Increased wakefulness as measured by the WAKE-16 is related to mindfulness and emotional self-regulation in experienced Buddhist meditators.

INTRODUCTION: We tested and validated the German version of a new instrument for measuring "wakefulness," defined as "an expansive, higher-functioning, and stable state of being in which a person's vision of and relationship to the world are transformed, along with their subjective experience, their sense of identity and their conceptual outlook" (Taylor, 2017, p. 22). METHODS: In order to test the construct validity of the new instrument (Inventory of Secular/Spiritual Wakefulness; WAKE-16), we performed a parametric comparison between a group of expert meditators (n=36) with a history of predominantly meditating in silence and demographically matched non-meditators (n=36) for the WAKE-16 and two conceptually related questionnaires of mindfulness and emotion regulation. RESULTS: Significantly higher scores for the meditators on the WAKE-16 indicate construct validity of the new instrument. Meditators scored higher on the two mindfulness subscales "presence" and "acceptance," as well as on the SEE subscales of emotion regulation and body-related symbolization of emotions. Within the group of meditators, there were significant correlations between wakefulness and mindfulness, accepting one's own emotions, and experiencing overwhelming emotions. The only significant correlation in non-meditators was found between wakefulness and accepting one's own emotions. DISCUSSION: The new instrument shows construct validity by discriminating between the two groups. Correlations between wakefulness and related psychological constructs indicate convergent validity. Future studies could attempt to increase discriminatory accuracy of the definition of wakefulness, as well as finding objective methods of measuring.

Existence of multiple transitions of the critical state due to anesthetics.

Scale-free statistics of coordinated neuronal activity, suggesting a universal operating mechanism across spatio-temporal scales, have been proposed as a necessary condition of healthy resting-state brain activity. Recent studies have focused on anesthetic agents to induce distinct neural states in which consciousness is altered to understand the importance of critical dynamics. However, variation in experimental techniques, species, and anesthetics, have made comparisons across studies difficult. Here we conduct a survey of several common anesthetics (isoflurane, pentobarbital, ketamine) at multiple dosages, using calcium wide-field optical imaging of the mouse cortex. We show that while low-dose anesthesia largely preserves scale-free statistics, surgical plane anesthesia induces multiple dynamical modes, most of which do not maintain critical avalanche dynamics. Our findings indicate multiple pathways away from default critical dynamics associated with quiet wakefulness, not only reflecting differences between these common anesthetics but also showing significant variations in individual responses. This is suggestive of a non-trivial relationship between criticality and the underlying state of the subject.

Unobtrusive Skin Temperature Estimation on a Smart Bed.

The transition from wakefulness to sleep occurs when the core body temperature decreases. The latter is facilitated by an increase in the cutaneous blood flow, which dissipates internal heat into the micro-environment surrounding the sleeper's body. The rise in cutaneous blood flow near sleep onset causes the distal (hands and feet) and proximal (abdomen) temperatures to increase by about 1 °C and 0.5 °C, respectively. Characterizing the dynamics of skin temperature changes throughout sleep phases and understanding its relationship with sleep quality requires a means to unobtrusively and longitudinally estimate the skin temperature. Leveraging the data from a temperature sensor strip (TSS) with five individual temperature sensors embedded near the surface of a smart bed's mattress, we have developed an algorithm to estimate the distal skin temperature with a minute-long temporal resolution. The data from 18 participants who recorded TSS and ground-truth temperature data from sleep during 14 nights at home and 2 nights in a lab were used to develop an algorithm that uses a two-stage regression model (gradient boosted tree followed by a random forest) to estimate the distal skin temperature. A five-fold cross-validation procedure was applied to train and validate the model such that the data from a participant could only be either in the training or validation set but not in both. The algorithm verification was performed with the in-lab data. The algorithm presented in this research can estimate the distal skin temperature at a minute-level resolution, with accuracy characterized by the mean limits of agreement [-0.79 to +0.79 °C] and mean coefficient of determination R2=0.87. This method may enable the unobtrusive, longitudinal and ecologically valid collection of distal skin temperature values during sleep. Therelatively small sample size motivates the need for further validation efforts.

Prolonged vs shorter awake prone positioning for COVID-19 patients with acute respiratory failure: a multicenter, randomised controlled trial.

