Retuning of hippocampal representations during sleep.

Hippocampal representations that underlie spatial memory undergo continuous refinement following formation1. Here, to track the spatial tuning of neurons dynamically during offline states, we used a new Bayesian learning approach based on the spike-triggered average decoded position in ensemble recordings from freely moving rats. Measuring these tunings, we found spatial representations within hippocampal sharp-wave ripples that were stable for hours during sleep and were strongly aligned with place fields initially observed during maze exploration. These representations were explained by a combination of factors that included preconfigured structure before maze exposure and representations that emerged during θ-oscillations and awake sharp-wave ripples while on the maze, revealing the contribution of these events in forming ensembles. Strikingly, the ripple representations during sleep predicted the future place fields of neurons during re-exposure to the maze, even when those fields deviated from previous place preferences. By contrast, we observed tunings with poor alignment to maze place fields during sleep and rest before maze exposure and in the later stages of sleep. In sum, the new decoding approach allowed us to infer and characterize the stability and retuning of place fields during offline periods, revealing the rapid emergence of representations following new exploration and the role of sleep in the representational dynamics of the hippocampus.

Sleep pressure modulates single-neuron synapse number in zebrafish.

Sleep is a nearly universal behaviour with unclear functions1. The synaptic homeostasis hypothesis proposes that sleep is required to renormalize the increases in synaptic number and strength that occur during wakefulness2. Some studies examining either large neuronal populations3 or small patches of dendrites4 have found evidence consistent with the synaptic homeostasis hypothesis, but whether sleep merely functions as a permissive state or actively promotes synaptic downregulation at the scale of whole neurons is unclear. Here, by repeatedly imaging all excitatory synapses on single neurons across sleep-wake states of zebrafish larvae, we show that synapses are gained during periods of wake (either spontaneous or forced) and lost during sleep in a neuron-subtype-dependent manner. However, synapse loss is greatest during sleep associated with high sleep pressure after prolonged wakefulness, and lowest in the latter half of an undisrupted night. Conversely, sleep induced pharmacologically during periods of low sleep pressure is insufficient to trigger synapse loss unless adenosine levels are boosted while noradrenergic tone is inhibited. We conclude that sleep-dependent synapse loss is regulated by sleep pressure at the level of the single neuron and that not all sleep periods are equally capable of fulfilling the functions of synaptic homeostasis.

5-MeO-DMT induces sleep-like LFP spectral signatures in the hippocampus and prefrontal cortex of awake rats.

5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) is a potent classical psychedelic known to induce changes in locomotion, behaviour, and sleep in rodents. However, there is limited knowledge regarding its acute neurophysiological effects. Local field potentials (LFPs) are commonly used as a proxy for neural activity, but previous studies investigating psychedelics have been hindered by confounding effects of behavioural changes and anaesthesia, which alter these signals. To address this gap, we investigated acute LFP changes in the hippocampus (HP) and medial prefrontal cortex (mPFC) of freely behaving rats, following 5-MeO-DMT administration. 5-MeO-DMT led to an increase of delta power and a decrease of theta power in the HP LFPs, which could not be accounted for by changes in locomotion. Furthermore, we observed a dose-dependent reduction in slow (20-50 Hz) and mid (50-100 Hz) gamma power, as well as in theta phase modulation, even after controlling for the effects of speed and theta power. State map analysis of the spectral profile of waking behaviour induced by 5-MeO-DMT revealed similarities to electrophysiological states observed during slow-wave sleep (SWS) and rapid-eye-movement (REM) sleep. Our findings suggest that the psychoactive effects of classical psychedelics are associated with the integration of waking behaviours with sleep-like spectral patterns in LFPs.

Neuronal PAS domain 1 identifies a major subpopulation of wakefulness-promoting GABAergic neurons in the basal forebrain.

