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Alpha-synuclein induced degeneration of the midbrain substantia nigra pars compact (SNc) dopaminergic neurons causes Parkinson's disease (PD). Rodent studies demonstrate that nigrostriatal dopamine stimulates pallidal neurons which, via the topographical pallidocortical pathway, regulate cortical activity and functions. We hypothesize that nigrostriatal dopamine acting at the basal ganglia regulates cortical activity in sleep and wake state, and its depletion systemically alters electroencephalogram (EEG) across frequencies during sleep-wake state. Compared to control rats, 6-hydroxydopamine induced selective SNc lesions increased overall EEG power (positive synchronization) across 0.5-60 Hz during wake, NREM (non-rapid eye movement) sleep, and REM sleep. Application of machine learning (ML) to seven EEG features computed at a single or combined spectral bands during sleep-wake differentiated SNc lesions from controls at high accuracy. ML algorithms construct a model based on empirical data to make predictions on subsequent data. The accuracy of the predictive results indicate that nigrostriatal dopamine depletion increases global EEG spectral synchronization in wake, NREM sleep, and REM sleep. The EEG changes can be exploited by ML to identify SNc lesions at a high accuracy.

PURPOSE: To address the consequences of living with supraventricular tachycardia and to improve the quality of treatment, there is a need to highlight patient experiences of treatment with catheter ablation. Therefore, the aim was to describe the phenomenon of catheter ablation, as it is experienced by patients being treated awake. METHODS: A descriptive design was applied based on a reflective lifeworld research founded on phenomenological epistemology. Interviews were conducted between December 2021 and Mars 2022 with seven women and five men, three to twelve months after they underwent catheter ablation. RESULTS: Patients undergoing catheter ablation while awake during treatment, which includes experiences of relying on others expertise, being actively passive, and striving to be cured. It entails experiences of having a foreign object moving in one's body and heart and can be endured through strategies of mainly shifted one's mental focus. CONCLUSIONS: The effort of undergoing a catheter ablation procedure is worthwhile as the confirmation of a physical curable condition that opens a future with possibilities instead of the obstacle in daily life that tachycardia entails. For the patients, an informative and caring conversation was needed that would have provided the support they lacked before and during the ablation., CC BY 4.0Taylor & Francis Group an informa businessCONTACT Ann-Katrin Nordblom ann-katrin.nordblom@vgregion.se Department of Cardiology, Skaraborgs Hospital Skövde, Skövde SE-541 85, SwedenThe study was conducted with support from the Research Fund at Skaraborg Hospital, Sweden [VGSKAS-930160] and the Skaraborg Institute [Dnr:19/1037].

This study delves into the impact of aromatherapy on influencing both sleep and wakefulness via the use of essential oils including lavender and peppermint. Firstly, the study challenges the misconception that scents can't wake you up by showing strong evidence that our bodies naturally respond to smells, even when in a state of slumber. Further, through the expansion of a diverse array of studies, the research uncovers the ways in which aromatherapy exerts a strong influence on levels of drowsiness and alertness, alongside the numerous advantages that ensue. Ultimately, this study attests to the significance of essential oils and the influence they have on bodily processes that inherently transpire.

Discriminating between temporal features in sensory stimuli is critical to complex behavior and decision-making. However, how sensory cortical circuit mechanisms contribute to discrimination between subsecond temporal components in sensory events is unclear. To elucidate the mechanistic underpinnings of timing in primary visual cortex (V1), we recorded from V1 using two-photon calcium imaging in awake-behaving mice performing a go/no-go discrimination timing task, which was composed of patterns of subsecond audiovisual stimuli. In both conditions, activity during the early stimulus period was temporally coordinated with the preferred stimulus. However, while network activity increased in the preferred condition, network activity was increasingly suppressed in the nonpreferred condition over the stimulus period. Multiple levels of analyses suggest that discrimination between subsecond intervals that are contained in rhythmic patterns can be accomplished by local neural dynamics in V1.

ObjectiveElectrocortical stimulation mapping (ECS) is widely used to identify essential language areas, but sentence-level processing has rarely been investigated.MethodsWhile undergoing awake surgery in the dominant left hemisphere, 6 subjects were asked to comprehend sentences varying in their demands on syntactic processing.ResultsIn all 6 subjects, stimulation of the inferior frontal gyrus disrupted comprehension of passive sentences, which critically depend on syntactic processing to correctly assign grammatical roles, without disrupting comprehension of simpler tasks. In 4 of the 6 subjects, these sites were localized to the pars opercularis. Sentence comprehension was also disrupted by stimulation of other perisylvian sites, but in a more variable manner.ConclusionsThese findings suggest that there may be language regions that differentially contribute to sentence processing and which therefore are best identified using sentence-level tasks. The functional consequences of resecting these sites remain to be investigated.

IntroductionObstructive sleep apnea (OSA) is a common disorder with major neurocognitive and cardiovascular sequelae. The treatment of symptomatic patients with mild OSA remains controversial given that adherence to positive airway pressure (PAP) has historically been suboptimal. With this notion in mind, we assessed a daily transoral neuromuscular electrical stimulation (NMES) device for individuals with mild OSA.MethodsThe sample represents a subset of participants with a baseline AHI 5-14.9 events/hour, drawn from a parent study which also included participants with primary snoring. Outcome measures for the current study included changes in apnea-hypopnea index (AHI), Epworth Sleepiness Scale (ESS), Pittsburgh Sleep Quality Index (PSQI) and snoring levels before and after use of the NMES.  RESULTS: Among 65 participants (68% men) with median age of 49 years (range 24 to 79) and median BMI of 27.7 kg/m2 (range 20 to 34), the NMES device was used daily for 6 weeks. We observed a significant improvement in the AHI from 10.2 to 6.8 events/hour among all participants and from 10.4 to 5.0 events/h among responders. Statistically significant improvements in the ESS, PSQI, objectively measured snoring, and bed partner-reported snoring were observed. Adherence among all participants was 85%.DiscussionThis NMES device has the benefit of being a treatment modality of daytime therapy which confers a high level of tolerability and patient acceptance. It alleviates the need for an in situ device during sleep and leads to improvements in OSA severity, snoring, and subjective sleep metrics, potentially crucial in mild OSA. Further studies are needed to define which individuals may benefit most from the device across the wider spectrum of OSA severity and assess long-term therapeutic outcomes.Trial registrationClinicalTrials.gov Identifier: NCT03829956.

Most accounts of single- and multi-unit responses in auditory cortex under anesthetized conditions have emphasized V-shaped frequency tuning curves and low-pass sensitivity to rates of repeated sounds. In contrast, single-unit recordings in awake marmosets also show I-shaped and O-shaped response areas having restricted tuning to frequency and (for O units) sound level. That preparation also demonstrates synchrony to moderate click rates and representation of higher click rates by spike rates of non-synchronized tonic responses, neither of which are commonly seen in anesthetized conditions. The spectral and temporal representation observed in the marmoset might reflect special adaptations of that species, might be due to single- rather than multi-unit recording, or might indicate characteristics of awake-versus-anesthetized recording conditions. We studied spectral and temporal representation in the primary auditory cortex of alert cats. We observed V-, I-, and O-shaped response areas like those demonstrated in awake marmosets. Neurons could synchronize to click trains at rates about an octave higher than is usually seen with anesthesia. Representations of click rates by rates of non-synchronized tonic responses exhibited dynamic ranges that covered the entire range of tested click rates. The observation of these spectral and temporal representations in cats demonstrates that they are not unique to primates and, indeed, might be widespread among mammalian species. Moreover, we observed no significant difference in stimulus representation between single- and multi-unit recordings. It appears that the principal factor that has hindered observations of high spectral and temporal acuity in the auditory cortex has been the use of general anesthesia.

