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Liang Z, Fan L, Zhang B, Shu W, Li D, Li X, Yu T. The changes in neural complexity and connectivity in thalamocortical and cortico-cortical systems after propofol-induced unconsciousness in different temporal scales. Neuroimage 2025; 311:121193. [PMID: 40204075 DOI: 10.1016/j.neuroimage.2025.121193] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2024] [Revised: 02/20/2025] [Accepted: 04/07/2025] [Indexed: 04/11/2025] Open
Abstract
Existing studies have indicated neural activity across diverse temporal and spatial scales. However, the alterations in complexity, functional connectivity, and directional connectivity within the thalamocortical and corticocortical systems across various scales during propofol-induced unconsciousness remain uncertain. We analyzed the stereo-electroencephalography (SEEG) from wakefulness to unconsciousness among the brain regions of the prefrontal cortex, temporal lobe, and anterior nucleus of the thalamus. The complexity (examined by permutation entropy (PE)), functional connectivity (permutation mutual information (PMI)), and directional connectivity (symbolic conditional mutual information (SCMI) and directionality index (DI)) were calculated across various scales. In the lower-band frequency (0.1-45 Hz) SEEG, after the loss of consciousness, PE significantly decreased (p < 0.001) in all regions and scales, except for the thalamus, which remained relatively unchanged at large scales (τ=32 ms). Following the loss of consciousness, inter-regional PMI either significantly increased or remained stable across different scales (τ=4 ms to 32 ms). During the unconscious state, SCMI between brain regions exhibited inconsistent changes across scales. In the late unconscious stage, the inter-regional DI across all scales indicated a shift from a balanced state of information flow between brain regions to a pattern where the prefrontal cortex and thalamus drive the temporal lobe. Our findings demonstrate that propofol-induced unconsciousness is associated with reduced cortical complexity, diverse functional connectivity, and a disrupted balance of information integration among thalamocortical and cortico-cortical systems. This study enhances the theoretical understanding of anesthetic-induced loss of consciousness by elucidating the scale- and region-specific effects of propofol on thalamocortical and cortico-cortical systems.
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Affiliation(s)
- Zhenhu Liang
- Key Laboratory of Intelligent Control and Neural Information Processing of the Ministry of Education of China, Yanshan University, Qinhuangdao 066004, Hebei, China; Key Laboratory of Intelligent Rehabilitation and Neuromodulation of Hebei Province, Yanshan University, Qinhuangdao 066004, China
| | - Luxin Fan
- Key Laboratory of Intelligent Control and Neural Information Processing of the Ministry of Education of China, Yanshan University, Qinhuangdao 066004, Hebei, China; Key Laboratory of Intelligent Rehabilitation and Neuromodulation of Hebei Province, Yanshan University, Qinhuangdao 066004, China
| | - Bin Zhang
- Key Laboratory of Intelligent Control and Neural Information Processing of the Ministry of Education of China, Yanshan University, Qinhuangdao 066004, Hebei, China; Key Laboratory of Intelligent Rehabilitation and Neuromodulation of Hebei Province, Yanshan University, Qinhuangdao 066004, China
| | - Wei Shu
- Department of Functional Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing 100053, China.
| | - Duan Li
- Center for Consciousness Science, Department of Anesthesiology, University of Michigan Medical School, Ann Arbor, MI, United States
| | - Xiaoli Li
- State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing 100875, China.
| | - Tao Yu
- Department of Functional Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing 100053, China.
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2
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Gil R, Valente M, Fernandes FF, Shemesh N. Evidence for a push-pull interaction between superior colliculi in monocular dynamic vision mode. Commun Biol 2025; 8:642. [PMID: 40263386 PMCID: PMC12015290 DOI: 10.1038/s42003-025-08081-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2024] [Accepted: 04/11/2025] [Indexed: 04/24/2025] Open
Abstract
Visual perception can operate in two distinct vision modes-static and dynamic-that have been associated with different neural activity regimes in the superior colliculus (SC). However, the associated pathway-wide mechanisms remain poorly understood, especially in terms of corticotectal and tectotectal feedback upon encoding the continuity illusion during the dynamic vision mode. Here, we harness functional MRI combined with rat brain lesions to investigate whole-pathway neural interactions in the dynamic vision mode. We find a push-pull mechanism embodying contralateral suppression of SC activity opposing positive ipsilateral neural activation upon monocular visual stimulation. Cortical amplification is confirmed through cortical lesions, while further lesioning the ipsilateral SC leads to a boost in the contralateral SC negative signals, suggesting a tectal origin for the push-pull interaction. These results highlight hitherto unreported frequency-dependent modulations in the tectotectal pathway and further challenge the notion that intertectal connections solely serve as reciprocal inhibitory mechanisms for avoiding visual blur during saccades.
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Affiliation(s)
- Rita Gil
- Champalimaud Research, Champalimaud Foundation, Lisbon, Portugal
| | - Mafalda Valente
- Champalimaud Research, Champalimaud Foundation, Lisbon, Portugal
| | | | - Noam Shemesh
- Champalimaud Research, Champalimaud Foundation, Lisbon, Portugal.
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3
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Li D, Hudetz AG. Anesthesia alters complexity of spontaneous and stimulus-related neuronal firing patterns in rat visual cortex. Neuroscience 2025; 565:440-456. [PMID: 39631661 DOI: 10.1016/j.neuroscience.2024.11.076] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2024] [Revised: 11/27/2024] [Accepted: 11/29/2024] [Indexed: 12/07/2024]
Abstract
Complexity of neuronal firing patterns may serve as an indicator of sensory information processing across different states of consciousness. Recent studies have shown that spontaneous changes in brain states can occur during general anesthesia, which may influence neuronal complexity and the state of consciousness. In this study, we investigated how the firing patterns of cortical neurons, both at rest and during visual stimulation, are affected by spontaneously changing brain states under varying levels of anesthesia. Extracellular unit activity was measured in the primary visual cortex of unrestrained rats as the inhaled concentration of desflurane was incrementally reduced to 6%, 4%, 2%, and 0%. Using dimensionality reduction and density-based clustering on individual unit activities, we identified five distinct population states, which underwent dynamic transitions independent of the anesthetic level during both resting and stimulus conditions. One population state that occurred mainly in deep anesthesia exhibited a paradoxically increased number of active neurons and asynchronous spiking, suggesting a spontaneous reversal towards an awake-like condition. However, this was contradicted by the observation of low neuronal complexity in both spontaneous and stimulus-related spike activity, which more closely aligns with unconsciousness. Our findings reveal that transient neuronal states with distinct spiking patterns can emerge in visual cortex at constant anesthetic concentrations. The reduced complexity in states associated with deep anesthesia likely indicates a disruption of conscious sensory information processing.
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Affiliation(s)
- Duan Li
- Center for Consciousness Science, Department of Anesthesiology, University of Michigan, Ann Arbor, MI, USA
| | - Anthony G Hudetz
- Center for Consciousness Science, Department of Anesthesiology, University of Michigan, Ann Arbor, MI, USA.
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Mazurie Z, Branchereau P, Cattaert D, Henkous N, Savona-Baron C, Vouimba RM. Acute stress differently modulates interneurons excitability and synaptic plasticity in the primary motor cortex of wild-type and SOD1 G93A mouse model of ALS. J Physiol 2024; 602:4987-5015. [PMID: 39216080 DOI: 10.1113/jp285210] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2023] [Accepted: 07/12/2024] [Indexed: 09/04/2024] Open
Abstract
Primary motor cortex (M1) network stability depends on activity of inhibitory interneurons, for which susceptibility to stress was previously demonstrated in limbic regions. Hyperexcitability in M1 following changes in the excitatory/inhibitory balance is a key pathological hallmark of amyotrophic lateral sclerosis (ALS). Using electrophysiological approaches, we assessed the impact of acute restraint stress on inhibitory interneurons excitability and global synaptic plasticity in M1 of the SOD1G93A ALS mouse model at a late pre-symptomatic stage (10-12.5 weeks). Based on their firing type (continuous, discontinuous, with accommodation or not) and electrophysiological characteristics (resting potential, rheobase, firing frequency), interneurons from M1 slices were separated into four clusters, labelled from 1 to 4. Among them, only interneurons from the first cluster, presenting continuous firing with few accommodations, tended to show increased excitability in wild-type (WT) and decreased excitability in SOD1G93A animals following stress. In vivo analyses of evoked field potentials showed that stress suppressed the theta burst-induced plasticity of an excitatory component (N1) recorded in the superficial layers of M1 in WT, with no impact on an inhibitory complex (N2-P1) from the deeper layers. In SOD1G93A mice, stress did not affect N1 but suppressed the N2-P1 plasticity. These data suggest that stress can alter M1 network functioning in a different manner in WT and SOD1G93A mice, possibly through changes of inhibitory interneurons excitability and synaptic plasticity. This suggests that stress-induced activity changes in M1 may therefore influence ALS outcomes. KEY POINTS: Disruption of the excitatory/inhibitory balance in the primary motor cortex (M1) has been linked to cortical hyperexcitability development, a key pathological hallmark of amyotrophic lateral sclerosis (ALS). Psychological stress was reported to influence excitatory/inhibitory balance in limbic regions, but very little is known about its influence on the M1 functioning under physiological or pathological conditions. Our study revealed that acute stress influences the excitatory/inhibitory balance within the M1, through changes in interneurons excitability along with network plasticity. Such changes were different in pathological (SOD1G93A ALS mouse model) vs. physiological (wild-type) conditions. The results of our study help us to better understand how stress modulates the M1 and highlight the need to further characterize stress-induced motor cortex changes because it may be of importance when evaluating ALS outcomes.
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Affiliation(s)
- Zoé Mazurie
- Institut de Neurosciences Cognitives et Intégratives d'Aquitaine (INCIA), CNRS, UMR 5287, University of Bordeaux, Bordeaux, France
| | - Pascal Branchereau
- Institut de Neurosciences Cognitives et Intégratives d'Aquitaine (INCIA), CNRS, UMR 5287, University of Bordeaux, Bordeaux, France
| | - Daniel Cattaert
- Institut de Neurosciences Cognitives et Intégratives d'Aquitaine (INCIA), CNRS, UMR 5287, University of Bordeaux, Bordeaux, France
| | - Nadia Henkous
- Institut de Neurosciences Cognitives et Intégratives d'Aquitaine (INCIA), CNRS, UMR 5287, University of Bordeaux, Bordeaux, France
| | - Catherine Savona-Baron
- Present address: BoRdeaux Institute of onCology (BRIC), INSERM U1312, University of Bordeaux, Bordeaux, France
| | - Rose-Marie Vouimba
- Institut de Neurosciences Cognitives et Intégratives d'Aquitaine (INCIA), CNRS, UMR 5287, University of Bordeaux, Bordeaux, France
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Kim H, Min BK, Lee U, Sim JH, Noh GJ, Lee EK, Choi BM. Electroencephalographic Features of Elderly Patients during Anesthesia Induction with Remimazolam: A Substudy of a Randomized Controlled Trial. Anesthesiology 2024; 141:681-692. [PMID: 38207285 DOI: 10.1097/aln.0000000000004904] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2024]
Abstract
BACKGROUND Although remimazolam is used as a general anesthetic in elderly patients due to its hemodynamic stability, the electroencephalogram characteristics of remimazolam are not well known. The purpose of this study was to identify the electroencephalographic features of remimazolam-induced unconsciousness in elderly patients and compare them with propofol. METHODS Remimazolam (n = 26) or propofol (n = 26) were randomly administered for anesthesia induction in surgical patients. The hypnotic agent was blinded only to the patients. During the induction of anesthesia, remimazolam was administered at a rate of 6 mg · kg-1 · h-1, and propofol was administered at a target effect-site concentration of 3.5 μg/ml. The electroencephalogram signals from eight channels (Fp1, Fp2, Fz, F3, F4, Pz, P3, and P4, referenced to A2, using the 10 to 20 system) were acquired during the induction of anesthesia and in the postoperative care unit. Power spectrum analysis was performed, and directed functional connectivity between frontal and parietal regions was evaluated using normalized symbolic transfer entropy. Functional connectivity in unconscious processes induced by remimazolam or propofol was compared with baseline. To compare each power of frequency over time of the two hypnotic agents, a permutation test with t statistic was conducted. RESULTS Compared to the baseline in the alpha band, the feedback connectivity decreased by averages of 46% and 43%, respectively, after the loss of consciousness induced by remimazolam and propofol (95% CI for the mean difference: -0.073 to -0.044 for remimazolam [P < 0.001] and -0.068 to -0.042 for propofol [P < 0.001]). Asymmetry in the feedback and feedforward connectivity in the alpha band was suppressed after the loss of consciousness induced by remimazolam and propofol. There were no significant differences in the power of each frequency over time between the two hypnotic agents (minimum q value = 0.4235). CONCLUSIONS Both regimens showed a greater decrease in feedback connectivity compared to a decrease in feedforward connectivity after loss of consciousness, leading to a disruption of asymmetry between the frontoparietal connectivity. EDITOR’S PERSPECTIVE
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Affiliation(s)
- Hyoungkyu Kim
- Center for Neuroscience Imaging Research, Institute for Basic Science (IBS), Sungkyunkwan University, Suwon, Republic of Korea
| | - Byoung-Kyong Min
- Department of Brain and Cognitive Engineering, Korea University, Seoul, Republic of Korea
| | - UnCheol Lee
- Department of Anesthesiology, Center for Consciousness Science, Center for the Study of Complex Systems, University of Michigan Medical School, Ann Arbor, Michigan
| | - Ji-Hoon Sim
- Department of Anesthesiology and Pain Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Gyu-Jeong Noh
- Department of Anesthesiology and Pain Medicine and Department of Clinical Pharmacology and Therapeutics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Eun-Kyung Lee
- Department of Statistics, Ewha Womans University, Seoul, Korea
| | - Byung-Moon Choi
- Department of Anesthesiology and Pain Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
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6
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Mashour GA. Anesthesia and the neurobiology of consciousness. Neuron 2024; 112:1553-1567. [PMID: 38579714 PMCID: PMC11098701 DOI: 10.1016/j.neuron.2024.03.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2024] [Revised: 03/05/2024] [Accepted: 03/06/2024] [Indexed: 04/07/2024]
Abstract
In the 19th century, the discovery of general anesthesia revolutionized medical care. In the 21st 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.