Here, we describe a group of basal forebrain (BF) neurons expressing neuronal Per-Arnt-Sim (PAS) domain 1 (Npas1), a developmental transcription factor linked to neuropsychiatric disorders. Immunohistochemical staining in Npas1-cre-2A-TdTomato mice revealed BF Npas1+ neurons are distinct from well-studied parvalbumin or cholinergic neurons. Npas1 staining in GAD67-GFP knock-in mice confirmed that the vast majority of Npas1+ neurons are GABAergic, with minimal colocalization with glutamatergic neurons in vGlut1-cre-tdTomato or vGlut2-cre-tdTomato mice. The density of Npas1+ neurons was high, five to six times that of neighboring cholinergic, parvalbumin, or glutamatergic neurons. Anterograde tracing identified prominent projections of BF Npas1+ neurons to brain regions involved in sleep-wake control, motivated behaviors, and olfaction such as the lateral hypothalamus, lateral habenula, nucleus accumbens shell, ventral tegmental area, and olfactory bulb. Chemogenetic activation of BF Npas1+ neurons in the light period increased the amount of wakefulness and the latency to sleep for 2 to 3 h, due to an increase in long wake bouts and short NREM sleep bouts. NREM slow-wave and sigma power, as well as sleep spindle density, amplitude, and duration, were reduced, reminiscent of findings in several neuropsychiatric disorders. Together with previous findings implicating BF Npas1+ neurons in stress responsiveness, the anatomical projections of BF Npas1+ neurons and the effect of activating them suggest a possible role for BF Npas1+ neurons in motivationally driven wakefulness and stress-induced insomnia. Identification of this major subpopulation of BF GABAergic neurons will facilitate studies of their role in sleep disorders, dementia, and other neuropsychiatric conditions involving BF.

Spatio-temporal electroencephalographic power distribution in experimental pigs receiving propofol.

INTRODUCTION: When assessing the spatio-temporal distribution of electroencephalographic (EEG) activity, characteristic patterns have been identified for several anesthetic drugs in humans. A shift in EEG power from the occipital to the prefrontal regions has been widely observed during anesthesia induction. This has been called "anteriorization" and has been correlated with loss of consciousness in humans. The spatio-temporal distribution of EEG spectral power in pigs and its modulation by anesthetics have not been described previously. The aim of the present study was to analyze EEG power across an anterior-posterior axis in pigs receiving increasing doses of propofol to 1) characterize the region of highest EEG power during wakefulness, 2) depict its spatio-temporal modification during propofol infusion, and 3) determine the region demonstrating the most significant modulations across different doses administered. MATERIALS AND METHODS: Six pigs with a body weight of 33.3 ± 3.6 kg and aged 11.3 ± 0.5 weeks were included in a prospective experimental study. Electroencephalographic activity was collected at the occipital, parietal and prefrontal regions at increasing doses of propofol (starting at 10 mg kg-1 h-1 and increasing it by 10 mg kg-1 h-1 every 15 minutes). The EEG power was assessed using a generalized linear mixed model in which propofol doses and regions were treated as fixed effects, whereas pig was used as a random effect. Pairwise comparisons of marginal linear predictions were used to assess the change in power when the specific propofol dose (or region) was considered. RESULTS: During both wakefulness and propofol infusion, the highest EEG power was located in the prefrontal region (p<0.001). The EEG power, both total and for each frequency band, mostly followed the same pattern, increasing from awake until propofol 20 mg kg-1 h-1 and then decreasing at propofol 30 mg kg-1 h-1. The region showing the strongest differences in EEG power across propofol doses was the prefrontal. CONCLUSION: In juvenile pigs receiving increasing doses of propofol, the prefrontal region showed the highest EEG power both during wakefulness and propofol administration and was the area in which the largest frequency-band specific variations were observed across different anesthetic doses. The assessment of the spectral EEG activity at this region could be favorable to distinguish DoA levels in pigs.

An update on tests used for intraoperative monitoring of cognition during awake craniotomy.

