The relationship between mental health, sleep quality and the immunogenicity of COVID-19 vaccinations.

Sleep modulates the immune response, and sleep loss can reduce vaccine immunogenicity; vice versa, immune responses impact sleep. We aimed to investigate the influence of mental health and sleep quality on the immunogenicity of COVID-19 vaccinations and, conversely, of COVID-19 vaccinations on sleep quality. The prospective CoVacSer study monitored mental health, sleep quality and Anti-SARS-CoV-2-Spike IgG titres in a cohort of 1082 healthcare workers from 29 September 2021 to 19 December 2022. Questionnaires and blood samples were collected before, 14 days, and 3 months after the third COVID-19 vaccination, as well as in 154 participants before and 14 days after the fourth COVID-19 vaccination. Healthcare workers with psychiatric disorders had slightly lower Anti-SARS-CoV-2-Spike IgG levels before the third COVID-19 vaccination. However, this effect was mediated by higher median age and body mass index in this subgroup. Antibody titres following the third and fourth COVID-19 vaccinations ("booster vaccinations") were not significantly different between subgroups with and without psychiatric disorders. Sleep quality did not affect the humoral immunogenicity of the COVID-19 vaccinations. Moreover, the COVID-19 vaccinations did not impact self-reported sleep quality. Our data suggest that in a working population neither mental health nor sleep quality relevantly impact the immunogenicity of COVID-19 vaccinations, and that COVID-19 vaccinations do not cause a sustained deterioration of sleep, suggesting that they are not a precipitating factor for insomnia. The findings from this large-scale real-life cohort study will inform clinical practice regarding the recommendation of COVID-19 booster vaccinations for individuals with mental health and sleep problems.

Differential modulation of global and local neural oscillations in REM sleep by homeostatic sleep regulation.

Homeostatic rebound in rapid eye movement (REM) sleep normally occurs after acute sleep deprivation, but REM sleep rebound settles on a persistently elevated level despite continued accumulation of REM sleep debt during chronic sleep restriction (CSR). Using high-density EEG in mice, we studied how this pattern of global regulation is implemented in cortical regions with different functions and network architectures. We found that across all areas, slow oscillations repeated the behavioral pattern of persistent enhancement during CSR, whereas high-frequency oscillations showed progressive increases. This pattern followed a common rule despite marked topographic differences. The findings suggest that REM sleep slow oscillations may translate top-down homeostatic control to widely separated brain regions whereas fast oscillations synchronizing local neuronal ensembles escape this global command. These patterns of EEG oscillation changes are interpreted to reconcile two prevailing theories of the function of sleep, synaptic homeostasis and sleep dependent memory consolidation.

Face Memorization Using AIM Model for Mobile Robot and Its Application to Name Calling Function.

We are developing a social mobile robot that has a name calling function using a face memorization system. It is said that it is an important function for a social robot to call to a person by her/his name, and the name calling can make a friendly impression of the robot on her/him. Our face memorization system has the following features: (1) When the robot detects a stranger, it stores her/his face images and name after getting her/his permission. (2) The robot can call to a person whose face it has memorized by her/his name. (3) The robot system has a sleep-wake function, and a face classifier is re-trained in a REM sleep state, or execution frequencies of information processes are reduced when it has nothing to do, for example, when there is no person around the robot. In this paper, we confirmed the performance of these functions and conducted an experiment to evaluate the impression of the name calling function with research participants. The experimental results revealed the validity and effectiveness of the proposed face memorization system.

[Effects of Low Concentration Hydrogen Inhalation on Asthma and Sleep Function in Mice].