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Affiliation(s)
- George A Mashour
- Center for Consciousness Science, Department of Anesthesiology, Department of Pharmacology, Neuroscience Graduate Program, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
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7
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Tauber JM, Brincat SL, Stephen EP, Donoghue JA, Kozachkov L, Brown EN, Miller EK. Propofol-mediated Unconsciousness Disrupts Progression of Sensory Signals through the Cortical Hierarchy. J Cogn Neurosci 2024; 36:394-413. [PMID: 37902596 PMCID: PMC11161138 DOI: 10.1162/jocn_a_02081] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/31/2023]
Abstract
A critical component of anesthesia is the loss of sensory perception. Propofol is the most widely used drug for general anesthesia, but the neural mechanisms of how and when it disrupts sensory processing are not fully understood. We analyzed local field potential and spiking recorded from Utah arrays in auditory cortex, associative cortex, and cognitive cortex of nonhuman primates before and during propofol-mediated unconsciousness. Sensory stimuli elicited robust and decodable stimulus responses and triggered periods of stimulus-related synchronization between brain areas in the local field potential of Awake animals. By contrast, propofol-mediated unconsciousness eliminated stimulus-related synchrony and drastically weakened stimulus responses and information in all brain areas except for auditory cortex, where responses and information persisted. However, we found stimuli occurring during spiking Up states triggered weaker spiking responses than in Awake animals in auditory cortex, and little or no spiking responses in higher order areas. These results suggest that propofol's effect on sensory processing is not just because of asynchronous Down states. Rather, both Down states and Up states reflect disrupted dynamics.
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Affiliation(s)
- John M Tauber
- Massachusetts Institute of Technology, Cambridge, MA
| | | | | | | | - Leo Kozachkov
- Massachusetts Institute of Technology, Cambridge, MA
| | - Emery N Brown
- Massachusetts Institute of Technology, Cambridge, MA
- Massachusetts General Hospital, Boston
- Harvard University, Cambridge, MA
| | - Earl K Miller
- Massachusetts Institute of Technology, Cambridge, MA
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Wei S, Jiang A, Sun H, Zhu J, Jia S, Liu X, Xu Z, Zhang J, Shang Y, Fu X, Li G, Wang P, Xia Z, Jiang T, Cao A, Duan X. Shape-changing electrode array for minimally invasive large-scale intracranial brain activity mapping. Nat Commun 2024; 15:715. [PMID: 38267440 PMCID: PMC10808108 DOI: 10.1038/s41467-024-44805-2] [Citation(s) in RCA: 8] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2023] [Accepted: 01/03/2024] [Indexed: 01/26/2024] Open
Abstract
Large-scale brain activity mapping is important for understanding the neural basis of behaviour. Electrocorticograms (ECoGs) have high spatiotemporal resolution, bandwidth, and signal quality. However, the invasiveness and surgical risks of electrode array implantation limit its application scope. We developed an ultrathin, flexible shape-changing electrode array (SCEA) for large-scale ECoG mapping with minimal invasiveness. SCEAs were inserted into cortical surfaces in compressed states through small openings in the skull or dura and fully expanded to cover large cortical areas. MRI and histological studies on rats proved the minimal invasiveness of the implantation process and the high chronic biocompatibility of the SCEAs. High-quality micro-ECoG activities mapped with SCEAs from male rodent brains during seizures and canine brains during the emergence period revealed the spatiotemporal organization of different brain states with resolution and bandwidth that cannot be achieved using existing noninvasive techniques. The biocompatibility and ability to map large-scale physiological and pathological cortical activities with high spatiotemporal resolution, bandwidth, and signal quality in a minimally invasive manner offer SCEAs as a superior tool for applications ranging from fundamental brain research to brain-machine interfaces.
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Affiliation(s)
- Shiyuan Wei
- Department of Biomedical Engineering, College of Future Technology, Peking University, Beijing, 100871, China
- Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, 100871, China
| | - Anqi Jiang
- Department of Biomedical Engineering, College of Future Technology, Peking University, Beijing, 100871, China
| | - Hongji Sun
- Department of Biomedical Engineering, College of Future Technology, Peking University, Beijing, 100871, China
| | - Jingjun Zhu
- Department of Biomedical Engineering, College of Future Technology, Peking University, Beijing, 100871, China
- National Biomedical Imaging Centre, Peking University, Beijing, 100871, China
| | - Shengyi Jia
- Department of Biomedical Engineering, College of Future Technology, Peking University, Beijing, 100871, China
| | - Xiaojun Liu
- Department of Biomedical Engineering, College of Future Technology, Peking University, Beijing, 100871, China
| | - Zheng Xu
- Department of Biomedical Engineering, College of Future Technology, Peking University, Beijing, 100871, China
| | - Jing Zhang
- Department of Biomedical Engineering, College of Future Technology, Peking University, Beijing, 100871, China
- Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, 100871, China
| | - Yuanyuan Shang
- Key Laboratory of Material Physics, Ministry of Education, School of Physics and Microelectronics, Zhengzhou University, Zhengzhou, 450052, China
| | - Xuefeng Fu
- Department of Biomedical Engineering, College of Future Technology, Peking University, Beijing, 100871, China
| | - Gen Li
- Department of Biomedical Engineering, College of Future Technology, Peking University, Beijing, 100871, China
| | - Puxin Wang
- Department of Biomedical Engineering, College of Future Technology, Peking University, Beijing, 100871, China
- Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, 100871, China
| | - Zhiyuan Xia
- School of Materials Science and Engineering, Peking University, Beijing, China
| | - Tianzi Jiang
- Brainnetome Centre, Institute of Automation, Chinese Academy of Sciences (CAS), Beijing, 100190, China
| | - Anyuan Cao
- School of Materials Science and Engineering, Peking University, Beijing, China
| | - Xiaojie Duan
- Department of Biomedical Engineering, College of Future Technology, Peking University, Beijing, 100871, China.
- Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, 100871, China.
- National Biomedical Imaging Centre, Peking University, Beijing, 100871, China.
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9
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Toker D, Müller E, Miyamoto H, Riga MS, Lladó-Pelfort L, Yamakawa K, Artigas F, Shine JM, Hudson AE, Pouratian N, Monti MM. Criticality supports cross-frequency cortical-thalamic information transfer during conscious states. eLife 2024; 13:e86547. [PMID: 38180472 PMCID: PMC10805384 DOI: 10.7554/elife.86547] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2023] [Accepted: 11/27/2023] [Indexed: 01/06/2024] Open
Abstract
Consciousness is thought to be regulated by bidirectional information transfer between the cortex and thalamus, but the nature of this bidirectional communication - and its possible disruption in unconsciousness - remains poorly understood. Here, we present two main findings elucidating mechanisms of corticothalamic information transfer during conscious states. First, we identify a highly preserved spectral channel of cortical-thalamic communication that is present during conscious states, but which is diminished during the loss of consciousness and enhanced during psychedelic states. Specifically, we show that in humans, mice, and rats, information sent from either the cortex or thalamus via δ/θ/α waves (∼1-13 Hz) is consistently encoded by the other brain region by high γ waves (52-104 Hz); moreover, unconsciousness induced by propofol anesthesia or generalized spike-and-wave seizures diminishes this cross-frequency communication, whereas the psychedelic 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) enhances this low-to-high frequency interregional communication. Second, we leverage numerical simulations and neural electrophysiology recordings from the thalamus and cortex of human patients, rats, and mice to show that these changes in cross-frequency cortical-thalamic information transfer may be mediated by excursions of low-frequency thalamocortical electrodynamics toward/away from edge-of-chaos criticality, or the phase transition from stability to chaos. Overall, our findings link thalamic-cortical communication to consciousness, and further offer a novel, mathematically well-defined framework to explain the disruption to thalamic-cortical information transfer during unconscious states.
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Affiliation(s)
- Daniel Toker
- Department of Neurology, University of California, Los AngelesLos AngelesUnited States
- Department of Psychology, University of California, Los AngelesLos AngelesUnited States
| | - Eli Müller
- Brain and Mind Centre, University of SydneySydneyAustralia
| | - Hiroyuki Miyamoto
- Laboratory for Neurogenetics, RIKEN Center for Brain ScienceSaitamaJapan
- PRESTO, Japan Science and Technology AgencySaitamaJapan
- International Research Center for Neurointelligence, University of TokyoNagoyaJapan
| | - Maurizio S Riga
- Andalusian Center for Molecular Biology and Regenerative MedicineSevilleSpain
| | - Laia Lladó-Pelfort
- Departament de Ciències Bàsiques, Universitat de Vic-Universitat Central de CatalunyaBarcelonaSpain
| | - Kazuhiro Yamakawa
- Laboratory for Neurogenetics, RIKEN Center for Brain ScienceSaitamaJapan
- Department of Neurodevelopmental Disorder Genetics, Institute of Brain Science, Nagoya City University Graduate School of Medical ScienceNagoyaJapan
| | - Francesc Artigas
- Departament de Neurociències i Terapèutica Experimental, CSIC-Institut d’Investigacions Biomèdiques de BarcelonaBarcelonaSpain
- Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)BarcelonaSpain
- Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Instituto de Salud Carlos IIIMadridSpain
| | - James M Shine
- Brain and Mind Centre, University of SydneySydneyAustralia
| | - Andrew E Hudson
- Department of Anesthesiology, Veterans Affairs Greater Los Angeles Healthcare SystemLos AngelesUnited States
- Department of Anesthesiology and Perioperative Medicine, University of California, Los AngelesLos AngelesUnited States
| | - Nader Pouratian
- Department of Neurological Surgery, UT Southwestern Medical CenterDallasUnited States
| | - Martin M Monti
- Department of Psychology, University of California, Los AngelesLos AngelesUnited States
- Department of Neurosurgery, University of California, Los AngelesLos AngelesUnited States
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10
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Aru J, Larkum ME, Shine JM. The feasibility of artificial consciousness through the lens of neuroscience. Trends Neurosci 2023; 46:1008-1017. [PMID: 37863713 DOI: 10.1016/j.tins.2023.09.009] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2023] [Revised: 08/23/2023] [Accepted: 09/27/2023] [Indexed: 10/22/2023]
Abstract
Interactions with large language models (LLMs) have led to the suggestion that these models may soon be conscious. From the perspective of neuroscience, this position is difficult to defend. For one, the inputs to LLMs lack the embodied, embedded information content characteristic of our sensory contact with the world around us. Secondly, the architectures of present-day artificial intelligence algorithms are missing key features of the thalamocortical system that have been linked to conscious awareness in mammals. Finally, the evolutionary and developmental trajectories that led to the emergence of living conscious organisms arguably have no parallels in artificial systems as envisioned today. The existence of living organisms depends on their actions and their survival is intricately linked to multi-level cellular, inter-cellular, and organismal processes culminating in agency and consciousness.
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Affiliation(s)
- Jaan Aru
- Institute of Computer Science, University of Tartu, Tartu, Estonia.
| | - Matthew E Larkum
- Institute of Biology, Humboldt University Berlin, Berlin, Germany.
| | - James M Shine
- Brain and Mind Center, The University of Sydney, Sydney, Australia.
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11
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Wollstadt P, Rathbun DL, Usrey WM, Bastos AM, Lindner M, Priesemann V, Wibral M. Information-theoretic analyses of neural data to minimize the effect of researchers' assumptions in predictive coding studies. PLoS Comput Biol 2023; 19:e1011567. [PMID: 37976328 PMCID: PMC10703417 DOI: 10.1371/journal.pcbi.1011567] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2023] [Revised: 12/07/2023] [Accepted: 10/02/2023] [Indexed: 11/19/2023] Open
Abstract
Studies investigating neural information processing often implicitly ask both, which processing strategy out of several alternatives is used and how this strategy is implemented in neural dynamics. A prime example are studies on predictive coding. These often ask whether confirmed predictions about inputs or prediction errors between internal predictions and inputs are passed on in a hierarchical neural system-while at the same time looking for the neural correlates of coding for errors and predictions. If we do not know exactly what a neural system predicts at any given moment, this results in a circular analysis-as has been criticized correctly. To circumvent such circular analysis, we propose to express information processing strategies (such as predictive coding) by local information-theoretic quantities, such that they can be estimated directly from neural data. We demonstrate our approach by investigating two opposing accounts of predictive coding-like processing strategies, where we quantify the building blocks of predictive coding, namely predictability of inputs and transfer of information, by local active information storage and local transfer entropy. We define testable hypotheses on the relationship of both quantities, allowing us to identify which of the assumed strategies was used. We demonstrate our approach on spiking data collected from the retinogeniculate synapse of the cat (N = 16). Applying our local information dynamics framework, we are able to show that the synapse codes for predictable rather than surprising input. To support our findings, we estimate quantities applied in the partial information decomposition framework, which allow to differentiate whether the transferred information is primarily bottom-up sensory input or information transferred conditionally on the current state of the synapse. Supporting our local information-theoretic results, we find that the synapse preferentially transfers bottom-up information.
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Affiliation(s)
- Patricia Wollstadt
- MEG Unit, Brain Imaging Center, Goethe University, Frankfurt/Main, Germany
| | - Daniel L. Rathbun
- Center for Neuroscience, University of California, Davis, California, United States of America
- Center for Ophthalmology, University of Tübingen, Tübingen, Germany
| | - W. Martin Usrey
- Center for Neuroscience, University of California, Davis, California, United States of America
- Department of Neurobiology, Physiology, and Behavior, University of California, Davis, California, United States of America
| | - André Moraes Bastos
- Department of Psychology and Vanderbilt Brain Institute, Vanderbilt University, Nashville, Tennessee, United States of America
| | - Michael Lindner
- Campus Institute for Dynamics of Biological Networks, University of Göttingen, Göttingen, Germany
| | - Viola Priesemann
- Max Planck Institute for Dynamics and Self-Organization, Göttingen, Germany
| | - Michael Wibral
- Campus Institute for Dynamics of Biological Networks, University of Göttingen, Göttingen, Germany
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12
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Tanabe S, Lee H, Wang S, Hudetz AG. Spontaneous and Visual Stimulation Evoked Firing Sequences Are Distinct Under Desflurane Anesthesia. Neuroscience 2023; 528:54-63. [PMID: 37473851 DOI: 10.1016/j.neuroscience.2023.07.016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2023] [Revised: 07/09/2023] [Accepted: 07/12/2023] [Indexed: 07/22/2023]
Abstract
Recurring spike sequences are thought to underlie cortical computations and may be essential for information processing in the conscious state. How anesthesia at graded levels may influence spontaneous and stimulus-related spike sequences in visual cortex has not been fully elucidated. We recorded extracellular single-unit activity in the rat primary visual cortex in vivo during wakefulness and three levels of anesthesia produced by desflurane. The latencies of spike sequences within 0-200 ms from the onset of spontaneous UP states and visual flash-evoked responses were compared. During wakefulness, spike latency patterns linked to the local field potential theta cycle were similar to stimulus-evoked patterns. Under desflurane anesthesia, spontaneous UP state sequences differed from flash-evoked sequences due to the recruitment of low-firing excitatory neurons to the UP state. Flash-evoked spike sequences showed higher reliability and longer latency when stimuli were applied during DOWN states compared to UP states. At deeper levels, desflurane altered both UP state and flash-evoked spike sequences by selectively suppressing inhibitory neuron firing. The results reveal desflurane-induced complex changes in cortical firing sequences that may influence visual information processing.
