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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.

Sleep disturbances are prominent in drug use disorders, including those involving opioids in both humans and animals. Recent studies have shown that administration of liraglutide, a glucagon-like peptide-1 agonist, significantly reduces heroin taking and seeking in rats. In an effort to further understand the action of this substance on physiological functions and to evaluate safety issues for its potential clinical use, the aim of the present study was to determine whether the dose of liraglutide found effective in reducing responding for an opioid also could improve sleep in drug-naïve rats.Using a within-subjects design, adult male rats chronically implanted with EEG and EMG electrodes received subcutaneous injection of saline or 0.06, 0.10, 0.30 or 0.60 mg/kg liraglutide. The 0.10 and 0.30 mg/kg doses are known to be most effective in reducing responding for heroin in rats at light or dark onset during a 12:12 h light-dark cycle (0.10 mg/kg for taking and seeking, 0.30 mg/kg for seeking). EEG and EMG were recorded across the 24 h period following each injection.After both dark and light onset injections, liraglutide dose-dependently decreased wakefulness and increased non-rapid eye movement (NREM) sleep except at the lowest dose. The bout length of wakefulness and NREM sleep were decreased and increased, respectively. Whether administered at light or dark onset, the above alterations occurred primarily during the dark period (i.e., during the active period). The animals' body weight was decreased after liraglutide treatments as expected since it is clinically used for the treatment of obesity.These data indicate that liraglutide, at doses known to reduce responding for heroin and fentanyl, also increases NREM sleep, suggesting that the increase in sleep may contribute to the protective effects of liraglutide and may promote overall general health.

BACKGROUND: Sleep problems can persist following the treatment of depression and remission of symptoms. The extent to which having a previous history of depression may be associated with current daytime sleepiness is largely unknown. METHODS: Data were obtained from the spring 2017 American College Health Association-National College Health Assessment (ACHA-NCHA) survey (92 institutions) which assessed self-reported health in U.S. college students (n=41,670). Among the sample, 93.5% were 18–24 year of age, and 69.6% women. Logistic regression estimated the association between reported prior lifetime diagnosis of depression and daytime sleepiness from the past 7 days, while adjusting for depressive symptoms and antidepressant use from the past year. Unadjusted and adjusted logistic regression models stratified by gender were performed. RESULTS: Among those who reported problems with sleepiness, 31.6% women and 19.4% men had a pre-existing depression diagnosis. Individuals with pre-existing depression were more likely than those without this diagnosis to report sleepiness problems (women: OR = 1.4, CI = 1.3 – 1.6, p < .001; men: OR = 1.2, CI = 1.0 – 1.4, p < .01). However, this association differed significantly by gender, with women with a pre-existing depression diagnosis having a 13.0% greater likelihood of sleepiness compared to men. CONCLUSIONS: Those with a pre-existing depression diagnosis, and specifically women, may be at risk for daytime sleepiness even in the absence of current depressive mood-related symptoms. Given that many individuals are at risk for daytime sleepiness, mental health initiatives, including those on college campuses, should incorporate sleep hygiene within their programming.

OBJECTIVE Intraoperative stimulation is used as a crucial adjunct in neurosurgical oncology, allowing for greater extent of resection while minimizing morbidity. However, limited data exist regarding the impact of cortical stimulation on the frequency of perioperative seizures in these patients. METHODS A retrospective chart review of patients undergoing awake craniotomy with electrocorticography data by a single surgeon at the authors’ institution between 2013 and 2020 was conducted. Eighty-three patients were identified, and electrocorticography, stimulation, and afterdischarge (AD)/seizure data were collected and analyzed. Stimulation characteristics (number, amplitude, density [stimulations per minute], composite score [amplitude × density], total and average stimulation duration, and number of positive stimulation sites) were analyzed for association with intraoperative seizures (ISs), ADs, and postoperative clinical seizures. RESULTS Total stimulation duration (p = 0.005), average stimulation duration (p = 0.010), and number of stimulations (p = 0.020) were found to significantly impact AD incidence. A total stimulation duration of more than 145 seconds (p = 0.04) and more than 60 total stimulations (p = 0.03) resulted in significantly higher rates of ADs. The total number of positive stimulation sites was associated with increased IS (p = 0.048). Lesions located within the insula (p = 0.027) were associated with increased incidence of ADs. Patients undergoing repeat awake craniotomy were more likely to experience IS (p = 0.013). Preoperative antiepileptic drug use, seizure history, and number of prior resections of any type showed no impact on the outcomes considered. The charge transferred to the cortex per second during mapping was significantly higher in the 10 seconds leading to AD than at any other time point examined in patients experiencing ADs, and was significantly higher than any time point in patients not experiencing ADs or ISs. Although the rate of transfer for patients experiencing ISs was highest in the 10 seconds prior to the seizure, it was not significantly different from those who did not experience an AD or IS. CONCLUSIONS The data suggest that intraoperative cortical stimulation is a safe and effective technique in maximizing extent of resection while minimizing neurological morbidity in patients undergoing awake craniotomies, and that surgeons may avoid ADs and ISs by minimizing duration and total number of stimulations and by decreasing the overall charge transferred to the cortex during mapping procedures.

Although several previous studies have suggested a relationship between sleep and the stress response, the mechanism underlying this relationship remains largely unknown. Here, we show that fibroblast growth factor 21 (FGF21), a lipid metabolism-related hormone, may play a role in this relationship. In this study, we examined differences in the stress response between FGF21 knockout (KO) mice and wild-type (WT) mice after social defeat stress (SDS). When the amount of non-rapid eye movement (NREM) sleep, rapid eye movement (REM) sleep and wakefulness were averaged over the dark period after SDS, only KO mice showed significant differences in NREM sleep and wakefulness. In the social interaction test, KO mice seemed to be more prone to social avoidance. Our real-time (RT) -PCR results revealed that the mRNA expression of the stress- and sleep-related gene gamma-aminobutyric acid A receptor subunit alpha 2 was significantly lower in WT mice than in KO mice. Moreover, KO mice showed lower plasma levels of ketone bodies, which also affect sleep/wake regulation, than WT mice. These results suggested that FGF21 might influence sleep/wake regulation by inducing production of an anti-stress agent and/or ketone bodies, which may result in resilience to social stress.