Previous research suggests that affectionate touch such as hugs might downregulate stress systems such as the hypothalamic pituitary adrenal (HPA) axis. However, the current literature lacks in generalizability beyond the laboratory setting and outside the context of romantic relationships. The cortisol awakening response (CAR) is a measure of the HPA axis and is responsive to daily fluctuations in stress and social information. However, associations between affectionate touch and the CAR have never been assessed. This study used ecological momentary assessment (EMA) to measure daily hugging behaviors in 104 first-year college students and salivary cortisol to assess the CAR. Participants who reported more daily hugs in their social interactions had significantly smaller CARs the next morning compared to days they reported fewer hugs. This study contributes to the literature on social interactions and stress responsive systems and emphasizes the importance of assessing affectionate touch behaviors such as hugs that can be exchanged outside the context of romantic relationships.

Gliomas synaptically integrate into neural circuits1,2. Previous research has demonstrated bidirectional interactions between neurons and glioma cells, with neuronal activity driving glioma growth1-4 and gliomas increasing neuronal excitability2,5-8. Here we sought to determine how glioma-induced neuronal changes influence neural circuits underlying cognition and whether these interactions influence patient survival. Using intracranial brain recordings during lexical retrieval language tasks in awake humans together with site-specific tumour tissue biopsies and cell biology experiments, we find that gliomas remodel functional neural circuitry such that task-relevant neural responses activate tumour-infiltrated cortex well beyond the cortical regions that are normally recruited in the healthy brain. Site-directed biopsies from regions within the tumour that exhibit high functional connectivity between the tumour and the rest of the brain are enriched for a glioblastoma subpopulation that exhibits a distinct synaptogenic and neuronotrophic phenotype. Tumour cells from functionally connected regions secrete the synaptogenic factor thrombospondin-1, which contributes to the differential neuron-glioma interactions observed in functionally connected tumour regions compared with tumour regions with less functional connectivity. Pharmacological inhibition of thrombospondin-1 using the FDA-approved drug gabapentin decreases glioblastoma proliferation. The degree of functional connectivity between glioblastoma and the normal brain negatively affects both patient survival and performance in language tasks. These data demonstrate that high-grade gliomas functionally remodel neural circuits in the human brain, which both promotes tumour progression and impairs cognition.

BackgroundIntraoperative neurophysiological monitoring (IONM) is utilized for both the localization of critical structures and for real time detection and prevention of intraoperative neurological injury. Use of IONM to monitor the hypoglossal nerve is performed during neurosurgical, otolaryngological, and vascular procedures to improve surgical outcomes. There is a paucity of literature describing potential complications of IONM of the hypoglossal nerve, especially with respect to airway compromise. Here we present our findings regarding a case of acute airway obstruction following hypoglossal nerve monitoring.Case presentationA 54-year-old male was admitted for left far-lateral craniotomy and microsurgical clipping of a left posterior inferior cerebellar artery (PICA) aneurysm. Following induction and intubation but prior to the procedure start, the patient was placed in the ¾ prone position with the left side up and his neck was flexed approximately 10 degrees. He then underwent placement of subdermal needle electrodes into the facial muscles, trapezius muscles, soft palate, and tongue for IONM. The procedure lasted 523 minutes and was completed without complication. However, approximately one hour after emergence from general anesthesia, the patient experienced progressive difficulty breathing secondary to severe lingual swelling. He required emergent placement of a nasotracheal tube guided by a fiberoptic bronchoscope. He remained intubated for 3 days and was treated with dexamethasone, after which the swelling resolved, and the patient was successfully extubated.ConclusionsAcute lingual edema is a potentially life-threatening phenomenon that can lead to rapid airway compromise. Generally, causes of acute lingual swelling include hemorrhage, edema, infarction, and infection. In the case described above, we suspect traumatic injury to the tongue's vascular supply caused a deep tissue hematoma leading to postoperative acute lingual swelling and airway obstru

PURPOSE: To address the consequences of living with supraventricular tachycardia and to improve the quality of treatment, there is a need to highlight patient experiences of treatment with catheter ablation. Therefore, the aim was to describe the phenomenon of catheter ablation, as it is experienced by patients being treated awake. METHODS: A descriptive design was applied based on a reflective lifeworld research founded on phenomenological epistemology. Interviews were conducted between December 2021 and Mars 2022 with seven women and five men, three to twelve months after they underwent catheter ablation. RESULTS: Patients undergoing catheter ablation while awake during treatment, which includes experiences of relying on others expertise, being actively passive, and striving to be cured. It entails experiences of having a foreign object moving in one's body and heart and can be endured through strategies of mainly shifted one's mental focus. CONCLUSIONS: The effort of undergoing a catheter ablation procedure is worthwhile as the confirmation of a physical curable condition that opens a future with possibilities instead of the obstacle in daily life that tachycardia entails. For the patients, an informative and caring conversation was needed that would have provided the support they lacked before and during the ablation., CC BY 4.0Taylor & Francis Group an informa businessCONTACT Ann-Katrin Nordblom ann-katrin.nordblom@vgregion.se Department of Cardiology, Skaraborgs Hospital Skövde, Skövde SE-541 85, SwedenThe study was conducted with support from the Research Fund at Skaraborg Hospital, Sweden [VGSKAS-930160] and the Skaraborg Institute [Dnr:19/1037].

Coordinated peri-ripple activity in the hippocampal-neocortical network is essential for mnemonic information processing in the brain. Hippocampal ripples likely serve different functions in sleep and awake states. Thus, the corresponding neocortical activity patterns may differ in important ways. We addressed this possibility by conducting voltage and glutamate wide-field imaging of the neocortex with concurrent hippocampal electrophysiology in awake mice. Contrary to our previously published sleep results, deactivation and activation were dominant in post-ripple neocortical voltage and glutamate activity, respectively, especially in the agranular retrosplenial cortex (aRSC). Additionally, the spiking activity of aRSC neurons, estimated by two-photon calcium imaging, revealed the existence of two subpopulations of excitatory neurons with opposite peri-ripple modulation patterns: one increases and the other decreases firing rate. These differences in peri-ripple spatiotemporal patterns of neocortical activity in sleep versus awake states might underlie the reported differences in the function of sleep versus awake ripples.

BACKGROUND: Humans routinely shift their sleepiness and wakefulness levels in response to emotional factors. The diversity of emotional factors that modulates sleep-wake levels suggests that the ascending arousal network may be intimately linked with networks that mediate mood. Indeed, while animal studies have identified select limbic structures that play a role in sleep-wake regulation, the breadth of corticolimbic structures that directly modulates arousal in humans remains unknown. OBJECTIVE: We investigated whether select regional activation of the corticolimbic network through direct electrical stimulation can modulate sleep-wake levels in humans, as measured by subjective experience and behavior. METHODS: We performed intensive inpatient stimulation mapping in two human participants with treatment resistant depression, who underwent intracranial implantation with multi-site, bilateral depth electrodes. Stimulation responses of sleep-wake levels were measured by subjective surveys (i.e. Stanford Sleepiness Scale and visual-analog scale of energy) and a behavioral arousal score. Biomarker analyses of sleep-wake levels were performed by assessing spectral power features of resting-state electrophysiology. RESULTS: Our findings demonstrated three regions whereby direct stimulation modulated arousal, including the orbitofrontal cortex (OFC), subgenual cingulate (SGC), and, most robustly, ventral capsule (VC). Modulation of sleep-wake levels was frequency-specific: 100Hz OFC, SGC, and VC stimulation promoted wakefulness, whereas 1Hz OFC stimulation increased sleepiness. Sleep-wake levels were correlated with gamma activity across broad brain regions. CONCLUSIONS: Our findings provide evidence for the overlapping circuitry between arousal and mood regulation in humans. Furthermore, our findings open the door to new treatment targets and the consideration of therapeutic neurostimulation for sleep-wake disorders.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) and insomnia frequently co-occur, making diagnosis and treatment challenging. We investigated differences in sleep structure between patients with OSA, insomnia, and comorbid insomnia and sleep apnea (COMISA) to identify characteristics that can be used to improve the diagnosis of COMISA.METHODS: We obtained polysomnography data of 326 patients from the Sleep and OSA Monitoring with Non-Invasive Applications database. The group included patients with OSA (n = 199), insomnia (n = 47), and COMISA (n = 80). We compared statistics related to sleep structure between the 3 patient groups.RESULTS: Wake after sleep onset was significantly shorter for the OSA group (median: 60.0 minutes) compared to the COMISA (median: 83.3 minutes, P < .01) and the insomnia (median: 83.5 minutes, P = .01) groups. No significant differences were found in the total number of awakenings and the number of short (up to and including 2 minutes) and medium-length awakenings (2.5 up to and including 4.5 minutes). However, the number of long awakenings (5 minutes or longer) and wake after sleep onset containing only long awakenings was significantly lower for patients with OSA (median: 2 awakenings and 25.5 minutes) compared to patients with COMISA (median: 3 awakenings, P < .01 and 43.3 minutes, P < .001) or with insomnia (median: 3 awakenings, P < .01 and 56.0 minutes, P < .001). Total sleep time was significantly longer and sleep efficiency was significantly higher for the OSA group (median: 418.5 minutes and 84.4%) compared to both the COMISA (median: 391.5 minutes, P < .001 and 77.3%, P < .001) and the insomnia (median: 381.5 minutes, P < .001 and 78.2%, P < .001) groups. The number of sleep-stage transitions during the night for patients with COMISA (median: 194.0) was lower compared to that for patients with OSA (median: 218.0, P < .01) and higher compared to that for patients with insomnia (median

