip. A midday nap could maintain individuals' vigilance at an optimal level. Thus, homeostatic sleep pressure is one of the main reasons for the post-noon dip in daytime vigilance. The current study focussed on the role of homeostatic sleep pressure in the diurnal variation of vigilance performance with normal circadian rhythms and the corresponding neural basis. With 34 healthy adults, we recorded the resting-state electroencephalogram activities and the following vigilance performance measured by psychomotor vigilance test in the morning, the no-nap mid afternoon, and the nap mid afternoon. The circadian process was controlled by measuring vigilance and resting-state electroencephalogram activities at the same time point in the nap and no-nap conditions. Homeostatic sleep pressure accumulated from morning to mid afternoon induced the declined vigilance performance and a global increase in resting-state delta, theta, alpha, and beta1 bands power, and a local increase in beta2 band power in the central region. Furthermore, the more the spontaneous beta2 power increased, the less vigilance declined from morning to mid afternoon. The current findings suggest that homeostatic sleep pressure increased cortical excitability but decreased cortical communication efficiency from morning to mid afternoon. In addition, the activity of the high beta waves probably reflected the compensatory effort to counteract the negative impact of the low arousal state on the following vigilance task by performing more action preparation in the no-nap afternoon., (© 2023 European Sleep Research Society.)

While short daytime naps have been found to provide alertness and performance benefits without inducing sleep inertia, the effects of a similar napping strategy during nights shifts are largely unknown. This study examined the effects of a 20-min nap (scheduled at 2:00 a.m.) during night shifts among 16 participants (mean [SD] age 22.0 [1.08] years) who worked in a simulated night shift from midnight (12:00 a.m.) to morning (ending at 6:00 or 8:00 a.m.). The participants underwent both a 'nap condition' and a 'no-nap condition' by engaging in repeated 10-min tasks (four-choice reaction time tasks and vigilance tasks) and 10-min rest. The results showed that compared to the no-nap condition, sleepiness was significantly lower in the nap condition between 3:20 and 5:20 a.m. (p < 0.05). The nap condition also yielded significantly better performance in the vigilance tasks between 2:40 and 5:40 a.m., except at 4:40 am (p < 0.05). However, no significant difference was found in sleepiness and performance in the vigilance task at 5:40 a.m. or immediately after the nap between the two conditions. The results showed that a 20-min nap at 2:00 a.m. did not induce sleep inertia upon waking. Furthermore, it mitigated sleepiness and sustained work performance for 3 h after the nap. However, the effect of napping was no longer observed near the end of the night shift. Considering risks of falling asleep while driving home from work that may cause a traffic accident, further research should examine ways to mitigate sleepiness after a night shift., (© 2023 European Sleep Research Society.)

Benzodiazepine, a classical medication utilized in the treatment of insomnia, operates by augmenting the activity of the GABA A receptor. This underscores the significance of GABAergic neurotransmission in both the initiation and maintenance of sleep. Nevertheless, an increasing body of evidence substantiates the notion that GABA-mediated neurotransmission also assumes a vital role in promoting wakefulness in specific neuronal circuits. Despite the longstanding belief in the pivotal function of GABA in regulating the sleep-wake cycle, there exists a dearth of comprehensive documentation regarding the specific regions within the central nervous system where GABAergic neurons are crucial for these functions. In this review, we delve into the involvement of GABAergic neurons in the regulation of sleep-wake cycles, with particular focus on those located in the preoptic area (POA) and ventral tegmental area (VTA). Recent research, including our own, has further underscored the importance of GABAergic neurotransmission in these areas for the regulation of sleep-wake cycles., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

Objective: This article focuses on novel neuronal mechanisms of sleep and wakefulness and relates basic science developments with potential translational implications in circadian neurobiology, pharmacology, behavioral factors, and the recently integrated potential pathways of sleep-related motor inhibition., Latest Developments: During the past decade, remarkable advances in the molecular biology of sleep and wakefulness have taken place, opening a promising path for the understanding of clinical sleep disorders. Newly gained insights include the role of astrocytes in sleep brain homeostasis through the glymphatic system, the promotion of memory consolidation during states of reduced cholinergic activity during slow wave sleep, and the differential functions of melatonin receptors involving regulation of both circadian rhythm and sleep initiation. Ongoing investigations exploring sleep and circadian rhythm disruptions are beginning to unlock pathophysiologic aspects of neurologic, psychiatric, and medical disorders., Essential Points: An understanding of sleep and circadian neurobiology provides coherent and biologically credible approaches to treatments, including the identification of potential targets for neuromodulation., (Copyright © 2023 American Academy of Neurology.)