Sleep impairment is a common comorbid and debilitating symptom for persons with opioid use disorder (OUD). Research into underlying mechanisms and efficacious treatment interventions for OUD-related sleep problems requires both precise and physiologic measurements of sleep-related outcomes and impairment. This pilot examined the feasibility of a wireless sleep electroencephalography (EEG) monitor (Sleep Profiler™) to measure sleep outcomes and architecture among participants undergoing supervised opioid withdrawal. Sleep outcomes were compared to a self-reported sleep diary and opioid withdrawal ratings. Participants (n = 8, 100% male) wore the wireless EEG 85.6% of scheduled nights. Wireless EEG detected measures of sleep architecture including changes in total, NREM and REM sleep time during study phases, whereas the diary detected changes in wakefulness only. Direct comparisons of five overlapping outcomes revealed lower sleep efficiency and sleep onset latency and higher awakenings and time spent awake from the wireless EEG versus sleep diary. Associations were evident between wireless EEG and increased withdrawal severity, lower sleep efficiency, less time in REM and non-REM stages 1 and 2, and more hydroxyzine treatment; sleep diary was associated with total sleep time and withdrawal only. Data provide initial evidence that a wireless EEG is a feasible and useful tool for objective monitoring of sleep in persons experiencing acute opioid withdrawal. Data are limited by the small and exclusively male sample, but provide a foundation for using wireless EEG sleep monitors for objective evaluation of sleep-related impairment in persons with OUD in support of mechanistic and treatment intervention research. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Abnormalities in cortical sources of resting-state eyes-closed electroencephalographic (rsEEG) rhythms recorded by hospital settings (10–20 electrode montage) with 19 scalp electrodes provide useful markers of neurophysiological dysfunctions in the vigilance regulation in patients with Alzheimer's disease dementia (ADD). Here we tested whether these markers may be effective from a few scalp electrodes towards the use of low-cost recording devices. Clinical and rsEEG data acquired in hospital settings (10–20 electrode montage) from 88 ADD participants and 68 age-, education-, and sex-matched normal elderly controls (Nold) were available in an international Eurasian database. Standard spectral FFT analysis of rsEEG data for individual delta, theta, and alpha frequency bands was from C3-P3, C4-P4, P3-O1, and P4-O2 bipolar channels. As compared to the Nold group, the ADD group showed increased delta, theta, low-frequency alpha power density and decreased high-frequency alpha power density at all those bipolar channels. The highest classification accuracy between the ADD and Nold individuals reached 90 % (area under the receiver operating characteristic curve) using Alpha2/Theta power density computed at the C3-P3 bipolar channel. Standard rsEEG power density computed from a few posterior bipolar channels successfully classified Nold and ADD individuals, thus encouraging a massive prescreening of neurophysiological mechanisms underpinning the vigilance dysregulation in underserved old seniors. Ministero della Salute

To study changes of thalamo-cortical and cortico-cortical connectivity during wakefulness, non-Rapid Eye Movement (non-REM) sleep, including N2 and N3 stages, and REM sleep, using stereoelectroencephalography (SEEG) recording in humans.We studied SEEG recordings of ten patients during wakefulness, non-REM sleep and REM sleep, in seven brain regions of interest including the thalamus. We calculated directed and undirected functional connectivity using a measure of non-linear correlation coefficient hThe thalamus was more connected to other brain regions during N2 stage and REM sleep than during N3 stage during which cortex was more connected than the thalamus. We found two significant directed links: the first from the prefrontal region to the lateral parietal region in the delta band during N3 sleep and the second from the thalamus to the insula during REM sleep.These results showed that cortico-cortical connectivity is more prominent in N3 stage than in N2 and REM sleep. During REM sleep we found significant thalamo-insular connectivity, with a driving role of the thalamus.We found a pattern of cortical connectivity during N3 sleep concordant with antero-posterior traveling slow waves. The thalamus seemed particularly involved as a hub of connectivity during REM sleep.

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 300mg/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 7.0min), 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 10.7min), 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.

The “sleep to forget and sleep to remember hypothesis” proposes that sleep weakens the emotional tone of an experience while preserving or even enhancing its content. Prior experimental research however shows contradictory findings on how emotional reactivity changes after a period of sleep, likely explained by methodological variations. By addressing these inconsistencies, we investigated the mitigating effect of overnight sleep on emotional reactivity triggered by memory reactivation. Using a karaoke paradigm, we recorded participants’ singing of two songs, followed by exposing them to one of the recordings (rec1) to induce an embarrassing episode. After a 12-hr period of either day-time wakefulness (N = 20) or including nighttime sleep (N = 20), we assessed emotional reactivity to the previously exposed recording (rec1) and the newly exposed recording (rec2). Emotional reactivity was assessed with a physiological measure of facial blushing as the main outcome and subjective ratings of embarrassment and valence. Sleep and wake were monitored with diaries and actigraphy. The embarrassing episode was successfully induced as indicated by objective and subjective measures. After controlling for an order effect in stimulus presentation, we found a reduction in blushing response to the reactivated recording (rec1) from pre- to post-sleep compared to wakefulness. However, emotional reactivity to the reactivated recording (rec1) and the new recording (rec2) did not differ after sleep and wakefulness. This study shows that facial blushing was reduced following overnight sleep, while subjective ratings were unaffected. Whether the beneficial effect of sleep is due to changes in memory representation or rather emotion regulation remains elusive.

Previous resting-state functional magnetic resonance imaging (fMRI) studies have revealed highly reproducible latency structures, reflecting the lead/lag relationship of BOLD fMRI signals in white matter (WM). With simultaneous electroencephalography and fMRI data from 35 healthy subjects who were instructed to sleep during imaging, we explored alterations of latency structures in the WM across wakefulness and nonrapid eye movement (NREM) sleep stages. Lagged cross-covariance was computed among voxelwise time series, followed by parabolic interpolation to determine the actual in-between latencies. WM regions, including the brainstem, internal capsule, optic radiation, genu of corpus callosum, and corona radiata, inconsistently changed temporal dynamics with respect to the rest of the WM across wakefulness and NREM sleep stages, as demonstrated when these regions were used as seeds for seed-based latency analysis. Latency analysis of resting-state networks, obtained by applying K-means clustering to a group-level functional connectivity matrix, identified a dominant direction of signaling, starting from the brainstem up to the internal capsule and then the corona radiata during wakefulness, which was reorganized according to stage transitions, e.g., the temporal organization of the internal capsule and corona radiata switched from unidirectional to bidirectional in the wakefulness to N3 transition. These findings suggest that WM BOLD signals are slow, dynamically modulated across wakefulness and NREM sleep stages and that they are involved in maintaining different levels of consciousness.