This study delves into the impact of aromatherapy on influencing both sleep and wakefulness via the use of essential oils including lavender and peppermint. Firstly, the study challenges the misconception that scents can't wake you up by showing strong evidence that our bodies naturally respond to smells, even when in a state of slumber. Further, through the expansion of a diverse array of studies, the research uncovers the ways in which aromatherapy exerts a strong influence on levels of drowsiness and alertness, alongside the numerous advantages that ensue. Ultimately, this study attests to the significance of essential oils and the influence they have on bodily processes that inherently transpire.

PURPOSE: To address the consequences of living with supraventricular tachycardia and to improve the quality of treatment, there is a need to highlight patient experiences of treatment with catheter ablation. Therefore, the aim was to describe the phenomenon of catheter ablation, as it is experienced by patients being treated awake. METHODS: A descriptive design was applied based on a reflective lifeworld research founded on phenomenological epistemology. Interviews were conducted between December 2021 and Mars 2022 with seven women and five men, three to twelve months after they underwent catheter ablation. RESULTS: Patients undergoing catheter ablation while awake during treatment, which includes experiences of relying on others expertise, being actively passive, and striving to be cured. It entails experiences of having a foreign object moving in one's body and heart and can be endured through strategies of mainly shifted one's mental focus. CONCLUSIONS: The effort of undergoing a catheter ablation procedure is worthwhile as the confirmation of a physical curable condition that opens a future with possibilities instead of the obstacle in daily life that tachycardia entails. For the patients, an informative and caring conversation was needed that would have provided the support they lacked before and during the ablation., CC BY 4.0Taylor & Francis Group an informa businessCONTACT Ann-Katrin Nordblom ann-katrin.nordblom@vgregion.se Department of Cardiology, Skaraborgs Hospital Skövde, Skövde SE-541 85, SwedenThe study was conducted with support from the Research Fund at Skaraborg Hospital, Sweden [VGSKAS-930160] and the Skaraborg Institute [Dnr:19/1037].

PURPOSE: To address the consequences of living with supraventricular tachycardia and to improve the quality of treatment, there is a need to highlight patient experiences of treatment with catheter ablation. Therefore, the aim was to describe the phenomenon of catheter ablation, as it is experienced by patients being treated awake. METHODS: A descriptive design was applied based on a reflective lifeworld research founded on phenomenological epistemology. Interviews were conducted between December 2021 and Mars 2022 with seven women and five men, three to twelve months after they underwent catheter ablation. RESULTS: Patients undergoing catheter ablation while awake during treatment, which includes experiences of relying on others expertise, being actively passive, and striving to be cured. It entails experiences of having a foreign object moving in one's body and heart and can be endured through strategies of mainly shifted one's mental focus. CONCLUSIONS: The effort of undergoing a catheter ablation procedure is worthwhile as the confirmation of a physical curable condition that opens a future with possibilities instead of the obstacle in daily life that tachycardia entails. For the patients, an informative and caring conversation was needed that would have provided the support they lacked before and during the ablation., CC BY 4.0Taylor & Francis Group an informa businessCONTACT Ann-Katrin Nordblom ann-katrin.nordblom@vgregion.se Department of Cardiology, Skaraborgs Hospital Skövde, Skövde SE-541 85, SwedenThe study was conducted with support from the Research Fund at Skaraborg Hospital, Sweden [VGSKAS-930160] and the Skaraborg Institute [Dnr:19/1037].

PURPOSE: To address the consequences of living with supraventricular tachycardia and to improve the quality of treatment, there is a need to highlight patient experiences of treatment with catheter ablation. Therefore, the aim was to describe the phenomenon of catheter ablation, as it is experienced by patients being treated awake. METHODS: A descriptive design was applied based on a reflective lifeworld research founded on phenomenological epistemology. Interviews were conducted between December 2021 and Mars 2022 with seven women and five men, three to twelve months after they underwent catheter ablation. RESULTS: Patients undergoing catheter ablation while awake during treatment, which includes experiences of relying on others expertise, being actively passive, and striving to be cured. It entails experiences of having a foreign object moving in one's body and heart and can be endured through strategies of mainly shifted one's mental focus. CONCLUSIONS: The effort of undergoing a catheter ablation procedure is worthwhile as the confirmation of a physical curable condition that opens a future with possibilities instead of the obstacle in daily life that tachycardia entails. For the patients, an informative and caring conversation was needed that would have provided the support they lacked before and during the ablation., CC BY 4.0Taylor & Francis Group an informa businessCONTACT Ann-Katrin Nordblom ann-katrin.nordblom@vgregion.se Department of Cardiology, Skaraborgs Hospital Skövde, Skövde SE-541 85, SwedenThe study was conducted with support from the Research Fund at Skaraborg Hospital, Sweden [VGSKAS-930160] and the Skaraborg Institute [Dnr:19/1037].

This study delves into the impact of aromatherapy on influencing both sleep and wakefulness via the use of essential oils including lavender and peppermint. Firstly, the study challenges the misconception that scents can't wake you up by showing strong evidence that our bodies naturally respond to smells, even when in a state of slumber. Further, through the expansion of a diverse array of studies, the research uncovers the ways in which aromatherapy exerts a strong influence on levels of drowsiness and alertness, alongside the numerous advantages that ensue. Ultimately, this study attests to the significance of essential oils and the influence they have on bodily processes that inherently transpire.

Humans and animals lacking orexin neurons exhibit daytime sleepiness, sleep attacks, and state instability. While the circuit basis by which orexin neurons contribute to consolidated wakefulness remains unclear, existing models posit that orexin neurons provide their wake-stabilizing influence by exerting excitatory tone on other brain arousal nodes. Here we show using in vivo optogenetics, in vitro optogenetic-based circuit mapping, and single-cell transcriptomics that orexin neurons also contribute to arousal maintenance through indirect inhibition of sleep-promoting neurons of the ventrolateral preoptic nucleus. Activation of this subcortical circuit rapidly drives wakefulness from sleep by differentially modulating the activity of ventrolateral preoptic neurons. We further identify and characterize a feedforward circuit through which orexin (and co-released glutamate) acts to indirectly target and inhibit sleep-promoting ventrolateral preoptic neurons to produce arousal. This revealed circuitry provides an alternate framework for understanding how orexin neurons contribute to the maintenance of consolidated wakefulness and stabilize behavioral state.