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Affiliation(s)
- Sean Tanabe
- Center for Consciousness Science, Department of Anesthesiology, University of Michigan, Ann Arbor, MI 48105, USA
| | - Heonsoo Lee
- Center for Consciousness Science, Department of Anesthesiology, University of Michigan, Ann Arbor, MI 48105, USA
| | - Shiyong Wang
- Center for Consciousness Science, Department of Anesthesiology, University of Michigan, Ann Arbor, MI 48105, USA
| | - Anthony G Hudetz
- Center for Consciousness Science, Department of Anesthesiology, University of Michigan, Ann Arbor, MI 48105, USA.
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13
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Tauber JM, Brincat SL, Stephen EP, Donaghue JA, Kozachkov L, Brown EN, Miller EK. Propofol Mediated Unconsciousness Disrupts Progression of Sensory Signals through the Cortical Hierarchy. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2023:2023.06.25.546463. [PMID: 37425684 PMCID: PMC10327085 DOI: 10.1101/2023.06.25.546463] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/11/2023]
Abstract
A critical component of anesthesia is the loss sensory perception. Propofol is the most widely used drug for general anesthesia, but the neural mechanisms of how and when it disrupts sensory processing are not fully understood. We analyzed local field potential (LFP) and spiking recorded from Utah arrays in auditory cortex, associative cortex, and cognitive cortex of non-human primates before and during propofol mediated unconsciousness. Sensory stimuli elicited robust and decodable stimulus responses and triggered periods of stimulus-induced coherence between brain areas in the LFP of awake animals. By contrast, propofol mediated unconsciousness eliminated stimulus-induced coherence and drastically weakened stimulus responses and information in all brain areas except for auditory cortex, where responses and information persisted. However, we found stimuli occurring during spiking Up states triggered weaker spiking responses than in awake animals in auditory cortex, and little or no spiking responses in higher order areas. These results suggest that propofol's effect on sensory processing is not just due to asynchronous down states. Rather, both Down states and Up states reflect disrupted dynamics.
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Affiliation(s)
- John M. Tauber
- The Picower Institute for Learning & Memory, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA
- Department of Brain & Cognitive Sciences, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA
- Institute for Data, Systems, and Society, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA
| | - Scott L. Brincat
- The Picower Institute for Learning & Memory, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA
- Department of Brain & Cognitive Sciences, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA
| | - Emily P. Stephen
- Department of Mathematics and Statistics, Boston University, Boston, MA 02215, USA
| | - Jacob A. Donaghue
- The Picower Institute for Learning & Memory, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA
- Department of Brain & Cognitive Sciences, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA
- Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA
| | - Leo Kozachkov
- Department of Brain & Cognitive Sciences, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA
| | - Emery N. Brown
- The Picower Institute for Learning & Memory, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA
- Department of Brain & Cognitive Sciences, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA
- Institute for Data, Systems, and Society, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA
- Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA
- Department of Anesthesia, Massachusetts General Hospital, Boston, MA 02114, USA
- Harvard Medical School, Harvard University, Boston, MA 02115, USA
| | - Earl K. Miller
- The Picower Institute for Learning & Memory, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA
- Department of Brain & Cognitive Sciences, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA
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14
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Hutt A, Hudetz AG. Arousal system stimulation and anesthetic state alter visuoparietal connectivity. Front Syst Neurosci 2023; 17:1157488. [PMID: 37139471 PMCID: PMC10150228 DOI: 10.3389/fnsys.2023.1157488] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2023] [Accepted: 03/27/2023] [Indexed: 05/05/2023] Open
Abstract
Cortical information processing is under the precise control of the ascending arousal system (AAS). Anesthesia suppresses cortical arousal that can be mitigated by exogenous stimulation of the AAS. The question remains to what extent cortical information processing is regained by AAS stimulation. We investigate the effect of electrical stimulation of the nucleus Pontis Oralis (PnO), a distinct source of ascending AAS projections, on cortical functional connectivity (FC) and information storage at mild, moderate, and deep anesthesia. Local field potentials (LFPs) recorded previously in the secondary visual cortex (V2) and the adjacent parietal association cortex (PtA) in chronically instrumented unrestrained rats. We hypothesized that PnO stimulation would induce electrocortical arousal accompanied by enhanced FC and active information storage (AIS) implying improved information processing. In fact, stimulation reduced FC in slow oscillations (0.3-2.5 Hz) at low anesthetic level and increased FC at high anesthetic level. These effects were augmented following stimulation suggesting stimulus-induced plasticity. The observed opposite stimulation-anesthetic impact was less clear in the γ-band activity (30-70 Hz). In addition, FC in slow oscillations was more sensitive to stimulation and anesthetic level than FC in γ-band activity which exhibited a rather constant spatial FC structure that was symmetric between specific, topographically related sites in V2 and PtA. Invariant networks were defined as a set of strongly connected electrode channels, which were invariant to experimental conditions. In invariant networks, stimulation decreased AIS and increasing anesthetic level increased AIS. Conversely, in non-invariant (complement) networks, stimulation did not affect AIS at low anesthetic level but increased it at high anesthetic level. The results suggest that arousal stimulation alters cortical FC and information storage as a function of anesthetic level with a prolonged effect beyond the duration of stimulation. The findings help better understand how the arousal system may influence information processing in cortical networks at different levels of anesthesia.
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Affiliation(s)
- Axel Hutt
- MLMS, MIMESIS, Université de Strasbourg, CNRS, lnria, ICube, Strasbourg, France
- *Correspondence: Axel Hutt,
| | - Anthony G. Hudetz
- Department of Anesthesiology, Center for Consciousness Science, University of Michigan, Ann Arbor, MI, United States
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15
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Margalit SN, Golomb NG, Tsur O, Ben Yehoshua E, Raz A, Slovin H. Spatiotemporal patterns of population response in the visual cortex under isoflurane: from wakefulness to loss of consciousness. Cereb Cortex 2022; 32:5512-5529. [PMID: 35169840 DOI: 10.1093/cercor/bhac031] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2021] [Revised: 12/22/2021] [Accepted: 01/18/2022] [Indexed: 01/25/2023] Open
Abstract
Anesthetic drugs are widely used in medicine and research to mediate loss of consciousness (LOC). Isoflurane is a commonly used anesthetic drug; however, its effects on cortical sensory processing, in particular around LOC, are not well understood. Using voltage-sensitive dye imaging, we measured visually evoked neuronal population response from the visual cortex in awake and anesthetized mice at 3 increasing concentrations of isoflurane, thus controlling the level of anesthesia from wakefulness to deep anesthesia. At low concentration of isoflurane, the effects on neuronal measures were minor relative to the awake condition. These effects augmented with increasing isoflurane concentration, while around LOC point, they showed abrupt and nonlinear changes. At the network level, we found that isoflurane decreased the stimulus-evoked intra-areal spatial spread of local neural activation, previously reported to be mediated by horizontal connections, and also reduced intra-areal synchronization of neuronal population. The synchronization between different visual areas decreased with higher isoflurane levels. Isoflurane reduced the population response amplitude and prolonged their latencies while higher visual areas showed increased vulnerability to isoflurane concentration. Our results uncover the changes in neural activity and synchronization at isoflurane concentrations leading to LOC and suggest reverse hierarchical shutdown of cortical areas.
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Affiliation(s)
- Shany Nivinsky Margalit
- The Gonda Multidisciplinary Brain Research Center, Bar-Ilan University, Ramat Gan 5290002, Israel
| | - Neta Gery Golomb
- Department of Anesthesiology, Rambam Health Care Campus, Haifa, 3109601, Israel and The Ruth and Bruce Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa 3200003, Israel
| | - Omer Tsur
- The Gonda Multidisciplinary Brain Research Center, Bar-Ilan University, Ramat Gan 5290002, Israel
| | - Eve Ben Yehoshua
- The Gonda Multidisciplinary Brain Research Center, Bar-Ilan University, Ramat Gan 5290002, Israel
| | - Aeyal Raz
- Department of Anesthesiology, Rambam Health Care Campus, Haifa, 3109601, Israel and The Ruth and Bruce Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa 3200003, Israel
| | - Hamutal Slovin
- The Gonda Multidisciplinary Brain Research Center, Bar-Ilan University, Ramat Gan 5290002, Israel
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16
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Nsugbe E, Connelly S. Multiscale depth of anaesthesia prediction for surgery using frontal cortex electroencephalography. Healthc Technol Lett 2022; 9:43-53. [PMID: 35662750 PMCID: PMC9160818 DOI: 10.1049/htl2.12025] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2021] [Revised: 04/12/2022] [Accepted: 04/20/2022] [Indexed: 01/23/2023] Open
Abstract
Hypnotic and sedative anaesthetic agents are employed during multiple medical interventions to prevent patient awareness. Careful titration of agent dosing is required to avoid negative side effects; the accuracy thereof may be improved by Depth of Anaesthesia Monitoring. This work investigates the potential of a patient specific depth monitoring prediction using electroencephalography recorded neural oscillation from the frontal lobe of 10 patients during sedation, where a comparison of the prediction accuracy was made across five different approaches to post‐processing; Noise Assisted‐Empirical Mode Decomposition, the Raw Signal, Linear Series Decomposition Learner, Deep Wavelet Scattering and Deep Learning features. These methods towards anaesthesia depth prediction were investigated using the Bispectral Index as ground truth, where it was seen that the Raw Signal, enhanced feature set and a low complexity classification model (Linear Discriminant Analysis) provided the best classification accuracy, in the region of 85.65 % ±10.23 % across the 10 subjects. Subsequent work in this area would now build on these results and validate the best performing methods on a wider cohort of patients, investigate means of continuous DoA estimation using regressions, and also feature optimisation exercises in order to further streamline and reduce the computation complexity of the designed model.
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17
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Cascella M. Anesthetics and translational research. PERIOPERATIVE NEUROSCIENCE 2022:25-40. [DOI: 10.1016/b978-0-323-91003-3.00008-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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18
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Nourski KV, Steinschneider M, Rhone AE, Krause BM, Mueller RN, Kawasaki H, Banks MI. Cortical Responses to Vowel Sequences in Awake and Anesthetized States: A Human Intracranial Electrophysiology Study. Cereb Cortex 2021; 31:5435-5448. [PMID: 34117741 PMCID: PMC8568007 DOI: 10.1093/cercor/bhab168] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2021] [Revised: 05/22/2021] [Accepted: 05/22/2021] [Indexed: 02/07/2023] Open
Abstract
Elucidating neural signatures of sensory processing across consciousness states is a major focus in neuroscience. Noninvasive human studies using the general anesthetic propofol reveal differential effects on auditory cortical activity, with a greater impact on nonprimary and auditory-related areas than primary auditory cortex. This study used intracranial electroencephalography to examine cortical responses to vowel sequences during induction of general anesthesia with propofol. Subjects were adult neurosurgical patients with intracranial electrodes placed to identify epileptic foci. Data were collected before electrode removal surgery. Stimuli were vowel sequences presented in a target detection task during awake, sedated, and unresponsive states. Averaged evoked potentials (AEPs) and high gamma (70-150 Hz) power were measured in auditory, auditory-related, and prefrontal cortex. In the awake state, AEPs were found throughout studied brain areas; high gamma activity was limited to canonical auditory cortex. Sedation led to a decrease in AEP magnitude. Upon LOC, there was a decrease in the superior temporal gyrus and adjacent auditory-related cortex and a further decrease in AEP magnitude in core auditory cortex, changes in the temporal structure and increased trial-to-trial variability of responses. The findings identify putative biomarkers of LOC and serve as a foundation for future investigations of altered sensory processing.
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Affiliation(s)
- Kirill V Nourski
- Address correspondence to Kirill V. Nourski, MD, PhD, Department of Neurosurgery, The University of Iowa, 200 Hawkins Dr. 1815 JCP, Iowa City, IA 52242, USA.
| | - Mitchell Steinschneider
- Department of Neurology and Neuroscience, Albert Einstein College of Medicine, Bronx, NY 10461, USA
| | - Ariane E Rhone
- Department of Neurosurgery, The University of Iowa, Iowa City, IA 52242, USA
| | - Bryan M Krause
- Department of Anesthesiology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705, USA
| | - Rashmi N Mueller
- Department of Neurosurgery, The University of Iowa, Iowa City, IA 52242, USA,Department of Anesthesia, The University of Iowa, Iowa City, IA 52242, USA
| | - Hiroto Kawasaki
- Department of Neurosurgery, The University of Iowa, Iowa City, IA 52242, USA
| | - Matthew I Banks
- Department of Anesthesiology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705, USA,Department of Neuroscience, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705, USA
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19
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Pan Y, Yang J, Zhang T, Wen J, Pang F, Luo Y. Characterization of the abnormal cortical effective connectivity in patients with sleep apnea hypopnea syndrome during sleep. COMPUTER METHODS AND PROGRAMS IN BIOMEDICINE 2021; 204:106060. [PMID: 33813061 DOI: 10.1016/j.cmpb.2021.106060] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/22/2020] [Accepted: 03/16/2021] [Indexed: 06/12/2023]
Abstract
BACKGROUND AND OBJECTIVES Sleep apnea hypopnea syndrome (SAHS) is a prevalent sleep breathing disorder that can lead to brain damage and is also a risk factor for cognitive impairment and some common diseases. Studies on cortical effective connectivity (EC) during sleep may provide more direct and pathological information and shed new light on brain dysfunction due to SAHS. However, the EC is rarely explored in SAHS patients, especially during different sleep stages. METHODS To this end, six-channel EEG signals of 43 SAHS patients and 41 healthy participants were recorded by whole-night polysomnography (PSG). The symbolic transfer entropy (STE) was applied to measure the EC between cortical regions in different frequency bands. Posterior-anterior ratio (PA) was employed to evaluate the posterior-to-anterior pattern of information flow based on overall cortical EC. The statistical characteristics of the STE and PA and of the intra-individual normalized parameters (STE* and PA*) were served as different feature sets for classifying the severity of SAHS. RESULTS Although the patterns of STE across electrodes were similar, significant differences were found between the patient and the control groups. The variation trends across stages in the PA were also different in multiple frequency bands between groups. Important features extracted from the STE* and PA* were distributed in multiple rhythms, mainly in δ, α, and γ. The PA* feature set gave the best results, with accuracies of 98.8% and 83.3% for SAHS diagnosis (binary) and severity classification (four-way). CONCLUSIONS These results suggest that modifications in cortical EC were existed in SAHS patients during sleep, which may help characterize cortical abnormality in patients.
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Affiliation(s)
- Yu Pan
- School of Biomedical Engineering, Sun Yat-sen University, China
| | - Juan Yang
- School of Biomedical Engineering, Sun Yat-sen University, China
| | - Tingting Zhang
- School of Biomedical Engineering, Sun Yat-sen University, China
| | - Jinfeng Wen
- Psychology Department, Guangdong 999 Brain Hospital, China
| | - Feng Pang
- Sleep-Disordered Breathing Center, the Sixth Affiliated Hospital of Sun Yat-sen University, China
| | - Yuxi Luo
- School of Biomedical Engineering, Sun Yat-sen University, China; Key Laboratory of Sensing Technology and Biomedical Instrument of Guangdong Province, Sun Yat-sen University, China.