OBJECTIVE: This study was designed to investigate the effects of low concentration hydrogen inhalation on asthma and sleep function in mice and the potential mechanism. METHODS: In the asthma experiment, BALB/c mice were randomly divided into normal control group, asthma model group and hydrogen treatment group. After establishing ovalbumin (OVA)-induced asthma model, the hydrogen treatment group mice were treated by inhalation of hydrogen (24-26 mL/L per day) for 7 consecutive days, and the normal control group and asthma model group mice received similar treatment by inhalation of air. The levels of interleukin (IL)-4, IL-13, and interferon-γ (IFN-γ) in bronchoalveolar lavage fluid (BALF) were measured by commercially available ELISA kits. The levels of malondialdehyde (MDA) and glutathione (GSH), as well as the activity of superoxide dismutase (SOD) in lung tissue were detected by colorimetric assays. The pathological changes in lung tissue were assessed by HE staining. In the sleep experiment, ICR mice were randomly divided into blank control group and 1 d, 3 d, 5 d hydrogen treatment groups and diazepam group. The effects of inhalation of 24-26 mL/L per day hydrogen on the sleep duration induced by intraperitoneal injection of upper-threshold dose of sodium pentobarbital and the sleep latency in response to subthreshold dose were evaluated. RESULTS: In the asthma experiment, the asthma model group showed higher levels of IL-4 and IL-13 ( P<0.05) and lower levels of IFN-γ ( P<0.001) in BALF, as compared to the normal control group. The content of MDA in lung tissue was also significantly increased ( P<0.01), companied by a decreased GSH concentration ( P <0.05) and a mildly reduced SOD activity ( P>0.05). Compared to the asthma model group, treatment with hydrogen significantly decreased the levels of IL-4 and IL-13 and increased the level of IFN-γ in BALF ( P<0.05). Moreover, without alteration of the MDA production ( P>0.05), hydrogen inhalation greatly increased GSH level and restored the SOD activity ( P<0.05) in lung tissue. Additionally, the HE staining data showed that the hydrogen treatment attenuated the pulmonary histopathological changes. In the sleep experiment, compared with the blank control group, the sleep latency was significantly shorter ( P<0.05) and the sleep duration was longer ( P<0.001) in all the hydrogen treatment groups after receiving an upper-threshold dose of sodium pentobarbital. Meanwhile, in all the hydrogen treatment groups, the sleep latency was significantly longer ( P<0.001) and the sleep duration was shorter ( P<0.001) when compared to the diazepam group. Compared with the blank control group, after intraperitoneal injection of a subthreshold dose of sodium pentobarbital, the sleep latency was significantly increased in both 1 d and 5 d hydrogen treatment groups, and there was no significant difference as compared to the diazepam group. In the 3 d hydrogen treatment group, the sleep latency was only slightly increased ( P>0.05), which was significantly lower than that of the diazepam group ( P<0.05). CONCLUSION: Low concentration hydrogen inhalation could alleviate OVA-induced asthma in mice, and the mechanism might be related to the anti-oxidative and anti-inflammatory effects of hydrogen. Also, low concentration hydrogen inhalation could improve sleep function in mice.

Long-term effects of sleep deprivation on neuronal activity in four hypothalamic areas.

Lack of adequate sleep has become increasingly common in our 24/7 society. Unfortunately diminished sleep has significant health consequences including metabolic and cardiovascular disease and mental disorders including depression. The pathways by which reduced sleep adversely affects physiology and behavior are unknown. We found that 6h of sleep deprivation in adult male rats induces changes in neuronal activity in the lateral hypothalamus, the paraventricular nucleus, the arcuate nucleus and the mammillary bodies. Surprisingly, these alterations last for up to 48h. The data show that sleep loss has prolonged effects on the activity of multiple hypothalamic areas. Our data indicate also that measuring electroencephalographic slow wave activity underestimates the amount of time that the hypothalamus requires to recover from episodes of sleep deprivation. We propose that these hypothalamic changes underlie the well-established relationship between sleep loss and several diseases such as metabolic disorders, stress and depression and that sufficient sleep is vital for autonomic functions controlled by the hypothalamus.

The effect of alpha rhythm sleep on EEG activity and individuals' attention.

[Purpose] This study examined whether the alpha rhythm sleep alters the EEG activity and response time in the attention and concentration tasks. [Subjects and Methods] The participants were 30 healthy university students, who were randomly and equally divided into two groups, the experimental and control groups. They were treated using the Happy-sleep device or a sham device, respectively. All participants had a one-week training period. Before and after training sessions, a behavioral task test was performed and EEG alpha waves were measured to confirm the effectiveness of training on cognitive function. [Results] In terms of the behavioral task test, reaction time (RT) variations in the experimental group were significantly larger than in the control group for the attention item. Changes in the EEG alpha power in the experimental group were also significantly larger than those of the control group. [Conclusions] These findings suggest that sleep induced using the Happy-sleep device modestly enhances the ability to pay attention and focus during academic learning.

