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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.

Consolidating memories for long-term storage depends on reactivation. Reactivation occurs both consciously, during wakefulness, and unconsciously, during wakefulness and sleep. While considerable work has examined conscious awake and unconscious sleep reactivation, in this study, we directly compare the consequences of conscious and unconscious reactivation during wakefulness. Forty-one participants learned associations consisting of adjective-object-position triads. Objects were clustered into distinct semantic groups (e.g., fruits, vehicles) such that we could examine consequences of reactivation on semantically related memories. After an intensive learning protocol, we systematically reactivated some of the triads by presenting the adjective as a cue. Reactivation was done so that it was consciously experienced for some triads, and only unconsciously processed for others. Memory for spatial positions, the most distal part of the association, was affected by reactivation in a consciousness-dependent and memory-strength-dependent manner. Conscious reactivation resulted in weakening of semantically related memories that were strong initially, resonating with prior findings of retrieval-induced forgetting. Unconscious reactivation, on the other hand, selectively benefited weak reactivated memories, as previously shown for reactivation during sleep. Semantically linked memories were not impaired, but rather were integrated with the reactivated memory. These results taken together demonstrate that conscious and unconscious reactivation have qualitatively different consequences. Results support a consciousness-dependent inhibition account, whereby unconscious reactivation entails less inhibition than conscious reactivation, thus allowing more liberal spread of activation. Findings set the stage for additional exploration into the role of conscious experience in memory storage and structuring.

Enhanced memory for emotional experiences is hypothesized to depend on amygdala-hippocampal interactions during memory consolidation. Here we show using intracranial recordings from the human amygdala and the hippocampus during an emotional memory encoding and discrimination task increased awake ripples after encoding of emotional, compared to neutrally-valenced stimuli. Further, post-encoding ripple-locked stimulus similarity is predictive of later memory discrimination. Ripple-locked stimulus similarity appears earlier in the amygdala than in hippocampus and mutual information analysis confirms amygdala influence on hippocampal activity. Finally, the joint ripple-locked stimulus similarity in the amygdala and hippocampus is predictive of correct memory discrimination. These findings provide electrophysiological evidence that post-encoding ripples enhance memory for emotional events.

Experimental work across species has demonstrated that spontaneously generated behaviors are robustly coupled to variations in neural activity within the cerebral cortex. Functional magnetic resonance imaging data suggest that temporal correlations in cortical networks vary across distinct behavioral states, providing for the dynamic reorganization of patterned activity. However, these data generally lack the temporal resolution to establish links between cortical signals and the continuously varying fluctuations in spontaneous behavior observed in awake animals. Here, we used wide-field mesoscopic calcium imaging to monitor cortical dynamics in awake mice and developed an approach to quantify rapidly time-varying functional connectivity. We show that spontaneous behaviors are represented by fast changes in both the magnitude and correlational structure of cortical network activity. Combining mesoscopic imaging with simultaneous cellular-resolution two-photon microscopy demonstrated that correlations among neighboring neurons and between local and large-scale networks also encode behavior. Finally, the dynamic functional connectivity of mesoscale signals revealed subnetworks not predicted by traditional anatomical atlas-based parcellation of the cortex. These results provide new insights into how behavioral information is represented across the neocortex and demonstrate an analytical framework for investigating time-varying functional connectivity in neural networks.

[Display omitted] • Fentanyl was administered at dark onset and sleep-wakefulness (S-W) was examined. • Fentanyl administration significantly increased wakefulness for the first 6 h. • This initial increase in wakefulness was followed by a rebound sleep for next 6 h. • Sulpiride was injected in the accumbal core before fentanyl and S-W was examined. • D2R blockade by sulpiride in the core attenuated the effects of fentanyl on S-W. Fentanyl, a potent analgesic and addictive substance, significantly impacts sleep-wakefulness (S-W). Acutely, it promotes wake, whereas chronic abuse leads to severe sleep disruptions, including insomnia, which contributes to opioid use disorders (OUD), a chronic brain disease characterized by compulsive opioid use and harmful consequences. Although the critical association between sleep disruptions and fentanyl addiction is acknowledged, the precise mechanisms through which fentanyl influences sleep remain elusive. Recent studies highlight the role of the dopaminergic system of the nucleus accumbens (NAc) in S-W regulation, but its specific involvement in mediating fentanyl's effects on S-W remains unexplored. We hypothesized that dopamine D2 receptors mediate fentanyl-induced effects on S-W. To test this hypothesis, male C57BL/6J mice, instrumented with sleep recording electrodes and bilateral guide cannulas above the accumbal core region (NAcC), were utilized in this study. At dark onset, animals were bilaterally administered sulpiride (D2 receptors antagonist; 250 ng/side) in the NAcC followed by an intraperitoneal injection of fentanyl (1.2 mg/Kg). S-W was examined for the next 12 h. We found that systemic administration of fentanyl significantly increased wakefulness during the first 6 h of the dark which was followed by a significant increase in NREM and REM sleep during the second 6 h of the dark period. D2-receptor blockade significantly reduced this effect as evidenced by a significant reduction in fentanyl-induced wakefulness during first 6 h of dark period and sleep rebound during the second 6 h. Our findings suggest that D2 receptors in the NAcC plays a vital role in mediating the fentanyl-induced changes in S-W. [ABSTRACT FROM AUTHOR]

Entrepreneurship scholars have much to gain from including time perspective in developing theory about entrepreneurs' alertness. In this study, interviews with 22 French entrepreneurs revealed associations between their alertness and past-positive, present-hedonistic, and future time perspectives. Complementarily, a sample of 376 U.S. entrepreneurs provided evidence that their present-hedonistic and future time perspectives impacted their alertness; we found mixed support for the relationship between past-positive time perspective and entrepreneurial alertness. A replication analysis with 764 U.K. entrepreneurs corroborated support for our hypotheses. [ABSTRACT FROM AUTHOR]

The paper introduces a parametric resonance model for characterizing some features of the brain's electrical activity. This activity is assumed to be a fundamental aspect of brain functionality underpinning functions from basic sensory processing to complex cognitive operations such as memory, reasoning, and emotion. A pivotal element of the proposed parametric model is neuron synchronization which is crucial for generating detectable brain waves. The analysis of the frequency content of brain waves, categorized as delta (0÷4 Hz), theta (4÷7 Hz), alpha (8÷12 Hz), beta (13÷30 Hz), and gamma (30÷100 Hz) reveals, notably, that the mean frequency of each of these brain wave classes is, in sequence, approximately the double of that of the previous one. Based on this observation, the proposed parametric resonance model suggests a cascade of amplification effects. Following the proposed model, in the transition from wakefulness to sleep, the brain wave bands are energized at double frequency by higher frequency neighboring bands; on the contrary, in the sleep to awake transition, brain waves are energized at a half frequency by their lower frequency neighbor waves. Finally, the trend of increasing amplitude values from higher to lower frequencies lends empirical support to the parametric resonant brain model validity. [ABSTRACT FROM AUTHOR]

Anesthesia modifies sensory representations in the thalamo-cortical circuit but is considered to have a milder impact on peripheral sensory processing. Here, tracking the same neurons across wakefulness and isoflurane or ketamine medetomidine anesthesia, we show that the amplitude and sign of single neuron responses to sounds are massively modified by anesthesia in the cochlear nucleus of the brainstem, the first relay of the auditory system. The reorganization of activity is so profound that decoding of sound representation under anesthesia is not possible based on awake activity. However, population-level parameters, such as average tuning strength and population decoding accuracy, are weakly affected by anesthesia, explaining why its effect has previously gone unnoticed when comparing independently sampled neurons. Together, our results indicate that the functional organization of the auditory brainstem largely depends on the network state and is ill-defined under anesthesia. This demonstrates a remarkable sensitivity of an early sensory stage to anesthesia, which is bound to disrupt downstream processing. [ABSTRACT FROM AUTHOR]