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20
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Guo J, Ran M, Gao Z, Zhang X, Wang D, Li H, Zhao S, Sun W, Dong H, Hu J. Cell-type-specific imaging of neurotransmission reveals a disrupted excitatory-inhibitory cortical network in isoflurane anaesthesia. EBioMedicine 2021; 65:103272. [PMID: 33691246 PMCID: PMC7941179 DOI: 10.1016/j.ebiom.2021.103272] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2020] [Revised: 02/06/2021] [Accepted: 02/19/2021] [Indexed: 12/21/2022] Open
Abstract
BACKGROUND Despite the fundamental clinical significance of general anaesthesia, the cortical mechanism underlying anaesthetic-induced loss of consciousness (aLOC) remains elusive. METHODS Here, we measured the dynamics of two major cortical neurotransmitters, gamma-aminobutyric acid (GABA) and glutamate, through in vivo two-photon imaging and genetically encoded neurotransmitter sensors in a cell type-specific manner in the primary visual (V1) cortex. FINDINGS We found a general decrease in cortical GABA transmission during aLOC. However, the glutamate transmission varies among different cortical cell types, where in it is almost preserved on pyramidal cells and is significantly reduced on inhibitory interneurons. Cortical interneurons expressing vasoactive intestinal peptide (VIP) and parvalbumin (PV) specialize in disinhibitory and inhibitory effects, respectively. During aLOC, VIP neuronal activity was delayed, and PV neuronal activity was dramatically inhibited and highly synchronized. INTERPRETATION These data reveal that aLOC resembles a cortical state with a disrupted excitatory-inhibitory network and suggest that a functional inhibitory network is indispensable in the maintenance of consciousness. FUNDING This work was supported by the grants of the National Natural Science Foundation of China (grant nos. 81620108012 and 82030038 to H.D. and grant nos. 31922029, 61890951, and 61890950 to J.H.).
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Affiliation(s)
- Juan Guo
- Department of Anaesthesiology and Perioperative Medicine, Xijing Hospital, The Fourth Military Medical University, Xi'an 710032, China
| | - Mingzi Ran
- Department of Anaesthesiology and Perioperative Medicine, Xijing Hospital, The Fourth Military Medical University, Xi'an 710032, China
| | - Zilong Gao
- Chinese Institute for Brain Research, Beijing 102206, China
| | - Xinxin Zhang
- Chinese Institute for Brain Research, Beijing 102206, China
| | - Dan Wang
- Department of Anaesthesiology and Perioperative Medicine, Xijing Hospital, The Fourth Military Medical University, Xi'an 710032, China
| | - Huiming Li
- Department of Anaesthesiology and Perioperative Medicine, Xijing Hospital, The Fourth Military Medical University, Xi'an 710032, China
| | - Shiyi Zhao
- Department of Anaesthesiology and Perioperative Medicine, Xijing Hospital, The Fourth Military Medical University, Xi'an 710032, China
| | - Wenzhi Sun
- Chinese Institute for Brain Research, Beijing 102206, China; School of Basic Medical Sciences, Capital Medical University, Beijing 10069, China.
| | - Hailong Dong
- Department of Anaesthesiology and Perioperative Medicine, Xijing Hospital, The Fourth Military Medical University, Xi'an 710032, China.
| | - Ji Hu
- School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China; Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai 200030, China; Co-Innovation Center of Neuroregeneration, Nantong University, Nantong 226000, China; CAS Center for Excellence in Brain Science and Intelligence Technology, Shanghai 200030, China.
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21
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Cascella M, Bimonte S, Di Napoli R. Delayed Emergence from Anesthesia: What We Know and How We Act. Local Reg Anesth 2020; 13:195-206. [PMID: 33177867 PMCID: PMC7652217 DOI: 10.2147/lra.s230728] [Citation(s) in RCA: 62] [Impact Index Per Article: 12.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2020] [Accepted: 09/01/2020] [Indexed: 12/31/2022] Open
Abstract
The emergence from anesthesia is the stage of general anesthesia featuring the patient's progression from the unconsciousness status to wakefulness and restoration of consciousness. This complex process has precise neurobiology which differs from that of induction. Despite the medications commonly used in anesthesia allow recovery in a few minutes, a delay in waking up from anesthesia, called delayed emergence, may occur. This phenomenon is associated with delays in the operating room, and an overall increase in costs. Together with the emergence delirium, the phenomenon represents a manifestation of inadequate emergence. Nevertheless, in delayed emergence, the transition from unconsciousness to complete wakefulness usually occurs along a normal trajectory, although slowed down. On the other hand, this awakening trajectory could proceed abnormally, possibly culminating in the manifestation of emergence delirium. Clinically, delayed emergence often represents a challenge for clinicians who must make an accurate diagnosis of the underlying cause to quickly establish appropriate therapy. This paper aimed at presenting an update on the phenomenon, analyzing its causes. Diagnostic and therapeutic strategies are addressed. Finally, therapeutic perspectives on the "active awakening" are reported.
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Affiliation(s)
- Marco Cascella
- Division of Anesthesia and Pain Medicine, Istituto Nazionale Tumori – IRCCS – “Fondazione G. Pascale, Naples, Italy
| | - Sabrina Bimonte
- Division of Anesthesia and Pain Medicine, Istituto Nazionale Tumori – IRCCS – “Fondazione G. Pascale, Naples, Italy
| | - Raffaela Di Napoli
- Department of Anesthesiology, Institut Jules Bordet, Université Libre De Bruxelles, Bruxelles1000, Belgium
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22
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Suzuki M, Larkum ME. General Anesthesia Decouples Cortical Pyramidal Neurons. Cell 2020; 180:666-676.e13. [PMID: 32084339 DOI: 10.1016/j.cell.2020.01.024] [Citation(s) in RCA: 157] [Impact Index Per Article: 31.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2019] [Revised: 11/15/2019] [Accepted: 01/15/2020] [Indexed: 10/25/2022]
Abstract
The mystery of general anesthesia is that it specifically suppresses consciousness by disrupting feedback signaling in the brain, even when feedforward signaling and basic neuronal function are left relatively unchanged. The mechanism for such selectiveness is unknown. Here we show that three different anesthetics have the same disruptive influence on signaling along apical dendrites in cortical layer 5 pyramidal neurons in mice. We found that optogenetic depolarization of the distal apical dendrites caused robust spiking at the cell body under awake conditions that was blocked by anesthesia. Moreover, we found that blocking metabotropic glutamate and cholinergic receptors had the same effect on apical dendrite decoupling as anesthesia or inactivation of the higher-order thalamus. If feedback signaling occurs predominantly through apical dendrites, the cellular mechanism we found would explain not only how anesthesia selectively blocks this signaling but also why conscious perception depends on both cortico-cortical and thalamo-cortical connectivity.
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Affiliation(s)
- Mototaka Suzuki
- NeuroCure Cluster of Excellence, Institute for Biology, Humboldt University of Berlin, Chariteplatz 1, 10117 Berlin, Germany.
| | - Matthew E Larkum
- NeuroCure Cluster of Excellence, Institute for Biology, Humboldt University of Berlin, Chariteplatz 1, 10117 Berlin, Germany
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23
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Kreuzer M, Butovas S, García PS, Schneider G, Schwarz C, Rudolph U, Antkowiak B, Drexler B. Propofol Affects Cortico-Hippocampal Interactions via β3 Subunit-Containing GABA A Receptors. Int J Mol Sci 2020; 21:ijms21165844. [PMID: 32823959 PMCID: PMC7461501 DOI: 10.3390/ijms21165844] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2020] [Revised: 08/05/2020] [Accepted: 08/07/2020] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND General anesthetics depress neuronal activity. The depression and uncoupling of cortico-hippocampal activity may contribute to anesthetic-induced amnesia. However, the molecular targets involved in this process are not fully characterized. GABAA receptors, especially the type with β3 subunits, represent a main molecular target of propofol. We therefore hypothesized that GABAA receptors with β3 subunits mediate the propofol-induced disturbance of cortico-hippocampal interactions. METHODS We used local field potential (LFP) recordings from chronically implanted cortical and hippocampal electrodes in wild-type and β3(N265M) knock-in mice. In the β3(N265M) mice, the action of propofol via β3subunit containing GABAA receptors is strongly attenuated. The analytical approach contained spectral power, phase locking, and mutual information analyses in the 2-16 Hz range to investigate propofol-induced effects on cortico-hippocampal interactions. RESULTS Propofol caused a significant increase in spectral power between 14 and 16 Hz in the cortex and hippocampus of wild-type mice. This increase was absent in the β3(N265M) mutant. Propofol strongly decreased phase locking of 6-12 Hz oscillations in wild-type mice. This decrease was attenuated in the β3(N265M) mutant. Finally, propofol reduced the mutual information between 6-16 Hz in wild-type mice, but only between 6 and 8 Hz in the β3(N265M) mutant. CONCLUSIONS GABAA receptors containing β3 subunits contribute to frequency-specific perturbation of cortico-hippocampal interactions. This likely explains some of the amnestic actions of propofol.
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Affiliation(s)
- Matthias Kreuzer
- Department of Anesthesiology and Intensive Care, Klinikum rechts der Isar, Technical University of Munich, School of Medicine, Munich, Ismaninger Str. 22, 81675 München, Germany; (M.K.); (G.S.)
| | - Sergejus Butovas
- Werner Reichardt Centre for Integrative Neuroscience, Eberhard-Karls-University, Otfried-Müller-Str. 25, 72076 Tübingen, Germany; (S.B.); (C.S.)
| | - Paul S García
- Department of Anesthesiology, Neuroanesthesia Division, Columbia University Medical Center, New York Presbyterian Hospital, 622 West 168th Street, New York City, NY 10032, USA;
| | - Gerhard Schneider
- Department of Anesthesiology and Intensive Care, Klinikum rechts der Isar, Technical University of Munich, School of Medicine, Munich, Ismaninger Str. 22, 81675 München, Germany; (M.K.); (G.S.)
| | - Cornelius Schwarz
- Werner Reichardt Centre for Integrative Neuroscience, Eberhard-Karls-University, Otfried-Müller-Str. 25, 72076 Tübingen, Germany; (S.B.); (C.S.)
| | - Uwe Rudolph
- Department of Comparative Biosciences, College of Veterinary Medicine, University of Illinois at Urbana-Champaign, 2001 South Lincoln Avenue, Urbana, IL 61802-6178, USA;
- Carl R. Woese Institute for Genomic Biology, University of Illiniois at Urbana-Champaign, Urbana, IL 61801, USA
| | - Bernd Antkowiak
- Department of Anaesthesiology, Experimental Anaesthesiology Section, Eberhard-Karls-University, Waldhörnlestrasse 22, 72072 Tübingen, Germany;
| | - Berthold Drexler
- Department of Anaesthesiology, Experimental Anaesthesiology Section, Eberhard-Karls-University, Waldhörnlestrasse 22, 72072 Tübingen, Germany;
- Correspondence:
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Desflurane Anesthesia Alters Cortical Layer-specific Hierarchical Interactions in Rat Cerebral Cortex. Anesthesiology 2020; 132:1080-1090. [PMID: 32101967 DOI: 10.1097/aln.0000000000003179] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
BACKGROUND Neurocognitive investigations suggest that conscious sensory perception depends on recurrent neuronal interactions among sensory, parietal, and frontal cortical regions, which are suppressed by general anesthetics. The purpose of this work was to investigate if local interactions in sensory cortex are also altered by anesthetics. The authors hypothesized that desflurane would reduce recurrent neuronal interactions in cortical layer-specific manner consistent with the anatomical disposition of feedforward and feedback pathways. METHODS Single-unit neuronal activity was measured in freely moving adult male rats (268 units; 10 animals) using microelectrode arrays chronically implanted in primary and secondary visual cortex. Layer-specific directional interactions were estimated by mutual information and transfer entropy of multineuron spike patterns within and between cortical layers three and five. The effect of incrementally increasing and decreasing steady-state concentrations of desflurane (0 to 8% to 0%) was tested for statistically significant quadratic trend across the successive anesthetic states. RESULTS Desflurane produced robust, state-dependent reduction (P = 0.001) of neuronal interactions between primary and secondary visual areas and between layers three and five, as indicated by mutual information (37 and 41% decrease at 8% desflurane from wakeful baseline at [mean ± SD] 0.52 ± 0.51 and 0.53 ± 0.51 a.u., respectively) and transfer entropy (77 and 78% decrease at 8% desflurane from wakeful baseline at 1.86 ± 1.56 a.u. and 1.87 ± 1.67 a.u., respectively). In addition, a preferential suppression of feedback between secondary and primary visual cortex was suggested by the reduction of directional index of transfer entropy overall (P = 0.001; 89% decrease at 8% desflurane from 0.11 ± 0.18 a.u. at baseline) and specifically, in layer five (P = 0.001; 108% decrease at 8% desflurane from 0.12 ± 0.19 a.u. at baseline). CONCLUSIONS Desflurane anesthesia reduces neuronal interactions in visual cortex with a preferential effect on feedback. The findings suggest that neuronal disconnection occurs locally, among hierarchical sensory regions, which may contribute to global functional disconnection underlying anesthetic-induced unconsciousness.
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Krom AJ, Marmelshtein A, Gelbard-Sagiv H, Tankus A, Hayat H, Hayat D, Matot I, Strauss I, Fahoum F, Soehle M, Boström J, Mormann F, Fried I, Nir Y. Anesthesia-induced loss of consciousness disrupts auditory responses beyond primary cortex. Proc Natl Acad Sci U S A 2020; 117:11770-11780. [PMID: 32398367 PMCID: PMC7261054 DOI: 10.1073/pnas.1917251117] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Despite its ubiquitous use in medicine, and extensive knowledge of its molecular and cellular effects, how anesthesia induces loss of consciousness (LOC) and affects sensory processing remains poorly understood. Specifically, it is unclear whether anesthesia primarily disrupts thalamocortical relay or intercortical signaling. Here we recorded intracranial electroencephalogram (iEEG), local field potentials (LFPs), and single-unit activity in patients during wakefulness and light anesthesia. Propofol infusion was gradually increased while auditory stimuli were presented and patients responded to a target stimulus until they became unresponsive. We found widespread iEEG responses in association cortices during wakefulness, which were attenuated and restricted to auditory regions upon LOC. Neuronal spiking and LFP responses in primary auditory cortex (PAC) persisted after LOC, while responses in higher-order auditory regions were variable, with neuronal spiking largely attenuated. Gamma power induced by word stimuli increased after LOC while its frequency profile slowed, thus differing from local spiking activity. In summary, anesthesia-induced LOC disrupts auditory processing in association cortices while relatively sparing responses in PAC, opening new avenues for future research into mechanisms of LOC and the design of anesthetic monitoring devices.
