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Background: Intraoperative awareness with explicit recall occurs in approximately 0.15% of all surgical cases. Efficacy trials based on the Bispectral Index® (BIS) monitor (Covidien, Boulder, CO) and anesthetic concentrations have focused on high-risk patients, but there are no effectiveness data applicable to an unselected surgical population.Methods: We conducted a randomized controlled trial of unselected surgical patients at three hospitals of a tertiary academic medical center. Surgical cases were randomized to alerting algorithms based on either BIS values or anesthetic concentrations. The primary outcome was the incidence of definite intraoperative awareness; prespecified secondary outcomes included postanesthetic recovery variables.Results: The study was terminated because of futility. At interim analysis the incidence of definite awareness was 0.12% (11/9,376) (95% CI: 0.07-0.21%) in the anesthetic concentration group and 0.08% (8/9,460) (95% CI: 0.04-0.16%) in the BIS group (P = 0.48). There was no significant difference between the two groups in terms of meeting criteria for recovery room discharge or incidence of nausea and vomiting. By post hoc secondary analysis, the BIS protocol was associated with a 4.7-fold reduction in definite or possible awareness events compared with a cohort receiving no intervention (P = 0.001; 95% CI: 1.7-13.1).Conclusion: This negative trial could not detect a difference in the incidence of definite awareness or recovery variables between monitoring protocols based on either BIS values or anesthetic concentration. By post hoc analysis, a protocol based on BIS monitoring reduced the incidence of definite or possible intraoperative awareness compared with routine care. [ABSTRACT FROM AUTHOR]

BACKGROUND: : Stroke is a leading cause of morbidity and mortality in the United States and occurs in the perioperative period. The authors studied the incidence, predictors, and outcomes of perioperative stroke using the American College of Surgeons National Surgical Quality Improvement Program. METHODS: : Data on 523,059 noncardiac, nonneurologic patients in the American College of Surgeons National Surgical Quality Improvement Program database were analyzed for the current study. The incidence of perioperative stroke was identified. Logistic regression was applied to a derivation cohort of 350,031 patients to generate independent predictors of stroke and develop a risk model. The risk model was subsequently applied to a validation cohort of 173,028 patients. The role of perioperative stroke in 30-day mortality was also assessed. RESULTS: : The incidence of perioperative stroke in both the derivation and validation cohorts was 0.1%. Multivariate analysis revealed the following independent predictors of stroke in the derivation cohort: age >=62 yr, history of myocardial infarction within 6 months before surgery, acute renal failure, history of stroke, dialysis, hypertension, history of transient ischemic attack, chronic obstructive pulmonary disease, current tobacco use, and body mass index 35-40 kg/m (protective). These risk factors were confirmed in the validation cohort. Surgical procedure also influenced the incidence of stroke. Perioperative stroke was associated with an 8-fold increase in perioperative mortality within 30 days (95% CI, 4.6-12.6). CONCLUSIONS: : Noncardiac, nonneurologic surgery carries a risk of perioperative stroke, which is associated with higher mortality. The models developed in this study may be informative for clinicians and patients regarding risk and prevention of this complication. [ABSTRACT FROM AUTHOR]

Consciousness requires a dynamic balance of integration and segregation in brain networks. We report an fMRI-based metric, the integration-segregation difference (ISD), which captures two key network properties: network efficiency (integration) and clustering (segregation). With this metric, we quantify brain state transitions from conscious wakefulness to unresponsiveness induced by the anesthetic propofol. The observed changes in ISD suggest a profound shift towards the segregation of brain networks during anesthesia. A common unimodal-transmodal sequence of disintegration and reintegration occurs in brain networks during, respectively, loss and return of responsiveness. Machine learning models using integration and segregation data accurately identify awake vs. unresponsive states and their transitions. Metastability (dynamic recurrence of non-equilibrium transient states) is more effectively explained by integration, while complexity (diversity of neural activity) is more closely linked with segregation. A parallel analysis of sleep states produces similar findings. Our results demonstrate that the ISD reliably indexes states of consciousness., (© 2024. The Author(s).)