PURPOSE: Awake prone positioning has been reported to reduce endotracheal intubation in patients with coronavirus disease 2019 (COVID-19)-related acute hypoxemic respiratory failure (AHRF). However, it is still unclear whether using the awake prone positioning for longer periods can further improve outcomes. METHODS: In this randomized, open-label clinical trial conducted at 12 hospitals in China, non-intubated patients with COVID-19-related AHRF were randomly assigned to prolonged awake prone positioning (target > 12 h daily for 7 days) or standard care with a shorter period of awake prone positioning. The primary outcome was endotracheal intubation within 28 days after randomization. The key secondary outcomes included mortality and adverse events. RESULTS: In total, 409 patients were enrolled and randomly assigned to prolonged awake prone positioning (n = 205) or standard care (n = 204). In the first 7 days after randomization, the median duration of prone positioning was 12 h/d (interquartile range [IQR] 12-14 h/d) in the prolonged awake prone positioning group vs. 5 h/d (IQR 2-8 h/d) in the standard care group. In the intention-to-treat analysis, intubation occurred in 35 (17%) patients assigned to prolonged awake prone positioning and in 56 (27%) patients assigned to standard care (relative risk 0.62 [95% confidence interval (CI) 0.42-0.9]). The hazard ratio (HR) for intubation was 0.56 (0.37-0.86), and for mortality was 0.63 (0.42-0.96) for prolonged awake prone positioning versus standard care, within 28 days. The incidence of pre-specified adverse events was low and similar in both groups. CONCLUSION: Prolonged awake prone positioning of patients with COVID-19-related AHRF reduces the intubation rate without significant harm. These results support prolonged awake prone positioning of patients with COVID-19-related AHRF.

Electroencephalography Measurements in Awake Marmosets Listening to Conspecific Vocalizations.

Vocal communication plays a crucial role in the social interactions of primates, particularly in survival and social organization. Humans have developed a unique and advanced vocal communication strategy in the form of language. To study the evolution of human language, it is necessary to investigate the neural mechanisms underlying vocal processing in humans, as well as to understand how brain mechanisms have evolved by comparing them with those in nonhuman primates. Herein, we developed a method to noninvasively measure the electroencephalography (EEG) of awake nonhuman primates. This recording method allows for long-term studies without harming the animals, and, importantly, allows us to directly compare nonhuman primate EEG data with human data, providing insights into the evolution of human language. In the current study, we used the scalp EEG recording method to investigate brain activity in response to species-specific vocalizations in marmosets. This study provides novel insights by using scalp EEG to capture widespread neural representations in marmosets during vocal perception, filling gaps in existing knowledge.

A BARRage of firing while asleep.

Memory reactivation requires counterbalancing to consolidate memories.

EEG-fMRI in awake rat and whole-brain simulations show decreased brain responsiveness to sensory stimulations during absence seizures.

In patients suffering absence epilepsy, recurring seizures can significantly decrease their quality of life and lead to yet untreatable comorbidities. Absence seizures are characterized by spike-and-wave discharges on the electroencephalogram associated with a transient alteration of consciousness. However, it is still unknown how the brain responds to external stimuli during and outside of seizures. This study aimed to investigate responsiveness to visual and somatosensory stimulation in Genetic Absence Epilepsy Rats from Strasbourg (GAERS), a well-established rat model for absence epilepsy. Animals were imaged under non-curarized awake state using a quiet, zero echo time, functional magnetic resonance imaging (fMRI) sequence. Sensory stimulations were applied during interictal and ictal periods. Whole-brain hemodynamic responses were compared between these two states. Additionally, a mean-field simulation model was used to explain the changes of neural responsiveness to visual stimulation between states. During a seizure, whole-brain responses to both sensory stimulations were suppressed and spatially hindered. In the cortex, hemodynamic responses were negatively polarized during seizures, despite the application of a stimulus. The mean-field simulation revealed restricted propagation of activity due to stimulation and agreed well with fMRI findings. Results suggest that sensory processing is hindered or even suppressed by the occurrence of an absence seizure, potentially contributing to decreased responsiveness during this absence epileptic process.

Restoration of sleep-wake behavior following short photoperiod exposure in ventral subicular lesioned male Wistar rats: A 24-h sleep-wake electroencephalographical study.