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Affiliation(s)
- Aaron J Krom
- Department of Physiology & Pharmacology, Sackler School of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel
- Department of Anesthesiology and Critical Care Medicine, Hadassah-Hebrew University Medical Center, Jerusalem 91120, Israel
- Hadassah School of Medicine, Hebrew University, Jerusalem 91120, Israel
| | - Amit Marmelshtein
- Sagol School of Neuroscience, Tel Aviv University, Tel Aviv 6997801, Israel
| | - Hagar Gelbard-Sagiv
- Department of Physiology & Pharmacology, Sackler School of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel
| | - Ariel Tankus
- Sagol School of Neuroscience, Tel Aviv University, Tel Aviv 6997801, Israel
- Functional Neurosurgery Unit, Tel Aviv Sourasky Medical Center, Tel Aviv 6423906, Israel
- Department of Neurology & Neurosurgery, Sackler School of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel
| | - Hanna Hayat
- Department of Physiology & Pharmacology, Sackler School of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel
| | - Daniel Hayat
- Department of Anesthesia, Intensive Care and Pain, Tel Aviv Medical Center, Sackler Medical School, Tel Aviv University, Tel Aviv 6997801, Israel
| | - Idit Matot
- Department of Anesthesia, Intensive Care and Pain, Tel Aviv Medical Center, Sackler Medical School, Tel Aviv University, Tel Aviv 6997801, Israel
| | - Ido Strauss
- Functional Neurosurgery Unit, Tel Aviv Sourasky Medical Center, Tel Aviv 6423906, Israel
- Department of Neurology & Neurosurgery, Sackler School of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel
| | - Firas Fahoum
- Department of Neurology & Neurosurgery, Sackler School of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel
- EEG and Epilepsy Unit, Department of Neurology, Tel Aviv Sourasky Medical Center, Tel Aviv 6423906, Israel
| | - Martin Soehle
- Department of Anesthesiology and Intensive Care Medicine, University of Bonn Medical Center, 53127 Bonn, Germany
| | - Jan Boström
- Department of Neurosurgery, University of Bonn Medical Center, 53127 Bonn, Germany
| | - Florian Mormann
- Department of Epileptology, University of Bonn Medical Center, 53127 Bonn, Germany
| | - Itzhak Fried
- Functional Neurosurgery Unit, Tel Aviv Sourasky Medical Center, Tel Aviv 6423906, Israel;
- Department of Neurology & Neurosurgery, Sackler School of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel
- Department of Neurosurgery, University of California, Los Angeles, CA 90095
| | - Yuval Nir
- Department of Physiology & Pharmacology, Sackler School of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel;
- Sagol School of Neuroscience, Tel Aviv University, Tel Aviv 6997801, Israel
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Reimann HM, Niendorf T. The (Un)Conscious Mouse as a Model for Human Brain Functions: Key Principles of Anesthesia and Their Impact on Translational Neuroimaging. Front Syst Neurosci 2020; 14:8. [PMID: 32508601 PMCID: PMC7248373 DOI: 10.3389/fnsys.2020.00008] [Citation(s) in RCA: 35] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2019] [Accepted: 01/27/2020] [Indexed: 12/11/2022] Open
Abstract
In recent years, technical and procedural advances have brought functional magnetic resonance imaging (fMRI) to the field of murine neuroscience. Due to its unique capacity to measure functional activity non-invasively, across the entire brain, fMRI allows for the direct comparison of large-scale murine and human brain functions. This opens an avenue for bidirectional translational strategies to address fundamental questions ranging from neurological disorders to the nature of consciousness. The key challenges of murine fMRI are: (1) to generate and maintain functional brain states that approximate those of calm and relaxed human volunteers, while (2) preserving neurovascular coupling and physiological baseline conditions. Low-dose anesthetic protocols are commonly applied in murine functional brain studies to prevent stress and facilitate a calm and relaxed condition among animals. Yet, current mono-anesthesia has been shown to impair neural transmission and hemodynamic integrity. By linking the current state of murine electrophysiology, Ca2+ imaging and fMRI of anesthetic effects to findings from human studies, this systematic review proposes general principles to design, apply and monitor anesthetic protocols in a more sophisticated way. The further development of balanced multimodal anesthesia, combining two or more drugs with complementary modes of action helps to shape and maintain specific brain states and relevant aspects of murine physiology. Functional connectivity and its dynamic repertoire as assessed by fMRI can be used to make inferences about cortical states and provide additional information about whole-brain functional dynamics. Based on this, a simple and comprehensive functional neurosignature pattern can be determined for use in defining brain states and anesthetic depth in rest and in response to stimuli. Such a signature can be evaluated and shared between labs to indicate the brain state of a mouse during experiments, an important step toward translating findings across species.
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Affiliation(s)
- Henning M. Reimann
- Berlin Ultrahigh Field Facility (B.U.F.F.), Max-Delbrück Center for Molecular Medicine, Helmholtz Association of German Research Centers (HZ), Berlin, Germany
| | - Thoralf Niendorf
- Berlin Ultrahigh Field Facility (B.U.F.F.), Max-Delbrück Center for Molecular Medicine, Helmholtz Association of German Research Centers (HZ), Berlin, Germany
- Experimental and Clinical Research Center, A Joint Cooperation Between the Charité Medical Faculty and the Max-Delbrück Center for Molecular Medicine, Berlin, Germany
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27
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Probing dynamical cortical gating of attention with concurrent TMS-EEG. Sci Rep 2020; 10:4959. [PMID: 32188883 PMCID: PMC7080792 DOI: 10.1038/s41598-020-61590-2] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2019] [Accepted: 02/25/2020] [Indexed: 11/08/2022] Open
Abstract
Attention facilitates the gating of information from the sending brain area to the receiving areas, with this being achieved by dynamical changes in effective connectivity, which refers to the directional influences between cortical areas. To probe the effective connectivity and cortical excitability modulated by covertly shifted attention, transcranial magnetic stimulation (TMS) was used to directly perturb the right retinotopic visual cortex with respect to attended and unattended locations, and the impact of this was tracked from the stimulated area to other areas by concurrent use of electroencephalography (EEG). TMS to the contralateral visual hemisphere led to a stronger evoked potential than stimulation to the ipsilateral hemisphere. Moreover, stronger beta- and gamma-band effective connectivities assessed as time-delayed phase synchronizations between stimulated areas and other areas were observed when TMS was delivered to the contralateral hemisphere. These effects were more enhanced when they preceded more prominent alpha lateralization, which is known to be associated with attentional gating. Our results indicate that attention-regulated cortical feedforward effective connectivity can be probed by TMS-EEG with direct cortical stimulation, thereby bypassing thalamic gating. These results suggest that cortical gating of the feedforward input is achieved by regulating the effective connectivity in the phase dynamics between cortical areas.
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28
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Mashour GA, Roelfsema P, Changeux JP, Dehaene S. Conscious Processing and the Global Neuronal Workspace Hypothesis. Neuron 2020; 105:776-798. [PMID: 32135090 PMCID: PMC8770991 DOI: 10.1016/j.neuron.2020.01.026] [Citation(s) in RCA: 466] [Impact Index Per Article: 93.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2019] [Revised: 10/31/2019] [Accepted: 01/22/2020] [Indexed: 10/24/2022]
Abstract
We review the central tenets and neuroanatomical basis of the global neuronal workspace (GNW) hypothesis, which attempts to account for the main scientific observations regarding the elementary mechanisms of conscious processing in the human brain. The GNW hypothesis proposes that, in the conscious state, a non-linear network ignition associated with recurrent processing amplifies and sustains a neural representation, allowing the corresponding information to be globally accessed by local processors. We examine this hypothesis in light of recent data that contrast brain activity evoked by either conscious or non-conscious contents, as well as during conscious or non-conscious states, particularly general anesthesia. We also discuss the relationship between the intertwined concepts of conscious processing, attention, and working memory.
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Affiliation(s)
- George A Mashour
- Center for Consciousness Science, Neuroscience Graduate Program, and Department of Anesthesiology, University of Michigan, Ann Arbor, MI, USA
| | - Pieter Roelfsema
- Department of Vision & Cognition, Netherlands Institute for Neuroscience, Meibergdreef 47, 1105 BA, Amsterdam, the Netherlands; Department of Integrative Neurophysiology, Center for Neurogenomics and Cognitive Research, VU University, Amsterdam, the Netherlands; Department of Psychiatry, Academic Medical Center, Amsterdam, the Netherlands
| | - Jean-Pierre Changeux
- CNRS UMR 3571, Institut Pasteur, 75724 Paris, France; Collège de France, 11 Place Marcelin Berthelot, 75005 Paris, France; Kavli Institute for Brain & Mind, University of California, San Diego, La Jolla, CA, USA.
| | - Stanislas Dehaene
- Collège de France, 11 Place Marcelin Berthelot, 75005 Paris, France; Cognitive Neuroimaging Unit, CEA, INSERM, Université Paris-Sud, Université Paris-Saclay, NeuroSpin Center, 91191 Gif/Yvette, France.
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29
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Banks MI, Krause BM, Endemann CM, Campbell DI, Kovach CK, Dyken ME, Kawasaki H, Nourski KV. Cortical functional connectivity indexes arousal state during sleep and anesthesia. Neuroimage 2020; 211:116627. [PMID: 32045640 DOI: 10.1016/j.neuroimage.2020.116627] [Citation(s) in RCA: 39] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2019] [Revised: 01/28/2020] [Accepted: 02/07/2020] [Indexed: 02/06/2023] Open
Abstract
Disruption of cortical connectivity likely contributes to loss of consciousness (LOC) during both sleep and general anesthesia, but the degree of overlap in the underlying mechanisms is unclear. Both sleep and anesthesia comprise states of varying levels of arousal and consciousness, including states of largely maintained conscious experience (sleep: N1, REM; anesthesia: sedated but responsive) as well as states of substantially reduced conscious experience (sleep: N2/N3; anesthesia: unresponsive). Here, we tested the hypotheses that (1) cortical connectivity will exhibit clear changes when transitioning into states of reduced consciousness, and (2) these changes will be similar for arousal states of comparable levels of consciousness during sleep and anesthesia. Using intracranial recordings from five adult neurosurgical patients, we compared resting state cortical functional connectivity (as measured by weighted phase lag index, wPLI) in the same subjects across arousal states during natural sleep [wake (WS), N1, N2, N3, REM] and propofol anesthesia [pre-drug wake (WA), sedated/responsive (S), and unresponsive (U)]. Analysis of alpha-band connectivity indicated a transition boundary distinguishing states of maintained and reduced conscious experience in both sleep and anesthesia. In wake states WS and WA, alpha-band wPLI within the temporal lobe was dominant. This pattern was largely unchanged in N1, REM, and S. Transitions into states of reduced consciousness N2, N3, and U were characterized by dramatic changes in connectivity, with dominant connections shifting to prefrontal cortex. Secondary analyses indicated similarities in reorganization of cortical connectivity in sleep and anesthesia. Shifts from temporal to frontal cortical connectivity may reflect impaired sensory processing in states of reduced consciousness. The data indicate that functional connectivity can serve as a biomarker of arousal state and suggest common mechanisms of LOC in sleep and anesthesia.
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Affiliation(s)
- Matthew I Banks
- Department of Anesthesiology, University of Wisconsin, Madison, WI, 52704, USA; Department of Neuroscience, University of Wisconsin, Madison, WI, 53706, USA.
| | - Bryan M Krause
- Department of Anesthesiology, University of Wisconsin, Madison, WI, 52704, USA
| | | | - Declan I Campbell
- Department of Anesthesiology, University of Wisconsin, Madison, WI, 52704, USA
| | | | - Mark Eric Dyken
- Department of Neurology, The University of Iowa, Iowa City, IA, 52242, USA
| | - Hiroto Kawasaki
- Department of Neurosurgery, The University of Iowa, Iowa City, IA, 52242, USA
| | - Kirill V Nourski
- Department of Neurosurgery, The University of Iowa, Iowa City, IA, 52242, USA; Iowa Neuroscience Institute, The University of Iowa, Iowa City, IA, 52242, USA
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30
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Pavel B, Menardy F, Rotaru D, Paslaru AC, Acatrinei C, Zagrean L, Popa D, Zagrean AM. Electrical Stimulation in the Claustrum Area Induces a Deepening of Isoflurane Anesthesia in Rat. Brain Sci 2019; 9:brainsci9110304. [PMID: 31683949 PMCID: PMC6895863 DOI: 10.3390/brainsci9110304] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2019] [Revised: 10/29/2019] [Accepted: 10/30/2019] [Indexed: 11/16/2022] Open
Abstract
The role of the claustrum in consciousness and vigilance states was proposed more than two decades ago; however, its role in anesthesia is not yet understood, and this requires more investigation. The aim of our study was to assess the impact of claustrum electrical stimulation during isoflurane anesthesia in adult rats. The claustrum in the left hemisphere was electrically stimulated using a bipolar tungsten electrode inserted stereotaxically. In order to monitor the anesthetic depth, the electrocorticogram (ECoG) was recorded before, during, and after claustrum stimulation using frontal and parietal epidural electrodes placed over the left hemisphere. After reaching stabilized slow-wave isoflurane anesthesia, twenty stimuli, each of one second duration with ten seconds interstimulus duration, were applied. ECoG analysis has shown that, after a delay from the beginning of stimulation, the slow-wave ECoG signal changed to a transient burst suppression (BS) pattern. Our results show that electrical stimulation of the claustrum area during slow-wave isoflurane anesthesia induces a transitory increase in anesthetic depth, documented by the appearance of a BS ECoG pattern, and suggests a potential role of claustrum in anesthesia.
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Affiliation(s)
- Bogdan Pavel
- Division of Physiology and Neuroscience, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania.
- Institut de Biologie de l'Ecole Normale Supérieure (IBENS), Ecole Normale Supérieure, CNRS, INSERM, PSL Research University, 75005 Paris, France.
| | - Fabien Menardy
- Institut de Biologie de l'Ecole Normale Supérieure (IBENS), Ecole Normale Supérieure, CNRS, INSERM, PSL Research University, 75005 Paris, France.
| | - Diana Rotaru
- Department of Neuroimaging, Centre for Neuroimaging Sciences, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London SE58AF, UK.
| | - Alexandru Catalin Paslaru
- Division of Physiology and Neuroscience, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania.
| | - Camelia Acatrinei
- Division of Physiology and Neuroscience, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania.
| | - Leon Zagrean
- Division of Physiology and Neuroscience, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania.
| | - Daniela Popa
- Division of Physiology and Neuroscience, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania.
- Institut de Biologie de l'Ecole Normale Supérieure (IBENS), Ecole Normale Supérieure, CNRS, INSERM, PSL Research University, 75005 Paris, France.
| | - Ana-Maria Zagrean
- Division of Physiology and Neuroscience, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania.