Understanding neural mechanisms of consciousness remains a challenging question in neuroscience. A central debate in the field concerns whether consciousness arises from global interactions that involve multiple brain regions or focal neural activity, such as in sensory cortex. Additionally, global theories diverge between the Global Neuronal Workspace (GNW) hypothesis, which emphasizes frontal and parietal areas, and the Integrated Information Theory (IIT), which focuses on information integration within posterior cortical regions. To disentangle the global vs. local and frontoparietal vs. posterior dilemmas, we measured global functional connectivity and local neural synchrony with functional magnetic resonance imaging (fMRI) data across a spectrum of conscious states in humans induced by psychedelics, sleep, and deep sedation. We found that psychedelic states are associated with increased global functional connectivity and decreased local neural synchrony. In contrast, non-REM sleep and deep sedation displayed the opposite pattern, suggesting that consciousness arises from global brain network interactions rather than localized activity. This mirror-image pattern between enhanced and diminished states was observed in both anterior-posterior (A-P) and posterior-posterior (P-P) brain regions but not within the anterior part of the brain alone. Moreover, anterior transmodal regions played a key role in A-P connectivity, while both posterior transmodal and posterior unimodal regions were critical for P-P connectivity. Overall, these findings provide empirical evidence supporting global theories of consciousness in relation to varying states of consciousness. They also bridge the gap between two prominent theories, GNW and IIT, by demonstrating how different theories can converge on shared neuronal mechanisms.

The neural basis of conscious perception remains incompletely understood. While cortical mechanisms of conscious content have been extensively investigated, the role of subcortical structures, including the thalamus, remains less explored. We aim to elucidate the causal contributions of different thalamic regions to conscious perception using transcranial low-intensity focused ultrasound (LIFU) neuromodulation. We hypothesize that modulating different thalamic regions would result in distinct perceptual outcomes. We apply LIFU in human volunteers to investigate region-specific and sonication parameter-dependent effects. We target anterior (transmodal-dominant) and posterior (unimodal-dominant) thalamic regions, further divided into ventral and dorsal regions, while participants perform a near-threshold visual perception task. Task performance is evaluated using Signal Detection Theory metrics. We find that the high duty cycle stimulation of the ventral anterior thalamus enhanced object recognition sensitivity. We also observe a general (i.e., region-independent) effect of LIFU on decision bias (i.e., a tendency toward a particular response) and object categorization accuracy. Specifically, high duty cycle stimulation decreases categorization accuracy, whereas low duty cycle shifts decision bias towards a more conservative stance. In conclusion, our results provide causal insight into the functional organization of the thalamus in shaping human visual experience and highlight the unique role of the transmodal-dominant ventral anterior thalamus., Competing Interests: COMPETING INTERESTS STATEMENT The authors declare no competing interests.