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

Derivative Method to Detect Sleep and Awake States through Heart Rate Variability Analysis Using Machine Learning Algorithms.

Sleep disorders can have harmful consequences in both the short and long term. They can lead to attention deficits, as well as cardiac, neurological and behavioral repercussions. One of the most widely used methods for assessing sleep disorders is polysomnography (PSG). A major challenge associated with this method is all the cables needed to connect the recording devices, making the examination more intrusive and usually requiring a clinical environment. This can have potential consequences on the test results and their accuracy. One simple way to assess the state of the central nervous system (CNS), a well-known indicator of sleep disorder, could be the use of a portable medical device. With this in mind, we implemented a simple model using both the RR interval (RRI) and its second derivative to accurately predict the awake and napping states of a subject using a feature classification model. For training and validation, we used a database providing measurements from nine healthy young adults (six men and three women), in which heart rate variability (HRV) associated with light-on, light-off, sleep onset and sleep offset events. Results show that using a 30 min RRI time series window suffices for this lightweight model to accurately predict whether the patient was awake or napping.

Sleep-wake changes and incident depressive symptoms in midlife women.

Our study aimed to investigate the relationship between sleep-wake changes and depressive symptoms events among midlife women. We enrolled 1579 women aged 44-56 years who had no clinically relevant depressive symptoms at baseline. Depressive symptoms were assessed at each visit using the Center for Epidemiologic Studies Depression scale. At the third and fourth follow-up visits, women reported their sleep habits. The sleep midpoint was defined as the time to fall asleep plus one-half of the sleep duration. Sleep-wake changes were determined by the difference in the midpoint of sleep between the third and fourth visits, which were 1 year apart. The median follow-up time was 7 years (range 1-7 years). Cox proportional hazard models were fitted to calculate hazard ratios and 95% confidence intervals for the incidence of depressive symptoms associated with sleep-wake changes. After adjusting for potential confounding factors, the hazard ratio (95% confidence interval) of depressive symptoms for severe sleep midpoint changes was 1.51 (1.12, 2.05) compared with mild sleep midpoint changes. This relationship remained statistically significant and changed little when additionally controlling for sleep duration, sleep quality, insomnia symptoms, use of sleep medications, use of nervous medications, glucose, insulin, lipids, dietary energy intake, and C-reactive protein. Our findings indicate that exposure to long-term severe sleep-wake changes increases the risk of depressive symptoms in midlife women.

Astrocytic metabolic control of orexinergic activity in the lateral hypothalamus regulates sleep and wake architecture.

Neuronal activity undergoes significant changes during vigilance states, accompanied by an accommodation of energy demands. While the astrocyte-neuron lactate shuttle has shown that lactate is the primary energy substrate for sustaining neuronal activity in multiple brain regions, its role in regulating sleep/wake architecture is not fully understood. Here we investigated the involvement of astrocytic lactate supply in maintaining consolidated wakefulness by downregulating, in a cell-specific manner, the expression of monocarboxylate transporters (MCTs) in the lateral hypothalamus of transgenic mice. Our results demonstrate that reduced expression of MCT4 in astrocytes disrupts lactate supply to wake-promoting orexin neurons, impairing wakefulness stability. Additionally, we show that MCT2-mediated lactate uptake is necessary for maintaining tonic firing of orexin neurons and stabilizing wakefulness. Our findings provide both in vivo and in vitro evidence supporting the role of astrocyte-to-orexinergic neuron lactate shuttle in regulating proper sleep/wake stability.

Cortical parvalbumin neurons are responsible for homeostatic sleep rebound through CaMKII activation.

The homeostatic regulation of sleep is characterized by rebound sleep after prolonged wakefulness, but the molecular and cellular mechanisms underlying this regulation are still unknown. In this study, we show that Ca2+/calmodulin-dependent protein kinase II (CaMKII)-dependent activity control of parvalbumin (PV)-expressing cortical neurons is involved in homeostatic regulation of sleep in male mice. Prolonged wakefulness enhances cortical PV-neuron activity. Chemogenetic suppression or activation of cortical PV neurons inhibits or induces rebound sleep, implying that rebound sleep is dependent on increased activity of cortical PV neurons. Furthermore, we discovered that CaMKII kinase activity boosts the activity of cortical PV neurons, and that kinase activity is important for homeostatic sleep rebound. Here, we propose that CaMKII-dependent PV-neuron activity represents negative feedback inhibition of cortical neural excitability, which serves as the distributive cortical circuits for sleep homeostatic regulation.