Sleep-mediated memory benefits are modulated by several factors. Prior knowledge is assumed critical for consolidation during sleep, despite inconclusive empirical findings. Additionally, prior knowledge facilitates encoding, leading to differences in memory strength already before the retention filled with sleep. We tested whether increasing memory strength of unfamiliar learning material pre-sleep can restore sleep-mediated memory benefits in cases of low prior knowledge. One-hundred and fifty-four healthy young students learned translations of Dutch words. One group was German-speaking, the other French-speaking. As French is less similar to Dutch than German, we expected a lower prior knowledge in French participants. We manipulated memory strength during pre-sleep encoding by varying the number of learning possibilities (one and two rounds for German-speaking, two and three rounds for French-speaking participants). When using the same learning paradigm for both groups (two rounds), lower prior knowledge modulated sleep-mediated memory benefits: French-speaking participants showed no advantage in memory after nighttime sleep compared with daytime wakefulness. In contrast, German-speaking participants showed robust sleep-mediated memory benefits. However, increasing memory strength before sleep restored sleep-mediated memory benefits in French subjects to a level of German-speaking participants. Conversely, reducing the training in German-speaking participants reduced sleep-mediated memory benefits. Our results show that prior knowledge and memory strength strongly modulate sleep-associated memory benefits. However, in cases of low prior knowledge, sleep-mediated memory benefits can be successfully restored by additional training. While prior knowledge might modulate encoding and consolidation processes more generally, its effect on sleep-specific processes of memory retention might be less important than previously assumed., (© 2023 The Authors. Journal of Sleep Research published by John Wiley & Sons Ltd on behalf of European Sleep Research Society.)

The classic view of sleep and vigilance states is a global stationary perspective driven by the interaction between neuromodulators and thalamocortical systems. However, recent data are challenging this view by demonstrating that vigilance states are highly dynamic and regionally complex. Spatially, sleep- and wake-like states often co-occur across distinct brain regions, as in unihemispheric sleep, local sleep in wakefulness, and during development. Temporally, dynamic switching prevails around state transitions, during extended wakefulness, and in fragmented sleep. This knowledge, together with methods monitoring brain activity across multiple regions simultaneously at millisecond resolution with cell-type specificity, is rapidly shifting how we consider vigilance states. A new perspective incorporating multiple spatial and temporal scales may have important implications for considering the governing neuromodulatory mechanisms, the functional roles of vigilance states, and their behavioral manifestations. A modular and dynamic view highlights novel avenues for finer spatiotemporal interventions to improve sleep function., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

It is now well established that memories can reactivate during non-rapid eye movement (non-REM) sleep, but the question of whether equivalent reactivation can be detected in rapid eye movement (REM) sleep is hotly debated. To examine this, we used a technique called targeted memory reactivation (TMR) in which sounds are paired with learned material in wake, and then re-presented in subsequent sleep, in this case REM, to trigger reactivation. We then used machine learning classifiers to identify reactivation of task-related motor imagery from wake in REM sleep. Interestingly, the strength of measured reactivation positively predicted overnight performance improvement. These findings provide the first evidence for memory reactivation in human REM sleep after TMR that is directly related to brain activity during wakeful task performance., Competing Interests: MA, AK, MT, PL No competing interests declared, (© 2023, Abdellahi et al.)

This article describes the changes in normal sleep regulation, structure, and organization and sleep-related changes in respiration from infancy to adolescence. The first 2 years of age are striking, with more time asleep than awake. With development, the electroencephalogram architecture has a marked reduction in rapid eye movement sleep and the acquisition of K-complexes, sleep spindles, and slow-wave sleep. During adolescence there is a reduction in slow-wave sleep and a delay in the circadian phase. Infants have a more collapsible upper airway and lower lung volumes than older children, which predisposes them to obstructive sleep apnea and sleep-related hypoxemia., Competing Interests: Conflicts of Interest No conflicts of interests with any of the authors., (Copyright © 2023 Elsevier Inc. All rights reserved.)