Background: Anesthetics like propofol increase electroencephalography (EEG) power in delta frequencies (0.1-4 Hz), with a decrease of power in bandwidths >30 Hz. Propofol is nonselective for gamma amino butyric acid type A receptor subtypes (GABAAR) as it enhances all 3 GABAAR subtypes (slow, fast, and tonic). Our newly developed anesthetic class selectively targets GABAAR-slow synapses to depress brain responsiveness. We hypothesized that a selective GABAAR-slow agonist, KSEB 01-S2, would produce a different EEG signature compared to the broad-spectrum GABAAR agonist (propofol), and tested this using rat EEG recordings., Methods: Male rats were studied after Institutional Animal Care and Use Committees (IACUC) approval from the US Army Medical Research Institute of Chemical Defense and the University of Michigan. Rats were anesthetized using isoflurane (3%-5% induction, 1%-3% maintenance) with oxygen at 0.5 to 1.0 L/min. Stainless steel screws were placed in the skull and used to record subcranial cortical EEG signals. After recovery, either propofol or KSEB 01-S2 was administered and effects on EEG signals were analyzed., Results: As previously reported, propofol produced increased power in delta frequencies (0.1-4 Hz) compared to predrug recordings and produced a decrease in EEG power >30 Hz but no significant changes were seen within ±20 seconds of losing the righting reflex. By contrast, KSEB 01-S2 produced a significant increase in theta frequency percent power (median 14.7%, 16.2/13.8, 75/25 confidence interval; to 34.7%, 35/31.8; P < .015) and a significant decrease in low gamma frequency percent power (16.9%, 18.6/15.8; to 5.45%, 5.5/5.39; P < .015) for all rats at ± 20 seconds of loss of consciousness (LOC). Both anesthetics produced a flattening of chaotic attractor plots from nonlinear dynamic analyses, like that produced by volatile and dissociative anesthetics at LOC., Conclusions: KSEB 01-S2 produced a markedly different EEG pattern, with a selective increase observed in the theta frequency range. KSEB 01-S2 also differs markedly in its activity at the GABAAR-slow receptor subtype, suggesting a possible mechanistic link between receptor subtype specificity and EEG frequency band signatures. Increased theta together with depressed gamma frequencies is interesting because GABAAR slow synapses have previously been suggested to underlie theta frequency oscillations, while fast synapses control gamma activity. These reciprocal effects support a previous model for theta and nested gamma oscillations based on inhibitory connections between GABAAR fast and slow interneurons. Although each anesthetic produced a unique EEG response, propofol and KSEB 01-S2 both increased slow wave activity and flattened chaotic attractor plots at the point of LOC., Competing Interests: Conflicts of Interest, Funding: Please see DISCLOSURES at the end of this article., (Copyright © 2024 International Anesthesia Research Society.)

Research into the role of thalamocortical circuits in anesthesia-induced unconsciousness is difficult due to anatomical and functional complexity. Prior neuroimaging studies have examined either the thalamus as a whole or focused on specific subregions, overlooking the distinct neuronal subtypes like core and matrix cells. We conducted a study of heathy volunteers and functional magnetic resonance imaging during conscious baseline, deep sedation, and recovery. We advanced the functional gradient mapping technique to delineate the functional geometry of thalamocortical circuits, within a framework of the unimodal-transmodal functional axis of the cortex. Here we show a significant shift in this geometry during deep sedation, marked by a transmodal-deficient geometry. This alteration is closely linked to the spatial variations in the matrix cell composition within the thalamus. This research bridges cellular and systems-level understanding, highlighting the crucial role of thalamic core-matrix functional architecture in understanding the neural mechanisms of states of consciousness., (© 2024. The Author(s).)

Accurate and generalizable classification of brain states is essential for understanding their neural underpinnings and improving clinical diagnostics. Traditionally, functional connectivity patterns and graph-theoretic metrics have been utilized. However, cortical gradient features, which reflect global brain organization, offer a complementary approach. We hypothesized that a machine learning model integrating these three feature sets would effectively discriminate between baseline and atypical brain states across a wide spectrum of conditions, even though the underlying neural mechanisms vary. To test this, we extracted features from brain states associated with three meta-conditions including unconsciousness (NREM2 sleep, propofol deep sedation, and propofol general anesthesia), psychedelic states induced by hallucinogens (subanesthetic ketamine, lysergic acid diethylamide, and nitrous oxide), and neuropsychiatric disorders (attention-deficit hyperactivity disorder, bipolar disorder, and schizophrenia). We used support vector machine with nested cross-validation to construct our models. The soft voting ensemble model marked the average balanced accuracy (average of specificity and sensitivity) of 79% (62-98% across all conditions), outperforming individual base models (70-76%). Notably, our models exhibited varying degrees of transferability across different datasets, with performance being dependent on the specific brain states and feature sets used. Feature importance analysis across meta-conditions suggests that the underlying neural mechanisms vary significantly, necessitating tailored approaches for accurate classification of specific brain states. This finding underscores the value of our feature-integrated ensemble models, which leverage the strengths of multiple feature types to achieve robust performance across a broader range of brain states. While our approach offers valuable insights into the neural signatures of different brain states, future work is needed to develop and validate even more generalizable models that can accurately classify brain states across a wider array of conditions.