Awake fiberoptic intubation of a patient with severe multiple trauma in prone position: a case report.

BACKGROUND: Fiberoptic-guided intubation is considered as "gold standard" of difficult airway management. Management of the airway in prone position in patients with severe trauma presenting with penetrating waist and hip injury poses a major challenge to the anesthesiologist. CASE PRESENTATION: A man presented with severe multiple trauma and hemorrhagic shock as a result of an industrial accident with several deformed steel bars penetrating the left lower waist and hip. It was decided to schedule an exploratory laparotomy following extracting the deformed steel bars. Successful administration of awake fiberoptic nasotracheal intubation, performed in a prone position under airway blocks and appropriate sedation, allowed for the procedure. The exploratory laparotomy revealed damage to multiple organs, which were repaired sequentially during a 7-hour surgical operation. The patient's recovery was uneventful, and he was discharged from the hospital one month after the surgery. CONCLUSIONS: Awake fiberoptic nasotracheal intubation, along with airway blocks and appropriate sedation, can be a viable option in patients with severe multiple trauma in the prone position.

GABAA receptor subunit composition regulates circadian rhythms in rest-wake and synchrony among cells in the suprachiasmatic nucleus.

The mammalian circadian clock located in the suprachiasmatic nucleus (SCN) produces robust daily rhythms including rest-wake. SCN neurons synthesize and respond to γ-aminobutyric acid (GABA), but its role remains unresolved. We tested the hypothesis that γ2- and δ-subunits of the GABAA receptor in the SCN differ in their regulation of synchrony among circadian cells. We used two approaches: 1) shRNA to knock-down (KD) the expression of either γ2 or δ subunits in the SCN or 2) knock-in mice harboring a point mutation in the M2 domains of the endogenous GABAA γ2 or δ subunits. KD of either γ2 or δ subunits in the SCN increased daytime running and reduced nocturnal running by reducing their circadian amplitude by a third. Similarly, δ subunit knock-in mice showed decreased circadian amplitude, increased duration of daily activity, and decreased total daily activity. Reduction, or mutation of either γ2 or δ subunits halved the synchrony among, and amplitude of, circadian SCN cells as measured by firing rate or expression of the PERIOD2 protein, in vitro. Surprisingly, overexpression of the γ2 subunit rescued these phenotypes following KD or mutation of the δ subunit, and overexpression of the δ subunit rescued deficiencies due to γ2 subunit KD or mutation. We conclude that γ2 and δ GABAA receptor subunits play similar roles in maintaining circadian synchrony in the SCN and amplitude of daily rest-wake rhythms, but that modulation of their relative densities can change the duration and amplitude of daily activities.

Energetic demands regulate sleep-wake rhythm circuit development.

Sleep and feeding patterns lack strong daily rhythms during early life. As diurnal animals mature, feeding is consolidated to the day and sleep to the night. In Drosophila, circadian sleep patterns are initiated with formation of a circuit connecting the central clock to arousal output neurons; emergence of circadian sleep also enables long-term memory (LTM). However, the cues that trigger the development of this clock-arousal circuit are unknown. Here, we identify a role for nutritional status in driving sleep-wake rhythm development in Drosophila larvae. We find that in the 2nd instar larval period (L2), sleep and feeding are spread across the day; these behaviors become organized into daily patterns by the 3rd instar larval stage (L3). Forcing mature (L3) animals to adopt immature (L2) feeding strategies disrupts sleep-wake rhythms and the ability to exhibit LTM. In addition, the development of the clock (DN1a)-arousal (Dh44) circuit itself is influenced by the larval nutritional environment. Finally, we demonstrate that larval arousal Dh44 neurons act through glucose metabolic genes to drive onset of daily sleep-wake rhythms. Together, our data suggest that changes to energetic demands in developing organisms trigger the formation of sleep-circadian circuits and behaviors.