Why study sleep in flatworms?

The behaviors that characterize sleep have been observed across a broad range of different species. While much attention has been placed on vertebrates (mostly mammals and birds), the grand diversity of invertebrates has gone largely unexplored. Here, we introduce the intrigue and special value in the study of sleeping platyhelminth flatworms. Flatworms are closely related to annelids and mollusks, and yet are comparatively simple. They lack a circulatory system, respiratory system, endocrine glands, a coelom, and an anus. They retain a central and peripheral nervous system, various sensory systems, and an ability to learn. Flatworms sleep, like other animals, a state which is regulated by prior sleep/wake history and by the neurotransmitter GABA. Furthermore, they possess a remarkable ability to regenerate from a mere fragment of the original animal. The regenerative capabilities of flatworms make them a unique bilaterally symmetric animal to study a link between sleep and neurodevelopment. Lastly, the recent applications of tools for probing the flatworm genome, metabolism, and brain activity make their entrance into the field of sleep research all the more timely.

Tripping on the edge of consciousness.

Herein the major accomplishments, trials and tribulations, and epiphanies experienced by James M. Krueger over the course of his career in sleep research are presented. They include the characterization of a) the supranormal EEG delta waves occurring during NREMS post sleep loss, b) Factor S as a muramyl peptide, c) the physiological roles of cytokines in sleep regulation, d) multiple other sleep regulatory substances, e) the dramatic changes in sleep over the course of infectious diseases, and f) sleep initiation within small neuronal/glial networks. The theory that the preservation of brain plasticity is the primordial sleep function is briefly discussed. These accomplishments resulted from collaborations with many outstanding scientists including James M. Krueger's mentors (John Pappenheimer and Manfred Karnovsky) and collaborators later in life, including Charles Dinarello, Louis Chedid, Mark Opp, Ferenc Obal jr., Dave Rector, Ping Taishi, Linda Toth, Jeannine Majde, Levente Kapas, Eva Szentirmai, Jidong Fang, Chris Davis, Sandip Roy, Tetsuya Kushikata, Fabio Garcia-Garcia, Ilia Karatsoreos, Mark Zielinski, and Alok De, plus many students, e.g. Jeremy Alt, Kathryn Jewett, Erika English, and Victor Leyva-Grado.

TRANSLATION OF BRAIN ACTIVITY INTO SLEEP.

Cytokines including tumor necrosis factor alpha (TNF) play a role in sleep regulation in health and disease. Hypothalamic and cerebral cortical levels of TNF mRNA or TNF protein have diurnal variations with higher levels associated with greater sleep propensity. Sleep loss is associated with enhanced brain TNF. Central or systemic TNF injections enhance sleep. Inhibition of TNF using the soluble TNF receptor, or anti-TNF antibodies, or a TNF siRNA reduces spontaneous sleep. Mice lacking the TNF 55 kD receptor have less spontaneous sleep. Injection of TNF into sleep regulatory circuits, e.g. the hypothalamus, promotes sleep. In normal humans, plasma levels of TNF co-vary with EEG slow wave activity (SWA) and in multiple disease states plasma TNF increases in parallel with sleep propensity. Downstream mechanisms of TNF-enhanced sleep include nitric oxide, adenosine, prostaglandins and activation of nuclear factor kappa B. Neuronal use induces cortical neurons to express TNF and if applied directly to cortical columns TNF induces a functional sleep-like state within the column. TNF mechanistically has several synaptic functions. TNF-sleep data led to the idea that sleep is a fundamental property of neuronal/glial networks such as cortical columns and is dependent upon past activity within such assemblies. This view of brain organization of sleep has profound implications for sleep function that are briefly reviewed herein.

A hypothesis regarding how sleep can calibrate neuronal excitability in the central nervous system and thereby offer stability, sensitivity and the best possible cognitive function.