We performed a mathematical analysis of functional connectivity in electroencephalography (EEG) of patients with obstructive sleep apnea (OSA) (N = 10; age: 52.8 ± 13 years; median age: 49 years; male/female ratio: 7/3), compared with a group of apparently healthy participants (N = 15; age: 51.5 ± 29.5 years; median age: 42 years; male/female ratio: 8/7), based on the calculation of wavelet bicoherence from nighttime polysomnograms. Having observed the previously known phenomenon of interhemispheric synchronization deterioration, we demonstrated a compensatory increase in intrahemispheric connectivity, as well as a slight increase in the connectivity of the central and occipital areas for high-frequency EEG activity. Significant changes in functional connectivity were extremely stable in groups of apparently healthy participants and OSA patients, maintaining the overall pattern when comparing different recording nights and various sleep stages. The maximum variability of the connectivity was observed at fast oscillatory processes during REM sleep. The possibility of observing some changes in functional connectivity of brain activity in OSA patients in a state of passive wakefulness opens up prospects for further research. Developing the methods of hypnogram evaluation that are independent of functional connectivity may be useful for implementing a medical decision support system., (© 2023. The Author(s).)

Investigative interviews (e.g., interrogations) are a critical component of criminal, military, and civil investigations. However, how levels of alertness (vs. sleepiness) of the interviewer impact outcomes of actual interviews is unknown. To this end, the current study tracked daily fluctuations in alertness among professional criminal investigators to predict their daily experiences with actual field interviews. Fifty law-enforcement investigators wore a sleep-activity tracker for two weeks while keeping a daily-diary of investigative interviews conducted in the field. For each interview, the investigators indicated how well they established rapport with the subject, how much resistance they encountered, how well they maintained their own focus and composure, and the overall utility of intelligence obtained. Daily alertness was biomathematically modeled from actigraphic sleep duration and continuity estimates and used to predict interview characteristics. Investigators consistently reported more difficulties maintaining their focus and composure as well as encountering more subject resistance during interviews on days with lower alertness. Better interview outcomes were also reported on days with subjectively better sleep, while findings were generally robust to inclusion of covariates. The findings implicate adequate sleep as a modifiable fitness factor for collectors of human intelligence., (© 2023. The Author(s).)

Sleep deprivation consistently decreases vigilant attention, which can lead to difficulty in performing a variety of cognitive tasks. However, sleep-deprived individuals may be able to compensate for degraded vigilant attention by means of top-down attentional control. We employed a novel task to measure the degree to which individuals overcome impairments in vigilant attention by using top-down attentional control, the Flexible Attentional Control Task (FACT). The FACT is a two-choice task that has trials with valid, invalid, and neutral cues, along with an unexpected switch in the probability of cue validity about halfway in the task. The task provides indices that isolate performance components reflecting vigilant attention and top-down attentional control. Twelve healthy young adults completed an in-laboratory study. After a baseline day, the subjects underwent 39 hours of total sleep deprivation (TSD), followed by a recovery day. The FACT was administered at 03:00, 11:00, and 19:00 during sleep deprivation (TSD condition) and at 11:00 and 19:00 after baseline sleep and at 11:00 after recovery sleep (rested condition). When rested, the subjects demonstrated both facilitation and interference effects on cued trials. While sleep deprived, the subjects showed vigilant attention deficits on neutral cue trials, and an impaired ability to reduce these deficits by using predictive contextual cues. Our results indicate that the FACT can dissociate vigilant attention from top-down attentional control. Furthermore, they show that during sleep deprivation, contextual cues help individuals to compensate partially for impairments in vigilant attention, but the effectiveness of top-down attentional control is diminished., (© 2022 The Authors. Journal of Sleep Research published by John Wiley & Sons Ltd on behalf of European Sleep Research Society.)

Rapid eye movement (REM) sleep is an enigmatic and intriguing sleep state. REM sleep differs from non-REM sleep by its characteristic brain activity and from wakefulness by a reduced anti-gravity muscle tone. In addition to these key traits, diverse physiological phenomena appear across the whole body during REM sleep. However, it remains unclear whether these phenomena are the causes or the consequences of REM sleep. Experimental approaches using humans and animal models have gradually revealed the functional roles of REM sleep. Extensive efforts have been made to interpret the characteristic brain activity in the context of memory functions. Numerous physical and psychological functions of REM sleep have also been proposed. Moreover, REM sleep has been implicated in aspects of brain development. Here, we review the variety of functional roles of REM sleep, mainly as revealed by animal models. In addition, we discuss controversies regarding the functional roles of REM sleep., Competing Interests: Competing interests The authors declare no competing interests regarding this work., (Copyright © 2023 Elsevier Ltd and Japan Neuroscience Society. All rights reserved.)