The brain is a complex non-equilibrium system capable of expressing many different dynamics as well as the transitions between them. We hypothesized that the level of non-equilibrium can serve as a signature of a given brain state, which was quantified using the arrow of time (the level of irreversibility). Using this thermodynamic framework, the irreversibility of emergent cortical activity was quantified from local field potential recordings in male Lister-hooded rats at different anesthesia levels and during the sleep-wake cycle. This measure was carried out on five distinct brain states: slow-wave sleep, awake, deep anesthesia–slow waves, light anesthesia–slow waves, and microarousals. Low levels of irreversibility were associated with synchronous activity found both in deep anesthesia and slow-wave sleep states, suggesting that slow waves were the state closest to the thermodynamic equilibrium (maximum symmetry), thus requiring minimum energy. Higher levels of irreversibility were found when brain dynamics became more asynchronous, for example, in wakefulness. These changes were also reflected in the hierarchy of cortical dynamics across different cortical areas. The neural dynamics associated with different brain states were characterized by different degrees of irreversibility and hierarchy, also acting as markers of brain state transitions. This could open new routes to monitoring, controlling, and even changing brain states in health and disease. [ABSTRACT FROM AUTHOR]

Background: This narrative review was written by an expert panel to the members of the jury to help in the development of clinical practice guidelines on oxygen therapy. Results: According to the expert panel, acute hypoxemic respiratory failure was defined as PaO2 < 60 mm Hg or SpO2 < 90% on room air, or PaO2/FiO2 ≤ 300 mm Hg. Supplemental oxygen should be administered according to the monitoring of SpO2, with the aim at maintaining SpO2 above 92% and below 98%. Noninvasive respiratory supports are generally reserved for the most hypoxemic patients with the aim of relieving dyspnea. High-flow nasal cannula oxygen (HFNC) seems superior to conventional oxygen therapy (COT) as a means of avoiding intubation and may therefore be should probably be used as a first-line noninvasive respiratory support in patients requiring more than 6 L/min of oxygen or PaO2/FiO2 ≤ 200 mm Hg and a respiratory rate above 25 breaths/minute or clinical signs of respiratory distress, but with no benefits on mortality. Continuous positive airway pressure (CPAP) cannot currently be recommended as a first-line noninvasive respiratory support, since its beneficial effects on intubation remain uncertain. Despite older studies favoring noninvasive ventilation (NIV) over COT, recent clinical trials fail to show beneficial effects with NIV compared to HFNC. Therefore, there is no evidence to support the use of NIV or CPAP as first-line treatment if HFNC is available. Clinical trials do not support the hypothesis that noninvasive respiratory supports may lead to late intubation. The potential benefits of awake prone positioning on the risk of intubation in patients with COVID-19 cannot be extrapolated to patients with another etiology. Conclusions: Whereas oxygen supplementation should be initiated for patients with acute hypoxemic respiratory failure defined as PaO2 below 60 mm Hg or SpO2 < 90% on room air, HFNC should be the first-line noninvasive respiratory support in patients with PaO2/FiO2 ≤ 200 mm Hg with increased respiratory rate. Further studies are needed to assess the potential benefits of CPAP, NIV through a helmet and awake prone position in patients with acute hypoxemic respiratory failure not related to COVID-19. [ABSTRACT FROM AUTHOR]

Summary Wakefulness and sleep have often been treated as distinct and global brain states. However, an emerging body of evidence on the local regulation of sleep stages challenges this conventional view. Apart from unihemispheric sleep, the current data that support local variations of neural oscillations during sleep are focused on the homeostatic regulation of local sleep, i.e., the role preceding awake activity. Here, to examine local differences in brain activity during natural sleep, we recorded the electroencephalogram and the local field potential across multiple sites within the avian pallium of zebra finches without perturbing the previous awake state. We scored the sleep stages independently in each pallial site and found that the sleep stages are not pallium‐wide phenomena but rather deviate widely across electrode sites. Importantly, deeper electrode sites had a dominant role in defining the temporal aspects of sleep state congruence. Altogether, these findings show that local regulation of sleep oscillations also occurs in the avian brain without prior awake recruitment of specific pallial circuits and in the absence of mammalian cortical neural architecture. [ABSTRACT FROM AUTHOR]

Objective: This study aims to present a case of persistent mycetoma caused by Scedosporium boydii and undertake a systematic literature overview to elucidate the clinical characteristics and antifungal treatment exhibited by such patients. Methods: We report the case of a 24-year-old female who sustained a Scedosporium boydii infection in her right foot over a decade ago following a nail puncture. Concurrently, a comprehensive literature overview was conducted on PubMed, focusing on documented cases of Scedosporium boydii infections with the intent of extracting relevant clinical data. Results: Our analysis revealed that post-transplantation, trauma, near drowning, corticosteroid administration, and prior surgical history were the main risk factors for Scedosporium boydii infection. Prevalent infection sites included skin/bone tissues, the central nervous system, and ocular regions. Among the 49 patients identified, 24 received itraconazole therapy and 25 received voriconazole, with no significant difference in patient outcomes (P = 0.158). Of these, 12 patients experienced treatment failure. Notably, prolonged antifungal treatment duration was identified as a protective factor against mortality in Scedosporium boydii infections [P = 0.022, OR(95%CI): 0.972(0.949–0.996)]. Conversely, a history of post-transplantation emerged as a potential risk factor for mortality[P = 0.046, OR(95%CI): 7.017(1.034–47.636)]. Conclusion: While uncommon, Scedosporium boydii infections carry a significant burden of morbidity and adverse outcomes. Heightened clinical vigilance is warranted in individuals presenting with risk factors for this pathogen. Timely and effective antifungal intervention is crucial, with both voriconazole and itraconazole demonstrating positive treatment outcomes for Scedosporium boydii infection. Therefore, prioritizing these antifungal agents should be considered a key therapeutic strategy in the management of this patient population. [ABSTRACT FROM AUTHOR]

The Raphe Pallidus (RPa) is a brainstem nucleus containing sympathetic premotor neurons that control thermogenesis and modulate cardiovascular function. It receives inputs from various hypothalamic areas, including the Lateral Hypothalamus (LH), a heterogeneous region intricately involved in several autonomic and behavioral functions. A key subpopulation of neurons in the LH expresses orexin/hypocretin, a neuropeptide which is crucially involved in the regulation of the wake-sleep states and feeding behavior. The RPa receives orexinergic projections from the LH and orexinergic signalling in the RPa has been shown to enhance thermogenesis in the anaesthetized rat, but only in the presence of an already existing thermogenic drive, without significantly affecting cardiovascular function. The present work was aimed at exploring the effects on thermoregulation and autonomic function and the possible role in the modulation of the wake-sleep states and feeding behavior of orexin injection in the RPa in the free-behaving rat. In order to assess the influence of an already present thermogenic drive on orexinergic signalling in the RPa, animals were studied at three different ambient temperatures (Ta, 10°C, 24°C, and 32°C). We found that orexin injection into the RPa variably affected the wake-sleep states, autonomic functions, motor activity, and feeding behavior, at the different Tas. In particular, in the first post-injection hour, we observed an increase in wakefulness, which was large at Ta 24°C and Ta 10°C and rather mild at Ta 32°C. Deep brain temperature was increased by orexin injection at Ta 10°C, but not at either Ta 24°C or Ta 32°C. Moreover, an increase in mean arterial blood pressure occurred at Ta 24°C, which was probably masked by the high baseline levels at Ta 10°C and was completely absent at Ta 32°C. Finally, an enhancement in feeding behavior was observed at Ta 24°C and 10°C only. In accordance with what observed in anaesthetized rats, orexinergic signalling in the RPa seems to be ineffective in the absence of any thermogenic drive. Moreover, the effects observed on the wake-sleep states and feeding behavior introduce the RPa as a novel player in the central neural network promoting wakefulness and feeding. [ABSTRACT FROM AUTHOR]