The function of sleep in mammal and other vertebrates is one of the great mysteries of biology. Many hypotheses have been proposed, but few of these have made even the slightest attempt to explain the essence of sleep - the uncompromising need for reversible unconsciousness. During sleep, epiphenomena - often of a somatic character - occur, but these cannot explain the core function of sleep. One answer could be hidden in the observations made for long periods of time of the function of the central nervous system (CNS). The CNS is faced with conflicting requirements on stability and excitability. A high level of excitability is desirable, and is also a prerequisite for sensitivity and quick reaction times; however, it can also lead to instability and the risk of feedback, with life-threatening epileptic seizures. Activity-dependent negative feedback in neuronal excitability improves stability in the short term, but not to the degree that is required. A hypothesis is presented here demonstrating how calibration of individual neurons - an activity which occurs only during sleep - can establish the balanced and highest possible excitability while also preserving stability in the CNS. One example of a possible mechanism is the observation of slow oscillations in EEGs made on birds and mammals during slow wave sleep. Calibration to a genetically determined level of excitability could take place in individual neurons during the slow oscillation. This is only possible offline, which explains the need for sleep. The hypothesis can explain phenomena such as the need for unconsciousness during sleep, with the disconnection of sensory stimuli, slow EEG oscillations, the relationship of sleep and epilepsy, age, the effects of sleep on neuronal firing rate and the effects of sleep deprivation and sleep homeostasis. This is with regard primarily to mammals, including humans, but also all other vertebrates.

Dynamic REM Sleep Modulation by Ambient Temperature and the Critical Role of the Melanin-Concentrating Hormone System.

Ambient temperature (Ta) warming toward the high end of the thermoneutral zone (TNZ) preferentially increases rapid eye movement (REM) sleep over non-REM (NREM) sleep across species. The control and function of this temperature-induced REM sleep expression have remained unknown. Melanin-concentrating hormone (MCH) neurons play an important role in REM sleep control. We hypothesize that the MCH system may modulate REM sleep as a function of Ta. Here, we show that wild-type (WT) mice dynamically increased REM sleep durations specifically during warm Ta pulsing within the TNZ, compared to both the TNZ cool and baseline constant Ta conditions, without significantly affecting either wake or NREM sleep durations. However, genetically engineered MCH receptor-1 knockout (MCHR1-KO) mice showed no significant changes in REM sleep as a function of Ta, even with increased sleep pressure following a 4-h sleep deprivation. Using MCH-cre mice transduced with channelrhodopsin, we then optogenetically activated MCH neurons time locked with Ta warming, showing an increase in REM sleep expression beyond what Ta warming in yellow fluorescent protein (YFP) control mice achieved. Finally, in mice transduced with archaerhodopsin-T, semi-chronic optogenetic MCH neuronal silencing during Ta warming completely blocked the increase in REM sleep seen in YFP controls. These data demonstrate a previously unknown role for the MCH system in the dynamic output expression of REM sleep during Ta manipulation. These findings are consistent with the energy allocation hypothesis of sleep function, suggesting that endotherms have evolved neural circuits to opportunistically express REM sleep when the need for thermoregulatory defense is minimized.

Pleasure: The missing link in the regulation of sleep.

Although largely unrecognized by sleep scholars, sleeping is a pleasure. This report aims first, to fill the gap: sleep, like food, water and sex, is a primary reinforcer. The levels of extracellular mesolimbic dopamine show circadian oscillations and mark the "wanting" for pro-homeostatic stimuli. Further, the dopamine levels decrease during waking and are replenished during sleep, in opposition to sleep propensity. The wanting of sleep, therefore, may explain the homeostatic and circadian regulation of sleep. Accordingly, sleep onset occurs when the displeasure of excessive waking is maximal, coinciding with the minimal levels of mesolimbic dopamine. Reciprocally, sleep ends after having replenished the limbic dopamine levels. Given the direct relation between waking and mesolimbic dopamine, sleep must serve primarily to gain an efficient waking. Pleasant sleep (i.e. emotional sleep), can only exist in animals capable of feeling emotions. Therefore, although sleep-like states have been described in invertebrates and primitive vertebrates, the association sleep-pleasure clearly marks a difference between the sleep of homeothermic vertebrates and cool blooded animals.