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Jovellar DB, Doudet DJ. fMRI in Non-human Primate: A Review on Factors That Can Affect Interpretation and Dynamic Causal Modeling Application. Front Neurosci 2019; 13:973. [PMID: 31619951 PMCID: PMC6759819 DOI: 10.3389/fnins.2019.00973] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2019] [Accepted: 08/30/2019] [Indexed: 11/13/2022] Open
Abstract
Dynamic causal modeling (DCM)-a framework for inferring hidden neuronal states from brain activity measurements (e. g., fMRI) and their context-dependent modulation-was developed for human neuroimaging, and has not been optimized for non-human primate (NHP) studies, which are usually done under anesthesia. Animal neuroimaging studies offer the potential to improve effective connectivity modeling using DCM through combining functional imaging with invasive procedures such as in vivo optogenetic or electrical stimulation. Employing a Bayesian approach, model parameters are estimated based on prior knowledge of conditions that might be related to neural and BOLD dynamics (e.g., requires empirical knowledge about the range of plausible parameter values). As such, we address the following questions in this review: What factors need to be considered when applying DCM to NHP data? What differences in functional networks, cerebrovascular architecture and physiology exist between human and NHPs that are relevant for DCM application? How do anesthetics affect vascular physiology, BOLD contrast, and neural dynamics-particularly, effective communication within, and between networks? Considering the factors that are relevant for DCM application to NHP neuroimaging, we propose a strategy for modeling effective connectivity under anesthesia using an integrated physiologic-stochastic DCM (IPS-DCM).
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Affiliation(s)
- D Blair Jovellar
- Division of Neurology, Department of Medicine, University of British Columbia, Vancouver, BC, Canada.,Center of Neurology, Hertie Institute for Clinical Brain Research, University Hospital, Tuebingen, Germany
| | - Doris J Doudet
- Division of Neurology, Department of Medicine, University of British Columbia, Vancouver, BC, Canada
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32
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Mashour GA. Role of cortical feedback signalling in consciousness and anaesthetic-induced unconsciousness. Br J Anaesth 2019; 123:404-405. [DOI: 10.1016/j.bja.2019.07.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2019] [Accepted: 07/01/2019] [Indexed: 12/20/2022] Open
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Gross WL, Lauer KK, Liu X, Roberts CJ, Liu S, Gollapudy S, Binder JR, Li SJ, Hudetz AG. Propofol Sedation Alters Perceptual and Cognitive Functions in Healthy Volunteers as Revealed by Functional Magnetic Resonance Imaging. Anesthesiology 2019; 131:254-265. [PMID: 31314747 PMCID: PMC6640651 DOI: 10.1097/aln.0000000000002669] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND Elucidating networks underlying conscious perception is important to understanding the mechanisms of anesthesia and consciousness. Previous studies have observed changes associated with loss of consciousness primarily using resting paradigms. The authors focused on the effects of sedation on specific cognitive systems using task-based functional magnetic resonance imaging. The authors hypothesized deepening sedation would degrade semantic more than perceptual discrimination. METHODS Discrimination of pure tones and familiar names were studied in 13 volunteers during wakefulness and propofol sedation targeted to light and deep sedation. Contrasts highlighted specific cognitive systems: auditory/motor (tones vs. fixation), phonology (unfamiliar names vs. tones), and semantics (familiar vs. unfamiliar names), and were performed across sedation conditions, followed by region of interest analysis on representative regions. RESULTS During light sedation, the spatial extent of auditory/motor activation was similar, becoming restricted to the superior temporal gyrus during deep sedation. Region of interest analysis revealed significant activation in the superior temporal gyrus during light (t [17] = 9.71, P < 0.001) and deep sedation (t [19] = 3.73, P = 0.001). Spatial extent of the phonologic contrast decreased progressively with sedation, with significant activation in the inferior frontal gyrus maintained during light sedation (t [35] = 5.17, P < 0.001), which didn't meet criteria for significance in deep sedation (t [38] = 2.57, P = 0.014). The semantic contrast showed a similar pattern, with activation in the angular gyrus during light sedation (t [16] = 4.76, P = 0.002), which disappeared in deep sedation (t [18] = 0.35, P = 0.731). CONCLUSIONS Results illustrate broad impairment in cognitive cortex during sedation, with activation in primary sensory cortex beyond loss of consciousness. These results agree with clinical experience: a dose-dependent reduction of higher cognitive functions during light sedation, despite partial preservation of sensory processes through deep sedation.
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Affiliation(s)
| | | | - Xiaolin Liu
- Medical College of Wisconsin, Department of Radiology
| | | | - Suyan Liu
- Medical College of Wisconsin, Department of Anesthesiology
| | | | | | - Shi-Jiang Li
- Medical College of Wisconsin, Department of Neurology
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Zhang Y, Li Z, Zhang J, Zhao Z, Zhang H, Vreugdenhil M, Lu C. Near-Death High-Frequency Hyper-Synchronization in the Rat Hippocampus. Front Neurosci 2019; 13:800. [PMID: 31417353 PMCID: PMC6684736 DOI: 10.3389/fnins.2019.00800] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2019] [Accepted: 07/17/2019] [Indexed: 12/30/2022] Open
Abstract
Near-death experiences (NDE) are episodes of enhanced perception with impending death, which have been associated with increased high-frequency (13-100 Hz) synchronization of neuronal activity, which is implicated in cognitive processes like perception, attention and memory. To test whether the NDE-associated high-frequency oscillations surge is related to cardiac arrest, recordings were made from the hippocampus of anesthetized rats dying from an overdose of the sedative chloral hydrate (CH). At a lethal dose, CH caused a surge in beta band power in CA3 and CA1 and a surge in gamma band power in CA1. CH increased the inter-regional coherence of high-frequency oscillations within and between hippocampi. Whereas the surge in beta power developed at non-lethal chloral hydrate doses, the surge in gamma power was specific for impending death. In contrast, CH strongly suppressed theta band power in both CA1 and CA3 and reduced inter-regional coherence in the theta band. The simultaneously recorded electrocardiogram showed a small decrease in heart rate but no change in waveform during the high-frequency oscillation surge, with cardiac arrest only developing after the cessation of breathing and collapse of all oscillatory activity. These results demonstrate that the high-frequency oscillation surge just before death is not limited to cardiac arrest and that especially the increase in gamma synchronization in CA1 may contribute to NDE observed both with and without cardiac arrest.
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Affiliation(s)
- Yujiao Zhang
- School of Psychology, Xinxiang Medical University, Xinxiang, China.,International-Joint Lab for Non-Invasive Neural Modulation of Henan Province, Department of Neurobiology and Physiology, Xinxiang Medical University, Xinxiang, China
| | - Zhenyi Li
- School of Psychology, Xinxiang Medical University, Xinxiang, China
| | - Jing Zhang
- School of Psychology, Xinxiang Medical University, Xinxiang, China
| | - Zongya Zhao
- School of Biomedical Engineering, Xinxiang Medical University, Xinxiang, China
| | - Hongxing Zhang
- School of Psychology, Xinxiang Medical University, Xinxiang, China
| | - Martin Vreugdenhil
- School of Psychology, Xinxiang Medical University, Xinxiang, China.,Department of Life Sciences, School of Health Sciences, Birmingham City University, Birmingham, United Kingdom
| | - Chengbiao Lu
- School of Psychology, Xinxiang Medical University, Xinxiang, China.,International-Joint Lab for Non-Invasive Neural Modulation of Henan Province, Department of Neurobiology and Physiology, Xinxiang Medical University, Xinxiang, China
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35
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Ki S, Kim KM, Lee YH, Bang JY, Choi BM, Noh GJ. Phase lag entropy as a hypnotic depth indicator during propofol sedation. Anaesthesia 2019; 74:1033-1040. [PMID: 31106853 DOI: 10.1111/anae.14704] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/25/2019] [Indexed: 11/29/2022]
Abstract
Phase lag entropy, an electro-encephalography-based hypnotic depth indicator, calculates diversity in temporal patterns of phase relationship. We compared the performance of phase lag entropy with the bispectral index™ in 30 patients scheduled for elective surgery. We initiated a target-controlled infusion of propofol using the Schnider model, and assessed sedation levels using the Modified Observer's Assessment of Alertness/Sedation scale every 30 s with each stepwise increase in the effect-site propofol concentration. Phase lag entropy and bispectral index values were recorded. The correlation coefficient and prediction probability between phase lag entropy or bispectral index and the sedation level or effect-site propofol concentration were analysed. We calculated baseline variabilities of phase lag entropy and bispectral index. In addition, we applied a non-linear mixed-effects model to obtain the pharmacodynamic relationships among the effect-site propofol concentration, phase lag entropy or bispectral index and sedation level. As sedation increased, phase lag entropy and bispectral index both decreased. The prediction probability values of phase lag entropy and bispectral index for sedation levels were 0.697 and 0.700 (p = 0.261) and for the effect-site concentration of propofol were 0.646 and 0.630 (p = 0.091), respectively. Baseline variability in phase lag entropy and bispectral index was 3.3 and 5.7, respectively. The predicted propofol concentrations, using the Schnider pharmacokinetic model, producing a 50% probability of moderate and deep sedation were 1.96 and 3.01 μg.ml-1 , respectively. Phase lag entropy was found to be useful as a hypnotic depth indicator in patients receiving propofol sedation.
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Affiliation(s)
- S Ki
- Department of Anesthesiology and Pain Medicine, Busan Paik Hospital, Inje University, Busan, Korea
| | - K M Kim
- Department of Anesthesiology and Pain Medicine, Hallym University Sacred Heart Hospital, Hallym University of College of Medicine, Anyang, Korea
| | - Y H Lee
- Department of Anaesthesiology and Pain Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - J Y Bang
- Department of Anaesthesiology and Pain Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - B M Choi
- Department of Anaesthesiology and Pain Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - G J Noh
- Department of Anaesthesiology and Pain Medicine and Department of Clinical Pharmacology and Therapeutics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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36
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Oh J, Ham J, Cho D, Park JY, Kim JJ, Lee B. The Effects of Transcranial Direct Current Stimulation on the Cognitive and Behavioral Changes After Electrode Implantation Surgery in Rats. Front Psychiatry 2019; 10:291. [PMID: 31156472 PMCID: PMC6531794 DOI: 10.3389/fpsyt.2019.00291] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/26/2018] [Accepted: 04/15/2019] [Indexed: 11/22/2022] Open
Abstract
Postoperative delirium can lead to increased morbidity and mortality, and may even be a potentially life-threatening clinical syndrome. However, the neural mechanism underlying this condition has not been fully understood and there is little knowledge regarding potential preventive strategies. To date, investigation of transcranial direct current stimulation (tDCS) for the relief of symptoms caused by neuropsychiatric disorders and the enhancement of cognitive performance has led to promising results. In this study, we demonstrated that tDCS has a possible effect on the fast recovery from delirium in rats after microelectrode implant surgery, as demonstrated by postoperative behavior and neurophysiology compared with sham stimulation. This is the first study to describe the possible effects of tDCS for the fast recovery from delirium based on the study of both electroencephalography and behavioral changes. Postoperative rats showed decreased attention, which is the core symptom of delirium. However, anodal tDCS over the right frontal area immediately after surgery exhibited positive effects on acute attentional deficit. It was found that relative power of theta was lower in the tDCS group than in the sham group after surgery, suggesting that the decrease might be the underlying reason for the positive effects of tDCS. Connectivity analysis revealed that tDCS could modulate effective connectivity and synchronization of brain activity among different brain areas, including the frontal cortex, parietal cortex, and thalamus. It was concluded that anodal tDCS on the right frontal regions may have the potential to help patients recover quickly from delirium.
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Affiliation(s)
- Jooyoung Oh
- Department of Psychiatry, Gangnam Severance Hospital, Yonsei University Health System, Seoul, South Korea
- Institute of Behavioral Science in Medicine, Yonsei University College of Medicine, Seoul, South Korea
| | - Jinsil Ham
- Department of Biomedical Science and Engineering (BMSE), Institute of Integrated Technology (IIT), Gwangju Institute of Science and Technology (GIST), Gwangju, South Korea
| | - Dongrae Cho
- Department of Biomedical Science and Engineering (BMSE), Institute of Integrated Technology (IIT), Gwangju Institute of Science and Technology (GIST), Gwangju, South Korea
| | - Jin Young Park
- Department of Psychiatry, Gangnam Severance Hospital, Yonsei University Health System, Seoul, South Korea
- Institute of Behavioral Science in Medicine, Yonsei University College of Medicine, Seoul, South Korea
| | - Jae-Jin Kim
- Department of Psychiatry, Gangnam Severance Hospital, Yonsei University Health System, Seoul, South Korea
- Institute of Behavioral Science in Medicine, Yonsei University College of Medicine, Seoul, South Korea
| | - Boreom Lee
- Department of Biomedical Science and Engineering (BMSE), Institute of Integrated Technology (IIT), Gwangju Institute of Science and Technology (GIST), Gwangju, South Korea
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Alonso LM, Solovey G, Yanagawa T, Proekt A, Cecchi GA, Magnasco MO. Single-trial classification of awareness state during anesthesia by measuring critical dynamics of global brain activity. Sci Rep 2019; 9:4927. [PMID: 30894626 PMCID: PMC6426977 DOI: 10.1038/s41598-019-41345-4] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2018] [Accepted: 03/01/2019] [Indexed: 11/09/2022] Open
Abstract
In daily life, in the operating room and in the laboratory, the operational way to assess wakefulness and consciousness is through responsiveness. A number of studies suggest that the awake, conscious state is not the default behavior of an assembly of neurons, but rather a very special state of activity that has to be actively maintained and curated to support its functional properties. Thus responsiveness is a feature that requires active maintenance, such as a homeostatic mechanism to balance excitation and inhibition. In this work we developed a method for monitoring such maintenance processes, focusing on a specific signature of their behavior derived from the theory of dynamical systems: stability analysis of dynamical modes. When such mechanisms are at work, their modes of activity are at marginal stability, neither damped (stable) nor exponentially growing (unstable) but rather hovering in between. We have previously shown that, conversely, under induction of anesthesia those modes become more stable and thus less responsive, then reversed upon emergence to wakefulness. We take advantage of this effect to build a single-trial classifier which detects whether a subject is awake or unconscious achieving high performance. We show that our approach can be developed into a means for intra-operative monitoring of the depth of anesthesia, an application of fundamental importance to modern clinical practice.