Negligence of public transport drivers due to drowsiness poses risks not only to their own lives but also to the lives of passengers. The designed journey tracker system alerts the drivers and activates potential penalties. A custom EfficientNet model architecture, based on EfficientNet design principles, is built and trained using the Media Research Lab (MRL) eye dataset. Reflections in frames are filtered out to ensure accurate detections. A 10 min initial period is utilized to understand the driver's baseline behavior, enhancing the reliability of drowsiness detections. Input from drivers is considered to determine the frame rate for more precise real-time monitoring. Only the eye regions of individual drivers are captured to maintain privacy and ethical standards, fostering driver comfort. Hyperparameter tuning and testing of different activation functions during model training aim to strike a balance between model complexity, performance and computational cost. Obtained an accuracy rate of 95% and results demonstrate that the "swish" activation function outperforms ReLU, sigmoid and tanh activation functions in extracting hierarchical features. Additionally, models trained from scratch exhibit superior performance compared to pretrained models. This system promotes safer public transportation and enhances professionalism by monitoring driver alertness. The system detects closed eyes and performs a cross-reference using personalization data and pupil detection to trigger appropriate alerts and impose penalties. [ABSTRACT FROM AUTHOR]

Background/Objectives: A well-established association exists between the development of hypertension and sleep quality. The connection between self-reported sleep quality and the onset of hypertension is particularly significant in populations with metabolic deterioration, such as in Mexico. Methods: The Tlalpan 2020 Cohort was analyzed to explore this association. Clinical and anthropometric characteristics, along with the Medical Outcomes Study Sleep Scale (MOS-SS), were compared between participants who developed hypertension and those who did not over a follow-up period of 30.8 months. The potential role of poor sleep quality in the development of hypertension was assessed. Results: Among 1520 participants, 12% developed hypertension. These individuals had higher anthropometric and laboratory values and reported poorer sleep quality. An elevated sleep problems index was associated with a 50% higher relative risk of developing hypertension (OR: 1.5; 95% CI: 1.087 to 2.069). Additionally, self-reported snoring was associated with hypertension onset (36.3 vs. 43.3; p = 0.019). Conclusions: Poor sleep quality and respiratory disturbances during sleep increase the risk of developing hypertension. Furthermore, hypertension was associated with snoring, highlighting the importance of early interventions to improve sleep quality. [ABSTRACT FROM AUTHOR]

Consciousness, defined as being aware of and responsive to one's surroundings, is characteristic of normal waking life and typically is lost during sleep and general anaesthesia. The traditional view of consciousness as a global brain state has evolved toward a more sophisticated interplay between global and local states, with the presence of local sleep in the awake brain and local wakefulness in the sleeping brain. However, this interplay is not clear for general anaesthesia, where loss of consciousness was recently suggested to be associated with a global state of brain‐wide synchrony that selectively involves layer 5 cortical pyramidal neurons across sensory, motor and associative areas. According to this global view, local wakefulness of layer 5 cortex should be incompatible with deep anaesthesia, a hypothesis that deserves to be scrutinised with causal manipulations. Here, we show that unilateral chemogenetic activation of layer 5 pyramidal neurons in the sensorimotor cortex of isoflurane‐anaesthetised mice induces a local state transition from slow‐wave activity to tonic firing in the transfected hemisphere. This wakefulness‐like activity dramatically disrupts layer 5 interhemispheric synchrony with mirror‐image locations in the contralateral hemisphere, but does not reduce the level of unconsciousness under deep anaesthesia, nor in the transitions to/from anaesthesia. Global layer 5 synchrony may thus be a sufficient condition for anaesthesia‐induced unconsciousness, but is not a necessary one, at least under isoflurane anaesthesia. Local wakefulness‐like activity of layer 5 cortex can be induced and maintained under deep anaesthesia, encouraging further investigation into the local vs. global aspects of anaesthesia‐induced unconsciousness. Key points: The neural correlates of consciousness have evolved from global brain states to a nuanced interplay between global and local states, evident in terms of local sleep in awake brains and local wakefulness in sleeping brains.The concept of local wakefulness remains unclear for general anaesthesia, where the loss of consciousness has been recently suggested to involve brain‐wide synchrony of layer 5 cortical neurons.We found that local wakefulness‐like activity of layer 5 cortical can be chemogenetically induced in anaesthetised mice without affecting the depth of anaesthesia or the transitions to and from unconsciousness.Global layer 5 synchrony may thus be a sufficient but not necessary feature for the unconsciousness induced by general anaesthesia.Local wakefulness‐like activity of layer 5 neurons is compatible with general anaesthesia, thus promoting further investigation into the local vs. global aspects of anaesthesia‐induced unconsciousness. [ABSTRACT FROM AUTHOR]

High‐frequency oscillatory activity in cognition‐related neural circuits during wakefulness consistently induces the growth of dendritic spines and axonal terminals. Although these structural changes are essential for cognitive functions, it is hypothesized that if these newly expanded structures fail to establish functional connections, they may become superfluous. Sleep is believed to facilitate the reduction of such redundant structures to maintain neural homeostasis. However, the mechanisms underlying this pruning process during sleep remain poorly understood. In this study, that melatonin type 3 receptors (MT3Rs) are selectively expressed in the stellate neurons of the medial entorhinal cortex (MEC) is demonstrated, an area where high melatonin levels are detected during sleep. Activation of MT3Rs during sleep initiates the shrinkage of dendritic spines in stellate neurons by downregulating neural network activity and dephosphorylating synaptic proteins in the MEC. This process is disrupted when MT3R expression is knocked down or when MT3Rs are blocked during sleep. Notably, interference with MT3Rs in the MEC during sleep impairs the acquisition of spatial memory but does not affect object memory acquisition following sleep. These findings reveal novel molecular mechanisms involving melatonin and MT3Rs in the regulation of dendritic spine shrinkage during sleep, which is crucial for the acquisition and consolidation of spatial memory. [ABSTRACT FROM AUTHOR]

Introduction: Light is a key factor in moderating human alertness, both subjective and objective. However, the methodology applies in research on the effects of exposure to light of different wavelengths and intensities on objective and subjective alertness varies greatly and evidence on objective alertness in particular is still inconclusive. Thus, the present, highly standardized within-subject laboratory study on N = 44 healthy males explored how LED light of different intensities (dim vs. bright light) and wavelengths (red vs. blue) affected objective (reaction time/RT) as well as subjective (sleepiness) alertness in the morning after wake-up. Methods: Participants spent two separate nights in the laboratory and were exposed to either one of the two light intensities or colors for 60 min after wake-up. Additionally, they indicated their sleepiness on the Karolinska Sleepiness Scale and participated in an auditory RT task before and after light intervention. It was hypothesized that both bright and blue light would lead to greater subjective and objective alertness when compared to dim and red light, respectively. Results: Results indicated that average RTs were longer for participants in the bright light condition (p = 0.004, f2 = 0.07) and that RTs decreased post-light exposure irrespective of light being dim or bright (p = 0.026, f2 = 0.07). However, dim versus bright light and RT did not interact (p = 0.758, f2 = 0.07). Chronotype was a significant covariate in the interaction of dim versus bright light and subjective sleepiness (p = 0.008, f2 = 0.22). There was no difference in RTs when comparing exposure to red or blue light (p = 0.488, f2 = 0.01). Findings on subjective sleepiness and light of different wavelengths revealed that sleepiness was reduced after light exposure (p = 0.007, f2 = 0.06), although the wavelength of light did not appear to play a role in this effect (p = 0.817, f2 = 0.06). Conclusion: Hence, neither of the hypotheses could be confirmed. However, they indicated that evening types might benefit from exposure to bright light regarding sleepiness, but not morning types. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a progressive neurodegenerative condition marked by memory impairments and distinct histopathological features such as amyloid-beta (Aβ) accumulations. Alzheimer's patients experience sleep disturbances at early stages of the disease. APPswe/PS1dE9 (APP) mice exhibit sleep disruptions, including reductions in non-rapid eye movement (NREM) sleep, that contribute to their disease progression. In addition, astrocytic calcium transients associated with a sleep-dependent brain rhythm, slow oscillations prevalent during NREM sleep, are disrupted in APP mice. However, at present it is unclear whether restoration of circuit function by targeting astrocytic activity could improve sleep in APP mice. To that end, APP mice expressing channelrhodopsin-2 (ChR2) targeted to astrocytes underwent optogenetic stimulation at the slow oscillation frequency. Optogenetic stimulation of astrocytes significantly increased NREM sleep duration but not duration of rapid eye movement (REM) sleep. Optogenetic treatment increased delta power and reduced sleep fragmentation in APP mice. Thus, optogenetic activation of astrocytes increased sleep quantity and improved sleep quality in an AD mouse model. Astrocytic activity provides a novel therapeutic avenue to pursue for enhancing sleep and slowing AD progression. [ABSTRACT FROM AUTHOR]