PURPOSE: Mapping higher-order cognitive functions during awake brain surgery is important for cognitive preservation which is related to postoperative quality of life. A systematic review from 2018 about neuropsychological tests used during awake craniotomy made clear that until 2017 language was most often monitored and that the other cognitive domains were underexposed (Ruis, J Clin Exp Neuropsychol 40(10):1081-1104, 218). The field of awake craniotomy and cognitive monitoring is however developing rapidly. The aim of the current review is therefore, to investigate whether there is a change in the field towards incorporation of new tests and more complete mapping of (higher-order) cognitive functions. METHODS: We replicated the systematic search of the study from 2018 in PubMed and Embase from February 2017 to November 2023, yielding 5130 potentially relevant articles. We used the artificial machine learning tool ASReview for screening and included 272 papers that gave a detailed description of the neuropsychological tests used during awake craniotomy. RESULTS: Comparable to the previous study of 2018, the majority of studies (90.4%) reported tests for assessing language functions (Ruis, J Clin Exp Neuropsychol 40(10):1081-1104, 218). Nevertheless, an increasing number of studies now also describe tests for monitoring visuospatial functions, social cognition, and executive functions. CONCLUSIONS: Language remains the most extensively tested cognitive domain. However, a broader range of tests are now implemented during awake craniotomy and there are (new developed) tests which received more attention. The rapid development in the field is reflected in the included studies in this review. Nevertheless, for some cognitive domains (e.g., executive functions and memory), there is still a need for developing tests that can be used during awake surgery.

Modafinil Subjectively Does Not Impair Sleep in Aviators After a Period of Extended Wakefulness.

INTRODUCTION: Modafinil is used as a countermeasure to limit the effects of fatigue in military aviation. However, literature is conflicting about its negative effects on subsequent sleep.METHODS: This randomized placebo-controlled trial conducted by the Center of Man in Aviation of the Royal Netherlands Airforce is part of a larger study. It included 32 subjects (mean age 35 yr old, 84% male) who followed a normal daily routine and stayed awake the subsequent night. At midnight, all subjects received either 300 mg caffeine, 200 mg modafinil, or placebo. At the end of the test night, subjects were awake for a median period of 26 h. Afterwards, sleep questionnaires containing qualitative (Groningen Sleep Quality Scale) and quantitative parameters of sleep for the subsequent day (recovery sleep) and consecutive night (post-test sleep) were completed and statistically analyzed using Friedman and Wilcoxon signed rank tests.RESULTS: A statistically significant difference in the reported recovery sleep was observed. The modafinil group slept 30% shorter than placebo, but sleep efficiency was not statistically different. Quantitatively post-test sleep did not vary statistically significantly between the three groups. However, Groningen Sleep Quality Scale scores were lower post-test than pre-test in the modafinil group, while this was not the case in the caffeine and placebo group.DISCUSSION:This study found that modafinil subjectively does not negatively impact recovery sleep or subsequent nighttime sleep after an extended period of wakefulness and suggests it may decrease the need for recovery sleep compared to placebo or caffeine.Wingelaar-Jagt YQ, Wingelaar TT, Riedel WJ, Ramaekers JG. Modafinil subjectively does not impair sleep in aviators after a period of extended wakefulness. Aerosp Med Hum Perform. 2024; 95(6):290-296.

Lateral parabrachial FoxP2 neurons regulate respiratory responses to hypercapnia.

About half of the neurons in the parabrachial nucleus (PB) that are activated by CO2 are located in the external lateral (el) subnucleus, express calcitonin gene-related peptide (CGRP), and cause forebrain arousal. We report here, in male mice, that most of the remaining CO2-responsive neurons in the adjacent central lateral (PBcl) and Kölliker-Fuse (KF) PB subnuclei express the transcription factor FoxP2 and many of these neurons project to respiratory sites in the medulla. PBclFoxP2 neurons show increased intracellular calcium during wakefulness and REM sleep and in response to elevated CO2 during NREM sleep. Photo-activation of the PBclFoxP2 neurons increases respiration, whereas either photo-inhibition of PBclFoxP2 or genetic deletion of PB/KFFoxP2 neurons reduces the respiratory response to CO2 stimulation without preventing awakening. Thus, augmenting the PBcl/KFFoxP2 response to CO2 in patients with sleep apnea in combination with inhibition of the PBelCGRP neurons may avoid hypoventilation and minimize EEG arousals.

Association of salivary testosterone levels during the post-awakening period with age and symptoms suggestive of late-onset hypogonadism in men.