Although many brain regions have been shown to participate in sleep-wake regulation usingmodel organisms, we sought to identify a novel region relevant to human sleep duration regulation. We used a sleep duration gene (ADRB1) identified in humans and an unbiased approach to identify the peri tegmental reticular nucleus (pTRNADRB1) as a new region participating in sleep-wake regulation, uncovering a role for a poorly-understood brain area. We found that the endogenous activity of pTRNADRB1 neurons is wake- and REM-active. Furthermore, we found that pTRNADRB1 ablation increased wakefulness and that pTRNADRB1 neuron stimulation strongly promote wakefulness, even after stimulation offset. Using combinatorial genetics, we found that excitatory pTRNADRB1 neurons promote wakefulness. pTRN neurons can be characterized as anterior- or posterior-projecting neurons based on MAPseq analysis. Finally, we found that pTRNADRB1 neurons promote wakefulness, in part, through projections to the lateral hypothalamus (LH). Thus, human genetic information from a human sleep trait allowed us to identify a role for the pTRN in sleep–wake regulation.

During sleep, sensory stimuli rarely trigger a behavioral response or conscious perception. However, it remains unclear whether sleep inhibits specific aspects of sensory processing, such as feedforward or feedback signaling. Here, we presented auditory stimuli (for example, click-trains, words, music) during wakefulness and sleep in patients with epilepsy, while recording neuronal spiking, microwire local field potentials, intracranial electroencephalogram and polysomnography. Auditory stimuli induced robust and selective spiking and high-gamma (80-200 Hz) power responses across the lateral temporal lobe during both non-rapid eye movement (NREM) and rapid eye movement (REM) sleep. Sleep only moderately attenuated response magnitudes, mainly affecting late responses beyond early auditory cortex and entrainment to rapid click-trains in NREM sleep. By contrast, auditory-induced alpha-beta (10-30 Hz) desynchronization (that is, decreased power), prevalent in wakefulness, was strongly reduced in sleep. Thus, extensive auditory responses persist during sleep whereas alpha-beta power decrease, likely reflecting neural feedback processes, is deficient. More broadly, our findings suggest that feedback signaling is key to conscious sensory processing.

Although many brain regions have been shown to participate in sleep-wake regulation usingmodel organisms, we sought to identify a novel region relevant to human sleep duration regulation. We used a sleep duration gene (ADRB1) identified in humans and an unbiased approach to identify the peri tegmental reticular nucleus (pTRNADRB1) as a new region participating in sleep-wake regulation, uncovering a role for a poorly-understood brain area. We found that the endogenous activity of pTRNADRB1 neurons is wake- and REM-active. Furthermore, we found that pTRNADRB1 ablation increased wakefulness and that pTRNADRB1 neuron stimulation strongly promote wakefulness, even after stimulation offset. Using combinatorial genetics, we found that excitatory pTRNADRB1 neurons promote wakefulness. pTRN neurons can be characterized as anterior- or posterior-projecting neurons based on MAPseq analysis. Finally, we found that pTRNADRB1 neurons promote wakefulness, in part, through projections to the lateral hypothalamus (LH). Thus, human genetic information from a human sleep trait allowed us to identify a role for the pTRN in sleep–wake regulation.

Declarative memory encoding, consolidation, and retrieval require the integration of elements encoded in widespread cortical locations. The mechanism whereby such "binding" of different components of mental events into unified representations occurs is unknown. The "binding-by-synchrony" theory proposes that distributed encoding areas are bound by synchronous oscillations enabling enhanced communication. However, evidence for such oscillations is sparse. Brief high-frequency oscillations ("ripples") occur in the hippocampus and cortex and help organize memory recall and consolidation. Here, using intracranial recordings in humans, we report that these ∼70-ms-duration, 90-Hz ripples often couple (within ±500 ms), co-occur (≥ 25-ms overlap), and, crucially, phase-lock (have consistent phase lags) between widely distributed focal cortical locations during both sleep and waking, even between hemispheres. Cortical ripple co-occurrence is facilitated through activation across multiple sites, and phase locking increases with more cortical sites corippling. Ripples in all cortical areas co-occur with hippocampal ripples but do not phase-lock with them, further suggesting that cortico-cortical synchrony is mediated by cortico-cortical connections. Ripple phase lags vary across sleep nights, consistent with participation in different networks. During waking, we show that hippocampo-cortical and cortico-cortical coripples increase preceding successful delayed memory recall, when binding between the cue and response is essential. Ripples increase and phase-modulate unit firing, and coripples increase high-frequency correlations between areas, suggesting synchronized unit spiking facilitating information exchange. co-occurrence, phase synchrony, and high-frequency correlation are maintained with little decrement over very long distances (25 cm). Hippocampo-cortico-cortical coripples appear to possess the essential properties necessary to support binding by synchrony during memor

Study objectivesObstructive sleep apnea (OSA) is defined by pauses in breathing during sleep, but daytime breathing dysregulation may also be present. Sleep may unmask breathing instability in OSA that is usually masked by behavioral influences during wakefulness. A breath-hold (BH) challenge has been used to demonstrate breathing instability. One measure of breathing stability is breathing rate variability (BRV). We aimed to assess BRV during rest and in response to BH in OSA.MethodsWe studied 62 participants (31 with untreated OSA: respiratory event index [mean ± SD] 20 ± 15 events/h, 12 females, age 51 ± 14 years, body mass index [BMI] 32 ± 8 kg/m2; 31 controls: 17 females, age 47 ± 13 years; BMI 26 ± 4 kg/m2). Breathing movements were collected using a chest belt for 5 minutes of rest and during a BH protocol (60 seconds baseline, 30 seconds BH, 90 seconds recovery, 3 repeats). From the breathing movements, we calculated median breathing rate (BR) and interquartile BRV at rest. We calculated change in BRV during BH recovery from baseline. Group comparisons of OSA vs control were conducted using analysis of covariance with age, sex, and BMI as covariates.ResultsWe found 10% higher BRV in OSA vs controls (P < .05) during rest. In response to BH, BRV increased 7% in OSA vs 1% in controls (P < .001). Resting BR was not significantly different in OSA and controls, and sex and age did not have any significant interaction effects. BMI was associated with BR at rest (P < .05) and change in BRV with BH (P < .001), but no significant BMI-by-group interaction effect was observed.ConclusionsThe findings suggest breathing instability as reflected by BRV is high in OSA during wakefulness, both at rest and in response to a stimulus. Breathing instability together with high blood pressure variability in OSA may reflect a compromised cardiorespiratory consequence in OSA during wakefulness.CitationPal A, Martinez F, Akey MA, et al. Breathing rate variability in o

Humans and animals lacking orexin neurons exhibit daytime sleepiness, sleep attacks, and state instability. While the circuit basis by which orexin neurons contribute to consolidated wakefulness remains unclear, existing models posit that orexin neurons provide their wake-stabilizing influence by exerting excitatory tone on other brain arousal nodes. Here we show using in vivo optogenetics, in vitro optogenetic-based circuit mapping, and single-cell transcriptomics that orexin neurons also contribute to arousal maintenance through indirect inhibition of sleep-promoting neurons of the ventrolateral preoptic nucleus. Activation of this subcortical circuit rapidly drives wakefulness from sleep by differentially modulating the activity of ventrolateral preoptic neurons. We further identify and characterize a feedforward circuit through which orexin (and co-released glutamate) acts to indirectly target and inhibit sleep-promoting ventrolateral preoptic neurons to produce arousal. This revealed circuitry provides an alternate framework for understanding how orexin neurons contribute to the maintenance of consolidated wakefulness and stabilize behavioral state.

During sleep, sensory stimuli rarely trigger a behavioral response or conscious perception. However, it remains unclear whether sleep inhibits specific aspects of sensory processing, such as feedforward or feedback signaling. Here, we presented auditory stimuli (for example, click-trains, words, music) during wakefulness and sleep in patients with epilepsy, while recording neuronal spiking, microwire local field potentials, intracranial electroencephalogram and polysomnography. Auditory stimuli induced robust and selective spiking and high-gamma (80-200 Hz) power responses across the lateral temporal lobe during both non-rapid eye movement (NREM) and rapid eye movement (REM) sleep. Sleep only moderately attenuated response magnitudes, mainly affecting late responses beyond early auditory cortex and entrainment to rapid click-trains in NREM sleep. By contrast, auditory-induced alpha-beta (10-30 Hz) desynchronization (that is, decreased power), prevalent in wakefulness, was strongly reduced in sleep. Thus, extensive auditory responses persist during sleep whereas alpha-beta power decrease, likely reflecting neural feedback processes, is deficient. More broadly, our findings suggest that feedback signaling is key to conscious sensory processing.