The spatiotemporal representation of neural activity during rest and upon sensory stimulation in cortical areas is highly dynamic and may be predominantly governed by cortical state. On the mesoscale level, intrinsic neuronal activity ranges from a persistent state, generally associated with a sustained depolarization of neurons, to a bimodal, slow wave-like state with bursts of neuronal activation alternating with silent periods. These different activity states are prevalent under certain types of sedatives or are associated with specific behavioral or vigilance conditions. Neurophysiological experiments assessing circuit activity usually assume a constant underlying state, yet reports of variability of neuronal responses under seemingly constant conditions are common in the field. Even when a certain type of neural activity or cortical state can be stably maintained over time, the associated response properties are highly relevant for explaining experimental outcomes. Here we describe the spatiotemporal characteristics of ongoing activity and sensory-evoked responses under two predominant functional states in the sensory cortices of mice: persistent activity (PA) and slow wave activity (SWA). Using electrophysiological recordings and local and wide-field calcium recordings, we examine whether spontaneous and sensory-evoked neuronal activity propagate throughout the cortex in a state-dependent manner. We find that PA and SWA differ in their spatiotemporal characteristics, which determine the cortical network's response to a sensory stimulus. During PA state, sensory stimulation elicits gamma-based short-latency responses that precisely follow each stimulation pulse and are prone to adaptation upon higher stimulation frequencies. Sensory responses during SWA are more variable, dependent on refractory periods following spontaneous slow waves. Although spontaneous slow waves propagated in anterior-posterior direction in a majority of observations, the direction of propagation of stimulus-elicited wave depends on the sensory modality. These findings suggest that cortical state explains variance and should be considered when investigating multiscale correlates of functional neurocircuit activity.bNEWamp; NOTEWORTHY/bHere we dissect the cortical representation of brain states based on local photometry recordings and on mesoscale cortical calcium imaging, complemented by electrophysiological recordings in mice. We identify two distinct functional states in the sensory cortices, which differ in their spatiotemporal characteristics on the local and global cortical scales. We examine how intrinsic and stimulus-evoked neuronal activity propagates throughout the cortex in a state-dependent manner, supporting the notion that cortical state is a relevant variable to consider for a wide range of neurophysiological experiments.

General anesthesia might disrupt neuronal network communications measured by functional connectivity (FC; undirected connectivity) and directional information flow (directed connectivity). We sought to characterize the state-dependent effects of propofol on cortico-cortical undirected and directed FC.We collected 256-channel high-density EEGs from 14 patients undergoing surgery while awake (AWA) or in propofol-induced moderate sedation (SED) or loss of consciousness (LOC) states. Using source-space EEG, we estimated neuronal oscillatory activity for 68 cortical regions of interest. FC was analyzed using the weighted phase lag index. Directed connectivity was computed using directed phase transfer entropy (dPTE) as a measure of information flow in the bilateral prefrontal, frontal, parietal, and occipital areas.FC strength evidently reduced during LOC compared with those during the AWA and SED states. The dPTE analysis showed significant propofol-induced changes in directed connectivity. In the alpha band, the prefrontal-to-frontal information flow was significantly stronger in the AWA than in the SED (p = 0.033) and LOC states (p = 0.033). The parietal-to-frontal dPTE was significantly weaker during LOC than during the AWA (p = 0.033) and SED states (p = 0.007). Finally, a loss of occipital-to-frontal connectivity occurred during LOC but not the AWA state (p = 0.001). In the beta band, the dominant occipital-to-frontal direction of information flow in the AWA state was gradually converted to a frontal-to-occipital direction during LOC.Propofol-induced unconsciousness is marked by a decrease in FC and posterior-to-anterior (feedforward) directed connectivity, which may be useful as a measure to discriminate different conscious states caused by propofol administration.The study demonstrates that propofol produces state-dependent effects on cortico-cortical undirected and directed FC, supporting the idea that propofol induces loss of consciousness may through disrupting network interactions and cortical coordination.

SARS-CoV-2 with a dramatical worldwide spread, impacted greatly daily life and healthcare. In order to avoid delay in cancer treatment, many strategies and measures were implemented. The Awake breast surgery was a strategy implemented in our Unit during the pandemic, aimed to reduce operatory room occupancy and increase the number of procedures performed during the daily surgical session. The aim of the study was to evaluate how the use of this strategy has changed before and after the advent of the COVID-19 pandemic, and its relative benefits.This was a retrospective study analysing all patients subjected to breast conservative surgery for oncological disease from July 2018 to December 2021.Out of 498 patients enrolled in the study, 253 (50.8%) cases were treated before the pandemic and were designated as "pre-COVID-19" group. The remaining 245 (49.1%) cases were considered the "COVID-19" group. Cases of awake surgery in COVID-19 group were 141 (54.7%) vs. 84 (33.2%), p0.001. Length of hospitalization and surgical time were comparable between the groups: relative p=0.188 and 0.264, respectively. Differently, operation room occupation was significantly shorter in the COVID-19 group, p0.001; and number of outpatient surgical procedures was higher, p=0.0304. Multivariate analysis identified the period of surgery (OR=1.47) as a statistically significant factor, p=0.011, predictive of prolonged operatory room occupancy.Awake surgery was one of the strategies which made more operating rooms available and allowed avoiding further delays.

Sustained attention describes our ability to keep a constant focus on a given task. This ability is modulated by our physiological state of arousal. Although lapses of sustained attention have been linked with dysregulations of arousal, the underlying physiological mechanisms remain unclear. An emerging body of work proposes that the intrusion during wakefulness of sleep-like slow waves, a marker of the transition toward sleep, could mechanistically account for attentional lapses. This study aimed to expose, via pharmacological manipulations of the monoamine system, the relationship between the occurrence of sleep-like slow waves and the behavioural consequences of sustained attention failures. In a double-blind, randomised-control trial, 32 healthy human male participants received methylphenidate, atomoxetine, citalopram or placebo during four separate experimental sessions. During each session, electroencephalography (EEG) was used to measure neural activity whilst participants completed a visual task requiring sustained attention. Methylphenidate, which increases wake-promoting dopamine and noradrenaline across cortical and subcortical areas, improved behavioural performance whereas atomoxetine, which increases dopamine and noradrenaline predominantly over frontal cortices, led to more impulsive responses. Additionally, citalopram, which increases sleep-promoting serotonin, led to more missed trials. Based on EEG recording, citalopram was also associated with an increase in sleep-like slow waves. Importantly, compared to a classical marker of arousal such as alpha power, only slow waves differentially predicted both misses and faster responses in a region-specific fashion. These results suggest that a decrease in arousal can lead to local sleep intrusions during wakefulness which could be mechanistically linked to impulsivity and sluggishness.Significance StatementWe investigated whether the modulation of attention and arousal could not only share the same neuromodulatory pathways but also rely on similar neuronal mechanisms; for example, the intrusion of sleep-like activity within wakefulness. To do so, we pharmacologically manipulated noradrenaline, dopamine, and serotonin in a four-arm, randomised, placebo-controlled trial and examined the consequences on behavioural and EEG indices of attention and arousal. We showed that sleep-like slow waves can predict opposite behavioural signatures: impulsivity and sluggishness. Slow waves may be a candidate mechanism for the occurrence of attentional lapses since the relationship between slow-wave occurrence and performance is region-specific and the consequences of these local sleep intrusions are in line with the cognitive functions carried by the underlying brain regions.