The near-death experience has been reported since antiquity and is often characterized by the perception of light, interactions with other entities, and life recall. Near-death experiences can occur in a variety of situations, but they have been studied systematically after in-hospital cardiac arrest, with an incidence of 10 to 20%. Long attributed to metaphysical or supernatural causes, there have been recent advances in understanding the neurophysiologic basis of this unique category of conscious experience. This article reviews the epidemiology and neurobiology of near-death experiences, with a focus on clinical and laboratory evidence for a surge of neurophysiologic gamma oscillations and cortical connectivity after cardiac and respiratory arrest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc., on behalf of the American Society of Anesthesiologists.)

Background: Sleep disruption is a common occurrence during medical care and is detrimental to patient recovery. Long-term sedation in the critical care setting is a modifiable factor that affects sleep, but the impact of different sedative-hypnotics on sleep homeostasis is not clear., Methods: We conducted a systematic comparison of the effects of prolonged sedation (8 h) with i.v. and inhalational agents on sleep homeostasis. Adult Sprague-Dawley rats (n=10) received dexmedetomidine or midazolam on separate days. Another group (n=9) received propofol or sevoflurane on separate days. A third group (n=12) received coadministration of dexmedetomidine and sevoflurane. Wakefulness (wake), slow-wave sleep (SWS), and rapid eye movement (REM) sleep were quantified during the 48-h post-sedation period, during which we also assessed wake-associated neural dynamics using two electroencephalographic measures: theta-high gamma phase-amplitude coupling and high gamma weighted phase-lag index., Results: Dexmedetomidine-, midazolam-, or propofol-induced sedation increased wake and decreased SWS and REM sleep (P<0.0001) during the 48-h post-sedation period. Sevoflurane produced no change in SWS, decreased wake for 3 h, and increased REM sleep for 6 h (P<0.02) post-sedation. Coadministration of dexmedetomidine and sevoflurane induced no change in wake (P>0.05), increased SWS for 3 h, and decreased REM sleep for 9 h (P<0.02) post-sedation. Dexmedetomidine, midazolam, and coadministration of dexmedetomidine with sevoflurane reduced wake-associated phase-amplitude coupling (P≤0.01). All sedatives except sevoflurane decreased wake-associated high gamma weighted phase-lag index (P<0.01)., Conclusions: In contrast to i.v. drugs, prolonged sevoflurane sedation produced minimal changes in sleep homeostasis and neural dynamics. Further studies are warranted to assess inhalational agents for long-term sedation and sleep homeostasis., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

In the 19 th century, the discovery of general anesthesia revolutionized medical care. In the 21 st century, anesthetics have become indispensable tools to study consciousness. Here, I review key aspects of the relationship between anesthesia and the neurobiology of consciousness, including interfaces of sleep and anesthetic mechanisms, anesthesia and primary sensory processing, the effects of anesthetics on large-scale functional brain networks, and mechanisms of arousal from anesthesia. I discuss the implications of the data derived from the anesthetized state for the science of consciousness and then conclude with outstanding questions, reflections, and future directions., Competing Interests: Declaration of interests The author declares no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Urethane is a general anaesthetic widely used in animal research. The state of urethane anaesthesia is unique because it alternates between macroscopically distinct electrographic states: a slow-wave state that resembles non-rapid eye movement (NREM) sleep and an activated state with features of both REM sleep and wakefulness. Although it is assumed that urethane produces unconsciousness, this has been questioned because of states of cortical activation during drug exposure. Furthermore, the similarities and differences between urethane anaesthesia and physiological sleep are still unclear. In this study, we recorded the electroencephalogram (EEG) and electromyogram in chronically prepared rats during natural sleep-wake states and during urethane anaesthesia. We subsequently analysed the power, coherence, directed connectivity and complexity of brain oscillations and found that EEG under urethane anaesthesia has clear signatures of unconsciousness, with similarities to other general anaesthetics. In addition, the EEG profile under urethane is different in comparison with natural sleep states. These results suggest that consciousness is disrupted during urethane. Furthermore, despite similarities that have led others to conclude that urethane is a model of sleep, the electrocortical traits of depressed and activated states during urethane anaesthesia differ from physiological sleep states., (© 2022 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