A surprising finding of recent studies in mouse is the dominance of widespread movement-related activity throughout the brain, including in early sensory areas. In awake subjects, failing to account for movement risks misattributing movement-related activity to other (e.g., sensory or cognitive) processes. In this article, we (1) review task designs for separating task-related and movement-related activity, (2) review three "case studies" in which not considering movement would have resulted in critically different interpretations of neuronal function, and (3) discuss functional couplings that may prevent us from ever fully isolating sensory, motor, and cognitive-related activity. Our main thesis is that neural signals related to movement are ubiquitous, and therefore ought to be considered first and foremost when attempting to correlate neuronal activity with task-related processes.

Sleep is critical for health, cognition, and restorative processes, and yet, many experience chronic sleep restriction. Sleep interventions have been designed to enhance overnight sleep quality and physiology. Components of these interventions, like relaxation-based progressive muscle relaxation (PMR), have been studied in isolation and have shown direct effects on sleep architecture, including increasing time in restorative, slow-wave sleep (SWS). These relaxation methods have been understudied in naps, which are effective fatigue countermeasures that reduce deleterious effects of chronic sleep restriction. We hypothesised that PMR should boost SWS in a nap, as compared to an active control. We used a between-subject design in which healthy young adults underwent PMR training or listened to Mozart music (control) prior to a 90-min nap opportunity. We assessed changes in the amount and lateralisation of SWS, as evidence suggests left hemispheric lateralisation may be a proxy for recuperative sleep needs, and changes to state-dependent anxiety and fatigue before and after the nap to assess intervention success. We found PMR participants spent ~10 min more in SWS, equivalent to 125% more time, than the control group, and concomitantly, significantly less time in rapid eye movement sleep. PMR participants also had greater right lateralised slow-wave activity and delta activity compared to the control suggesting a more well-rested brain profile during sleep. Further, pre-sleep anxiety levels predicted nap architecture in the intervention group, suggesting benefits may be impacted by anxiety. The feasibility and accessibility of PMR prior to a nap make this an interesting research avenue to pursue with strong translational application.

Study objectivesThe clinical benefits of positive airway pressure (PAP) therapy for obstructive sleep apnea are assumed to require adherent PAP usage, defined by the Centers for Medicare & Medicaid Services as ≥ 4 hours of use ≥ 70% of nights. However, this definition is based on early data and does not necessarily capture improvements at subthreshold adherence. We explored dose-response relationships between PAP adherence measures and excessive daytime sleepiness from the HomePAP randomized controlled trial.MethodsParticipants aged ≥ 18 years with an apnea-hypopnea index ≥ 15 events/h and baseline sleepiness (Epworth Sleepiness Scale [ESS] ≥ 12) received PAP therapy. Data were collected at baseline, 1-month follow-up, and 3-months follow-up. Regression models and receiver operating characteristic curves evaluated PAP measures as predictors of ESS change and normalization (ESS < 10).ResultsIn 119 participants (aged 49.4 ± 12.6 years, 66.4% male, 72.3% White), > 50% were PAP nonadherent per Centers for Medicare & Medicaid Services criteria at 3 months. The percentage of nights with PAP use ≥ 4 hours predicted ESS change (P = .023), but not when controlling for the apnea-hypopnea index. The percentage of nights with ≥ 4 hours and average PAP use provided the best discrimination for predicting ESS normalization; each 10% increase in PAP use ≥ 4 hours increased the odds of ESS normalization by 22% (P = .007); those using PAP ≥ 4 hours had a nearly 3-fold greater odds of ESS normalization (P = .025). PAP use for at least 4 hours and on 70% of nights provided the best balance between specificity (0.50) and sensitivity (0.73).ConclusionsAlthough subadherent PAP usage may still confer some benefit for patients with obstructive sleep apnea, adherence to current criteria confers the highest likelihood for ESS change and normalization.Clinical trial registrationRegistry: ClinicalTrials.gov; Name: Portable Monitoring for Diagnosis and Management of Sleep Apnea (Ho

What is the common denominator of consciousness across divergent regimes of cortical dynamics? Does consciousness show itself in decibels or in bits? To address these questions, we introduce a testbed for evaluating electroencephalogram (EEG) biomarkers of consciousness using dissociations between neural oscillations and consciousness caused by rare genetic disorders. Children with Angelman syndrome (AS) exhibit sleep-like neural dynamics during wakefulness. Conversely, children with duplication 15q11.2-13.1 syndrome (Dup15q) exhibit wake-like neural dynamics during non-rapid eye movement (NREM) sleep. To identify highly generalizable biomarkers of consciousness, we trained regularized logistic regression classifiers on EEG data from wakefulness and NREM sleep in children with AS using both entropy measures of neural complexity and spectral (i.e., neural oscillatory) EEG features. For each set of features, we then validated these classifiers using EEG from neurotypical (NT) children and abnormal EEGs from children with Dup15q. Our results show that the classification performance of entropy-based EEG biomarkers of conscious state is not upper-bounded by that of spectral EEG features, which are outperformed by entropy features. Entropy-based biomarkers of consciousness may thus be highly adaptable and should be investigated further in situations where spectral EEG features have shown limited success, such as detecting covert consciousness or anesthesia awareness.

The ventrolateral preoptic area (VLPO) predominantly contains sleep-active neurons and is involved in sleep regulation. The perifornical-hypothalamic area (PF-HA) is a wake-regulatory region and predominantly contains wake-active neurons. VLPO GABAergic/galaninergic neurons project to the PF-HA. Previously, the specific contribution of VLPO neurons projecting to the PF-HA (VLPO > PF-HAPRJ) in sleep regulation in rats could not be investigated due to the lack of tools that could selectively target these neurons. We determined the contribution of VLPO > PF-HAPRJ neurons in sleep regulation by selectively activating them using designer receptors exclusively activated by designer drugs (DREADDs) in wild-type Fischer-344 rats. We used a combination of two viral vectors to retrogradely deliver the Cre-recombinase gene, specifically, in VLPO > PF-HA neurons, and further express hM3Dq in those neurons to selectively activate them for delineating their specific contributions to sleep−wake functions. Compared to the control, in DREADD rats, clozapine-N-oxide (CNO) significantly increased fos-expression, a marker of neuronal activation, in VLPO > PF-HAPRJ neurons (2% vs. 20%, p < 0.01) during the dark phase. CNO treatment also increased nonREM sleep (27% vs. 40%, p < 0.01) during the first 3 h of the dark phase, when rats are typically awake, and after exposure to the novel environment (55% vs. 65%; p < 0.01), which induces acute arousal during the light phase. These results support a hypothesis that VLPO > PF-HAPRJ neurons constitute a critical component of the hypothalamic sleep−wake regulatory circuitry and promote sleep by suppressing wake-active PF-HA neurons.

Rodent sensory cortex contains salt-and-pepper maps of sensory features, whose structure is not fully known. Here we investigated the structure of the salt-and-pepper whisker somatotopic map among L2/3 pyramidal neurons in somatosensory cortex, in awake mice performing one-vs-all whisker discrimination. Neurons tuned for columnar (CW) and non-columnar (non-CW) whiskers were spatially intermixed, with co-tuned neurons forming local (20 µm) clusters. Whisker tuning was markedly unstable in expert mice, with 35-46% of pyramidal cells significantly shifting tuning over 5-18 days. Tuning instability was highly concentrated in non-CW tuned neurons, and thus was structured in the map. Instability of non-CW neurons was unchanged during chronic whisker paralysis and when mice discriminated individual whiskers, suggesting it is an inherent feature. Thus, L2/3 combines two distinct components: a stable columnar framework of CW-tuned cells that may promote spatial perceptual stability, plus an intermixed, non-columnar surround with highly unstable tuning.