Recent studies in both humans and animal models call into question the completeness of recovery after chronic sleep disruption. Studies in humans have identified cognitive domains particularly vulnerable to delayed or incomplete recovery after chronic sleep disruption, including sustained vigilance and episodic memory. These findings, in turn, provide a focus for animal model studies to critically test the lasting impact of sleep loss on the brain. Here, we summarize the human response to sleep disruption and then discuss recent findings in animal models examining recovery responses in circuits pertinent to vigilance and memory. We then propose pathways of injury common to various forms of sleep disruption and consider the implications of this injury in aging and in neurodegenerative disorders.

Idiopathic hypersomnia (IH) is characterized by excessive daytime sleepiness despite normal or prolonged sleep. IH is distinguished from narcolepsy by the female predominance, severe morning inertia, continuous drowsiness (rather than sleep attacks), unrefreshing naps, absence of cataplexy, sleep onset in REM periods, and hypocretin deficiency. In IH, the multiple sleep latency test demonstrates low sensitivity, specificity, and reproducibility, compared with prolonged sleep monitoring. In some IH cases, an endogenous hypnotic peptide stimulating GABA receptors during wakefulness is suspected, which are improved by anti-GABA drugs. The benefits of modafinil, sodium oxybate, mazindol, and pitolisant were found in mostly retrospective studies.

Narcolepsy and idiopathic hypersomnia cannot be cured; all available treatments are symptomatic. It is of paramount importance for patients, and their relatives, to be informed about the consequences of these chronic diseases and to become ready to accept the consequences of the diagnosis before starting any treatment. This facilitates the implementation of behavioral modifications and the proper use of medication to decrease the disease burden. A supportive social environment (eg, family members, friends, employer, colleagues, and patient support groups) is instrumental. Current treatment options are discussed with a focus on pharmacologic treatment, including future directions.

Excessive daytime sleepiness (EDS) is defined as "irresistible sleepiness in a situation when an individual would be expected to be awake, and alert." EDS has been a big concern not only from a medical but also from a public health point of view. Patients with EDS have the possibility of falling asleep even when they should wake up and concentrate, for example, when they drive, play sports, or walk outside. In this article, clinical characteristics of common hypersomnia and pharmacologic treatments of each hypersomnia are described.

With the versatility of lumbar spine surgery continually expanding, intraoperative electromyography (EMG) has become a common adjunct used to reduce risk of nerve injury and postoperative neurologic deficit. EMG monitoring has been deemed particularly useful in the minimally invasive transforaminal lumbar interbody fusion. A more recent evolution of the minimally invasive transforaminal lumbar interbody fusion entails complete percutaneous access to the disc through Kambin's triangle, followed by a percutaneous lumbar interbody fusion. Given the lack of direct visualization of nervous structures with percutaneous entrance into the disc, there is risk of injury to surrounding nervous structures with this approach. In effort to reduce risk of nerve injury, application of triggered EMG to gauge proximity of nervous tissue has been evaluated. Recently, patients presenting with contraindications or concerns for general anesthesia have been offered the alternative to undergo their procedure with spinal anesthesia, allowing them to remain awake. Spinal anesthesia entails intrathecal administration of local anesthetic, which mechanistically acts to reduce overall excitability of surrounding neural structures. However, nerve activation under conditions of local anesthetic is relatively unknown, and the ability of triggered EMG monitoring to reliably detect nerve proximity becomes questionable. This case report demonstrates nerve activation at thresholds comparable with those seen under general anesthesia. Although this has sparked interest in the possibility that local anesthetic may not remarkably affect nerve excitability as measured by triggered EMG activation, further investigation is recommended to reliably apply triggered EMG monitoring in awake spine surgery.

We investigated the behavioural and neuronal functional consequences of age-related differences in sleep for gaining insight into novel cognitive strategies. Forty healthy young adults (20-35 years), and twenty-nine healthy older adults (60-85 years) were assigned to either nap or wake conditions. Participants were trained on the Tower of Hanoi in the AM, followed by either a 90-minute nap opportunity or period of wakefulness, and were retested afterward. Functional magnetic resonance imaging scans examined differences in brain activation from training to retest in young versus older adults as a function of sleep. Sleep enhanced performance and transformed the memory trace in young adults via hippocampal-neocortical transfer, but not older adults. This is consistent with the notion that as the consolidation of a newly formed memory trace progresses, the hippocampus becomes less involved; especially so when sleep occurs during that time. These results demonstrate a critical role for sleep in supporting problem-solving skills and suggest that the benefit of sleep for consolidation of these skills is reduced with age.

Background: As shift workers, nurses are at an increased risk of drowsy driving because of long hours at work and/or short sleep periods between shifts. Methods: In this study, a descriptive cross-sectional cohort design was used to examine the prevalence of drowsy driving among nurses. Findings: An electronic survey was sent to 7,217 nurses of which 2,205 (30.5%) completed the survey. Thirty percent (672 nurses) reported having dozed off while driving during their commute to work. In addition, 44.6% (976) of nurses disclosed feeling unsafe or uncomfortable during their commute due to drowsiness or fatigue. Conclusion/Application to Practice: As shift workers, nurses are subject to drowsy driving and its untoward effects. Healthcare leaders and nurse executives are in a position to evaluate and explore fatigue mitigation strategies such as napping, as this may prove to be beneficial in supporting nurse well-being and public safety.

Tractography is one way to predict the distribution of cortical functional domains preoperatively. Diffusion tensor tractography (DTT) is commonly used in clinical practice, but is known to have limitations in delineating crossed fibers, which can be overcome by Q-ball imaging tractography (QBT). We aimed to compare the reliability of these 2 methods based on the spatial correlation between the arcuate fasciculus depicted by tractography and direct cortical stimulation during awake surgery.In this study, 15 patients with glioma underwent awake surgery with direct cortical stimulation. Tractography was depicted in a three-dimensional computer graphic model preoperatively, which was integrated with a photograph of the actual brain cortex using our novel mixed-reality technology. The termination of the arcuate fasciculus depicted by either DTT or QBT and the results of direct cortical stimulation were compared, and sensitivity and specificity were calculated in speech-associated brain gyri: pars triangularis, pars opercularis, ventral precentral gyrus, and middle frontal gyrus.QBT had significantly better sensitivity and lower false-positive rate than DTT in the pars opercularis. The same trend was noted for the other gyri.QBT is more reliable than DTT in identification of the motor speech area and may be clinically useful in brain tumor surgery.