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Affiliation(s)
- Leandro M Alonso
- Laboratory of integrative neuroscience, The Rockefeller University, New York, NY, 10065, USA. .,Volen Center for Complex Systems, Department of Biology, Brandeis University, Waltham, MA, 02454, USA.
| | - Guillermo Solovey
- Instituto del Cálculo, FCEyN, Universidad de Buenos Aires, (C1428EGA), Buenos Aires, Argentina.
| | - Toru Yanagawa
- Laboratory for Adaptive Intelligence, Brain Science Institute, RIKEN, Saitama, 351-0198, Japan
| | - Alex Proekt
- Anesthesiology and Critical Care, University of Pennsylvania, Philadelphia, PA, 19104, USA
| | | | - Marcelo O Magnasco
- Laboratory of integrative neuroscience, The Rockefeller University, New York, NY, 10065, USA.,Volen Center for Complex Systems, Department of Biology, Brandeis University, Waltham, MA, 02454, USA
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38
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Hentschke H, Raz A, Krause BM, Murphy CA, Banks MI. Disruption of cortical network activity by the general anaesthetic isoflurane. Br J Anaesth 2019; 119:685-696. [PMID: 29121295 DOI: 10.1093/bja/aex199] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/02/2017] [Indexed: 02/03/2023] Open
Abstract
Background Actions of general anaesthetics on activity in the cortico-thalamic network likely contribute to loss of consciousness and disconnection from the environment. Previously, we showed that the general anaesthetic isoflurane preferentially suppresses cortically evoked synaptic responses compared with thalamically evoked synaptic responses, but how this differential sensitivity translates into changes in network activity is unclear. Methods We investigated isoflurane disruption of spontaneous and stimulus-induced cortical network activity using multichannel recordings in murine auditory thalamo-cortical brain slices. Results Under control conditions, afferent stimulation elicited short latency, presumably monosynaptically driven, spiking responses, as well as long latency network bursts that propagated horizontally through the cortex. Isoflurane (0.05-0.6 mM) suppressed spiking activity overall, but had a far greater effect on network bursts than on early spiking responses. At isoflurane concentrations >0.3 mM, network bursts were almost entirely blocked, even with increased stimulation intensity and in response to paired (thalamo-cortical + cortical layer 1) stimulation, while early spiking responses were <50% blocked. Isoflurane increased the threshold for eliciting bursts, decreased their propagation speed and prevented layer 1 afferents from facilitating burst induction by thalamo-cortical afferents. Conclusions Disruption of horizontal activity spread and of layer 1 facilitation of thalamo-cortical responses likely contribute to the mechanism by which suppression of cortical feedback connections disrupts sensory awareness under anaesthesia.
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Affiliation(s)
- H Hentschke
- Department of Anesthesiology, Experimental Anesthesiology Section, University Hospital of Tübingen, Tübingen, Germany
| | - A Raz
- Department of Anesthesiology, University of Wisconsin, Madison, WI, USA.,Department of Anesthesiology, Rambam Health Care Campus, Haifa, Israel
| | - B M Krause
- Department of Anesthesiology, University of Wisconsin, Madison, WI, USA
| | - C A Murphy
- Department of Anesthesiology, University of Wisconsin, Madison, WI, USA.,Physiology Graduate Training Program, University of Wisconsin, Madison, WI, USA
| | - M I Banks
- Department of Anesthesiology, University of Wisconsin, Madison, WI, USA
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Palanca BJA, Avidan MS, Mashour GA. Human neural correlates of sevoflurane-induced unconsciousness. Br J Anaesth 2019; 119:573-582. [PMID: 29121298 DOI: 10.1093/bja/aex244] [Citation(s) in RCA: 71] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/11/2017] [Indexed: 01/01/2023] Open
Abstract
Sevoflurane, a volatile anaesthetic agent well-tolerated for inhalation induction, provides a useful opportunity to elucidate the processes whereby halogenated ethers disrupt consciousness and cognition. Multiple molecular targets of sevoflurane have been identified, complementing imaging and electrophysiologic markers for the mechanistically obscure progression from wakefulness to unconsciousness. Recent investigations have more precisely detailed scalp EEG activity during this transition, with practical clinical implications. The relative timing of scalp potentials in frontal and parietal EEG signals suggests that sevoflurane might perturb the propagation of neural information between underlying cortical regions. Spatially distributed brain activity during general anaesthesia has been further investigated with positron emission tomography (PET) and resting-state functional magnetic resonance imaging (fMRI). Combined EEG and PET investigations have identified changes in cerebral blood flow and metabolic activity in frontal, parietal, and thalamic regions during sevoflurane-induced loss of consciousness. More recent fMRI investigations have revealed that sevoflurane weakens the signal correlations among brain regions that share functionality and specialization during wakefulness. In particular, two such resting-state networks have shown progressive breakdown in intracortical and thalamocortical connectivity with increasing anaesthetic concentrations: the Default Mode Network (introspection and episodic memory) and the Ventral Attention Network (orienting of attention to salient feature of the external world). These data support the hypotheses that perturbations in temporally correlated activity across brain regions contribute to the transition between states of sevoflurane sedation and general anaesthesia.
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Affiliation(s)
- B J A Palanca
- Division of Biology and Biomedical Sciences.,Department of Anesthesiology, Washington University School of Medicine in St. Louis, St. Louis, MO, USA
| | - M S Avidan
- Department of Anesthesiology, Washington University School of Medicine in St. Louis, St. Louis, MO, USA.,Division of Cardiothoracic Surgery, Department of Surgery, Washington University School of Medicine in St. Louis, St. Louis, MO, USA
| | - G A Mashour
- Department of Anesthesiology, Center for Consciousness Science and Neuroscience Graduate Program, University of Michigan Medical School, Ann Arbor, MI, USA
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40
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Abstract
The heterogeneity of molecular mechanisms, target neural circuits, and neurophysiologic effects of general anesthetics makes it difficult to develop a reliable and drug-invariant index of general anesthesia. No single brain region or mechanism has been identified as the neural correlate of consciousness, suggesting that consciousness might emerge through complex interactions of spatially and temporally distributed brain functions. The goal of this review article is to introduce the basic concepts of networks and explain why the application of network science to general anesthesia could be a pathway to discover a fundamental mechanism of anesthetic-induced unconsciousness. This article reviews data suggesting that reduced network efficiency, constrained network repertoires, and changes in cortical dynamics create inhospitable conditions for information processing and transfer, which lead to unconsciousness. This review proposes that network science is not just a useful tool but a necessary theoretical framework and method to uncover common principles of anesthetic-induced unconsciousness.
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Affiliation(s)
- UnCheol Lee
- From the Center for Consciousness Science, Department of Anesthesiology, University of Michigan Medical School, Ann Arbor, Michigan
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41
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Huang Z, Zhang J, Wu J, Liu X, Xu J, Zhang J, Qin P, Dai R, Yang Z, Mao Y, Hudetz AG, Northoff G. Disrupted neural variability during propofol-induced sedation and unconsciousness. Hum Brain Mapp 2018; 39:4533-4544. [PMID: 29974570 PMCID: PMC6223306 DOI: 10.1002/hbm.24304] [Citation(s) in RCA: 37] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2017] [Revised: 06/04/2018] [Accepted: 06/24/2018] [Indexed: 12/16/2022] Open
Abstract
Variability quenching is a widespread neural phenomenon in which trial-to-trial variability (TTV) of neural activity is reduced by repeated presentations of a sensory stimulus. However, its neural mechanism and functional significance remain poorly understood. Recurrent network dynamics are suggested as a candidate mechanism of TTV, and they play a key role in consciousness. We thus asked whether the variability-quenching phenomenon is related to the level of consciousness. We hypothesized that TTV reduction would be compromised during reduced level of consciousness by propofol anesthetics. We recorded functional magnetic resonance imaging signals of resting-state and stimulus-induced activities in three conditions: wakefulness, sedation, and unconsciousness (i.e., deep anesthesia). We measured the average (trial-to-trial mean, TTM) and variability (TTV) of auditory stimulus-induced activity under the three conditions. We also examined another form of neural variability (temporal variability, TV), which quantifies the overall dynamic range of ongoing neural activity across time, during both the resting-state and the task. We found that (a) TTM deceased gradually from wakefulness through sedation to anesthesia, (b) stimulus-induced TTV reduction normally seen during wakefulness was abolished during both sedation and anesthesia, and (c) TV increased in the task state as compared to resting-state during both wakefulness and sedation, but not anesthesia. Together, our results reveal distinct effects of propofol on the two forms of neural variability (TTV and TV). They imply that the anesthetic disrupts recurrent network dynamics, thus prevents the stabilization of cortical activity states. These findings shed new light on the temporal dynamics of neuronal variability and its alteration during anesthetic-induced unconsciousness.
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Affiliation(s)
- Zirui Huang
- Department of Anesthesiology and Center for Consciousness ScienceUniversity of MichiganAnn ArborMichigan
| | - Jun Zhang
- Department of AnesthesiologyHuashan Hospital, Fudan UniversityShanghaiPeople's Republic of China
| | - Jinsong Wu
- Neurological Surgery DepartmentHuashan Hospital, Shanghai Medical College, Fudan UniversityShanghaiPeople's Republic of China
| | - Xiaoge Liu
- Department of AnesthesiologyHuashan Hospital, Fudan UniversityShanghaiPeople's Republic of China
| | - Jianghui Xu
- Department of AnesthesiologyHuashan Hospital, Fudan UniversityShanghaiPeople's Republic of China
| | - Jianfeng Zhang
- College of Biomedical Engineering and Instrument ScienceZhejiang UniversityHangzhouPeople's Republic of China
| | - Pengmin Qin
- School of PsychologySouth China Normal UniversityGuangzhouPeople's Republic of China
| | - Rui Dai
- State Key Laboratory of Brain and Cognitive ScienceInstitute of Biophysics, Chinese Academy of SciencesBeijingPeople's Republic of China
| | - Zhong Yang
- Department of RadiologyHuashan Hospital, Fudan UniversityShanghaiPeople's Republic of China
| | - Ying Mao
- Neurological Surgery DepartmentHuashan Hospital, Shanghai Medical College, Fudan UniversityShanghaiPeople's Republic of China
| | - Anthony G. Hudetz
- Department of Anesthesiology and Center for Consciousness ScienceUniversity of MichiganAnn ArborMichigan
| | - Georg Northoff
- Institute of Mental Health ResearchUniversity of OttawaOttawaOntarioCanada
- Center for Cognition and Brain DisordersHangzhou Normal UniversityHangzhouPeople's Republic of China
- Mental Health CentreZhejiang University School of MedicineHangzhouPeople's Republic of China
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42
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Cascella M, Bimonte S, Muzio MR. Towards a better understanding of anesthesia emergence mechanisms: Research and clinical implications. World J Methodol 2018; 8:9-16. [PMID: 30345225 PMCID: PMC6189114 DOI: 10.5662/wjm.v8.i2.9] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2018] [Revised: 08/01/2018] [Accepted: 08/26/2018] [Indexed: 02/06/2023] Open
Abstract
Emergence from anesthesia (AE) is the ending stage of anesthesia featuring the transition from unconsciousness to complete wakefulness and recovery of consciousness (RoC). A wide range of undesirable complications, including coughing, respiratory/cardiovascular events, and mental status changes such as emergence delirium, and delayed RoC, may occur during this critical phase. In general anesthesia processes, induction and AE represent a neurobiological example of "hysteresis". Indeed, AE mechanisms should not be simply considered as reverse events of those occurring in the induction phase. Anesthesia-induced loss of consciousness (LoC) and AE until RoC are quite distinct phenomena with, in part, a distinct neurobiology. Althoughanaesthetics produce LoC mostly by affecting cortical connectivity, arousal processes at the end of anesthesia are triggered by structures deep in the brain, rather than being induced within the neocortex. This work aimed to provide an overview on AE processes research, in terms of mechanisms, and EEG findings. Because most of the research in this field concerns preclinical investigations, translational suggestions and research perspectives are proposed. However, little is known about the relationship between AE neurobiology, and potential complications occurring during the emergence, and after the RoC. Thus, another scope of this review is to underline why a better understanding of AE mechanisms could have significant clinical implications, such as improving the patients' quality of recovery, and avoiding early and late postoperative complications.
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Affiliation(s)
- Marco Cascella
- Division of Anesthesia and Pain Management, Department of Supportive Care, Istituto Nazionale Tumori “Fondazione G. Pascale” - IRCSS, Naples 80131, Italy
| | - Sabrina Bimonte
- Division of Anesthesia and Pain Management, Department of Supportive Care, Istituto Nazionale Tumori “Fondazione G. Pascale” - IRCSS, Naples 80131, Italy
| | - Maria Rosaria Muzio
- Division of Infantile Neuropsychiatry, UOMI-Maternal and Infant Health, ASL NA3 SUD Torre del Greco, Naples 80059, Italy
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Sanders RD, Banks MI, Darracq M, Moran R, Sleigh J, Gosseries O, Bonhomme V, Brichant JF, Rosanova M, Raz A, Tononi G, Massimini M, Laureys S, Boly M. Propofol-induced unresponsiveness is associated with impaired feedforward connectivity in cortical hierarchy. Br J Anaesth 2018; 121:1084-1096. [PMID: 30336853 DOI: 10.1016/j.bja.2018.07.006] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2017] [Revised: 07/02/2018] [Accepted: 07/11/2018] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND Impaired consciousness has been associated with impaired cortical signal propagation after transcranial magnetic stimulation (TMS). We hypothesised that the reduced current propagation under propofol-induced unresponsiveness is associated with changes in both feedforward and feedback connectivity across the cortical hierarchy. METHODS Eight subjects underwent left occipital TMS coupled with high-density EEG recordings during wakefulness and propofol-induced unconsciousness. Spectral analysis was applied to responses recorded from sensors overlying six hierarchical cortical sources involved in visual processing. Dynamic causal modelling (DCM) of induced time-frequency responses and evoked response potentials were used to investigate propofol's effects on connectivity between regions. RESULTS Sensor space analysis demonstrated that propofol reduced both induced and evoked power after TMS in occipital, parietal, and frontal electrodes. Bayesian model selection supported a DCM with hierarchical feedforward and feedback connections. DCM of induced EEG responses revealed that the primary effect of propofol was impaired feedforward responses in cross-frequency theta/alpha-gamma coupling and within frequency theta coupling (F contrast, family-wise error corrected P<0.05). An exploratory analysis (thresholded at uncorrected P<0.001) also suggested that propofol impaired feedforward and feedback beta band coupling. Post hoc analyses showed impairments in all feedforward connections and one feedback connection from parietal to occipital cortex. DCM of the evoked response potential showed impaired feedforward connectivity between left-sided occipital and parietal cortex (T contrast P=0.004, Bonferroni corrected). CONCLUSIONS Propofol-induced loss of consciousness is associated with impaired hierarchical feedforward connectivity assessed by EEG after occipital TMS.