General anesthesia-a pharmacologically induced reversible state of unconsciousness-enables millions of life-saving procedures. Anesthetics induce unconsciousness in part by impinging upon sexually dimorphic and hormonally sensitive hypothalamic circuits regulating sleep and wakefulness. Thus, we hypothesized that anesthetic sensitivity should be sex-dependent and modulated by sex hormones. Using distinct behavioral measures, we show that at identical brain anesthetic concentrations, female mice are more resistant to volatile anesthetics than males. Anesthetic sensitivity is bidirectionally modulated by testosterone. Castration increases anesthetic resistance. Conversely, testosterone administration acutely increases anesthetic sensitivity. Conversion of testosterone to estradiol by aromatase is partially responsible for this effect. In contrast, oophorectomy has no effect. To identify the neuronal circuits underlying sex differences, we performed whole brain c-Fos activity mapping under anesthesia in male and female mice. Consistent with a key role of the hypothalamus, we found fewer active neurons in the ventral hypothalamic sleep-promoting regions in females than in males. In humans, we demonstrate that females regain consciousness and recover cognition faster than males after identical anesthetic exposures. Remarkably, while behavioral and neurocognitive measures in mice and humans point to increased anesthetic resistance in females, cortical activity fails to show sex differences under anesthesia in either species. Cumulatively, we demonstrate that sex differences in anesthetic sensitivity are evolutionarily conserved and not reflected in conventional electroencephalographic-based measures of anesthetic depth. This covert resistance to anesthesia may explain the higher incidence of unintended awareness under general anesthesia in females., Competing Interests: Competing interests statement:The authors declare no competing interest.

Despite the longstanding use of nitrous oxide and descriptions of its psychological effects more than a century ago, there is a paucity of neurobiological investigation of associated psychedelic experiences. We measure the brain's functional geometry (through analysis of cortical gradients) and temporal dynamics (through analysis of co-activation patterns) using human resting-state functional magnetic resonance imaging data acquired before and during administration of 35% nitrous oxide. Both analyses demonstrate that nitrous oxide reduces functional differentiation in frontoparietal and somatomotor networks. Importantly, the subjective psychedelic experience induced by nitrous oxide is inversely correlated with the degree of functional differentiation. Thus, like classical psychedelics acting on serotonin receptors, nitrous oxide flattens the functional geometry of the cortex and disrupts temporal dynamics in association with psychoactive effects., (© 2023. The Author(s).)

There is a renewed interest in psychedelic drugs as potential therapeutic agents for the treatment of psychiatric disorders. In particular, psilocybin has shown promise for the treatment of refractory depression 1 and major depressive disorder 2 , and has also been explored as a treatment for tobacco and alcohol abuse 3 , 4 . However, despite suggestive evidence 5 , 6 , there has been no systematic study to investigate the effectiveness of psilocybin in attenuating indices of chronic pain. To address this gap, we investigated the effect of psilocybin on mechanical hypersensitivity and thermal hyperalgesia in a well-established rat model of formalin-induced, centralized chronic pain 7 , 8 and demonstrate that a single intravenous bolus administration of psilocybin can attenuate mechanical hypersensitivity for 28 days., Competing Interests: Declaration of interests Jim Gilligan, PhD is President and Chief Scientific Officer at Tryp Therapeutics. Peter Guzzo, PhD is Consulting VP, Drug Development at Tryp Therapeutics., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Abstract: Fibromyalgia has been characterized by augmented cross-network functional communication between the brain's sensorimotor, default mode, and attentional (salience/ventral and dorsal) networks. However, the underlying mechanisms of these aberrant communication patterns are unknown. In this study, we sought to understand large-scale topographic patterns at instantaneous timepoints, known as co-activation patterns (CAPs). We found that a sustained pressure pain challenge temporally modulated the occurrence of CAPs. Using proton magnetic resonance spectroscopy, we found that greater basal excitatory over inhibitory neurotransmitter levels within the anterior insula orchestrated higher cross-network connectivity between the anterior insula and the default mode network through lower occurrence of a CAP encompassing the attentional networks during sustained pain. Moreover, we found that hyperalgesia in fibromyalgia was mediated through increased occurrence of a CAP encompassing the sensorimotor network during sustained pain. In conclusion, this study elucidates the role of momentary large-scale topographic brain patterns in shaping noxious information in patients with fibromyalgia, while laying the groundwork for using precise spatiotemporal dynamics of the brain for the potential development of therapeutics., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association for the Study of Pain.)