Under real-life conditions, increased light exposure during wakefulness seems associated with improved sleep quality, quantified as reduced time awake during bed time, increased time spent in non-rapid eye movement (NREM) sleep, or increased power of the electroencephalogram delta band (0.5-4 Hz). The causality of these important relationships and their dependency on circadian phase and/or time awake has not been studied in depth. To disentangle possible circadian and homeostatic interactions, we employed a forced desynchrony protocol under dim light (6 lux) and under bright light (1300 lux) during wakefulness. Our protocol consisted of a fast cycling sleep-wake schedule (13 h wakefulness—5 h sleep; 4 cycles), followed by 3 h recovery sleep in a within-subject cross-over design. Individuals (8 men) were equipped with 10 polysomnography electrodes. Subjective sleep quality was measured immediately after wakening with a questionnaire. Results indicated that circadian variation in delta power was only detected under dim light. Circadian variation in time in rapid eye movement (REM) sleep and wakefulness were uninfluenced by light. Prior light exposure increased accumulation of delta power and time in NREM sleep, while it decreased wakefulness, especially during the circadian wake phase (biological day). Subjective sleep quality scores showed that participants rated their sleep quality better after bright light exposure while sleeping when the circadian system promoted wakefulness. These results suggest that high environmental light intensity either increases sleep pressure buildup during wakefulness or prevents the occurrence of micro-sleep, leading to improved quality of subsequent sleep.

Objectives: To assess the efficacy of an awake venovenous extracorporeal membrane oxygenation (VV-ECMO) management strategy in preventing clinically relevant barotrauma in patients with coronavirus disease 2019 (COVID-19) with severe acute respiratory distress syndrome (ARDS) at high risk for pneumothorax (PNX)/pneumomediastinum (PMD), defined as the detection of the Macklin-like effect on chest computed tomography (CT) scan. Design: A case series. Setting: At the intensive care unit of a tertiary-care institution. Participants: Seven patients with COVID-19-associated severe ARDS and Macklin-like radiologic sign on baseline chest CT. Interventions: Primary VV-ECMO under spontaneous breathing instead of invasive mechanical ventilation (IMV). All patients received noninvasive ventilation or oxygen through a high-flow nasal cannula before and during ECMO support. The study authors collected data on cannulation strategy, clinical management, and outcome. Failure of awake VV-ECMO strategy was defined as the need for IMV due to worsening respiratory failure or delirium/agitation. The primary outcome was the development of PNX/PMD. Measurements and main results: No patient developed PNX/PMD. The awake VV-ECMO strategy failed in 1 patient (14.3%). Severe complications were observed in 4 (57.1%) patients and were noted as the following: intracranial bleeding in 1 patient (14.3%), septic shock in 2 patients (28.6%), and secondary pulmonary infections in 3 patients (42.8%). Two patients died (28.6%), whereas 5 were successfully weaned off VV-ECMO and were discharged home. Conclusions: VV-ECMO in awake and spontaneously breathing patients with severe COVID-19 ARDS may be a feasible and safe strategy to prevent the development of PNX/PMD in patients at high risk for this complication.

Sensory stimulation in Snoezelen room increased responsiveness after brain injury and dementia.To explore the physiological and clinical effects of Snoezelen stimulation in persons with unresponsive wakefulness syndrome or minimally conscious state (UWS or MCS).A comparative prospective observational cohort study.Ten patients with UWS and 25 in MCS were exposed to consecutive stimuli involving the 5 senses in a Snoezelen room. Heart rate (HR) and cerebral blood flow velocity (CBFV), and scores of the Loewenstein communication scale (LCS) were obtained before and during or after the stimuli.The stimuli increased HR values and decreased left hemisphere CBFV values in patients with MCS (p 0.05). Stimulation increased LCS scores (from 28.48 ± 6.55 to 31.13 ± 7.14; p 0.001) in patients with MCS, but not in the UWS group. LCS gain correlated with HR and right hemisphere CBFV gains in patients with MCS (r = 0.439 and 0.636 respectively, p 0.05).Snoezelen stimulation induced immediate improvement in communication and physiological changes in patients with MSC, and had a minor physiological effect in patients with UWS. If additional studies support these findings, it will be possible to suggest that Snoezelen stimulation can affect arousal, and possibly improve functioning.

Accumulating data have demonstrated that shift work causes a disturbance in circadian rhythms, which is detrimental to physiology and performance. However, the detailed effects of shift work and especially the underlying mechanisms remain to be further investigated. Frequently shifting schedules are widely used in industries, e.g., maritime tasks, oil mining, and aviation. In this work, we investigated the physiological changes and vigilance of 12 subjects who lived on a 30-day frequent shift working schedule in a confined environment, which mimics the common maritime schedules. Elevated and decreased cortisol levels were observed at different stages during the shift, suggesting the occurrence of stress and fatigue. The results of the Karolinska Sleepiness Scale (KSS) indicate increased sleepiness and a changed pattern of the rhythmicity of sleepiness during the shift. The tests of the Psychomotor Vigilance Task (PVT) reveal that the shift led to a continuously decreasing alertness as the shift working schedule progressed, which is prevalently due to the increasingly slower reaction speed. The PVT time-out errors were significantly increased in the early period but decreased in the late period. In addition, we found recoupling of the correlations between multiple physiological and cognitive variables. For instance, heartbeat rate (HR) and breath rate (BR) showed moderate correlations in the control and early periods but little in the late period. Together, these results reveal substantial alterations in diurnal rhythms, affected vigilance and changed coupling of the correlations of diurnal rhythms, physiology and cognition caused by a shift schedule. Our findings may help in the recognition of the detrimental effects of such working schedules and provide clues for the development of potential mitigations.

Attention deficit hyperactivity disorder (ADHD) can be a risk factor for repetitive mild traumatic brain injury (mTBI) or concussions such as those that can occur in contact sports. Individuals with ADHD also appear to have a higher risk of poor neurocognitive outcomes after repetitive mTBI. Findings from clinical studies examining the interactions between ADHD and repetitive mTBI vary, likely because of variabilities in experimental design and outcome measures. We used a mouse model of perinatal nicotine exposure (PNE), which displays behavioral, neuroanatomical, and neurotransmitter features consistent with ADHD and subjected the mice to repetitive mTBI. We used a closed head model of mTBI in awake, unanesthetized mice to mimic concussions in humans. The mTBI was repeated three times daily for seven days. The mice in the PNE-mTBI group took longer to regain consciousness after the mTBI and showed transient novelty-seeking and depression-like behaviors. Before the repetitive mTBI, the mice in the PNE group showed attention deficit, which persisted after the mTBI. The mice in the control (non-PNE) group showed a transient attention deficit after the repetitive mTBI but not any of the other behavioral changes seen in the PNE-mTBI group. These findings from an unanesthetized mouse model with a pre-existing condition show that ADHD and repetitive mTBI together contribute to transient novelty-seeking and depression-like behavior supporting the notion that untreated ADHD may be a risk factor for poor neurocognitive outcomes after concussions.