BACKGROUND: The lack of association between serum testosterone levels and symptoms suggestive of hypogonadism is a significant barrier in the determination of late-onset hypogonadism (LOH) in men. This study explored whether testosterone levels increase after morning awakening, likewise the cortisol awakening response (CAR) in the hypothalamic-pituitary-adrenal (HPA) axis, and whether testosterone levels during the post-awakening period are associated with age and symptoms suggestive of late-onset hypogonadism (LOH) in men. METHODS: Testosterone and cortisol levels were determined in saliva samples collected immediately upon awakening and 30 and 60 min after awakening, and scores of the Aging Males' Symptoms (AMS) questionnaire were obtained from 225 healthy adult men. RESULTS: A typical CAR (an increase in cortisol level ≥ 2.5 nmol/L above individual baseline) was observed in 155 participants (the subgroup exhibiting typical CAR). In the subgroup exhibiting CAR, testosterone levels sharply increased during the post-awakening period, showing a significant negative correlation with age, total AMS score, and the scores of 11 items on the somatic, psychological, and sexual AMS subscales. Of these items, three sexual items (AMS items #15-17) were correlated with age. Meanwhile, there was no notable increase in testosterone levels and no significant correlation of testosterone levels with age and AMS score in the subgroup exhibiting no typical CAR (n = 70). CONCLUSIONS: The results indicate that the hypothalamus-pituitary-gonad (HPG) axis responds to morning awakening, and determining testosterone levels during the post-awakening period in men with typical CAR may be useful for assessing HPG axis function and LOH.

The present study found that the HPG axis in healthy adult men responds to the morning awakening, characterized by increased salivary testosterone levels after the awakening period.The levels of salivary testosterone during the first hour after awakening are negatively associated with age and the severity of symptoms suggestive of LOH in adult men with typical CAR.

Thalamic contributions to the state and contents of consciousness.

Consciousness can be conceptualized as varying along at least two dimensions: the global state of consciousness and the content of conscious experience. Here, we highlight the cellular and systems-level contributions of the thalamus to conscious state and then argue for thalamic contributions to conscious content, including the integrated, segregated, and continuous nature of our experience. We underscore vital, yet distinct roles for core- and matrix-type thalamic neurons. Through reciprocal interactions with deep-layer cortical neurons, matrix neurons support wakefulness and determine perceptual thresholds, whereas the cortical interactions of core neurons maintain content and enable perceptual constancy. We further propose that conscious integration, segregation, and continuity depend on the convergent nature of corticothalamic projections enabling dimensionality reduction, a thalamic reticular nucleus-mediated divisive normalization-like process, and sustained coherent activity in thalamocortical loops, respectively. Overall, we conclude that the thalamus plays a central topological role in brain structures controlling conscious experience.

Multimodal MRI reveals brainstem connections that sustain wakefulness in human consciousness.

Consciousness is composed of arousal (i.e., wakefulness) and awareness. Substantial progress has been made in mapping the cortical networks that underlie awareness in the human brain, but knowledge about the subcortical networks that sustain arousal in humans is incomplete. Here, we aimed to map the connectivity of a proposed subcortical arousal network that sustains wakefulness in the human brain, analogous to the cortical default mode network (DMN) that has been shown to contribute to awareness. We integrated data from ex vivo diffusion magnetic resonance imaging (MRI) of three human brains, obtained at autopsy from neurologically normal individuals, with immunohistochemical staining of subcortical brain sections. We identified nodes of the proposed default ascending arousal network (dAAN) in the brainstem, hypothalamus, thalamus, and basal forebrain. Deterministic and probabilistic tractography analyses of the ex vivo diffusion MRI data revealed projection, association, and commissural pathways linking dAAN nodes with one another and with DMN nodes. Complementary analyses of in vivo 7-tesla resting-state functional MRI data from the Human Connectome Project identified the dopaminergic ventral tegmental area in the midbrain as a widely connected hub node at the nexus of the subcortical arousal and cortical awareness networks. Our network-based autopsy methods and connectivity data provide a putative neuroanatomic architecture for the integration of arousal and awareness in human consciousness.

Towards a better diagnosis of mouth breathing: validity and reliability of a protocol for assessing the awake breathing pattern in preschool children.