Background: Perioperative neurocognitive disorders are a major public health issue, although there are no validated neurophysiologic biomarkers that predict cognitive function after surgery. This study tested the hypothesis that preoperative posterior electroencephalographic alpha power, alpha frontal-parietal connectivity, and cerebral oximetry would each correlate with postoperative neurocognitive function., Methods: This was a single-center, prospective, observational study of adult (older than 18 yr) male and female noncardiac surgery patients. Whole-scalp, 16-channel electroencephalography and cerebral oximetry were recorded in the preoperative, intraoperative, and immediate postoperative settings. The primary outcome was the mean postoperative T-score of three National Institutes of Health Toolbox Cognition tests-Flanker Inhibitory Control and Attention, List Sorting Working Memory, and Pattern Comparison Processing Speed. These tests were obtained at preoperative baseline and on the first two postoperative mornings. The lowest average score from the first two postoperative days was used for the primary analysis. Delirium was a secondary outcome (via 3-min Confusion Assessment Method) measured in the postanesthesia care unit and twice daily for the first 3 postoperative days. Last, patient-reported outcomes related to cognition and overall well-being were collected 3 months postdischarge., Results: Sixty-four participants were recruited with a median (interquartile range) age of 59 (48 to 66) yr. After adjustment for baseline cognitive function scores, no significant partial correlation (ρ) was detected between postoperative cognition scores and preoperative relative posterior alpha power (%; ρ = -0.03, P = 0.854), alpha frontal-parietal connectivity (via weight phase lag index; ρ = -0.10, P = 0.570, respectively), or preoperative cerebral oximetry (%; ρ = 0.21, P = 0.246). Only intraoperative frontal-parietal theta connectivity was associated with postoperative delirium (F[1,6,291] = 4.53, P = 0.034). No electroencephalographic or oximetry biomarkers were associated with cognitive or functional outcomes 3 months postdischarge., Conclusions: Preoperative posterior alpha power, frontal-parietal connectivity, and cerebral oximetry were not associated with cognitive function after noncardiac surgery., (Copyright © 2023 American Society of Anesthesiologists. All Rights Reserved.)