Night wakings are common during infancy, with variability in infant self-soothing or requiring parent involvement to fall back asleep. Reasons for variable soothing behaviors are unclear and may be influenced by early-life sleep parenting practices. The study applied a novel method using sleep actigraphy in mother-father-infant triads to quantify infant-only wake bouts (i.e., "self-soothing") and examined associations between sleep parenting practices from 6 to 24 weeks of age.Mother-father-infant triads (N = 20) wore sleep monitors for 1 week at infant ages 6, 15, and 24 weeks. Data were time-matched within families to quantify infant-only wake bouts (when infants woke in the night and parents remained asleep) to be indicative of infant self-soothing. Mothers reported on sleep parenting practices (e.g., feeding to sleep, putting infants to bed while awake) using the Brief Infant Sleep Questionnaire at each age. Mixed models tested associations between parenting practices and infant-only wake bouts.Most mothers (69.5%) reported typically feeding their infants to sleep at bedtime; 27.1% reported typically putting infants to bed while still awake. Parenting practices associated with a greater proportion and frequency of infant-only wake bouts included not typically feeding infants to sleep during night wakings, putting infants to bed while still awake (at 24 weeks of age), and using a greater proportion of low-, rather than high-, stimulus soothing strategies during night wakings.These data suggest parenting practices, such as putting infants to bed when drowsy but still awake, are important strategies for promoting infant self-soothing during night wakings.

Brain-injured patients in a state of cognitive motor dissociation exhibit a lack of command following using conventional neurobehavioral examination tools but a high level of awareness and language processing when assessed using advanced imaging and electrophysiology techniques. Because of their behavioral unresponsiveness, cognitive motor dissociation patients may seem clinically indistinguishable from those suffering from a “true” disorder of consciousness that affects awareness on a substantial level (coma, vegetative state/unresponsive wakefulness state, or minimally conscious state ‘minus’). Yet, by expanding the range of motor testing across limb, facial and ocular motricity, we may detect subtle, purposeful movements even in the subset of patients classified as vegetative state/unresponsive wakefulness state. We propose the term of clinical cognitive motor dissociation to describe patients showing these slight but determined motor responses and exhibiting a characteristic akinetic motor behavior as opposed to a pyramidal motor system behavior. These patients may harbor hidden cognitive capabilities and significant potential for a good long-term outcome. Indeed, we envision cognitive motor dissociation as ranging from complete (no motor response) to partial (subtle clinical motor response) forms, falling within a spectrum of progressively better motor output in patients with considerable cognitive capabilities. In addition to providing a decisional flowchart, we present this novel approach to classification as a graphical model that illustrates the range of clinical manifestations and recovery trajectories fundamentally differentiating “true” disorders of consciousness from the spectrum of cognitive motor dissociation.

The timing, duration, and consolidation of sleep result from the interaction of the circadian timing system with a sleep-wake homeostatic process. When aligned and functioning optimally, this allows for wakefulness throughout the day and a long consolidated sleep episode at night. Changes to either the sleep regulatory process or how they interact can result in an inability to fall asleep at the desired time, difficulty remaining asleep, waking too early, and/or difficulty remaining awake throughout the day. This mismatch between the desired timing of sleep and the ability to fall asleep and remain asleep is a hallmark of a class of sleep disorders called the circadian rhythm sleep-wake disorders. In this updated article, we discuss typical changes in the circadian regulation of sleep with aging; how age influences the prevalence, diagnosis, and treatment of circadian rhythm sleep disorders; and how neurologic diseases in older patient impact circadian rhythms and sleep.

Recurrent laryngeal nerve (RLN) injury is one of the main complications of total thyroidectomy. If the injury is bilateral, total airway obstruction, aphonia and hoarseness of voice could be precipitated. Hence, it is wise for the operating surgeon to be guided by neural monitoring during thyroidectomy. We present a valuable experience handling a middle-aged man with a huge papillary thyroid carcinoma . He needed an urgent thyroidectomy due to obstructive symptoms. We highlight our intraoperative dexterity in handling his surgery in the context of continuous monitoring of RLN using electromyography.

In the present investigation, we examined the role of different cortical fields in the fronto-parietal reaching and grasping network in awake, behaving macaque monkeys. This network is greatly expanded in primates compared to other mammals and coevolved with glabrous hands with opposable thumbs and the extraordinary dexterous behaviors employed by a number of primates, including humans. To examine this, we reversibly deactivated the primary motor area (M1), anterior parietal area 2, and posterior parietal areas 5L and 7b individually while monkeys were performing two types of reaching and grasping tasks. Reversible deactivation was accomplished with small microfluidic thermal regulators abutting specifically targeted cortical areas. Placement of these devices in the different cortical fields was confirmed post hoc in histologically processed tissue. Our results indicate that the different areas examined form a complex network of motor control that is overlapping. However, several consistent themes emerged that suggest the independent roles that motor cortex, area 2, area 7b, and area 5L play in the motor planning and execution of reaching and grasping movements. Area 5L is involved in the early stages and area 7b the later stages of a reaching and grasping movement, motor cortex is involved in all aspects of the execution of the movement, and area 2 provides proprioceptive feedback throughout the movement. We discuss our results in the context of previous studies that explored the fronto-parietal network, the overlapping (but also independent) functions of different nodes of this network, and the rapid compensatory plasticity of this network. NEW & NOTEWORTHY This is the first study to directly compare the results of cooling different portions of the fronto-parietal reaching and grasping network (motor cortex, anterior and posterior parietal cortex) in the same animals and the first to employ a complex, bimanual reaching and grasping task that is ethologically relevant. Whereas cooling area 7b or area 5L evoked deficits at distinct task phases, cooling M1 evoked a general set of deficits and cooling area 2 evoked proprioceptive deficits.

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.

Background Intraoperative 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 Presentation A 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. Conclusions Acute 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 obstruction. With the widespread use of IONM, it becomes essential for providers to be aware that perioperative airway compromise is a potentially life-threatening complication, especially with respect to monitoring of the hypoglossal nerve. Awake fiberoptic nasotracheal intubation can successfully be employed to establish an emergency airway in such situations.