Given the high rate of depression associated with narcolepsy or obstructive sleep apnea (OSA), this analysis compared effects of solriamfetol treatment of excessive daytime sleepiness (EDS) in participants with/without a history of depression (DHx+/DHx-). This secondary analysis included data from two randomized, controlled trials in which participants were randomized to 12 weeks placebo or solriamfetol 37.5 (OSA only), 75, 150, or 300 mg/day. Efficacy/safety (combined solriamfetol doses) was summarized for DHx+/DHx-subgroups. 27.5% (65/236) with narcolepsy and 23.4% (111/474) with OSA were DHx+. In narcolepsy (DHx+ and DHx-), 40-min Maintenance of Wakefulness Test (MWT40) mean sleep latency increased (5.4 and 7.0 min), Epworth Sleepiness Scale (ESS) score decreased (3.8 and 3.5 points), and percentage of participants improved on Patient Global Impression of Change (PGI-C) was higher (31.7% and 39.4%) relative to placebo. In OSA (DHx+ and DHx-), MWT40 mean sleep latency increased (7.7 and 10.7 min), ESS decreased (3.5 and 3.7 points), and percentage of participants improved on PGI-C was higher (41.1% and 29.4%) relative to placebo. Common treatment-emergent adverse events (headache, decreased appetite, nausea, anxiety) were similar in DHx+/DHx-. This study suggests that safety and efficacy of solriamfetol for treating EDS in narcolepsy and OSA are not affected by depression history. Moreover, the findings emphasize the high prevalence of depression in people with sleep disorders and suggest that increased awareness of this association may have clinical significance.

Sleep is defined as a state of physiological rest characterized by relative suspension of consciousness and inaction of voluntary muscles. The study considered "gold standard" for its diagnosis is polysomnography through continuous monitoring of the electroencephalogram. It is notorious to see this condition becoming more frequent in the population and its causes are divided between environmental factors such as long working hours and irregular sleep schedules, as well as organic disorders. The clinical evaluation, as in other pathologies, is mainly defined by a complete clinical history from the pathological personal history as well as important hereditary family history, including a complete physical examination, all this with the purpose of identifying the disease in time. which significantly affects the daily life of those who suffer from it. Medical treatment includes from non-pharmacological therapies with adequate sleep hygiene measures to drugs that allow improving the quality of sleep and with this favor the functionality of daily activities., El sueño se define como un estado de reposo fisiológico que se caracteriza por la suspensión relativa de la conciencia y la inacción de los músculos voluntarios. El estudio considerado “estándar de oro” para su diagnóstico es la polisomnografía a través del monitoreo continuo del electroencefalograma. Es notorio ver este padecimiento cada día más frecuente en la población y sus causas se encuentran divididas entre los factores ambientales como largas horas de trabajo y horarios irregulares de sueño, así como trastornes orgánicas. La evaluación clínica, al igual que en otras patologías, esta principalmente definida por una historia clínica completa desde los antecedentes personales patológicos así como antecedentes heredofamiliares de importancia, incluyendo un examen físico completo , todo esto con la finalidad de identificar a tiempo la enfermedad, la cual afecta de manera importante la vida diaria de quien la padece. El tratamiento medico incluye desde terapias no farmacológicas con adecuadas medidas de higiene de sueño hasta fármacos que permitan mejorar la calidad del dormir y con esto favorecer las funcionalidad de las actividades diarias.

After falling asleep, the brain needs to detach from waking activity and reorganize into a functionally distinct state. A functional MRI (fMRI) study has recently revealed that the transition to unconsciousness induced by propofol involves a global decline of brain activity followed by a transient reduction in cortico-subcortical coupling. We have analyzed the relationships between transitional brain activity and breathing changes as one example of a vital function that needs the brain to readapt. Thirty healthy participants were originally examined. The analysis involved the correlation between breathing and fMRI signal upon loss of consciousness. We proposed that a decrease in ventilation would be coupled to the initial decline in fMRI signal in brain areas relevant for modulating breathing in the awake state, and that the subsequent recovery would be coupled to fMRI signal in structures relevant for controlling breathing during the unconscious state. Results showed that a slight reduction in breathing from wakefulness to unconsciousness was distinctively associated with decreased activity in brain systems underlying different aspects of consciousness including the prefrontal cortex, the default mode network and somatosensory areas. Breathing recovery was distinctively coupled to activity in deep brain structures controlling basic behaviors such as the hypothalamus and amygdala. Activity in the brainstem, cerebellum and hippocampus was associated with breathing variations in both states. Therefore, our brain maps illustrate potential drives to breathe, unique to wakefulness, in the form of brain systems underlying cognitive awareness, self-awareness and sensory awareness, and to unconsciousness involving structures controlling instinctive and homeostatic behaviors., Peer Reviewed, Postprint (published version)

AIM: Separating infants and their parents after a Caesarean section is still the routine care worldwide. This study investigated three caregiving models on the wakefulness and physiological parameters of full-term infants after an elective Caesarean section. METHODS: Newborn infants born in a Chilean public hospital in 2009-12 were randomised to three groups: cot, fathers' arms or skin-to-skin contact with their father. They were assessed at 15-minute intervals, from 45 to 120 minutes after the Caesarean section. Their physiological parameters were measured, and their wakefulness was assessed using the Neonatal Behavioural Assessment Scale. RESULTS: We studied 95 infant (53% girls) born at a mean gestational age of 38.9 ± 0.9 weeks. Heart rates were significantly higher in the skin-to-skin than cot or fathers' arms groups and showed greater stability over time. Wakefulness was initially higher in the skin-to-skin group, but there were no significant differences by the end of the observation. There were no differences between the groups in peripheral oxygen saturation. Skin-to-skin contact had no negative impact on the infants. CONCLUSION: The skin-to-skin group showed some advantages over the cot and fathers' arms groups when it came to establishing stable physiological parameters and wakefulness. This approach should be supported during mother-infant separation.

AIM: Separating infants and their parents after a Caesarean section is still the routine care worldwide. This study investigated three caregiving models on the wakefulness and physiological parameters of full-term infants after an elective Caesarean section. METHODS: Newborn infants born in a Chilean public hospital in 2009-12 were randomised to three groups: cot, fathers' arms or skin-to-skin contact with their father. They were assessed at 15-minute intervals, from 45 to 120 minutes after the Caesarean section. Their physiological parameters were measured, and their wakefulness was assessed using the Neonatal Behavioural Assessment Scale. RESULTS: We studied 95 infant (53% girls) born at a mean gestational age of 38.9 ± 0.9 weeks. Heart rates were significantly higher in the skin-to-skin than cot or fathers' arms groups and showed greater stability over time. Wakefulness was initially higher in the skin-to-skin group, but there were no significant differences by the end of the observation. There were no differences between the groups in peripheral oxygen saturation. Skin-to-skin contact had no negative impact on the infants. CONCLUSION: The skin-to-skin group showed some advantages over the cot and fathers' arms groups when it came to establishing stable physiological parameters and wakefulness. This approach should be supported during mother-infant separation.

AIM: Separating infants and their parents after a Caesarean section is still the routine care worldwide. This study investigated three caregiving models on the wakefulness and physiological parameters of full-term infants after an elective Caesarean section. METHODS: Newborn infants born in a Chilean public hospital in 2009-12 were randomised to three groups: cot, fathers' arms or skin-to-skin contact with their father. They were assessed at 15-minute intervals, from 45 to 120 minutes after the Caesarean section. Their physiological parameters were measured, and their wakefulness was assessed using the Neonatal Behavioural Assessment Scale. RESULTS: We studied 95 infant (53% girls) born at a mean gestational age of 38.9 ± 0.9 weeks. Heart rates were significantly higher in the skin-to-skin than cot or fathers' arms groups and showed greater stability over time. Wakefulness was initially higher in the skin-to-skin group, but there were no significant differences by the end of the observation. There were no differences between the groups in peripheral oxygen saturation. Skin-to-skin contact had no negative impact on the infants. CONCLUSION: The skin-to-skin group showed some advantages over the cot and fathers' arms groups when it came to establishing stable physiological parameters and wakefulness. This approach should be supported during mother-infant separation.