Hallucinations can have rather heterogeneous aetiology and presentation. This inspired the concept of different subtypes based on symptom profiles, especially in the field of auditory hallucinations. As many people experience hallucinations in more than one sensory modality, it seems important to investigate potential hallucination subtypes across different sensory modalities. We assessed the content of hallucinations as part of a large survey among the general Dutch population (n = 10,448) using the Questionnaire for Psychotic Experiences. Based on their descriptions, thematic categories were created in a data-driven cluster analysis. 2594 participants who experienced hallucinations over the past week that contained at least 2 different thematic categories were selected. Clustering of their hallucination content was performed with the HDBSCAN method. We identified 4 clusters, i.e., subtypes, which can be typified as 1. hallucinations of foul odors, 2. complex visual scenes, 3. a vast variety of rather common hallucinations possibly related to heightened alertness, and 4. possibly bereavement hallucinations. The bereavement subtype showed an increase in emotional loneliness and the presence of delusions. Our findings suggest that the content of hallucinations can be informative, especially when investigated across sensory modalities. Such subtypes may help to better understand their underlying mechanisms. [ABSTRACT FROM AUTHOR]

Sleep, constituting approximately one‐third of the human lifespan, is a crucial physiological process essential for physical and mental well‐being. Normal sleep consists of an orderly progression through wakefulness, non‐rapid eye movement (NREM) sleep, and rapid eye movement (REM) sleep, all of which are tightly regulated. Melatonin, often referred to as the "hormone of sleep," plays a pivotal role as a regulator of the sleep/wake cycle and exerts its effects through high‐affinity G‐protein coupled receptors known as MT1 and MT2. Selective modulation of these receptors presents a promising therapeutic avenue for sleep disorders. This review examines research on the multifaceted role of melatonin in sleep regulation, focusing on selective ligands targeting MT1 and MT2 receptors, as well as studies involving MT1 and MT2 knockout mice. Contrary to common beliefs, growing evidence suggests that melatonin, through MT1 and MT2 receptors, might not only influence circadian aspects of sleep but likely, also modulate the homeostatic process of sleep and sleep architecture, or could be the molecule linking the homeostatic and circadian regulation of sleep. Furthermore, the distinct brain localization of MT1 and MT2 receptors, with MT1 receptors primarily regulating REM sleep and MT2 receptors regulating NREM sleep, is discussed. Collectively, sleep regulation extends beyond the circulating levels and circadian peak of melatonin; it also critically involves the expression, molecular activation, and regulatory functions of MT1 and MT2 receptors across various brain regions and nuclei involved in the regulation of sleep. This research underscores the importance of ongoing investigation into the selective roles of MT1 and MT2 receptors in sleep. Such research efforts are expected to pave the way for the development of targeted MT1 or MT2 receptors ligands, thereby optimizing therapeutic interventions for sleep disorders. [ABSTRACT FROM AUTHOR]

Sleep/wake cycles intricately shape physiological activities including cognitive brain functions, yet the precise molecular orchestrators of sleep remain elusive. Notably, the clinical impact of benzodiazepine drugs underscores the pivotal role of GABAergic neurotransmission in sleep regulation. However, the specific contributions of distinct GABAA receptor subtypes and their principal scaffolding protein, gephyrin, in sleep dynamics remain unclear. The evolving role of synaptic phospho‐proteome alterations at excitatory and inhibitory synapses suggests a potential avenue for modulating gephyrin and, consequently, GABAARs for sleep through on‐demand kinase recruitment. Our study unveils the distinctive roles of two prevalent GABAA receptor subtypes, α1‐ and α2‐GABAARs, in influencing sleep duration and electrical sleep activity. Notably, the absence of α1‐GABAARs emerges as central in sleep regulation, manifesting significant alterations in both non‐rapid eye movement (NREM) and rapid eye movement (REM) sleep during dark or active phases, accompanied by altered electroencephalogram (EEG) patterns across various frequencies. Gephyrin proteomics analysis reveals sleep/wake‐dependent interactions with a repertoire of known and novel kinases. Crucially, we identify the regulation of gephyrin interaction with ERK1/2, and phosphorylations at serines 268 and 270 are dictated by sleep/wake cycles. Employing AAV‐eGFP‐gephyrin or its phospho‐null variant (S268A/S270A), we disrupt sleep either globally or locally to demonstrate gephyrin phosphorylation as a sleep regulator. In summary, our findings support the local cortical sleep hypothesis and we unveil a molecular mechanism operating at GABAergic synapses, providing critical insights into the intricate regulation of sleep. [ABSTRACT FROM AUTHOR]

Background: Limited research has examined the association between moderate to vigorous physical activity (MVPA), sedentary behavior (SB), and sleep-related outcomes in cancer survivors. Therefore, this study aimed to examine these associations using a nationally representative sample of US adults. Methods: Data from the 2005–2018 National Health and Nutrition Examination Survey (NHANES) were analyzed. A total of 3229 adults with cancer histories were included. Physical activity was measured through accelerometry, and questions on daily activities, sedentary time, and sleep were collected during the household interview. Weighted multivariable analyses were conducted after accounting for the complex sampling design of the NHANES dataset. Results: After adjustments, physical activity and SB outcomes were associated with several self-reported sleep-related parameters. Increases in minutes of self-reported MVPA and SB were associated with a decreased likelihood of reporting ≥ 8 h of sleep (OR = 0.92, 95% CI = 0.86, 0.99 and OR = 0.88, 95% CI = 0.82, 0.95). Converse associations were found between device-measured MVPA and SB with the likelihood of reporting often/always feeling overly sleepy during the day (OR = 0.86, 95% CI = 0.75 and OR = 1.13, 95% CI = 1.05, respectively). However, an increased likelihood of waking up too early in the morning (OR = 1.22, 95% CI = 1.04) was observed with increases in minutes of device-measured MVPA. Conclusions: A sensible strategy to decrease the frequency of sedentary breaks and increase minutes of physical activity throughout the day may reduce sleep complaints reported in cancer survivors. [ABSTRACT FROM AUTHOR]

Obstructive sleep apnea (OSA) is considered one of the major causes of sleep disorders and psychological disorders in individuals. Brain asymmetry (BA) demonstrates individual hemispheric activity and psychological disorders. This study aimed to explore the characteristics of BA and psychology in OSA. Enrolment of patients for sleep assessment at the Sleep Medicine Center. Clinical characteristics, handedness, and psychological scales were prospectively collected from subjects. Subsequently, EEG power in alpha, beta, and theta bilaterally was calculated for the rest and sleep phases. A total of 152 OSA and 21 non-OSA subjects were included in the study. In the frontal, central and occipital regions, OSA exhibited increased interhemispheric asymmetry with increasing apnea-hypopnea index (AHI) during rest and sleep. Simultaneously, the results showed that greater activity in the right hemisphere was positively associated with anxiety and extraversion, while inversely with positive and lie scale. In addition, the results show that OSA contributes to abnormal BA fluctuations during sleep. Our results suggest that sleep disorders associated with apnea-hypopnea and arousal may contribute to increased BA during sleep. Such changes may persist into wakefulness with psychological traits. • The association between sleep apnea and brain asymmetry. • Pathological mechanisms involved in OSA psychological disorders. • The correlation of brain asymmetry during sleep and wakefulness. [ABSTRACT FROM AUTHOR]