STUDY OBJECTIVES: The central disorders of hypersomnolence (CDH) manifest with daytime sleepiness, often accompanied by cognitive symptoms. Objective tests characterizing cognitive dysfunction may have diagnostic utility. Further, because some people with CDH report worsening cognition upon awakening, cognitive testing before and after napping may provide additional diagnostic information. METHODS: Patients with CDH with idiopathic hypersomnia (n = 76), narcolepsy type 1 (n = 19), narcolepsy type 2 (n = 22), and self-reported excessive daytime sleepiness not meeting current diagnostic criteria (n = 76) and nonsleepy controls (n = 33) underwent testing with the Psychomotor Vigilance Test (PVT), a 10-minute reaction-time test. A subset of participants underwent repeat testing during a Multiple Sleep Latency Test, before and immediately after naps 2 and 4. RESULTS: Most PVT metrics were significantly better in controls than in patients with CDH. Minimal group differences in PVT performance were observed by CDH diagnosis. PVT performance was weakly correlated to Epworth Sleepiness Scale and Multiple Sleep Latency Test mean sleep latency in the CDH group. Before and after naps, PVT metrics were minimally different for controls, while PVT performance generally worsened following naps in the CDH group, with significant worsening compared with controls for nap 2 mean, median, lapses, and fastest 10% of responses and nap 4 lapses and slowest 10% of responses. Change in performance did not differ based on CDH diagnostic group for any metric on either nap. CONCLUSIONS: The PVT, at baseline and following a short nap, may provide adjunctive diagnostic utility in separating individuals with CDH from controls. CITATION: Trotti LM, Saini P, Bremer E, et al. The Psychomotor Vigilance Test as a measure of alertness and sleep inertia in people with central disorders of hypersomnolence. J Clin Sleep Med. 2022;18(5):1395–1403.

OBJECTIVE Electrocortical stimulation mapping (ECS) is widely used to identify essential language areas, but sentence-level processing has rarely been investigated. METHODS While undergoing awake surgery in the dominant left hemisphere, 6 subjects were asked to comprehend sentences varying in their demands on syntactic processing. RESULTS In 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. CONCLUSIONS These 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.

The number of awake craniotomies is increasing because of its beneficial features. However, not enough information is available regarding the current status of awake craniotomy in Japan. To evaluate the current status of awake craniotomy in institutes, a nationwide questionnaire survey was conducted. From June to August 2019, we conducted a questionnaire survey on awake craniotomy in the neurosurgery department of 45 institutes that perform awake craniotomies in Japan. Responses were obtained from 39 institutes (response rate, 86.7%). The main methods of awake craniotomy were almost the same in all institutes. Twenty-six institutes (66.7%) had fewer than 10 awake craniotomies (low-volume institutes) per year, and 13 high-volume institutes (33.3%) performed more than 10 awake craniotomies annually. Some institutes experienced a relatively high frequency of adverse events. In 11 institutes (28.2%), the frequency of intraoperative seizures was more than 10%. An intraoperative seizure frequency of 1%-9%, 10%-29%, and over 30% was identified in 12 (92%), 0 (0%), and 1 (8%) of the high-volume institutes, which was significantly less than in 16 (62%), 10 (38%), and 0 (0%) of the low-volume institutes (p = 0.0059). The routine usage of preoperative antiepileptic drugs was not different between them, but the old type was used more often in the low-volume institutes (p = 0.0022). Taken together, the annual number of awake craniotomies was less than 10 in over two-thirds of the institutes. Fewer intraoperative seizures were reported in the high-volume institutes, which tend not to preoperatively use the old type of antiepileptic drugs.

Light-induced improvements in alertness are more prominent during nighttime than during the day, suggesting that alerting effects of light may depend on internal clock time or wake duration. Relative contributions of both factors can be quantified using a forced desynchrony (FD) designs. FD designs have only been conducted under dim light conditions (

Driver drowsiness is one of the main factors leading to road fatalities and hazards in the transportation industry. Electroencephalography (EEG) has been considered as one of the best physiological signals to detect drivers' drowsy states, since it directly measures neurophysiological activities in the brain. However, designing a calibration-free system for driver drowsiness detection with EEG is still a challenging task, as EEG suffers from serious mental and physical drifts across different subjects. In this paper, we propose a compact and interpretable Convolutional Neural Network (CNN) to discover shared EEG features across different subjects for driver drowsiness detection. We incorporate the Global Average Pooling (GAP) layer in the model structure, allowing the Class Activation Map (CAM) method to be used for localizing regions of the input signal that contribute most for classification. Results show that the proposed model can achieve an average accuracy of 73.22% on 11 subjects for 2-class cross-subject EEG signal classification, which is higher than conventional machine learning methods and other state-of-art deep learning methods. It is revealed by the visualization technique that the model has learned biologically explainable features, e.g., Alpha spindles and Theta burst, as evidence for the drowsy state. It is also interesting to see that the model uses artifacts that usually dominate the wakeful EEG, e.g., muscle artifacts and sensor drifts, to recognize the alert state. The proposed model illustrates a potential direction to use CNN models as a powerful tool to discover shared features related to different mental states across different subjects from EEG signals. National Research Foundation (NRF) Submitted/Accepted version This research is supported by the National Research Foundation, Singapore under its International Research Centres in Singapore Funding Initiative.

Learning from others allows young children to acquire vast amounts of information quickly, but doing so effectively also requires epistemic vigilance. Although preschool-age children have some capacity to engage in such processes, they often have trouble resisting information from misleading informants. The present research takes a novel

To evaluate the association between headache, myofascial temporomandibular disorder (TMD), and awake bruxism (AB).Bruxism seems to act as a risk factor for TMD and its associated comorbidities, such as headaches.In total, 406 medical records of individuals who sought care at a university dental clinic were screened. The Research Diagnostic Criteria for Temporomandibular Disorders was used to assess and diagnose TMD, as well as to obtain self-reports of AB and headache.The sample consisted of 307 medical records. About 72.5% (221/305) of the sample reported having headaches, and 67.4% (180/267) and 68.4% (210/307) were diagnosed with AB and TMD, respectively. Individuals who reported having AB (odds ratio [OR], 2.28; 95% confidence interval [CI], 1.09-4.7) and who were diagnosed with myofascial TMD (OR, 2.53; 95% CI, 1.15-5.5) were more likely to have had headaches in the past 6 months when compared with patients without myofascial TMD and bruxism. Also, individuals who self-reported headache were 2.27 times (95% CI, 1.09-4.7) more likely to have AB and 2.45 times (95% CI, 1.13-5.34) more likely to have myofascial pain than individuals without headaches.Individuals with myofascial TMD, headaches, or AB were more likely to have at least one of the other conditions.

Background: Awake mapping has been associated with decreased neurological deficits and increased extent of resection in eloquent glioma resections. However, its effect within clinically relevant glioblastoma subgroups remains poorly understood. We aimed to assess the benefit of this technique in subgroups of patients with glioblastomas based on age, preoperative neurological morbidity, and Karnofsky Performance Score (KPS). Methods: In this propensity score-matched analysis of an international, multicentre, cohort study (GLIOMAP), patients were recruited at four tertiary centres in Europe (Erasmus MC, Rotterdam and Haaglanden MC, The Hague, Netherlands, and UZ Leuven, Leuven, Belgium) and the USA (Brigham and Women's Hospital, Boston, MA). Patients were eligible if they were aged 18–90 years, undergoing resection, had a histopathological diagnosis of primary glioblastoma, their tumour was in an eloquent or near-eloquent location, and they had a unifocal enhancing lesion. Patients either underwent awake mapping during craniotomy, or asleep resection, as per treating physician or multidisciplinary tumour board decision. We used propensity-score matching (1:3) to match patients in the awake group with those in the asleep group to create a matched cohort, and to match patients from subgroups stratified by age (

Abstract: A complex neurobiological network drives the sleep-wake cycle. In addition, external stimuli, including stimulants or depressor drugs, also influence the control of sleep. Here we review the recent advances that contribute to the comprehensive understanding of the actions of stimulants and depressor compounds, such as alcohol and cannabis, in sleep regulation. The objective of this review is to highlight the neurobiological mechanism engaged by alcohol and cannabis in sleep control.