Some people report being able to spontaneously "time" the end of their sleep. This ability to self-awaken challenges the idea of sleep as a passive cognitive state. Yet, current evidence on this phenomenon is limited, partly because of the varied definitions of self-awakening and experimental approaches used to study it. Here, we provide a review of the literature on self-awakening. Our aim is to i) contextualise the phenomenon, ii) propose an operating definition, and iii) summarise the scientific approaches used so far. The literature review identified 17 studies on self-awakening. Most of them adopted an objective sleep evaluation (76%), targeted nocturnal sleep (76%), and used a single criterion to define the success of awakening (82%); for most studies, this corresponded to awakening occurring in a time window of 30 minutes around the expected awakening time. Out of 715 total participants, 125 (17%) reported to be self-awakeners, with an average age of 23.24 years and a slight predominance of males compared to females. These results reveal self-awakening as a relatively rare phenomenon. To facilitate the study of self-awakening, and based on the results of the literature review, we propose a quick paper-and-pencil screening questionnaire for self-awakeners and provide an initial validation for it. Taken together, the combined results of the literature review and the proposed questionnaire help in characterising a theoretical framework for self-awakenings, while providing a useful tool and empirical suggestions for future experimental studies, which should ideally employ objective measurements., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Verga et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Ventromedial prefrontal cortex (vmPFC) processes many critical brain functions, such as decision-making, value-coding, thinking, and emotional arousal/recognition, but whether vmPFC plays a role in sleep-wake promotion circuitry is still unclear. Here, we find that photoactivation of dorsomedial hypothalamus (DMH)-projecting vmPFC neurons, their terminals, or their postsynaptic DMH neurons rapidly switches non-rapid eye movement (NREM) but not rapid eye movement sleep to wakefulness, which is blocked by photoinhibition of DMH outputs in lateral hypothalamus (LHs). Chemoactivation of DMH glutamatergic but not GABAergic neurons innervated by vmPFC promotes wakefulness and suppresses NREM sleep, whereas chemoinhibition of vmPFC projections in DMH produces opposite effects. DMH-projecting vmPFC neurons are inhibited during NREM sleep and activated during wakefulness. Thus, vmPFC neurons innervating DMH likely represent the first identified set of cerebral cortical neurons for promotion of physiological wakefulness and suppression of NREM sleep., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Sleep is a complex biological state characterized by large populations of neurons firing in a rhythmic or synchronized manner. HCN channels play a critical role in generating and sustaining synchronized neuronal firing and are involved in the actions of anaesthetics. However, the role of these channels in sleep-wakefulness per se has yet to be studied. We conducted polysomnographic recordings of Hcn1 constitutive knockout (Hcn1 KO) and wild-type (WT) mice in order to investigate the potential role of HCN1 channels in sleep/wake regulation. EEG and EMG data were analysed using the Somnivore™ machine learning algorithm. Time spent in each vigilance state, bout number and duration, and EEG power spectral activity were compared between genotypes. There were no significant differences in the time spent in wake, rapid eye movement (REM) or non-REM (NREM) sleep between Hcn1 KO and WT mice. Wake bout duration during the inactive phase was significantly shorter in Hcn1 KO mice whilst no other bout parameters were affected by genotype. Hcn1 KO mice showed a reduction in overall EEG power which was particularly prominent in the theta (5-9 Hz) and alpha (9-15 Hz) frequency bands and most evident during NREM sleep. Together these data suggest that HCN1 channels do not play a major role in sleep architecture or modulation of vigilance states. However, loss of these channels significantly alters underlying neuronal activity within these states which may have functional consequences., Competing Interests: Declarations of interest No authors report disclosures relevant to the manuscript., (Crown Copyright © 2022. Published by Elsevier B.V. All rights reserved.)