Anatomical correlates of rapid eye movement sleep-dependent plasticity in the developing cortex.

Rapid eye movement (REM) sleep is expressed at its highest levels during early life when the brain is rapidly developing. This suggests that REM sleep may play important roles in brain maturation and developmental plasticity. We investigated this possibility by examining the role of REM sleep in the regulation of plasticity-related proteins known to govern synaptic plasticity in vitro and in vivo. We combined immunohistochemistry with a classic model of experience-dependent plasticity in the developing brain known to be consolidated during sleep. We found that after the developing visual cortex is triggered to remodel, it is reactivated during REM sleep (as measured by FOS+ and ARC+ cells). This is accompanied by expression of several proteins implicated in synaptic long-term potentiation (PSD95 and phosphorylated (p), mTOR, cofilin, and CREB) across the different cortical layers. These changes did not occur in animals deprived of REM sleep, but were preserved in control animals that were instead awakened in non- (N) REM sleep. Collectively, these findings support a role for REM sleep in developmental brain plasticity.

Tumor necrosis factor alpha in sleep regulation.

This review details tumor necrosis factor alpha (TNF) biology and its role in sleep, and describes how TNF medications influence sleep/wake activity. Substantial evidence from healthy young animals indicates acute enhancement or inhibition of endogenous brain TNF respectively promotes and inhibits sleep. In contrast, the role of TNF in sleep in most human studies involves pathological conditions associated with chronic elevations of systemic TNF and disrupted sleep. Normalization of TNF levels in such patients improves sleep. A few studies involving normal healthy humans and their TNF levels and sleep are consistent with the animal studies but are necessarily more limited in scope. TNF can act on established sleep regulatory circuits to promote sleep and on the cortex within small networks, such as cortical columns, to induce sleep-like states. TNF affects multiple synaptic functions, e.g., its role in synaptic scaling is firmly established. The TNF-plasticity actions, like its role in sleep, can be local network events suggesting that sleep and plasticity share biochemical regulatory mechanisms and thus may be inseparable from each other. We conclude that TNF is involved in sleep regulation acting within an extensive tightly orchestrated biochemical network to niche-adapt sleep in health and disease.

Sleep-Wake Cycling and Energy Conservation: Role of Hypocretin and the Lateral Hypothalamus in Dynamic State-Dependent Resource Optimization.

The hypocretin (Hcrt) system has been implicated in a wide range of physiological functions from sleep-wake regulation to cardiovascular, behavioral, metabolic, and thermoregulagtory control. These wide-ranging physiological effects have challenged the identification of a parsimonious function for Hcrt. A compelling hypothesis suggests that Hcrt plays a role in the integration of sleep-wake neurophysiology with energy metabolism. For example, Hcrt neurons promote waking and feeding, but are also sensors of energy balance. Loss of Hcrt function leads to an increase in REM sleep propensity, but a potential role for Hcrt linking energy balance with REM sleep expression has not been addressed. Here we examine a potential role for Hcrt and the lateral hypothalamus (LH) in state-dependent resource allocation as a means of optimizing resource utilization and, as a result, energy conservation. We review the energy allocation hypothesis of sleep and how state-dependent metabolic partitioning may contribute toward energy conservation, but with additional examination of how the loss of thermoregulatory function during REM sleep may impact resource optimization. Optimization of energy expenditures at the whole organism level necessitates a top-down network responsible for coordinating metabolic operations in a state-dependent manner across organ systems. In this context, we then specifically examine the potential role of the LH in regulating this output control, including the contribution from both Hcrt and melanin concentrating hormone (MCH) neurons among a diverse LH cell population. We propose that this hypothalamic integration system is responsible for global shifts in state-dependent resource allocations, ultimately promoting resource optimization and an energy conservation function of sleep-wake cycling.

Sleep Ecophysiology: Integrating Neuroscience and Ecology.