This paper aims to do a study about the relations between theories on sleep, wakefulness and death, Logos and soul in Heraclitus. According to the Ephesian, man is in touch with death when he sleeps, because the burning of his soul, composed of fire, decreases. Whoever sleeps resembles one who is dead, due to the fact that sleeping is an intermediate state between the waking life and death. For this paper we established three instances of research that sought to elucidate the relationship between soul, Logos, sleep, death and wakefulness. From the fragments that remained, firstly we tried to understand what Heraclitus described as sleep, death and wakefulness, as well as the relationship between these states. Secondly, we needed to delineate the conception of soul proposed by the philosopher. This step was essential to the proposed research, because it revealed a possible connection of man with the fire that constitutes everything and could validate the idea that, for Heraclitus, man is part of a whole. Having established this relation between man and the existing whole, made explicit by the description of his soul, which sometimes burns, and sometimes diminishes in ardor. In a third part of the text, it was possible to think about the conception of Logos to reinforce, at the end of the study, that the Heraclitus’s theories about the relations between sleep, death and wakefulness are a part of a philosophy that unites his ideas about the human life with his theories about everything that exists., Este artigo propõe um estudo sobre as relações do sono, da vigília e da morte com a alma e o com Lógos heraclítico. Conforme a teoria de Heráclito de Éfeso sobre o sono e a vigília, o homem está em contato com a morte quando dorme, pois o arder de sua alma-fogo se abranda. Assim, quem dorme se assemelha àquele que está morto, sendo o sono um estado intermediário entre a vida acordada e a morte. Para defender essa leitura dos fragmentos e para que a pesquisa fosse realizada, estabelecemos três momentos de pesquisa que buscaram elucidar a relação entre alma, Lógos, sono, vigília e morte. Em um primeiro momento, tentamos compreender o que Heráclito descreveu como sono, vigília e morte, bem como buscamos entender a relação entre eles. Em um segundo momento, foi preciso abordar os fragmentos sobre a alma propostos pelo filósofo em questão. Esse passo foi imprescindível à pesquisa proposta, pois revelou uma possível conexão do homem com o fogo constituinte de tudo e pudemos defender a ideia de que, para Heráclito, o homem é parte de um todo. A partir da descrição de uma alma-fogo, foi possível pensar, em um terceiro momento do texto, o que é o Lógos, tantas vezes e de tantos modos mencionado pelo filósofo. Esta reflexão foi feita para reforçar, por fim, o pensamento do efésio sobre as relações entre sono, vigília e morte como parte integrante de uma filosofia que une ideias a respeito da vida humana com as suas teorias acerca de tudo que existe.

This paper aims to do a study about the relations between theories on sleep, wakefulness and death, Logos and soul in Heraclitus. According to the Ephesian, man is in touch with death when he sleeps, because the burning of his soul, composed of fire, decreases. Whoever sleeps resembles one who is dead, due to the fact that sleeping is an intermediate state between the waking life and death. For this paper we established three instances of research that sought to elucidate the relationship between soul, Logos, sleep, death and wakefulness. From the fragments that remained, firstly we tried to understand what Heraclitus described as sleep, death and wakefulness, as well as the relationship between these states. Secondly, we needed to delineate the conception of soul proposed by the philosopher. This step was essential to the proposed research, because it revealed a possible connection of man with the fire that constitutes everything and could validate the idea that, for Heraclitus, man is part of a whole. Having established this relation between man and the existing whole, made explicit by the description of his soul, which sometimes burns, and sometimes diminishes in ardor. In a third part of the text, it was possible to think about the conception of Logos to reinforce, at the end of the study, that the Heraclitus’s theories about the relations between sleep, death and wakefulness are a part of a philosophy that unites his ideas about the human life with his theories about everything that exists., Este artigo propõe um estudo sobre as relações do sono, da vigília e da morte com a alma e o com Lógos heraclítico. Conforme a teoria de Heráclito de Éfeso sobre o sono e a vigília, o homem está em contato com a morte quando dorme, pois o arder de sua alma-fogo se abranda. Assim, quem dorme se assemelha àquele que está morto, sendo o sono um estado intermediário entre a vida acordada e a morte. Para defender essa leitura dos fragmentos e para que a pesquisa fosse realizada, estabelecemos três momentos de pesquisa que buscaram elucidar a relação entre alma, Lógos, sono, vigília e morte. Em um primeiro momento, tentamos compreender o que Heráclito descreveu como sono, vigília e morte, bem como buscamos entender a relação entre eles. Em um segundo momento, foi preciso abordar os fragmentos sobre a alma propostos pelo filósofo em questão. Esse passo foi imprescindível à pesquisa proposta, pois revelou uma possível conexão do homem com o fogo constituinte de tudo e pudemos defender a ideia de que, para Heráclito, o homem é parte de um todo. A partir da descrição de uma alma-fogo, foi possível pensar, em um terceiro momento do texto, o que é o Lógos, tantas vezes e de tantos modos mencionado pelo filósofo. Esta reflexão foi feita para reforçar, por fim, o pensamento do efésio sobre as relações entre sono, vigília e morte como parte integrante de uma filosofia que une ideias a respeito da vida humana com as suas teorias acerca de tudo que existe.

PURPOSE: To determine whether awake EEG criteria can differentiate epileptic encephalopathy with continuous spike and waves during sleep (EE-CSWS) at the time of cognitive regression from typical, self-limited focal epilepsy (SFE). METHODS: This retrospective case-control study was based on the analysis of awake EEGs and included 15 patients with EE-CSWS and 15 age-matched and sex-matched patients with typical SFE. The EEGs were anonymised and scored by four independent readers. The following qualitative and quantitative EEG indices were analysed: slow-wave index (SLWI), spike-wave index (SWI), spike-wave frequency (SWF), long spike-wave clusters (CLSW) and EEG score (between grades 0 and 4). Sensitivity and specificity were assessed using receiver operating characteristic (ROC) curves and their reproducibility with a kappa test. RESULTS: Based on a highly sensitive cut-off, EE-CSWS patients were 8.4 times more likely than those with SFE to have an SLWI > 6%, 15 times more likely to have an SWI > 10 % and six times more likely to have a CLSW of ≥ 1 s. There was substantial agreement between readers (with kappa values of 0.64, 0.69 and 0.67). EE-CSWS patients were 13 times more likely to have an SWF of > 11 % and 149 times more likely to have an EEG score of ≥ 3 than typical SFE patients. Agreement about these ratings was almost perfect (kappa 0.91 and 0.86). CONCLUSION: An EEG score of ≥ 3 on a 20-min awake EEG differentiates typical SFE from EE-CSWS at the time of cognitive regression, with good reliability across readers with different levels of expertise.

BackgroundSolriamfetol, a dopamine-norepinephrine reuptake inhibitor, is approved in the United States to improve wakefulness in adults with excessive daytime sleepiness (EDS) associated with OSA (37.5-150 mg/d).Research questionDoes solriamfetol have differential effects on EDS based on adherence to primary OSA therapy and does solriamfetol affect primary OSA therapy use?Study design and methodsParticipants were randomized to 12 weeks of placebo or solriamfetol 37.5, 75, 150, or 300 mg/d (stratified by primary OSA therapy adherence). Coprimary end points were week 12 change from baseline in 40-min Maintenance of Wakefulness Test (MWT) and Epworth Sleepiness Scale (ESS) in the modified intention-to-treat population. Primary OSA therapy use (hours per night, % nights) and safety were evaluated.ResultsAt baseline, 324 participants (70.6%) adhered to OSA therapy (positive airway pressure use ≥ 4 h/night on ≥ 70% nights, surgical intervention, or oral appliance use on ≥ 70% nights) and 135 participants (29.4%) did not adhere. Least squares (LS) mean differences from placebo in MWT sleep latency (minutes) in the 37.5-, 75-, 150-, and 300-mg/d groups among adherent participants were 4.8 (95% CI, 0.6-9.0), 8.4 (95% CI, 4.3-12.5), 10.2 (95% CI, 6.8-13.6), and 12.5 (95% CI, 9.0-15.9) and among nonadherent participants were 3.7 (95% CI, -2.0 to 9.4), 9.9 (95% CI, 4.4-15.4), 11.9 (95% CI, 7.5-16.3), and 13.5 (95% CI, 8.8-18.3). On ESS, LS mean differences from placebo in the 37.5-, 75-, 150-, and 300-mg/d groups among adherent participants were -2.4 (95% CI, -4.2 to -0.5), -1.3 (95% CI, -3.1 to 0.5), -4.2 (95% CI, -5.7 to -2.7), and -4.7 (95% CI, -6.1 to -3.2) and among nonadherent participants were -0.7 (95% CI, -3.5 to 2.1), -2.6 (95% CI, -5.4 to 0.1), -5.0 (95% CI, -7.2 to -2.9), and -4.6 (95% CI, -7.0 to -2.3). Common adverse events included headache