Airline cabin crew operate in dynamic work environments that are continuously changing, from unpredictable shift work hours to travelling through multiple time zones. These likely impact cabin crews' overall health and may affect their performance on safety-related tasks. Research on this population has been limited; therefore, the aim was to summarise the relevant literature regarding fatigue, sleepiness and mental health of cabin crew. This review followed the PRISMA-ScR guidelines and conducted a systematic search utilising five databases. The initial search identified 1223 studies, and through vigorous screening processes, 27 studies were selected for this review. Over half of the selected studies focused on international or long-haul flights, and a large proportion of the sample participants were women. Findings suggested a high prevalence of fatigue and sleepiness as well as unsatisfactory sleep quality with elevated susceptibility to sleep disorders. Factors identified with health outcomes were associated with flight operations (e.g., rosters) and individual differences (e.g., age and coping strategies). Regarding mental health, cabin crews are potentially at a greater risk for depression and anxiety compared to the general public. This review draws attention to the importance of using a standardised approach, such as validated measures for fair and consistent inferences.

The hypnagogic state refers to a transitional stage between wakefulness and sleep, in which sensory perceptions can be experienced. In this review, we compile and discuss the recent scientific literature on hypnagogia research regarding the future directions proposed by Schacter (1976; Psychological Bulletin, 83, 452). After a short introduction discussing the terminology used in hypnagogia research and the differentiation of hypnagogic states with other related phenomena, we review the reported prevalence of hypnagogic states. Then, we evaluate the six future directions suggested by Schacter and we propose three further future directions. First, a better understanding of the emotional quality of hypnagogic states is needed. Second, a better understanding of why hypnagogic states occur so frequently in the visual and kinaesthetic modalities is needed. Lastly, a better understanding of the purpose of hypnagogic states is needed. In conclusion, research has made great progress in recent years, and we are one step closer to demystifying the hypnagogic state., (© 2022 The Authors. Journal of Sleep Research published by John Wiley & Sons Ltd on behalf of European Sleep Research Society.)

Sleep state transitions are closely related to insomnia, drowsiness, and sleep maintenance. However, how the cortical network varies during such a transition process remains unclear. Changes in the cortical interaction during the short-term process of sleep stage transitions were investigated. In all, 40 healthy young participants underwent overnight polysomnography. The phase transfer entropy of six frequency bands was obtained from 16 electroencephalography channels to assess the strength and direction of information flow between the cortical regions. Differences in the cortical network between the first and the last 10 s in a 40-s transition period across wakefulness, N1, N2, N3, and rapid eye movement were, respectively, studied. Various frequency bands exhibited different patterns during the sleep stage transitions. It was found that the mutual transitions between the sleep stages were not necessarily the opposite. More significant changes were observed in the sleep deepening process than in the process of sleep awakening. During sleep stage transitions, changes in the inflow and outflow strength of various cortical regions led to regional differences, but for the entire sleep progress, such an imbalance did not intensify, and a dynamic balance was instead observed. The detailed findings of variations in cortical interactions during sleep stage transition promote understanding of sleep mechanism, sleep process, and sleep function. Additionally, it is expected to provide helpful clues for sleep improvement, like reducing the time required to fall asleep and maintaining sleep depth., (© 2022 Wiley Periodicals LLC.)

The review article enlightens contemporary concept about a role of sleep in cellular energy metabolism, neuroplasticity and glymphatic clearance of waste products. Many researches have demonstrated that prolonged wakefulness is an energetic and a neurophysiologic issue for the brain. The article provides description of biochemical processes that are responsive for energy restoration in sleep, particularly the role of ATP, adenosine and glycogen. Energy metabolism substrates depletion leads to endoplasmic reticulum stress and unfolded protein response. At the same time the conductance of synapses increases that worsens energetic problems. Level of the glymphatic clearance during wakefulness is substantially lower in comparison with sleep, and waste products are not removed fast enough.

To examine the effects of blindness on sleep/wakefulness states, we compared locomotor activity and delayed recovery from isoflurane anesthesia induced by hypnotics during light and dark periods in sighted CBA/N and blind CBA/J mice. Locomotor activity around the switch from the dark to light period significantly differed in both mice. Delayed recovery induced by brotizolam was attenuated in both periods in CBA/J mice. In addition, the period specificity of delayed recovery caused by suvorexant or diphenhydramine in CBA/N mice was abolished in CBA/J mice. These results suggest that blindness impairs sleep quality.