Sleepiness in patients with obstructive sleep apnea (OSA) is associated with accidental and economic burden, as well as cardiovascular risk. Despite OSA treatment, 10–28 % of patients report residual sleepiness. Its determinants, as well as those of objective impaired alertness remain poorly known. In this study, we investigated factors associated with residual subjective sleepiness and objective impaired alertness in patients treated for OSA. Consecutive OSA treated patients referred for maintenance of wakefulness tests (MWT) at a tertiary university center were recruited between 2017 and 2020. Clinical data and polysomnography parameters were compared between patients with vs without subjective sleepiness (Epworth Sleepiness Scale, ESS≥11) and those with vs without impaired alertness (at least one trial with sleep onset on MWT). A multivariate logistic model was used to assess explanatory variables of MWT and ESS results. We included 141 patients, of whom 12.8 % had both subjective sleepiness and objective impaired alertness, 17.7 % objective impaired alertness only and 9.2 % subjective sleepiness only. Self-reported history of car accident/near miss, smoking history and ESS≥11 were significantly associated with objective impaired alertness whereas residual Apnea-hypopnea Index and CPAP use were not. The only significant variable associated with ESS at the time of MWT evaluation was initial ESS. Patients with objective impaired alertness only were more often smokers (52 % vs 19 %, p = 0.01), had a higher body mass index (BMI) (32 vs 29 kg/m2, p = 0.05), and showed lower initial ESS (11 vs 13, p < 0.01). More than one third of OSA treated patients referred for MWT have objective impaired alertness and/or subjective sleepiness. Our findings highlight the need for a comprehensive medical assessment including accident history, subjective sleepiness and comorbidities. Particular attention should be paid to smoking patients with high BMI, who are at risk of impaired alertness with no report of subjective sleepiness. • Up to 40 % of treated OSA patients have residual sleepiness and/or impaired alertness. • Maintenance Wakefulness Test and Epworth sleepiness scale results discrepant in 25 % of treated OSA patients. • Self-reported history of car accident, smoking and ESS≥11 are associated with impaired alertness. • Smoking and high BMI are at risk of impaired alertness without report of sleepiness. [ABSTRACT FROM AUTHOR]

Pre-sleep stress or hyperarousal is a known key etiological component in insomnia disorder. Despite this, physiological alterations during the sleep onset are not well-understood. In particular, insomnia and obstructive sleep apnea (OSA) are highly prevalent co-morbid conditions, where autonomic regulation may be altered. We aimed to characterize heart rate variability (HRV) during sleep onset as a potential measure of pre-sleep hyperarousal. We described the profile of pre-sleep HRV measures and explore autonomic differences in participants with self-reported insomnia disorder (with no OSA, n = 69; with mild OSA, n = 70; with moderate or severe OSA, n = 66), compared to normal sleep controls (n = 123). Heart rate data during the sleep onset process were extracted for HRV analyses. During the sleep onset process, compared to normal sleep controls, participants with insomnia had altered HRV, indicated by higher heart rate (p = 0.004), lower SDNN (p = 0.003), reduced pNN20 (p < 0.001) and pNN50 (p = 0.010) and lower powers (p < 0.001). Participants with insomnia and moderate/severe OSA may have further deteriorated HRV outcomes compared to no/mild OSA patients with insomnia but differences were not significant. Insomnia itself was associated with significantly higher heart rate, lower pNN20, and lower high frequency power even after adjustment for age, gender, BMI and OSA severity. Participants with insomnia had lower vagal activity during the sleep onset period, which may be compounded by OSA, reflected in higher heart rates and lower HRV. These altered heart rate dynamics may serve as a physiological biomarker for insomnia during bedtime wakefulness, or as a potential tool to evaluate the efficacy of behavioral interventions which target bedtime stress. • Altered heart rate dynamics may present in subjects with insomnia even before sleep. • HRV may be a biomarker of hyper-arousal during wakefulness before sleep onset. • Tracking HRV during sleep onset may have value in evaluation/treatments for insomnia. • Bedtime HRV is a target marker for sleep onset difficulty due to hyperarousal/stress. [ABSTRACT FROM AUTHOR]

Dexmedetomidine (DEX) is a highly selective α2-adrenoceptor agonist with sedative effects on sleep homeostasis. Oxytocin-expressing (OXT) neurons in the paraventricular nucleus (PVN) of the hypothalamus (PVNOXT) regulate sexual reproduction, drinking, sleep-wakefulness, and other instinctive behaviors. To investigate the effect of DEX on the activity and signal transmission of PVNOXT in regulating the sleep-wakefulness cycle. Here, we employed OXT-cre mice to selectively target and express the designer receptors exclusively activated by designer drugs (DREADD)-based chemogenetic tool hM3D(Gq) in PVNOXT neurons. Combining chemogenetic methods with electroencephalogram (EEG) /electromyogram (EMG) recordings, we found that cannula injection of DEX in PVN significantly increased the duration of non-rapid eye movement (NREM) sleep in mice. Furthermore, the chemogenetic activation of PVNOXT neurons using i.p. injection of clozapine N-oxide (CNO) after cannula injection of DEX to PVN led to a substantial increase in wakefulness. Electrophysiological results showed that DEX decreased the frequency of action potential (AP) and the spontaneous excitatory postsynaptic current (sEPSC) of PVNOXT neurons through α2-adrenoceptors. Therefore, these results identify that DEX promotes sleep and maintains sleep homeostasis by inhibiting PVNOXT neurons through the α2-adrenoceptor. [ABSTRACT FROM AUTHOR]

The antecedents and determinants of entrepreneurial capabilities and competencies remain one of the incontestable questions that drive the exploitation and discovery of effective financial and digital opportunities. In the present paper, we propose a conceptual model based on Kirzner's alertness theory [entrepreneurial alertness] and rely on two factors [entrepreneurial orientation and marketing orientation] as key accelerators of entrepreneurial financial alertness. We assume that entrepreneurial financial alertness (EFA) might have a direct impact on entrepreneurial finance-based digital transformation (EFDT), which in turn, is expected to predict both innovation entrepreneurial finance (IEF) and SMEs' entrepreneurial performance (SMEEP). Structural equation modeling (SEM) was employed using data collected from a purposive sample size of 214 Jordanian entrepreneurs. Our findings largely support the impact of EFA on EFDT. EFDT was also supported having a significant impact on both IEF and SMEEP. Our study has many implications for both researchers and practitioners in the area of entrepreneurial finance-based digital transformation. The study has great added-value by proposing and examining a solid theoretical foundation covering the most influential factors that drive digital entrepreneurial transformation as such transformation stands as an emerging and pressing issue, not fully tackled by prior studies. [ABSTRACT FROM AUTHOR]

Sleep is regulated by homeostatic processes, yet the biological basis of sleep pressure that accumulates during wakefulness, triggers sleep, and dissipates during sleep remains elusive. We explored a causal relationship between cellular synaptic strength and electroencephalography delta power indicating macro-level sleep pressure by developing a theoretical framework and a molecular tool to manipulate synaptic strength. The mathematical model predicted that increased synaptic strength promotes the neuronal “down state” and raises the delta power. Our molecular tool (synapse-targeted chemically induced translocation of Kalirin-7, SYNCit-K), which induces dendritic spine enlargement and synaptic potentiation through chemically induced translocation of protein Kalirin-7, demonstrated that synaptic potentiation of excitatory neurons in the prefrontal cortex (PFC) increases nonrapid eye movement sleep amounts and delta power. Thus, synaptic strength of PFC excitatory neurons dictates sleep pressure in mammals. [ABSTRACT FROM AUTHOR]

Summary Cognitive and Behavioural Therapy for Insomnia (CBT‐I) is the gold standard treatment for chronic insomnia, with one crucial step being the restriction of time spent in bed. This restriction often intensifies early afternoon sleepiness, leading to a natural gateway for a short recuperative nap, which might foster adherence to CBT‐I over time. In practice, mental health professionals providing CBT‐I lack consensus on whether or not to tolerate short naps during the CBT‐I period for requesting patients. In this pilot study, we examined the effects of authorised napping on CBT‐I efficiency in patients with insomnia (a napping group was compared with a matched non‐napping group, n = 108). We report that napping enhanced early afternoon alertness and importantly did not affect CBT‐I‐mediated improvements in the Insomnia Severity Index and Beck Depression Inventory‐2 and in self‐reported sleep efficiency, latency, and wake after sleep onset (assessed by the sleep diaries). Further investigations using objective methods of sleep assessments are now needed to confirm that napping behaviour does not compromise the improvements enabled by CBT‐I and may even strengthen adherence to the treatment. [ABSTRACT FROM AUTHOR]