PURPOSE: The Awake Breathing Pattern Assessment (ABPA) is a prototypical clinical grid recently designed through an international consensus of Speech and Language Pathologists (SLPs) to categorize the awake and habitual breathing pattern during the orofacial myofunctional assessment. This cross-sectional study aims to explore the psychometric properties of the ABPA in a preschool population. METHODS: 133 children from 2;11 to 6 years old were assessed with the ABPA. The percentage of time spent breathing through the mouth was objectively measured by a CO2 sensor and used as a baseline measurement. We first performed a multivariate Latent Profile Analysis based on the CO2 measurement and a parental questionnaire to define the number of categories that best characterize the breathing pattern. Subsequently, we assessed the intra- and inter-rater reliability, internal consistency criterion validity, construct validity and sensitivity and specificity. RESULTS: The awake breathing pattern can best be described by two groups: nasal and mouth breathing. The ABPA, initially designed in three groups, was adjusted accordingly. This final version showed excellent intra-rater and inter-rater reliability. There was a significant correlation between the ABPA and the CO2 measurement. The ABPA showed a fair sensitivity and a good specificity. CONCLUSION: The reference tool based on CO2 data was used in children for the first time and was found to be reliable. The ABPA is a suitable tool for SLPs to confirm the diagnosis of mouth breathing in preschool children if more sensitive screening tools, like parental questionnaires, are used beforehand.

A multi-task learning model using RR intervals and respiratory effort to assess sleep disordered breathing.

BACKGROUND: Sleep-disordered breathing (SDB) affects a significant portion of the population. As such, there is a need for accessible and affordable assessment methods for diagnosis but also case-finding and long-term follow-up. Research has focused on exploiting cardiac and respiratory signals to extract proxy measures for sleep combined with SDB event detection. We introduce a novel multi-task model combining cardiac activity and respiratory effort to perform sleep-wake classification and SDB event detection in order to automatically estimate the apnea-hypopnea index (AHI) as severity indicator. METHODS: The proposed multi-task model utilized both convolutional and recurrent neural networks and was formed by a shared part for common feature extraction, a task-specific part for sleep-wake classification, and a task-specific part for SDB event detection. The model was trained with RR intervals derived from electrocardiogram and respiratory effort signals. To assess performance, overnight polysomnography (PSG) recordings from 198 patients with varying degree of SDB were included, with manually annotated sleep stages and SDB events. RESULTS: We achieved a Cohen's kappa of 0.70 in the sleep-wake classification task, corresponding to a Spearman's correlation coefficient (R) of 0.830 between the estimated total sleep time (TST) and the TST obtained from PSG-based sleep scoring. Combining the sleep-wake classification and SDB detection results of the multi-task model, we obtained an R of 0.891 between the estimated and the reference AHI. For severity classification of SBD groups based on AHI, a Cohen's kappa of 0.58 was achieved. The multi-task model performed better than a single-task model proposed in a previous study for AHI estimation, in particular for patients with a lower sleep efficiency (R of 0.861 with the multi-task model and R of 0.746 with single-task model with subjects having sleep efficiency < 60%). CONCLUSION: Assisted with automatic sleep-wake classification, our multi-task model demonstrated proficiency in estimating AHI and assessing SDB severity based on AHI in a fully automatic manner using RR intervals and respiratory effort. This shows the potential for improving SDB screening with unobtrusive sensors also for subjects with low sleep efficiency without adding additional sensors for sleep-wake detection.

Nocturnal exposure to a preferred ambient scent does not affect dream emotionality or post-sleep core affect valence in young adults.

Emotions experienced within sleep mentation (dreaming) affect mental functioning in waking life. There have been attempts at enhancing dream emotions using olfactory stimulation. Odors readily acquire affective value, but to profoundly influence emotional processing, they should bear personal significance for the perceiver rather than be generally pleasant. The main objective of the present sleep laboratory study was to examine whether prolonged nocturnal exposure to self-selected, preferred ambient room odor while asleep influences emotional aspects of sleep mentation and valence of post-sleep core affect. We asked twenty healthy participants (12 males, mean age 25 ± 4 years) to pick a commercially available scented room diffuser cartridge that most readily evoked positively valenced mental associations. In weekly intervals, the participants attended three sessions. After the adaptation visit, they were administered the odor exposure and odorless control condition in a balanced order. Participants were awakened five minutes into the first rapid eye movement (REM) stage that took place after 2:30 a.m. and, if they had been dreaming, they were asked to rate their mental sleep experience for pleasantness, emotional charge, and magnitude of positive and negative emotions and also to evaluate their post-sleep core affect valence. With rs < 0.20, no practically or statistically significant differences existed between exposure and control in any outcome measures. We conclude that in young, healthy participants, the practical value of olfactory stimulation with self-selected preferred scents for enhancement of dream emotions and post-sleep core affect valence is very limited.