Here, we propose an original approach to explain one of the great unresolved questions in animal biology: what is the function of sleep? Existing ecological and neurological approaches to this question have become roadblocks to an answer. Ecologists typically treat sleep as a simple behavior, instead of a heterogeneous neurophysiological state, while neuroscientists generally fail to appreciate the critical insights offered by the consideration of ecology and evolutionary history. Redressing these shortfalls requires cross-disciplinary integration. By bringing together aspects of behavioral ecology, evolution, and conservation with neurophysiology, we can achieve a more comprehensive understanding of sleep, including its implications for adaptive waking behavior and fitness.

The state of sleep and the current brain paradigm.

Up to the present time cerebral cortex was considered as substrate for realization of the highest psychical functions including consciousness. Cortical sensory areas were regarded as structures specialized for processing of information coming from one particular modality (visual, auditory, somatosensory, and so on). However, studies of cortical activity in sleep-wake cycle demonstrated that during sleep the same neurons in the same cortical areas switch to processing of signals coming from the various visceral systems. After awakening these visceral responses disappear and the neurons return to processing of the information coming from the exteroreceptors. These observations indicate that most likely cortical areas are universal processors, which perform particular operations with incoming information independent of its origin. During wakefulness, results of the information processing on the cortical level should be directed to structures connected with organization of behavior and consciousness, while during sleep cortical outputs should be redirected to structures performing integration of the visceral information. Thus, results of sleep studies indicate that current brain paradigm should be changed.

Unveiling sleep mysteries: functions / Revelando mistérios do sono: funções

Sleep occupies roughly one-third of human lives, yet it is still not entirely scientifically clear about its purpose or function. However, the latest research achievement concluded that sleeping has much more effect on the brain than formerly believed. Much of these studies are about the effects of sleep deprivation, and the glymphatic pathway initially identified in the rodent brain. In this paper, it is presented some of the theories about sleep functions, besides a review of some physiologic function of sleep. Now, it is accepted that sleep is involved with cleaning the brain toxins, physical restoration, information processing and recall, regulation, besides strengthening the immune system. Sleep implies in a neuronal activity markedly different along with its phases. It is regulated by two parallel mechanisms, homeostatic and circadian. Besides, the sleep-waking cycle involves diverse brain circuits and neurotransmitters and their interaction is explained using a flip-flop model. Several theories may help clarify the reasons human beings spend an important part of their lives sleeping such as those of Inactivity, Energy Conservation, Restorative, and Brain Plasticity. Recently, it was emphasized the importance of the glymphatic system that is a waste clearence system that acts mainly during sleep support efficient removal of soluble proteins and metabolites from the central nervous system. Indeed, sleep meet the needs of higher brain functions along with basic vital processes.

O sono ocupa cerca de um terço da vida humana, mas ainda não é totalmente claro cientificamente o seu propósito ou função. No entanto, a mais recente pesquisa concluiu que dormir tem muito mais efeito no cérebro do que se pensava anteriormente. Muitos desses estudos são sobre os efeitos da privação do sono e o sistema glinfático inicialmente identificada no cérebro de roedores. Neste artigo, são apresentadas algumas das teorias sobre as funções do sono, além de uma revisão de algumas funções fisiológicas do sono. Agora, aceita-se que o sono esteja envolvido com a limpeza de toxinas cerebrais, restauração física, processamento e memorização de informações, regulação do humor, além de fortalecer o sistema imunológico. O sono implica em uma atividade neuronal marcadamente diferente ao longo de suas fases. É regulado por dois mecanismos paralelos, homeostático e circadiano. Além disso, o ciclo de vigília envolve diversos circuitos cerebrais e neurotransmissores e sua interação é explicada por meio de um modelo de flip-flop. Várias teorias podem ajudar a esclarecer as razões pelas quais o ser humano passa uma parte importante de suas vidas dormindo, como as de inatividade, conservação de energia, restauração e plasticidade cerebral. Recentemente, enfatizou-se a importância do sistema glinfático agir principalmente durante o sono, que é um sistema de eliminação de resíduos para apoiar a remoção eficiente de proteínas e metabólitos solúveis do sistema nervoso central. De fato, o sono atende às necessidades de funções cerebrais superiores, juntamente com processos vitais básicos.