The role of experience in the development and maintenance of emergent network properties such as cortical oscillations and states is poorly understood. To define how early-life experience affects cortical dynamics in the visual cortex of adult, head-fixed mice, we examined the effects of two forms of blindness initiated before eye opening and continuing through recording: (1) bilateral loss of retinal input (enucleation) and (2) degradation of visual input (eyelid suture). Neither form of deprivation fundamentally altered the state-dependent regulation of firing rates or local field potentials. However, each deprivation caused unique changes in network behavior. Laminar analysis revealed two different generative mechanisms for low-frequency synchronization: one prevalent during movement and the other during quiet wakefulness. The former was absent in enucleated mice, suggesting a mouse homolog of human alpha oscillations. In addition, neurons in enucleated animals were less correlated and fired more regularly, but no change in mean firing rate. Eyelid suture decreased firing rates during quiet wakefulness, but not during movement, with no effect on neural correlations or regularity. Sutured animals showed a broadband increase in depth EEG power and an increased occurrence, but reduced central frequency, of narrowband gamma oscillations. The complementary—rather than additive—effects of lid suture and enucleation suggest that the development of emergent network properties does not require vision but is plastic to modified input. Our results suggest a complex interaction of internal set points and experience determines mature cortical activity, with low-frequency synchronization being particularly susceptible to early deprivation. [ABSTRACT FROM AUTHOR]

Introduction: Breast cancer is the most prevalent cancer among women, often necessitating surgical intervention. While surgeries like lumpectomy can be performed under local anesthesia, more extensive procedures typically require general anesthesia. Awake breast cancer surgery has emerged as an alternative due to risks associated with general anesthesia and patient preference. Methods: This prospective observational study, conducted from July 2022 to July 2023, evaluated the effectiveness of ultrasound-guided fascial plane blocks for awake breast surgery. Patients aged 18–80 years undergoing unilateral breast surgery were included, following ethical committee approval and written informed consent. Exclusion criteria were prior breast surgery, coagulopathies, infections, allergies to local anesthetics, psychiatric disorders, body mass index over 40 kg/m², and chest deformities. The combination of interpectoral, pecto-serratus, and deep serratus plane blocks was used as the primary anesthetic method, with a superficial parasternal block added in cases where complete cutaneous coverage was not achieved. Results: Seventeen patients were enrolled. The primary outcome, sufficient surgical anesthesia without deep sedation, was achieved in 15 patients. The combination of the aforementioned blocks proved effective, with an average surgery duration of 59.66 min, and propofol requirements averaging 1.77 mg/kg/hour. Most patients reported high satisfaction levels, and no early or late block-related complications were observed. Conclusion: The combination of fascial plane blocks is a viable option for awake breast cancer surgery, potentially eliminating the need for more invasive anesthesia techniques. Further studies are necessary to confirm these findings in larger, homogeneous patient groups. [ABSTRACT FROM AUTHOR]

Background: Stress cardiomyopathy (SCM) is an acute heart failure syndrome characterized by transient, usually reversible left ventricular systolic dysfunction with normal or enhanced basal compensatory wall motion abnormalities involving the left ventricular anterior septum and apex, resulting in a "ballooning" appearance. However, it has rarely been reported in patients undergoing spinal surgery. Case presentation: We report a case of severe stress cardiomyopathy in a scoliosis patient with pectus excavatum who underwent spinal corrective surgery. During the wake-up period, circulatory collapse occurred. After multidisciplinary consultation, the patient was diagnosed with stress cardiomyopathy. At last, she had a good prognosis after a series of treatments including ECMO. Conclusion: Stress cardiomyopathy is a reversible but uncommon condition. It can cause death if it is not diagnosed in time. Consequently, this report should improve the awareness of orthopedists and anesthesiologists for timely identification and management. For patients with potential risk factors, timely preoperative intervention should be performed to reduce the occurrence of stress cardiomyopathy. [ABSTRACT FROM AUTHOR]

This systematic review aims to identify the sleep parameters of Olympic athletes and the instruments used to assess and monitor the sleep of these athletes. The search was conducted until February 2023 and was performed in PubMed, Web of Science, and Scopus databases. This systematic review has included studies that investigated at least one of the following sleep parameters: total sleep time (TST), sleep onset latency (SOL), sleep efficiency (SE), awakenings after sleep onset (WASO), quality of sleep, daytime sleepiness, and chronotype; the participants were Olympic athletes. The search returned a total of 280 studies. After screening based on exclusion and inclusion criteria, 11 studies were included. The main results demonstrate that Olympic athletes have TST of 06:10 h, SE of 84%, SOL of 28 min, and WASO of 49 min. The most predominant chronotype is indifferent; over half of the athletes have poor sleep quality and complaints. Furthermore, actigraphy was the most used method to assess sleep. It is concluded that Olympic athletes have TST, SE, and WASO poor than the recommended values. In addition, sleep complaints and poor sleep quality were also observed. Among the objective sleep assessment methods, actigraphy was the method most frequently used in this population. [ABSTRACT FROM AUTHOR]

Narcolepsy type 1 (NT1) is associated with severe loss of orexin neurons and characterized by symptoms including excessive daytime sleepiness and cataplexy. Current medications indicated for NT1 often show limited efficacy, not addressing the full spectrum of symptoms, demonstrating a need for novel drugs. We discovered a parenteral orexin receptor 2 (OX2R) agonist, danavorexton, and an orally available OX2R agonist, TAK-994; both improving NT1 phenotypes in mouse models and individuals with NT1. However, danavorexton has limited oral availability and TAK-994 has a risk of off-target liver toxicity. To avoid off-target-based adverse events, a highly potent molecule with low effective dose is preferred. Here, we show that a novel OX2R-selective agonist, TAK-861 [N-{(2S,3R)-4,4-Difluoro-1-(2-hydroxy-2-methylpropanoyl)-2-[(2,3′,5′-trifluoro[1,1′-biphenyl]-3-yl)methyl]pyrrolidin-3-yl}ethanesulfonamide], activates OX2R with a half-maximal effective concentration of 2.5 nM and promotes wakefulness at 1 mg/kg in mice and monkeys, suggesting ~ tenfold higher potency and lower effective dosage than TAK-994. Similar to TAK-994, TAK-861 substantially ameliorates wakefulness fragmentation and cataplexy-like episodes in orexin/ataxin-3 and orexin-tTA;TetO DTA mice (NT1 mouse models). Compared with modafinil, TAK-861 induces highly correlated brain-wide neuronal activation in orexin-tTA;TetO DTA mice, suggesting efficient wake-promoting effects. Thus, TAK-861 has potential as an effective treatment for individuals with hypersomnia disorders including narcolepsy, potentially with a favorable safety profile. [ABSTRACT FROM AUTHOR]

This article emphasizes the importance of using subjective measures, such as sleep diaries, to assess insomnia. It argues that objective measures like polysomnography (PSG) are not suitable for diagnosing or treating insomnia, as they are only effective for sleep disorders with underlying pathologies. Sleep diaries are considered more accurate because they capture an individual's perception of sleep continuity over multiple nights. The article also discusses the limitations of objective measures, such as EEG-based devices and wearables, in accurately assessing sleep continuity in individuals with insomnia. It concludes that until a pathophysiological measure is discovered for insomnia, sleep diaries remain the optimal method for assessing sleep continuity disturbance. The Insomnia Severity Index (ISI) is often recommended as the best measure for assessing insomnia, but it has its own limitations. Insomnia is a psychophysiological condition that can be evaluated using a combination of subjective and objective measures, and it is important to understand the strengths and limitations of each method and explore discrepancies between them. The document also provides a list of references covering various aspects of insomnia, including its impact on neuropsychological performance, cognitive impairment, pharmacotherapy for older adults, perception of sleep, use of placebos in treatment, actigraphy as a measurement tool, and assessment and management of insomnia. These references offer a comprehensive overview of current research and understanding of insomnia. [Extracted from the article]

The article highlights the critical role of sleep as one of the three pillars of wellness, alongside nutrition and exercise, and highlights its often-overlooked importance among medical professionals. Topics discussed include the physiological mechanisms of sleep, the impact of aging on sleep quality, and the body's circadian and ultradian rhythms.