What happens in the brain when conscious awareness of the surrounding world fades? We manipulated consciousness in two experiments in a group of healthy males and measured brain activity with positron emission tomography. Measurements were made during wakefulness, escalating and constant levels of two anesthetic agents (experiment 1, n = 39), and during sleep-deprived wakefulness and non-rapid eye movement sleep (experiment 2, n = 37). In experiment 1, the subjects were randomized to receive either propofol or dexmedetomidine until unresponsiveness. In both experiments, forced awakenings were applied to achieve rapid recovery from an unresponsive to a responsive state, followed by immediate and detailed interviews of subjective experiences during the preceding unresponsive condition. Unresponsiveness rarely denoted unconsciousness, as the majority of the subjects had internally generated experiences. Unresponsive anesthetic states and verified sleep stages, where a subsequent report of mental content included no signs of awareness of the surrounding world, indicated a disconnected state. Functional brain imaging comparing responsive and connected versus unresponsive and disconnected states of consciousness during constant anesthetic exposure revealed that activity of the thalamus, cingulate cortices, and angular gyri are fundamental for human consciousness. These brain structures were affected independent from the pharmacologic agent, drug concentration, and direction of change in the state of consciousness. Analogous findings were obtained when consciousness was regulated by physiological sleep. State-specific findings were distinct and separable from the overall effects of the interventions, which included widespread depression of brain activity across cortical areas. These findings identify a central core brain network critical for human consciousness.SIGNIFICANCE STATEMENT Trying to understand the biological basis of human consciousness is currently one of the g

This paper aims to do a study about the relations between theories on sleep, wakefulness and death, Logos and soul in Heraclitus. According to the Ephesian, man is in touch with death when he sleeps, because the burning of his soul, composed of fire, decreases. Whoever sleeps resembles one who is dead, due to the fact that sleeping is an intermediate state between the waking life and death. For this paper we established three instances of research that sought to elucidate the relationship between soul, Logos, sleep, death and wakefulness. From the fragments that remained, firstly we tried to understand what Heraclitus described as sleep, death and wakefulness, as well as the relationship between these states. Secondly, we needed to delineate the conception of soul proposed by the philosopher. This step was essential to the proposed research, because it revealed a possible connection of man with the fire that constitutes everything and could validate the idea that, for Heraclitus, man is part of a whole. Having established this relation between man and the existing whole, made explicit by the description of his soul, which sometimes burns, and sometimes diminishes in ardor. In a third part of the text, it was possible to think about the conception of Logos to reinforce, at the end of the study, that the Heraclitus’s theories about the relations between sleep, death and wakefulness are a part of a philosophy that unites his ideas about the human life with his theories about everything that exists., Este artigo propõe um estudo sobre as relações do sono, da vigília e da morte com a alma e o com Lógos heraclítico. Conforme a teoria de Heráclito de Éfeso sobre o sono e a vigília, o homem está em contato com a morte quando dorme, pois o arder de sua alma-fogo se abranda. Assim, quem dorme se assemelha àquele que está morto, sendo o sono um estado intermediário entre a vida acordada e a morte. Para defender essa leitura dos fragmentos e para que a pesquisa fosse realizada, estabelecemos três momentos de pesquisa que buscaram elucidar a relação entre alma, Lógos, sono, vigília e morte. Em um primeiro momento, tentamos compreender o que Heráclito descreveu como sono, vigília e morte, bem como buscamos entender a relação entre eles. Em um segundo momento, foi preciso abordar os fragmentos sobre a alma propostos pelo filósofo em questão. Esse passo foi imprescindível à pesquisa proposta, pois revelou uma possível conexão do homem com o fogo constituinte de tudo e pudemos defender a ideia de que, para Heráclito, o homem é parte de um todo. A partir da descrição de uma alma-fogo, foi possível pensar, em um terceiro momento do texto, o que é o Lógos, tantas vezes e de tantos modos mencionado pelo filósofo. Esta reflexão foi feita para reforçar, por fim, o pensamento do efésio sobre as relações entre sono, vigília e morte como parte integrante de uma filosofia que une ideias a respeito da vida humana com as suas teorias acerca de tudo que existe.

Intraoperative language mapping of tumor and peritumor tissue is a well-established technique for avoiding permanent neurological deficits and maximizing extent of resection. Although there are several components of language that may be tested intraoperatively (eg, naming, writing, reading, and repetition), there is a lack of consistency in how patients are tested intraoperatively as well as the techniques involved to ensure safety during an awake procedure. Here, we review appropriate patient selection, neuroanesthetic techniques, cortical and subcortical language mapping stimulation paradigms, and selection of intraoperative language tasks used during awake craniotomies. We also expand on existing language mapping reviews by considering how intensity and timing of electrical stimulation may impact interpretation of mapping results.

Since the early descriptions of language function based on observations of patients with language deficits by Broca and Wernicke, neurosurgeons have been focused on characterizing the anatomic regions necessary for language perception and production, and preserving these structures during surgery to minimize patient deficits post operatively. In this supplementary issue on awake intraoperative mapping, we review language processing across multiple domains, highlighting key advances in direct electrical stimulation of different cortical and subcortical regions involved in naming, repetition, reading, writing, and syntax. We then discuss different intraoperative tasks for assessing the function of a given area and avoiding injury to critical, eloquent regions.

Sensorimotor integration in the trunk system is poorly understood despite its importance for functional recovery after neurological injury. To address this, a series of mapping studies were performed in the rat. First, the receptive fields (RFs) of cells recorded from thoracic dorsal root ganglia were identified. Second, the RFs of cells recorded from trunk primary sensory cortex (S1) were used to assess the extent and internal organization of trunk S1. Finally, the trunk motor cortex (M1) was mapped using intracortical microstimulation to assess coactivation of trunk muscles with hindlimb and forelimb muscles, and integration with S1. Projections from trunk S1 to trunk M1 were not anatomically organized, with relatively weak sensorimotor integration between trunk S1 and M1 compared to extensive integration between hindlimb S1/M1 and trunk M1. Assessment of response latency and anatomical tracing suggest that trunk M1 is abundantly guided by hindlimb somatosensory information that is derived primarily from the thalamus. Finally, neural recordings from awake animals during unexpected postural perturbations support sensorimotor integration between hindlimb S1 and trunk M1, providing insight into the role of the trunk system in postural control that is useful when studying recovery after injury.

This article updates the American Academy of Sleep Medicine protocols for the administration of the Multiple Sleep Latency Test and the Maintenance of Wakefulness Test. The American Academy of Sleep Medicine commissioned a task force of clinical experts in sleep medicine to review published literature on the performance of these tests since the publication of the 2005 American Academy of Sleep Medicine practice parameter paper. Although no evidence-based changes to the protocols were warranted, the task force made several changes based on consensus. These changes included guidance on patient preparation, medication and substance use, sleep before testing, test scheduling, optimum test conditions, and documentation. This article provides guidance to providers who order and administer the Multiple Sleep Latency Test and the Maintenance of Wakefulness Test.CitationKrahn LE, Arand DL, Avidan AY, et al. Recommended protocols for the Multiple Sleep Latency Test and the Maintenance of Wakefulness Test in adults: guidance from the American Academy of Sleep Medicine. J Clin Sleep Med. 2021;17(12):2489-2498.