We explored the possibility of publication bias in the sleep and explicit motor sequence learning literature by applying precision effect test (PET) and precision effect test with standard errors (PEESE) weighted regression analyses to the 88 effect sizes from a recent comprehensive literature review (Pan & Rickard, 2015). Basic PET analysis indicated pronounced publication bias; that is, the effect sizes were strongly predicted by their standard error. When variables that have previously been shown to both moderate the sleep gain effect and substantially reduce unaccounted for effect size heterogeneity were included in that analysis, evidence for publication bias remained strong. The estimated postsleep gain was negative, suggesting forgetting rather than facilitation, and it was statistically indistinguishable from the estimated postwake gain. In a qualitative review of a smaller group of more recent studies we observed that (a) small sample sizes-a major factor behind the publication bias-are still the norm, (b) use of demonstrably flawed experimental design and analysis remains prevalent, and (c) when authors conclude in favor of sleep-dependent consolidation, they frequently do not cite the articles in which those methodological flaws have been demonstrated. We conclude that there is substantial publication bias, that there is no consolidation-based, absolute performance gain following sleep, and that strong conclusions regarding the hypothesis of less forgetting after sleep than after wakefulness should await further research. Recommendations are made for reducing publication bias in future work. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

This study examined the effects of short sleep duration (SSD) on hemodynamic and psychological responses under long working hours (LWH) in a laboratory experiment. Sixteen subjects participated in a crossover design experiment consisting of two conditions: normal (7-hours) sleep and short (5-hours) sleep. In each condition, participants engaged in simulated LWH (13 hours a day), comprising 12 task sessions. Hemodynamic and psychological responses were measured in each session. Results showed that there were significant main effects of condition and session but no interaction for hemodynamic and psychological responses. Systolic blood pressure and fatigue were higher in the later sessions than the first one. Stroke volume, sleepiness, fatigue, and stress were higher in the 5-hour than the 7-hour sleep condition (all p<0.05). These results suggest that although the combined effect of LWH and SSD was not significant, both LWH and SSD caused a hemodynamic and psychological burden.

Overnight sleep can reduce perceived stress, and improve associated cognitive disruptions and negative affect after an acute stressor. Whether a brief nap can also bestow these benefits in a non-sleep-restricted population is currently unknown. In this study that used a between-subjects design, stress was triggered by administering a modified Trier Social Stress Test to two groups of participants (nap [n = 29], wake [n = 41]). All participants were instructed they would give a speech during the study but the topic would be withheld until later, and then completed a math task. After a 40-min break in which participants watched a neutral video or took a nap monitored with electroencephalography, stress was reinforced by presenting the speech topics and giving participants a 10-min preparation period. Next, instead of giving a speech, the study ended and participants were debriefed. Negative affect, perceived stress and working memory were measured at multiple time points before and after the break. Both groups showed lower perceived stress and improved working memory after the break than before, but a nap did not confer additional benefits for perceived stress or working memory beyond taking a break. However, the nap group exhibited lower negative affect after the break than the wake group, and only the nap group showed a reduction in negative affect compared with initial negative affect levels. These results indicate a nap can improve negative emotions accompanying a stressor to a greater extent than taking a break, and suggest that brief naps may be a useful way to improve mood while experiencing an acute stressor., (© 2022 The Authors. Journal of Sleep Research published by John Wiley & Sons Ltd on behalf of European Sleep Research Society.)

The borderland between wakefulness and sleep promotes creativity.