Orexin is exclusively produced in neurons localized within the lateral hypothalamic area (LHA) and perifornical area (PFA). Orexin has been identified as a key promotor of arousal. The selective loss of orexinergic neurons results in narcolepsy. It is known that the intrinsic electrophysiological properties are critical for neurons to perform their functions in corresponding brain regions. In addition to hypothalamic orexin, other brain nuclei are involved in the regulation of sleep and wakefulness. Quite a lot of studies focus on elucidating orexin‐induced regulation of sleep–wake states and modulation of neuronal electrophysiological properties in several brain regions. Here, we summarize that the orexinergic neurons exhibit spontaneous firing activity which is associated with the states of sleep–wake cycle. Orexin mainly exerts postsynaptic excitatory effects on multiple brain nuclei associated with the process of sleep and wakefulness. This review may provide a background to guide future research about the cellular mechanisms of orexin‐induced maintaining of arousal. [ABSTRACT FROM AUTHOR]

Background: The lateral hypothalamus (LHA) is an evolutionarily conserved structure that regulates basic functions of an organism, particularly wakefulness. To clarify the function of LHAGABA neurons and their projections on regulating general anesthesia is crucial for understanding the excitatory and inhibitory effects of anesthetics on the brain. The aim of the present study is to investigate whether LHAGABA neurons play either an inhibitory or a facilitatory role in sevoflurane‐induced anesthetic arousal regulation. Methods: We used fiber photometry and immunofluorescence staining to monitor changes in neuronal activity during sevoflurane anesthesia. Opto‐/chemogenetic modulations were employed to study the effect of neurocircuit modulations during the anesthesia. Anterograde tracing was used to identify a GABAergic projection from the LHA to a periaqueductal gray (PAG) subregion. Results: c‐Fos staining showed that LHAGABA activity was inhibited by induction of sevoflurane anesthesia. Anterograde tracing revealed that LHAGABA neurons project to multiple arousal‐associated brain areas, with the lateral periaqueductal gray (LPAG) being one of the dense projection areas. Optogenetic experiments showed that activation of LHAGABA neurons and their downstream target LPAG reduced the burst suppression ratio (BSR) during continuous sevoflurane anesthesia. Chemogenetic experiments showed that activation of LHAGABA and its projection to LPAG neurons prolonged the anesthetic induction time and promoted wakefulness. Conclusions: In summary, we show that an inhibitory projection from LHAGABA to LPAGGABA neurons promotes arousal from sevoflurane‐induced loss of consciousness, suggesting a complex control of wakefulness through intimate interactions between long‐range connections. [ABSTRACT FROM AUTHOR]

The article focuses on the complexities surrounding decisions to withdraw life-sustaining treatment in light of recent case studies. Topics include the impact of new research on the decision-making process for traumatic brain injury patients, the influence of high-profile recovery cases on family expectations, and the challenges of inconsistent prognostic information from different clinicians.

Following mild traumatic brain injury (mTBI), children show reduced processing speed (PS). Evidence suggests that slowed PS after TBI is associated with working memory deficits. Our aim was to investigate several forms of PS and to examine its impact on working and episodic memory performance in children after mTBI. We included data of 64 children after mTBI and 57 healthy control children aged 8–16 years. PS (Color Naming, Coding, Symbol Search, Alertness) was compared between groups 1 week (T1) and 3–6 months (T2) after the injury; working and episodic memory outcome was compared between groups at T2. Alertness at T1 and Color Naming at T1 and T2 were significantly reduced following mTBI compared to controls, although most group differences in PS disappeared when patients with previous impairments and mTBI were excluded. PS was predictive for episodic and working memory performance 3–6 months after injury, whereas group was a significant predictor of working memory. Compared to healthy controls, children after mTBI showed reduced performance in verbal PS, which was associated with working memory. In children who are symptomatic after mTBI, diagnostic screening of PS could be helpful in identifying patients that could profit from speed-improving strategies. [ABSTRACT FROM AUTHOR]

The rapid technology growth in the maritime defense sector demands efficient and effective human performance, particularly in roles involving navigation, tactical decision-making, and emergency responses. To accommodate this demand, our study aims to find the effects of the two most significant performance influencing factors i.e., mental alertness and workload on the performance of Electronic Support Measures (ESM) receiver operators in complex task environments of a surface combat ship. A Discrete Event Simulation model with the Task Network Modeling approach was developed in IPME software. Alertness, measured by the Karolinska Sleepiness Scale (KSS), was predicted for Crew Chiefs' schedules (4–8, 6–6, and 8–8) using the Three Process Model in FIPS software. The simulation integrated KSS predictions and VACP workload values, with 10 simulation runs, for each schedule, to assess the effects of mental alertness and workload on the total number of signals missed, the total number of signals logged, and percentage time at risk. The findings reveal that mental alertness variation due to different shift patterns in combination with mental workload significantly influence performance metrics, especially during night time operations, highlighting potential attention lapses and reduced efficiency. This comprehensive analysis provides valuable insights into the dynamics of shift work and task demands, aiming to enhance operational safety and performance in critical environments. The study's methodology and findings offer a foundation for further research and practical applications in various industries where managing mental alertness and workload is crucial for safety and efficient crew performance. [ABSTRACT FROM AUTHOR]

With vehicle automation becoming more commonplace, the role of the human driver is shifting from that of system operator to that of system supervisor. With this shift comes the risk of drivers becoming more disengaged from the task of supervising the system functioning, thus increasing the need for technology to keep drivers alert. This special issue includes the most up-to-date research on how drivers use vehicle automation, and the safety risks it may pose. It also investigates the accuracy that driver monitoring systems have in detecting conditions like driver distraction and drowsiness, and explores ways future drivers may respond to the broader introduction of this technology on passenger vehicles. [ABSTRACT FROM AUTHOR]

During the Covid‐19 pandemic new stressors were added to the usual challenges parents face, changing habits and reduced physical activity, all factors that negatively affect sleep quality in adults and children. This study examines (1) possible changes in the sleep‐wake patterns of parents and children before and after the March–May 2020 lockdown and during the new restrictions imposed by the Italian government in March 2021; (2) possible associations between children and parents' sleep quality reported by parents and intrinsic and extrinsic factors. A total of 264 Italian parents with children aged 1–6 years (M = 40 months, SD = 18.18) completed self‐report questionnaires. Children's sleep habits changed, and parental insomnia symptoms worsened after the March–May 2020 lockdown, while children's insomnia symptoms decreased. Positive associations between children's negative affectivity and insomnia symptoms emerged, as well as between generalized parental anxiety and parental insomnia symptoms and between parental fear of Covid‐19 and sleep‐related habits not in line with paediatric recommendations. Partner's involvement in children's care promoted good sleep habits. Results identified risks and protective factors that could impact Italian parents' and children's sleep during the second wave of the Covid‐19 pandemic, raising awareness among families, education practitioners, healthcare providers and the general public. Highlights: Italian children's sleep habits changed, and parental insomnia symptoms worsened after the March–May 2020 lockdown, while children's insomnia symptoms decreased.During the second wave of the Covid‐19 pandemic, higher levels of children's temperamental negative affectivity were associated with higher levels of parental and children's insomnia, higher levels of parental anxiety, and the presence of children's sleep‐related habits not in line with pediatric recommendations.Partner's involvement in children's care promoted good and healthy children's sleep habits. [ABSTRACT FROM AUTHOR]