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Affiliation(s)
- R D Sanders
- Department of Anesthesiology, University of Wisconsin, Madison, WI, USA.
| | - M I Banks
- Department of Anesthesiology, University of Wisconsin, Madison, WI, USA
| | - M Darracq
- Department of Anesthesiology, University of Wisconsin, Madison, WI, USA
| | - R Moran
- Faculty of Engineering, University of Bristol, Bristol, UK
| | - J Sleigh
- Department of Anaesthesia, Waikato Hospital, Hamilton, New Zealand
| | - O Gosseries
- Coma Science Group, GIGA-consciousness, University of Liège, Liège, Belgium
| | - V Bonhomme
- Anesthesia and Intensive Care Laboratory, GIGA-Consciousness, University of Liège, Liège, Belgium; Department of Anestheisa and ICM, CHU Liège, Liège, Belgium; University Department of Anesthesia and ICM, CHR Citadelle, Liège, Belgium
| | - J F Brichant
- Department of Anestheisa and ICM, CHU Liège, Liège, Belgium
| | - M Rosanova
- Department of Biomedical and Clinical Sciences, University of Milan, Milan, Italy
| | - A Raz
- Department of Anesthesiology, University of Wisconsin, Madison, WI, USA; Rambam Healthcare Campus, Haifa, Israel
| | - G Tononi
- Department of Psychiatry, University of Wisconsin, Madison, WI, USA
| | - M Massimini
- Department of Biomedical and Clinical Sciences, University of Milan, Milan, Italy
| | - S Laureys
- Coma Science Group, GIGA-consciousness, University of Liège, Liège, Belgium; Department of Neurology, CHU Liège, Liège, Belgium
| | - M Boly
- Department of Psychiatry, University of Wisconsin, Madison, WI, USA; Department of Neurology, University of Wisconsin, Madison, WI, USA
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44
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Schrödinger's cat: anaesthetised and not! Br J Anaesth 2018; 120:424-428. [DOI: 10.1016/j.bja.2017.11.068] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2017] [Revised: 11/10/2017] [Accepted: 11/14/2017] [Indexed: 01/17/2023] Open
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45
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Spatio-temporal dynamics of multimodal EEG-fNIRS signals in the loss and recovery of consciousness under sedation using midazolam and propofol. PLoS One 2017; 12:e0187743. [PMID: 29121108 PMCID: PMC5679575 DOI: 10.1371/journal.pone.0187743] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2017] [Accepted: 10/25/2017] [Indexed: 12/29/2022] Open
Abstract
On sedation motivated by the clinical needs for safety and reliability, recent studies have attempted to identify brain-specific signatures for tracking patient transition into and out of consciousness, but the differences in neurophysiological effects between 1) the sedative types and 2) the presence/absence of surgical stimulations still remain unclear. Here we used multimodal electroencephalography–functional near-infrared spectroscopy (EEG–fNIRS) measurements to observe electrical and hemodynamic responses during sedation simultaneously. Forty healthy volunteers were instructed to push the button to administer sedatives in response to auditory stimuli every 9–11 s. To generally illustrate brain activity at repetitive transition points at the loss of consciousness (LOC) and the recovery of consciousness (ROC), patient-controlled sedation was performed using two different sedatives (midazolam (MDZ) and propofol (PPF)) under two surgical conditions. Once consciousness was lost via sedatives, we observed gradually increasing EEG power at lower frequencies (<15 Hz) and decreasing power at higher frequencies (>15 Hz), as well as spatially increased EEG powers in the delta and lower alpha bands, and particularly also in the upper alpha rhythm, at the frontal and parieto-occipital areas over time. During ROC from unconsciousness, these spatio-temporal changes were reversed. Interestingly, the level of consciousness was switched on/off at significantly higher effect-site concentrations of sedatives in the brain according to the use of surgical stimuli, but the spatio-temporal EEG patterns were similar, regardless of the sedative used. We also observed sudden phase shifts in fronto-parietal connectivity at the LOC and the ROC as critical points. fNIRS measurement also revealed mild hemodynamic fluctuations. Compared with general anesthesia, our results provide insights into critical hallmarks of sedative-induced (un)consciousness, which have similar spatio-temporal EEG-fNIRS patterns regardless of the stage and the sedative used.
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Pavel B, Acatrinei CA, Corbu M, Zahiu CMD, Rosca AE, Zagrean L, Zagrean AM. ECoG spectrum changes at different xenon-isoflurane anaesthesia depths. Rom J Anaesth Intensive Care 2017; 24:41-46. [PMID: 28913497 DOI: 10.21454/rjaic.7518.241.pav] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022] Open
Abstract
BACKGROUND AND AIMS The purpose of this study is to assess the frontal and parietal ECoG spectrum (gamma range) changes during isoflurane and combined xenon-isoflurane anaesthesia in rats. METHODS Experiments were carried out on four adult male Sprague-Dawley rats (250-300 g). The anaesthesia was induced with isoflurane and maintained with isoflurane and a xenon-isoflurane mixture. The rats were maintained at two different anaesthetic depths: light (isoflurane anaesthesia) and deep (isoflurane and xenon-isoflurane anaesthesia). The frontal and the parietal cortical activity was assessed by computing the median frequency, spectral edge frequency and functional connectivity between these two areas during light and deep anaesthesia. RESULTS We noticed a decrease in cortical connectivity under deep isoflurane anaesthesia and an increase in connectivity under deep xenon-isoflurane anaesthesia. Moreover, during xenon-isoflurane anaesthesia, a trend of regularity of electro-cortical activity was present compared with isoflurane anaesthesia. CONCLUSIONS Xenon-isoflurane deep anaesthesia demonstrated a series of specific ECoG features regarding frontoparietal functional connectivity (gamma range connectivity increase) and regularity of the electrocortical activity compared with isoflurane anaesthesia.
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Affiliation(s)
- Bogdan Pavel
- "Carol Davila" University of Medicine and Pharmacy, Division of Physiology and Fundamental Neurosciences, Bucharest, Romania.,Clinical Emergency Hospital of Plastic Surgery and Burns, Bucharest, Romania
| | - Camelia Alexandra Acatrinei
- "Carol Davila" University of Medicine and Pharmacy, Division of Physiology and Fundamental Neurosciences, Bucharest, Romania
| | - Maria Corbu
- "Carol Davila" University of Medicine and Pharmacy, Division of Physiology and Fundamental Neurosciences, Bucharest, Romania
| | - Carmen Mihaela Denise Zahiu
- "Carol Davila" University of Medicine and Pharmacy, Division of Physiology and Fundamental Neurosciences, Bucharest, Romania
| | - Adrian Eugen Rosca
- "Carol Davila" University of Medicine and Pharmacy, Division of Physiology and Fundamental Neurosciences, Bucharest, Romania
| | - Leon Zagrean
- "Carol Davila" University of Medicine and Pharmacy, Division of Physiology and Fundamental Neurosciences, Bucharest, Romania
| | - Ana-Maria Zagrean
- "Carol Davila" University of Medicine and Pharmacy, Division of Physiology and Fundamental Neurosciences, Bucharest, Romania
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Neurophysiologic Correlates of Ketamine Sedation and Anesthesia: A High-density Electroencephalography Study in Healthy Volunteers. Anesthesiology 2017; 127:58-69. [PMID: 28486269 DOI: 10.1097/aln.0000000000001671] [Citation(s) in RCA: 79] [Impact Index Per Article: 9.9] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
BACKGROUND Previous studies have demonstrated inconsistent neurophysiologic effects of ketamine, although discrepant findings might relate to differences in doses studied, brain regions analyzed, coadministration of other anesthetic medications, and resolution of the electroencephalograph. The objective of this study was to characterize the dose-dependent effects of ketamine on cortical oscillations and functional connectivity. METHODS Ten healthy human volunteers were recruited for study participation. The data were recorded using a 128-channel electroencephalograph during baseline consciousness, subanesthetic dosing (0.5 mg/kg over 40 min), anesthetic dosing (1.5 mg/kg bolus), and recovery. No other sedative or anesthetic medications were administered. Spectrograms, topomaps, and functional connectivity (weighted and directed phase lag index) were computed and analyzed. RESULTS Frontal theta bandwidth power increased most dramatically during ketamine anesthesia (mean power ± SD, 4.25 ± 1.90 dB) compared to the baseline (0.64 ± 0.28 dB), subanesthetic (0.60 ± 0.30 dB), and recovery (0.68 ± 0.41 dB) states; P < 0.001. Gamma power also increased during ketamine anesthesia. Weighted phase lag index demonstrated theta phase locking within anterior regions (0.2349 ± 0.1170, P < 0.001) and between anterior and posterior regions (0.2159 ± 0.1538, P < 0.01) during ketamine anesthesia. Alpha power gradually decreased with subanesthetic ketamine, and anterior-to-posterior directed connectivity was maximally reduced (0.0282 ± 0.0772) during ketamine anesthesia compared to all other states (P < 0.05). CONCLUSIONS Ketamine anesthesia correlates most clearly with distinct changes in the theta bandwidth, including increased power and functional connectivity. Anterior-to-posterior connectivity in the alpha bandwidth becomes maximally depressed with anesthetic ketamine administration, suggesting a dose-dependent effect.
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Perreault ML, Fan T, Banasikowski TJ, Grace AA, George SR. The atypical dopamine receptor agonist SKF 83959 enhances hippocampal and prefrontal cortical neuronal network activity in a rat model of cognitive dysfunction. Eur J Neurosci 2017; 46:2015-2025. [PMID: 28677227 DOI: 10.1111/ejn.13635] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2017] [Revised: 06/23/2017] [Accepted: 06/25/2017] [Indexed: 12/11/2022]
Abstract
Deficits in neuronal network synchrony in hippocampus and prefrontal cortex have been widely demonstrated in disorders of cognitive dysfunction, including schizophrenia and Alzheimer's disease. The atypical dopamine agonist SKF 83959 has been shown to increase brain-derived neurotrophic factor signalling and suppress activity of glycogen synthase kinase-3 in PFC, two processes important to learning and memory. The purpose of this study was to therefore evaluate the impact of SKF 83959 on oscillatory deficits in methylazoxymethanol acetate (MAM) rat model of schizophrenia. To achieve this, local field potentials were recorded simultaneously from the hippocampus and prefrontal cortex of anesthetized rats at 15 and 90 min following both acute and repeated administration of SKF 83959 (0.4 mg/kg). In MAM rats, but not controls, repeated SKF 83959 treatment increased signal amplitude in hippocampus and enhanced the spectral power of low frequency delta and theta oscillations in this region. In PFC, SKF 83959 increased delta, theta and gamma spectral power. Increased HIP-PFC theta coherence was also evident following acute and repeated SKF 83959. In apparent contradiction to these oscillatory effects, in MAM rats, SKF 83959 inhibited spatial learning and induced a significant increase in thigmotactic behaviour. These findings have uncovered a previously unknown role for SKF 83959 in the positive regulation of hippocampal-prefrontal cortical oscillatory network activity. As SKF 83959 is known to have affinity for a number of receptors, delineating the receptor mechanisms that mediate the positive drug effects on neuronal oscillations could have significant future implications in disorders associated with cognitive dysfunction.
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Affiliation(s)
- Melissa L Perreault
- Department of Pharmacology and Toxicology, University of Toronto, Medical Sciences Bldg. Room 4358, 1 King's College Circle, Toronto, ON, M5S 1A8, Canada
| | - Theresa Fan
- Department of Pharmacology and Toxicology, University of Toronto, Medical Sciences Bldg. Room 4358, 1 King's College Circle, Toronto, ON, M5S 1A8, Canada
| | - Tomek J Banasikowski
- Departments of Neuroscience, Psychiatry and Psychology, University of Pittsburgh, Pittsburgh, PA, USA
| | - Anthony A Grace
- Departments of Neuroscience, Psychiatry and Psychology, University of Pittsburgh, Pittsburgh, PA, USA
| | - Susan R George
- Department of Pharmacology and Toxicology, University of Toronto, Medical Sciences Bldg. Room 4358, 1 King's College Circle, Toronto, ON, M5S 1A8, Canada.,Department of Medicine, University of Toronto, Toronto, ON, Canada
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Gallotto S, Sack AT, Schuhmann T, de Graaf TA. Oscillatory Correlates of Visual Consciousness. Front Psychol 2017; 8:1147. [PMID: 28736543 PMCID: PMC5500655 DOI: 10.3389/fpsyg.2017.01147] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2017] [Accepted: 06/23/2017] [Indexed: 11/21/2022] Open
Abstract
Conscious experiences are linked to activity in our brain: the neural correlates of consciousness (NCC). Empirical research on these NCCs covers a wide range of brain activity signals, measures, and methodologies. In this paper, we focus on spontaneous brain oscillations; rhythmic fluctuations of neuronal (population) activity which can be characterized by a range of parameters, such as frequency, amplitude (power), and phase. We provide an overview of oscillatory measures that appear to correlate with conscious perception. We also discuss how increasingly sophisticated techniques allow us to study the causal role of oscillatory activity in conscious perception (i.e., ‘entrainment’). This review of oscillatory correlates of consciousness suggests that, for example, activity in the alpha-band (7–13 Hz) may index, or even causally support, conscious perception. But such results also showcase an increasingly acknowledged difficulty in NCC research; the challenge of separating neural activity necessary for conscious experience to arise (prerequisites) from neural activity underlying the conscious experience itself (substrates) or its results (consequences).
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Affiliation(s)
- Stefano Gallotto
- Department of Cognitive Neuroscience, Faculty of Psychology and Neuroscience, Maastricht UniversityMaastricht, Netherlands.,Maastricht Brain Imaging CentreMaastricht, Netherlands
| | - Alexander T Sack
- Department of Cognitive Neuroscience, Faculty of Psychology and Neuroscience, Maastricht UniversityMaastricht, Netherlands.,Maastricht Brain Imaging CentreMaastricht, Netherlands
| | - Teresa Schuhmann
- Department of Cognitive Neuroscience, Faculty of Psychology and Neuroscience, Maastricht UniversityMaastricht, Netherlands.,Maastricht Brain Imaging CentreMaastricht, Netherlands
| | - Tom A de Graaf
- Department of Cognitive Neuroscience, Faculty of Psychology and Neuroscience, Maastricht UniversityMaastricht, Netherlands.,Maastricht Brain Imaging CentreMaastricht, Netherlands
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Abstract
A quest for a systems-level neuroscientific basis of anesthetic-induced loss and return of consciousness has been in the forefront of research for the past 2 decades. Recent advances toward the discovery of underlying mechanisms have been achieved using experimental electrophysiology, multichannel electroencephalography, magnetoencephalography, and functional magnetic resonance imaging. By the careful dosing of various volatile and IV anesthetic agents to the level of behavioral unresponsiveness, both specific and common changes in functional and effective connectivity across large-scale brain networks have been discovered and interpreted in the context of how the synthesis of neural information might be affected during anesthesia. The results of most investigations to date converge toward the conclusion that a common neural correlate of anesthetic-induced unresponsiveness is a consistent depression or functional disconnection of lateral frontoparietal networks, which are thought to be critical for consciousness of the environment. A reduction in the repertoire of brain states may contribute to the anesthetic disruption of large-scale information integration leading to unconsciousness. In future investigations, a systematic delineation of connectivity changes with multiple anesthetics using the same experimental design, and the same analytical method will be desirable. The critical neural events that account for the transition between responsive and unresponsive states should be assessed at similar anesthetic doses just below and above the loss or return of responsiveness. There will also be a need to identify a robust, sensitive, and reliable measure of information transfer. Ultimately, finding a behavior-independent measure of subjective experience that can track covert cognition in unresponsive subjects and a delineation of causal factors versus correlated events will be essential to understand the neuronal basis of human consciousness and unconsciousness.
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