Behavioral states naturally alternate between wakefulness and the sleep phases rapid eye movement and nonrapid eye movement sleep. Waking and sleep states are complex processes that are elegantly orchestrated by spatially fine-tuned neurochemical changes of neurotransmitters and neuromodulators including glutamate, acetylcholine, γ-aminobutyric acid, norepinephrine, dopamine, serotonin, histamine, hypocretin, melanin concentrating hormone, adenosine, and melatonin. However, as highlighted in this brief overview, no single neurotransmitter or neuromodulator, but rather their complex interactions within organized neuronal ensembles, regulate waking and sleep states. The neurochemical pathways presented here are aimed to provide a conceptual framework for the understanding of the effects of currently used sleep medications.

Blood oxygenation level-dependent (BOLD) signals in the white matter (WM) have been demonstrated to encode neural activities by showing structure-specific temporal correlations during resting-state and task-specific imaging of fiber pathways with various degrees of correlations in strength and time delay. Previous neuroimaging studies have shown state-dependent functional connectivity and regional amplitude of signal fluctuations in brain gray matter across wakefulness and nonrapid eye movement (NREM) sleep cycles. However, the functional characteristics of WM during sleep remain unknown. Using simultaneous electroencephalography and functional magnetic resonance imaging data during wakefulness and NREM sleep collected from 66 healthy participants, we constructed 10 stable WM functional networks using clustering analysis. Functional connectivity between these WM functional networks and regional amplitude of WM signal fluctuations across multiple low-frequency bands were evaluated. In general, decreased WM functional connectivity between superficial and middle layer WM functional networks was observed from wakefulness to sleep. In addition, functional connectivity between the deep and cerebellar networks was higher during light sleep and lower during both wakefulness and deep sleep. The regional fluctuation amplitude was always higher during light sleep and lower during deep sleep. Importantly, slow-wave activity during deep sleep negatively correlated with functional connectivity between WM functional networks but positively correlated with fluctuation strength in the WM. These observations provide direct physiological evidence that neural activities in the WM are modulated by the sleep-wake cycle. This study provided the initial mapping of functional changes in WM during sleep.

Relational memory, the ability to make and remember associations between objects, is an essential component of mammalian reasoning. In relational memory tasks, it has been shown that periods of offline processing, such as sleep, are critical to making indirect associations. To understand biophysical mechanisms behind the role of sleep in improving relational memory, we developed a model of the thalamocortical network to test how slow-wave sleep affects performance on an unordered relational memory task. First, the model was trained in the awake state on a paired associate inference task, in which the model learned to recall direct associations. After a period of subsequent slow-wave sleep, the model developed the ability to recall indirect associations. We found that replay, during sleep, of memory patterns learned in awake increased synaptic connectivity between neurons representing the item that was overlapping between tasks and neurons representing the unlinked items of the different tasks; this forms an attractor that enables indirect memory recall. Our study predicts that overlapping items between indirectly associated tasks are essential for relational memory, and sleep can reactivate pathways to and from overlapping items to the unlinked objects to strengthen these pathways and form new relational memories. SIGNIFICANCE STATEMENT Experimental studies have shown that some types of associative memory, such as transitive inference and relational memory, can improve after sleep. Still, it remains unknown what specific mechanisms are responsible for these sleep-related changes. In this new work, we addressed this problem by building a thalamocortical network model that can learn relational memory tasks and that can be simulated in awake or sleep states. We found that memory traces learned in awake were replayed during slow waves of NREM sleep and revealed that replay increased connections to and from overlapping memory items to form new relational memories. Our work discovered specific mechanisms behind the role of sleep in associative memory and made testable predictions about how sleep augments associative learning.

The treatment of patients with disorders of consciousness (DoC) remains a challenging issue, and spinal cord stimulation (SCS) has been reported to be a promising treatment for DoC in some studies.This study explores the efficiency of SCS in treating patients with DoC at different consciousness levels, including the vegetative state/unresponsive wakefulness syndrome (VS/UWS) and the minimally conscious state (MCS) and summarizes and analyzes the long-term effect and related factors of SCS in patients with DoC.An overall positive outcome was reached in 35 of 110 patients (31.8%). Among patients with positive outcomes, the MCS group improved 45.53% more than VS/UWS group, and this difference was statistically significant. In terms of the recommendation standard, positive outcomes occurred in 33 patients (94.3%) in the highly recommended group and 2 patients (5.7%) in the weakly recommended group (p 0.001). After adjustment for potential covariables, young age (age ≤ 19 years old) (p = 0.045) and MCS (p 0.001) were significantly correlated with positive outcome. A nomogram based on age, state of consciousness, and pathogeny showed good predictive performance, with a c-index of 0.794. The Hosmer-Lemeshow goodness-of-fit test showed that the model was well calibrated (χSCS is one of the most feasible treatments for patients with DoC, especially for patients with MCS. Younger age is significantly associated with better outcomes and could therefore serve as a basis for preoperative screening. However, more evidence-based randomized controlled trials are needed to confirm the efficacy of the treatment.

Biochemical mechanisms are temperature dependent. Brain temperature shows wide variations across brain states, and such changes may explain quantitative changes in network oscillations. Here, we report on the relationship between various hippocampal sharp wave ripple features to brain temperature. Ripple frequency, occurrence rate, and duration correlated with temperature dynamics. By focal manipulation of the brain temperature in the hippocampal CA1 region, we show that ripple frequency can be increased and decreased by local heating and cooling, respectively. Changes of other parameters, such as the rate of sharp wave-ripple complex (SPW-R) and ripple duration were not consistently affected. Our findings suggest that brain temperature in the CA1 region plays a leading role in affecting ripple frequency, whereas other parameters of SPW-Rs may be determined by mechanisms upstream from the CA1 region. These findings illustrate that physiological variations of brain temperature exert important effects on hippocampal circuit operations. NEW & NOTEWORTHY During physiological conditions, brain temperature fluctuates approximately 3°C between sleep and active waking. Here, we show that features of hippocampal ripples, including the rate of occurrence, peak frequency, and duration are correlated with brain temperature variations. Focal bidirectional manipulation of temperature in the hippocampal CA1 region in awake rodents show that ripple frequency can be altered in the direction expected from the correlational observations, implying that temperature plays a significant role.