The neurobiology of the psychedelic experience is not fully understood. Identifying common brain network changes induced by both classical (i.e., acting at the 5-HT 2 receptor) and non-classical psychedelics would provide mechanistic insight into state-specific characteristics. We analyzed whole-brain functional connectivity based on resting-state fMRI data in humans, acquired before and during the administration of nitrous oxide, ketamine, and lysergic acid diethylamide. We report that, despite distinct molecular mechanisms and modes of delivery, all three psychedelics reduced within-network functional connectivity and enhanced between-network functional connectivity. More specifically, all three drugs increased connectivity between right temporoparietal junction and bilateral intraparietal sulcus as well as between precuneus and left intraparietal sulcus. These regions fall within the posterior cortical "hot zone," posited to mediate the qualitative aspects of experience. Thus, both classical and non-classical psychedelics modulate networks within an area of known relevance for consciousness, identifying a biologically plausible candidate for their subjective effects., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Delirium is a major public health issue for surgical patients and their families because it is associated with increased mortality, cognitive and functional decline, prolonged hospital admission and increased healthcare expenditures. Based on preliminary data, this trial tests the hypothesis that intravenous caffeine, given postoperatively, will reduce the incidence of delirium in older adults after major non-cardiac surgery., Methods and Analysis: The CAffeine, Postoperative Delirium And CHange In Outcomes after Surgery-2 (CAPACHINOS-2) Trial is a single-centre, placebo-controlled, randomised clinical trial that will be conducted at Michigan Medicine. The trial will be quadruple-blinded, with clinicians, researchers, participants and analysts all masked to the intervention. The goal is to enrol 250 patients with a 1:1:1: allocation ratio: dextrose 5% in water placebo, caffeine 1.5 mg/kg and caffeine 3 mg/kg as a caffeine citrate infusion. The study drug will be administered intravenously during surgical closure and on the first two postoperative mornings. The primary outcome will be delirium, assessed via long-form Confusion Assessment Method. Secondary outcomes will include delirium severity, delirium duration, patient-reported outcomes and opioid consumption patterns. A substudy analysis will also be conducted with high-density electroencephalography (72-channel system) to identify neural abnormalities associated with delirium and Mild Cognitive Impairment at preoperative baseline., Ethics and Dissemination: This study was approved by the University of Michigan Medical School Institutional Review Board (HUM00218290). An independent data and safety monitoring board has also been empanelled and has approved the clinical trial protocol and related documents. Trial methodology and results will be disseminated via clinical and scientific journals along with social and news media., Trial Registration Number: NCT05574400., Competing Interests: Competing interests: PEV and AM receive support from Blue Cross Blue Shield of Michigan for quality improvement work related to delirium (but unrelated to this current study)., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The brain is assumed to be hypoactive during cardiac arrest. However, animal models of cardiac and respiratory arrest demonstrate a surge of gamma oscillations and functional connectivity. To investigate whether these preclinical findings translate to humans, we analyzed electroencephalogram and electrocardiogram signals in four comatose dying patients before and after the withdrawal of ventilatory support. Two of the four patients exhibited a rapid and marked surge of gamma power, surge of cross-frequency coupling of gamma waves with slower oscillations, and increased interhemispheric functional and directed connectivity in gamma bands. High-frequency oscillations paralleled the activation of beta/gamma cross-frequency coupling within the somatosensory cortices. Importantly, both patients displayed surges of functional and directed connectivity at multiple frequency bands within the posterior cortical "hot zone," a region postulated to be critical for conscious processing. This gamma activity was stimulated by global hypoxia and surged further as cardiac conditions deteriorated in the dying patients. These data demonstrate that the surge of gamma power and connectivity observed in animal models of cardiac arrest can be observed in select patients during the process of dying.

Background: The posterior dominant rhythm (PDR) was the first oscillatory pattern noted in the EEG. Evoked by wakeful eyelid closure, these oscillations dissipate over seconds during loss of arousal. The peak frequency of the PDR maintains stability over years, suggesting utility as a state biomarker in the surveillance of acute cognitive impairments. This EEG signature has not been systematically investigated for tracking cognitive dysfunction after anaesthetic-induced loss of consciousness., Methods: This substudy of Reconstructing Consciousness and Cognition (NCT01911195) investigated the PDR and cognitive function in 60 adult volunteers randomised to either 3 h of isoflurane general anaesthesia or resting wakefulness. Serial measurements of EEG power and cognitive task performance were assessed relative to pre-intervention baseline. Mixed-effects models allowed quantification of PDR and neurocognitive trajectories after return of responsiveness (ROR)., Results: Individuals in the control group showed stability in the PDR peak frequency over several hours (median difference/inter-quartile range [IQR] of 0.02/0.20 Hz, P=0.39). After isoflurane general anaesthesia, the PDR peak frequency was initially reduced at ROR (median difference/IQR of 0.88/0.65 Hz, P<0.001). PDR peak frequency recovered at a rate of 0.20 Hz h -1 . After ROR, the PDR peak frequency correlated with reaction time and accuracy on multiple cognitive tasks (P<0.001)., Conclusion: The temporal trajectory of the PDR peak frequency could be a useful perioperative marker for tracking cognitive dysfunction on the order of hours after surgery, particularly for cognitive domains of working memory, visuomotor speed, and executive function., Clinical Trial Registration: NCT01911195., (Copyright © 2022 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)