Like most young animals, babies must obtain enough nutrients and energy to grow, yet they also need to rest for their brains to mature properly. As many exhausted new parents know first-hand, balancing these conflicting needs results in frequent, rapid switches between eating and sleeping. Eventually, new-borns' internal biological clock system, which is aligned with the 24-hour light cycle, becomes fully operational. Exactly how this then translates into allowing them to stay alert during the day and be sleepy at night is still unclear. Like humans, the larvae of fruit flies first sleep haphazardly before developing a circadian pattern whereby they sleep at night and eat during the day. This shift occurs when a group of nerve cells called DN1a, whose job is to 'keep time', connects with Dh44, a subset of neurons which, when active, promote wakefulness. The trigger for these changes, however, has remained elusive. In response, Poe et al. hypothesized that feeding behaviour and nutrient availability coordinated the emergence of sleep rhythms in fruit flies. Forcing fruit fly larvae to keep feeding in an 'immature' pattern ­ by either genetic manipulations or reducing the sugar content of their food ­ not only prevented them from developing 'mature' sleeping rhythms but also resulted in memory problems. These experiments also showed that the DN1a-Dh44 connection depends on nutrient availability, as it did not form in larvae raised on the low-sugar food. Further genetic experiments showed that the Dh44 cells themselves act like nutrient sensors during the emergence of sleeping patterns. These results shed new light on the factors triggering sleep rhythm development. Poe et al. hope that the understanding gained can be extended to humans and eventually help manage nervous system disorders and health problems associated with disrupted sleep during early life.

The yin and yang of two opponent processes of sleep-wake regulation: Sex-associated differences in the spectral EEG markers of the drives for sleep and wake.

Although objectively measured characteristics of sleep efficiency and quality were found to be better in women than men, women more frequently than men suffer from poor or insufficient or non-restorative sleep. We explored this apparent paradox by testing the sex-associated differences in electroencephalographic (EEG) indicators of two opponent processes of sleep-wake regulation, the drives for sleep and wake. We tried to provide empirical support for the hypothesis that a stronger women's sleep drive can explain better objective characteristics of sleep quality in women than men, while a stronger women's wake drive can be an explanation of a higher frequency of sleep-related complaints in women than men. To our knowledge, this was the first attempt to examine the associations of sex with scores on the 1st and 2nd principal components of the EEG spectrum that can serve as objective spectral EEG markers of the opponent drives for sleep and wake, respectively. The particular prediction was that, in women compared to men, not only the 1st principal component score but also the 2nd principal component score could be higher (i.e. both drives could be stronger). In a sample of 80 university students (40 females), the EEG signals were recorded during 160 afternoon napping attempts (50 min or longer). The difference between male and female students in sleep latencies did not reach a statistically significant level. In accordance with our prediction, both principal component scores were found to be higher in female than in male students irrespective of sleep stage. It is likely that the influence of the wake drive is entirely overlooked in the polysomnographic studies due to the predominant contribution of the indicators of the sleep drive to the conventional objective characteristics of sleep quality. Therefore, a stronger women's sleep drive can be an explanation of women's better sleep quality in the results of polysomnographic studies. On the other hand, if a stronger women's wake drive can influence the perception of their sleep quality, this can explain their more frequent sleep-related complaints.

Daytime sleepiness in insomnia: Are we focusing on what truly matters?

Insomnia, the most prevalent sleep disorder, is commonly associated with other mental and somatic disorders, making it a significant health concern. It is characterized by nighttime symptoms and daytime dysfunction, with sleepiness being a potential criterion for the latter. Sleepiness is a normal physiological state that is typically experienced near usual bedtime, in normal circumstances. In insomnia, it seems somewhat logical the idea that there is significant daytime sleepiness. However, the topic has been the subject of various discussions in sleep medicine, with studies yielding contradictory and inconsistent results. In this article, we aim to critically examine daytime sleepiness in individuals with insomnia disorder and propose an alternative approach to addressing it, both in clinical practice and research settings. It is crucial to further investigate the role of daytime sleepiness in insomnia, particularly by focusing on sleepiness perception as a more relevant dimension to explore in majority of patients. It is plausible that certain insomnia phenotypes are objectively sleepy during the day, but more studies are necessary, particularly with well-defined clinical samples. The implications of assessing sleepiness perception in insomnia for clinical practice are discussed, and new avenues for research are suggested.