Naps are increasingly considered a means to boost cognitive performance. We quantified the cognitive effects of napping in 60 samples from 54 studies. 52 samples evaluated memory. We first evaluated effect sizes for all tests together, before separately assessing their effects on memory, vigilance, speed of processing and executive function. We next examined whether nap effects were moderated by study features of age, nap length, nap start time, habituality and prior sleep restriction. Naps showed significant benefits for the total aggregate of cognitive tests (Cohen's d = 0.379, CI 95  = 0.296-0.462). Significant domain specific effects were present for declarative (Cohen's d = 0.376, CI 95  = 0.269-0.482) and procedural memory (Cohen's d = 0.494, CI 95  = 0.301-0.686), vigilance (Cohen's d = 0.610, CI 95  = 0.291-0.929) and speed of processing (Cohen's d = 0.211, CI 95  = 0.052-0.369). There were no significant moderation effects of any of the study features. Nap effects were of comparable magnitude across subgroups of each of the 5 moderators (Q values = 0.009 to 8.572, p values > 0.116). Afternoon naps have a small to medium benefit over multiple cognitive tests. These effects transcend age, nap duration and tentatively, habituality and prior nocturnal sleep., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Statistical learning, the ability of the human brain to uncover patterns organized according to probabilistic relationships between elements and events of the environment, is a powerful learning mechanism underlying many cognitive processes. Here we examined how memory for statistical learning of probabilistic spatial configurations is impacted by interference at the time of initial exposure and varying degrees of wakefulness and sleep during subsequent offline processing. We manipulated levels of interference at learning by varying the time between exposures of different spatial configurations. During the subsequent offline period, participants either remained awake (active wake or quiet wake) or took a nap comprised of either non-rapid eye movement (NREM) sleep only or NREM and rapid eye movement (REM) sleep. Recognition of the trained spatial configurations, as well as a novel configuration exposed after the offline period, was tested approximately 6-7 h after initial exposure. We found that the sleep conditions did not provide any additional memory benefit compared to wakefulness for spatial statistical learning with low interference. For high interference, we found some evidence that memory may be impaired following quiet wake and NREM sleep only, but not active wake or combined NREM and REM sleep. These results indicate that learning conditions may interact with offline brain states to influence the long-term retention of spatial statistical learning., (Copyright © 2022. Published by Elsevier Inc.)

Sleep became a subject of scientific research in the second half of the 19th century. Since sleep, unlike other physiological functions, cannot be attributed to a specific organ, there was no distinct method available to study sleep until then. With the development of physiology and psychology, and a rapidly increasing knowledge of the structure and functioning of the nervous system, certain aspects of sleep became accessible to objective study. A first step was to measure responsiveness to external stimuli systematically, during sleep, allowing a first representation of the course of sleep (Schlaftiefe = sleep depth). A second method was to register continuously the motor activity across the sleep-wake cycle, which allowed the documentation in detail of rest-activity patterns of monophasic and polyphasic sleep-wake rhythms, or between day or night active animals. The central measurement for sleep research, however, became the electroencephalogram in the 1930s, which allowed observation of the sleeping brain with high temporal resolution. Beside the development of instruments to measure sleep, prolonged sleep deprivation was applied to study physiological and psychological effects of sleep loss. Another input came from clinical and neuropathological observations of patients with pronounced disorders of the sleep-wake cycle, which for the first time allowed localisation of brain areas that are essentially involved in the regulation of sleep and wakefulness. Experimental brain stimulation and lesion studies were carried out with the same aim at this time. Many of these activities came to a halt on the eve of World War II. It was only in the early 1950s, when periods with rapid eye movements during sleep were recognised, that sleep became a research topic of itself. Jouvet and his team explored the brain mechanisms and transmitters of paradoxical sleep, and experimental sleep research became established in all European countries. Sleep medicine evolving simultaneously in different countries, with early centres in Italy and France. In the late 1960s sleep research and chronobiology began to merge. In recent decades, sleep research, dream research, and sleep medicine have benefited greatly from new methods in genetic research and brain imaging techniques. Genes were identified that are involved in the regulation of sleep, circadian rhythms, or sleep disorders. Functional imaging enabled a high spatial resolution of the activity of the sleeping brain, complementing the high temporal resolution of the electroencephalogram., (© 2022 European Sleep Research Society.)

For nurses working long night shifts, it is imperative that they have the ability to take naps to reduce fatigue, and that an appropriate environment is prepared where such naps can be taken. We verified the effects of 90 min napping on fatigue and the associated factors among nurses working 16-h night shifts. We investigated 196-night shifts among 49 nurses for one month. Wearable devices, data logging devices, and questionnaires were used to assess nap parameters, fatigue, and environmental factors such as the napping environment, ways of spending breaks, and working environment. Nurses who nap at least 90 min on most night shifts had more nursing experience. Multivariable logistic regression analysis showed that the environmental factors significantly associated with total nap duration (TND) ≥ 90 min were noise, time spent on electronic devices such as cellphones and tablets during breaks, and nap break duration. The night shifts with TND ≥ 90 min showed lower drowsiness after nap breaks and less fatigue at the end of night shift compared to those with TND < 90 min. Nurses and nursing managers should recognize the importance of napping and make adjustments to nap for at least 90 min during long night shifts.