Beyond day and night: The importance of ultradian rhythms in mouse physiology.

Our circadian world shapes much of metabolic physiology. In mice ∼40% of the light and ∼80% of the dark phase time is characterized by bouts of increased energy expenditure (EE). These ultradian bouts have a higher body temperature (Tb) and thermal conductance and contain virtually all of the physical activity and awake time. Bout status is a better classifier of mouse physiology than photoperiod, with ultradian bouts superimposed on top of the circadian light/dark cycle. We suggest that the primary driver of ultradian bouts is a brain-initiated transition to a higher defended Tb of the active/awake state. Increased energy expenditure from brown adipose tissue, physical activity, and cardiac work combine to raise Tb from the lower defended Tb of the resting/sleeping state. Thus, unlike humans, much of mouse metabolic physiology is episodic with large ultradian increases in EE and Tb that correlate with the active/awake state and are poorly aligned with circadian cycling.

How astrocytic chloride modulates brain states.

The way the central nervous system (CNS) responds to diverse stimuli is contingent upon the specific brain state of the individual, including sleep and wakefulness. Despite the wealth of readout parameters and data delineating the brain states, the primary mechanisms are yet to be identified. Here we highlight the role of astrocytes, with a specific emphasis on chloride (Cl-) homeostasis as a modulator of brain states. Neuronal activity is regulated by the concentration of ions that determine excitability. Astrocytes, as the CNS homeostatic cells, are recognised for their proficiency in maintaining dynamic homeostasis of ions, known as ionostasis. Nevertheless, the contribution of astrocyte-driven ionostasis to the genesis of brain states or their response to sleep-inducing pharmacological agents has been overlooked. Our objective is to underscore the significance of astrocytic Cl- homeostasis, elucidating how it may underlie the modulation of brain states. We endeavour to contribute to a comprehensive understanding of the interplay between astrocytes and brain states.

Asleep versus awake GPi DBS surgery for Parkinson's disease: A systematic review and meta-analysis.

BACKGROUND: Patients with Parkinson's Disease (PD) who receive either asleep image-guided subthalamic nucleus deep brain stimulation (DBS) or the traditional awake technique have comparable motor outcomes. However, there are fewer studies regarding which technique should be chosen for globus pallidus internus (GPi) DBS. This systematic review and meta-analysis aims to compare the accuracy of lead placement and motor outcomes of asleep versus awake GPi DBS PD population. METHODS: We systematically searched PubMed, Embase, and Cochrane for studies comparing asleep vs. awake GPi DBS lead placement in patients with PD. Outcomes were spatial accuracy of lead placement, measured by radial error between intended and actual location, motor improvement measured using (UPDRS III), and postoperative stimulation parameters. Statistical analysis was performed with Review Manager 5.1.7. and OpenMeta [Analyst]. RESULTS: Three studies met inclusion criteria with a total of 247 patients. Asleep DBS was used to treat 192 (77.7 %) patients. Follow-up ranged from 6 to 48 months. Radial error was not statistically different between groups (MD -0.49 mm; 95 % CI -1.0 to 0.02; I2 = 86 %; p = 0.06), with a tendency for higher target accuracy with the asleep technique. There was no significant difference between groups in change on motor function, as measured by UPDRS III, from pre- to postoperative (MD 8.30 %; 95 % CI -4.78 to 21.37; I2 = 67 %, p = 0.2). There was a significant difference in postoperative stimulation voltage, with the asleep group requiring less voltage than the awake group (MD -0.27 V; 95 % CI -0.46 to - 0.08; I2 = 0 %; p = 0.006). CONCLUSION: Our meta-analysis indicates that asleep image-guided GPi DBS presents a statistical tendency suggesting superior target accuracy when compared with the awake standard technique. Differences in change in motor function were not statistically significant between groups.

Distinct lateral hypothalamic CaMKIIα neuronal populations regulate wakefulness and locomotor activity.