The state of the driver of being extremely tired or sleepy through the operation of the vehicle is called driver drowsiness. Different factors caused this state such as alcohol, lack of sleep, and the side effect of some medication. The drowsiness of drivers is a serious safety lead to accidents or fatalities on external and internal roads. The increased number of road accidents resulted from drowsy driving. A special smart, reliable, and accurate system, Using Python language 3.6 for Windows, was designed to build an alert system for drivers in detecting drowsiness driver. This system is crucial in reducing accidents road by the ability to concentrate, react quickly, and produce sound decisions through driving. This system implements a real-time detector that can monitor the states of drivers through driving. Smart cameras with 16-megapixel were used to ensure that capturing photos have a high quality. These cameras were used in gathering the driver's dataset in different alertness states, including both alert states and drowsy. The collected dataset is processed by extracting all relevant features such as head movement, yawning, and eye closure, which were used in identifying the driver's drowsiness. Python's libraries such as TensorFlow, OpenCV, Keras, and Pygame are used for extracting all the above features. Viola-Jones algorithm is used in face eye region detecting and extracting from the image of the face in the proposed system. A Support Vector Machine (SVM) algorithm was used in classifying between drowsy and non-drowsy drivers. The system is tested and evaluated in the real world, to ensure that the system is reliable and robust; it has high performance and accuracy, and the accuracy is about 99.1%. This system can be used in manufacturing vehicles. [ABSTRACT FROM AUTHOR]

Background: This study aimed to investigate the unique electroencephalography (EEG) patterns in neuronopathic Gaucher disease (GD) patients and explore the correlations between EEG findings and neurological phenotypes so as to optimize clinical outcomes. Methods: A retrospective analysis was conducted on 74 EEG recordings from 50 GD patients between January 2012 and July 2022. Results: Twenty-three patients exhibited abnormal EEG recordings, including 11 of the GD1 type (the transitional type) and 12 with neuronopathic GD. Of the 12 neuronopathic GD patients, 9 patients with epilepsy were analysed specifically in terms of the clinical course. The primary waveform observed in the neuronopathic EEG recordings was the spike-and-wave complex (SWC) during both awake and sleep states. This was significantly different from sharp waves observed only during sleep in the patients of the transitional type (P = 0.0230). The abnormal discharges in the neuronopathic patients were most commonly located in the bilateral Rolandic areas, while the transitional type commonly involved the bilateral frontal regions. Three patients with an epileptic EEG pattern reported their initial seizures years later. Seizures in the neuronopathic patients were effectively controlled with anti-seizure medications (ASMs), despite the ongoing presence of abnormal EEG patterns. The EEG patterns during ocular symptoms were characterized by sporadic or continuous unilateral SWC during sleep. Conclusions: Patients with neuronopathic GD exhibit distinct EEG patterns that can help differentiate them from GD1 patients. Early treatment with ASMs can effectively control seizures. EEG plays a crucial role in monitoring seizures and can facilitate prompt intervention for GD patients. [ABSTRACT FROM AUTHOR]

Qiaoting Huang,1 Changzheng Shi,2 Saurabh Sonkusare,3 Congrui Li,1 Valerie Voon,3 Jiyang Pan1 1Department of Psychiatry, The First Affiliated Hospital of Jinan University, Guangzhou, People’s Republic of China; 2Medical Imaging Center, The First Affiliated Hospital of Jinan University, Guangzhou, People’s Republic of China; 3Department of Psychiatry, University of Cambridge, Cambridge, UKCorrespondence: Jiyang Pan, Department of Psychiatry, The First Affiliated Hospital of Jinan University, 613 West Huangpu Avenue, Guangzhou, 510630, People’s Republic of China, Tel +86 20 38688651, Email jiypan@163.com Valerie Voon, Department of Psychiatry, University of Cambridge, Box 189, Level E4, Addenbrooke’s Hospital, Cambridge, CB2 0QQ, UK, Tel +44 1223 765088, Email vv247@cam.ac.ukPurpose: Converging evidence implicates the putamen in sleep-wake regulation. However, its role remains unclear. We hypothesized that metabolic abnormalities in the putamen are linked to insomnia disorder, which has not been previously addressed, and investigated putaminal N-acetylaspartate (NAA), choline (Cho), and creatine (Cr) in patients with insomnia disorder compared to healthy controls.Participants and Methods: In the present study, the concentrations of NAA, Cho, and Cr in the putamen of 23 patients with insomnia disorder and 18 healthy controls were determined using proton magnetic resonance spectroscopy. Sociodemographic, psychometric, and polysomnography data were obtained from all participants.Results: We found that the mean NAA/Cr ratio of the right putamen was significantly greater in the insomnia group compared to the control group and also greater than the left putamen within the insomnia group. The NAA/Cr ratio of the right putamen distinguished insomnia disorder from normal sleep with 78.3% sensitivity and 61.1% specificity. Furthermore, this ratio positively correlated with both objective and subjective insomnia severity and sleep quality.Conclusion: Our findings provide critical evidence for the dysfunctional putaminal metabolism of NAA/Cr in insomnia disorder, suggesting that the abnormal NAA/Cr ratio of the right putamen is linked to wakefulness in patients with insomnia disorder and may serve as a potential biomarker of insomnia disorder.Keywords: insomnia disorder, wakefulness, putamen, proton magnetic resonance spectroscopy, NAA/Cr ratio, polysomnography

Sleep is a highly stereotyped phenomenon, requiring robust spatiotemporal coordination of neural activity. Understanding how the brain coordinates neural activity with sleep onset can provide insights into the physiological functions subserved by sleep and the pathologic phenomena associated with sleep onset. We quantified whole-brain network changes in synchrony and information flow during the transition from wakefulness to light non-rapid eye movement (NREM) sleep, using MEG imaging in a convenient sample of 14 healthy human participants (11 female; mean 63.4 years [SD 11.8 years]). We furthermore performed computational modeling to infer excitatory and inhibitory properties of local neural activity. The transition from wakefulness to light NREM was identified to be encoded in spatially and temporally specific patterns of long-range synchrony. Within the delta band, there was a global increase in connectivity from wakefulness to light NREM, which was highest in frontoparietal regions. Within the theta band, there was an increase in connectivity in fronto-parieto-occipital regions and a decrease in temporal regions from wakefulness to Stage 1 sleep. Patterns of information flow revealed that mesial frontal regions receive hierarchically organized inputs from broad cortical regions upon sleep onset, including direct inflow from occipital regions and indirect inflow via parieto-temporal regions within the delta frequency band. Finally, biophysical neural mass modeling demonstrated changes in the anterior-to-posterior distribution of cortical excitation-to-inhibition with increased excitation-to-inhibition model parameters in anterior regions in light NREM compared with wakefulness. Together, these findings uncover whole-brain corticocortical structure and the orchestration of local and long-range, frequency-specific cortical interactions in the sleep-wake transition.SIGNIFICANCE STATEMENT Our work uncovers spatiotemporal cortical structure of neural synchrony and information flow upon the transition from wakefulness to light non-rapid eye movement sleep. Mesial frontal regions were identified to receive hierarchically organized inputs from broad cortical regions, including both direct inputs from occipital regions and indirect inputs via the parieto-temporal regions within the delta frequency range. Biophysical neural mass modeling revealed a spatially heterogeneous, anterior-posterior distribution of cortical excitation-to-inhibition. Our findings shed light on the orchestration of local and long-range cortical neural structure that is fundamental to sleep onset, and support an emerging view of cortically driven regulation of sleep homeostasis.

Background: Human circadian clocks are synchronized daily with the external light-dark cycle and entrained to the 24-hour day. There is increasing evidence that a lack of synchronization and circadian entrainment can lead to adverse health effects. Beyond vision, light plays a critical role in modulating many so-called non-visual functions, including sleep-wake cycles, alertness, mood and endocrine functions. To assess (and potentially optimize) the impact of light on non-visual functions, it is necessary to know the exact 'dose' (i.e. spectral irradiance and exposure duration at eye level) of 24-hour light exposures, but also to include metadata about the lighting environment, individual needs and resources. Problem statement: To address this problem, a new assessment tool is needed that uses existing metrics to provide metadata and information about light quality and quantity from all sources. In this commentary, we discuss the need to develop an evidence-based integrative lighting score that is tailored to specific audiences and lighting environments. We will summarize the most compelling evidence from the literature and outline a future plan for developing such a lighting score using internationally accepted metrics, stakeholder and user feedback. Conclusion: We propose a weighting system that combines light qualities with physiological and behavioral effects, and the use of mathematical modelling for an output score. Such a scoring system will facilitate a holistic assessment of a lighting environment, integrating all available light sources. [ABSTRACT FROM AUTHOR]