Sleep can be distinguished from wake by changes in brain electrical activity, typically assessed using electroencephalography (EEG). The hallmark of nonrapid-eye-movement (NREM) sleep is the shift from high-frequency, low-amplitude wake EEG to low-frequency, high-amplitude sleep EEG dominated by spindles and slow waves. Here we identified signatures of sleep in brain hemodynamic activity, using simultaneous functional MRI (fMRI) and EEG. We found that, at the transition from wake to sleep, fMRI blood oxygen level-dependent (BOLD) activity evolved from a mixed-frequency pattern to one dominated by two distinct oscillations: a low-frequency (<0.1 Hz) oscillation prominent in light sleep and correlated with the occurrence of spindles, and a high-frequency oscillation (>0.1 Hz) prominent in deep sleep and correlated with the occurrence of slow waves. The two oscillations were both detectable across the brain but exhibited distinct spatiotemporal patterns. During the falling-asleep process, the low-frequency oscillation first appeared in the thalamus, then the posterior cortex, and lastly the frontal cortex, while the high-frequency oscillation first appeared in the midbrain, then the frontal cortex, and lastly the posterior cortex. During the waking-up process, both oscillations disappeared first from the thalamus, then the frontal cortex, and lastly the posterior cortex. The BOLD oscillations provide local signatures of spindle and slow wave activity. They may be employed to monitor the regional occurrence of sleep or wakefulness, track which regions are the first to fall asleep or wake up at the wake-sleep transitions, and investigate local homeostatic sleep processes.

Our ability to recall memories is improved when sleep follows learning, suggesting that sleep facilitates memory consolidation. A number of factors are thought to influence the impact of sleep on newly learned information, such as whether or not we rehearse that information (e.g. via restudy or retrieval practice), or the extent to which the information is consistent with our pre-existing schematic knowledge. In this pre-registered, online study, we examined the effects of both rehearsal and schematic congruency on overnight consolidation. Participants learned noun-colour pairings (e.g. elephant-red) and rated each pairing as plausible or implausible before completing a baseline memory assessment. Afterwards, participants engaged in a period of restudy or retrieval practice for the pairings, and then entered a 12 h retention interval of overnight sleep or daytime wakefulness. Follow-up assessments were completed immediately after sleep or wake, and again 24 h after learning. Our data indicated that overnight consolidation was amplified for restudied relative to retested noun-colour pairings, but only when sleep occurred soon after learning. Furthermore, whereas plausible (i.e. schematically congruent) pairings were generally better remembered than implausible (i.e. schematically incongruent) pairings, the benefits of sleep were stronger for implausible relative to plausible memories. These findings challenge the notion that schema-conformant memories are preferentially strengthened during post-learning sleep., Competing Interests: The authors have declared that no competing interests exist.

Objectives: To review and meta-analyze existing evidence regarding the impact of school start times (SSTs) on youth sleep and developmental outcomes considering the moderating effects of youth and school characteristics. Scopus, ScienceDirect, JSTOR, Pubmed, PsychInfo, ERIC, Proquest, EBSCO, and Google Scholar were used through 2019 to select studies measuring (1) school start time and (2) sleep or other developmental outcomes. Data from 28 studies and 1 774 509 participants were extracted and analyzed using random-effects models with robust variance estimation., Results: Later SSTs were associated with better overall developmental outcomes, longer sleep duration, and less negative mood. Specifically, new SSTs between 8:30 and 8:59 were associated with better outcomes than 8:00 to 8:29 start times. Later SSTs were more strongly associated with lower levels of sleepiness for high school (versus middle school) youth, and youth in private (versus public) schools reported better sleep and later wake times with later SSTs. Although this meta-analysis suggests an overall benefit of later SSTs, there was limited research to test outcomes such as sleep hygiene, naps, and behavioral and physical health outcomes., Conclusions: There is converging evidence that later SSTs are associated with better overall developmental outcomes, longer sleep duration, and less negative mood. More research needs to consider student and school characteristics to obtain reliable estimates related to possible differences by sex, race, school size, percent free/reduced lunch, and percent minority., (Copyright © 2022 by the American Academy of Pediatrics.)