For nearly a century, evidence has accumulated indicating that the lateral hypothalamus (LH) contains neurons essential to sustain wakefulness. While lesion or inactivation of LH neurons produces a profound increase in sleep, stimulation of inhibitory LH neurons promotes wakefulness. To date, the primary wake-promoting cells that have been identified in the LH are the hypocretin/orexin (Hcrt) neurons, yet these neurons have little impact on total sleep or wake duration across the 24-h period. Recently, we and others have identified other LH populations that increase wakefulness. In the present study, we conducted microendoscopic calcium imaging in the LH concomitant with EEG and locomotor activity (LMA) recordings and found that a subset of LH neurons that express Ca2+/calmodulin-dependent protein kinase IIα (CaMKIIα) are preferentially active during wakefulness. Chemogenetic activation of these neurons induced sustained wakefulness and greatly increased LMA even in the absence of Hcrt signaling. Few LH CaMKIIα-expressing neurons are hypocretinergic or histaminergic while a small but significant proportion are GABAergic. Ablation of LH inhibitory neurons followed by activation of the remaining LH CaMKIIα neurons induced similar levels of wakefulness but blunted the LMA increase. Ablated animals showed no significant changes in sleep architecture but both spontaneous LMA and high theta (8 to 10 Hz) power during wakefulness were reduced. Together, these findings indicate the existence of two subpopulations of LH CaMKIIα neurons: an inhibitory population that promotes locomotion without affecting sleep architecture and an excitatory population that promotes prolonged wakefulness even in the absence of Hcrt signaling.

Neural assemblies coordinated by cortical waves are associated with waking and hallucinatory brain states.

The relationship between sensory stimuli and perceptions is brain-state dependent: in wakefulness, suprathreshold stimuli evoke perceptions; under anesthesia, perceptions are abolished; and during dreaming and in dissociated states, percepts are internally generated. Here, we exploit this state dependence to identify brain activity associated with internally generated or stimulus-evoked perceptions. In awake mice, visual stimuli phase reset spontaneous cortical waves to elicit 3-6 Hz feedback traveling waves. These stimulus-evoked waves traverse the cortex and entrain visual and parietal neurons. Under anesthesia as well as during ketamine-induced dissociation, visual stimuli do not disrupt spontaneous waves. Uniquely, in the dissociated state, spontaneous waves traverse the cortex caudally and entrain visual and parietal neurons, akin to stimulus-evoked waves in wakefulness. Thus, coordinated neuronal assemblies orchestrated by traveling cortical waves emerge in states in which perception can manifest. The awake state is privileged in that this coordination is reliably elicited by external visual stimuli.

Association of Visual-Based Signals with Electroencephalography Patterns in Enhancing the Drowsiness Detection in Drivers with Obstructive Sleep Apnea.

Individuals with obstructive sleep apnea (OSA) face increased accident risks due to excessive daytime sleepiness. PERCLOS, a recognized drowsiness detection method, encounters challenges from image quality, eyewear interference, and lighting variations, impacting its performance, and requiring validation through physiological signals. We propose visual-based scoring using adaptive thresholding for eye aspect ratio with OpenCV for face detection and Dlib for eye detection from video recordings. This technique identified 453 drowsiness (PERCLOS ≥ 0.3 || CLOSDUR ≥ 2 s) and 474 wakefulness episodes (PERCLOS < 0.3 and CLOSDUR < 2 s) among fifty OSA drivers in a 50 min driving simulation while wearing six-channel EEG electrodes. Applying discrete wavelet transform, we derived ten EEG features, correlated them with visual-based episodes using various criteria, and assessed the sensitivity of brain regions and individual EEG channels. Among these features, theta-alpha-ratio exhibited robust mapping (94.7%) with visual-based scoring, followed by delta-alpha-ratio (87.2%) and delta-theta-ratio (86.7%). Frontal area (86.4%) and channel F4 (75.4%) aligned most episodes with theta-alpha-ratio, while frontal, and occipital regions, particularly channels F4 and O2, displayed superior alignment across multiple features. Adding frontal or occipital channels could correlate all episodes with EEG patterns, reducing hardware needs. Our work could potentially enhance real-time drowsiness detection reliability and assess fitness to drive in OSA drivers.