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Manohara N, Ferrari A, Greenblatt A, Berardino A, Peixoto C, Duarte F, Moyiaeri Z, Robba C, Nascimento FA, Kreuzer M, Vacas S, Lobo FA. Electroencephalogram monitoring during anesthesia and critical care: a guide for the clinician. J Clin Monit Comput 2025; 39:315-348. [PMID: 39704777 DOI: 10.1007/s10877-024-01250-2] [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: 10/21/2024] [Accepted: 12/05/2024] [Indexed: 12/21/2024]
Abstract
Perioperative anesthetic, surgical and critical careinterventions can affect brain physiology and overall brain health. The clinical utility of electroencephalogram (EEG) monitoring in anesthesia and intensive care settings is multifaceted, offering critical insights into the level of consciousness and depth of anesthesia, facilitating the titration of anesthetic doses, and enabling the detection of ischemic events and epileptic activity. Additionally, EEG monitoring can aid in predicting perioperative neurocognitive disorders, assessing the impact of systemic insults on cerebral function, and informing neuroprognostication. This review provides a comprehensive overview of the fundamental principles of electroencephalography, including the foundations of processed and quantitative electroencephalography. It further explores the characteristic EEG signatures associated wtih anesthetic drugs, the interpretation of the EEG data during anesthesia, and the broader clinical benefits and applications of EEG monitoring in both anesthetic practice and intensive care environments.
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Affiliation(s)
- Nitin Manohara
- Division of Anesthesiology, Cleveland Clinic Abu Dhabi, Integrated Hospital Care Institute, Abu Dhabi, United Arab Emirates
| | | | - Adam Greenblatt
- Department of Neurology, Washington University in St Louis, St Louis, MO, USA
| | - Andrea Berardino
- Department of Surgical Sciences and Integrated Diagnostics, University of Genoa, Genoa, Italy
| | | | - Flávia Duarte
- Department of Anesthesiology, Hospital Garcia de Orta, Almada, Portugal
| | - Zahra Moyiaeri
- Division of Anesthesiology, Cleveland Clinic Abu Dhabi, Integrated Hospital Care Institute, Abu Dhabi, United Arab Emirates
| | | | - Fabio A Nascimento
- Department of Neurology, Washington University in St Louis, St Louis, MO, USA
| | - Matthias Kreuzer
- Department of Anesthesiology and Intensive Care Medicine, School of Medicine and Health, Technical University of Munich, Munich, Germany
| | - Susana Vacas
- Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Francisco A Lobo
- Division of Anesthesiology, Cleveland Clinic Abu Dhabi, Integrated Hospital Care Institute, Abu Dhabi, United Arab Emirates.
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Yang W, Jian M, Wang X, Zhou Y, Liang Y, Chen Y, Li Y, Li K, Ma B, Liu H, Han R. Dynamic Cortical Connectivity During Propofol Sedation in Glioma Patients. J Neurosurg Anesthesiol 2025; 37:166-173. [PMID: 38577956 DOI: 10.1097/ana.0000000000000964] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2023] [Accepted: 02/26/2024] [Indexed: 04/06/2024]
Abstract
BACKGROUND The behavioral manifestations and neurophysiological responses to sedation can assist in understanding brain function after neurological damage, and can be described by cortical functional connectivity. Glioma patients may experience neurological deficits that are not clinically detectable before sedation. We hypothesized that patients with gliomas exhibit distinct cortical connectivity patterns compared to non-neurosurgical patients during sedation. METHODS This is a secondary analysis of a previously published prospective observational study. Patients scheduled for resection of supratentorial glioma (n=21) or a non-neurosurgical procedure (n=21) under general anesthesia were included in this study. Frontal electroencephalography (EEG) signals were recorded at different sedation levels as assessed by the Observer Assessment of Alertness/Sedation (OAA/S) score. Kernel principal component analysis and k -means clustering were used to determine possible temporal dynamics from the weighted phase lag index characteristics. RESULTS Ten EEG connectivity states were identified by clustering (76% consistency), each with unique properties. At OAA/S 3, the median (Q1, Q3) occurrence rates of state 6 (glioma group, 0.110 [0.083, 0.155] vs. control group, 0.070 [0.030, 0.110]; P =0.008) and state 7 (glioma group, 0.105 [0.083, 0.148] vs. control group: 0.065 [0.038, 0.090]; P =0.001), which are dominated by beta connectivity, were significantly different between the 2 groups, reflecting differential conversion of the beta band between the left and right brain regions. In addition, the temporal dynamics of the brain's functional connectivity was also reflected in the transition relationships between metastable states. CONCLUSIONS There were differences in EEG functional connectivity, which is dynamic, between the glioma and nonglioma groups during sedation.
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Affiliation(s)
- Wanning Yang
- Department of Anesthesiology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
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Li X, Liu D, Li Z, Wang R, Li X, Zhou T. Spatiospectral dynamics of electroencephalography patterns during propofol-induced alterations of consciousness states. Neuroimage 2025; 309:121084. [PMID: 39952488 DOI: 10.1016/j.neuroimage.2025.121084] [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: 10/03/2024] [Revised: 01/29/2025] [Accepted: 02/10/2025] [Indexed: 02/17/2025] Open
Abstract
Altered consciousness induced by anesthetics is characterized by distinct spatial and spectral neural dynamics that are readily apparent in the human electroencephalogram. Despite considerable study, we remain uncertain which brain regions and neural oscillations are involved, as well as how they are impacted when consciousness is disrupted. The experimental data was obtained from the open-access dataset, which contains pre-processed EEG data recorded from 20 healthy participants during propofol sedation. Using unsupervised machine learning methods (i.e., non-negative matrix factorization, NMF), we investigated the spatiospectral dynamic evolution of brain activity from awake to sedation and back induced by propofol in healthy research volunteers. Our methods yielded six dynamical patterns that continuously reflect the neural activity changes in specific brain regions and frequency bands under propofol sedation. Temporal dynamic analyses showed that differences in alpha oscillation patterns were less pronounced in response group than drowsy group, with hemispheric asymmetry in posterior occipital lobe over the course of the sedation procedure. We designed an index 'hemispheric lateralization modulation of alpha [HLM(α)]' to measure asymmetry during awake state and predicting individual variability in propofol-induced alterations of consciousness states, obtaining prediction AUC of 0.8462. We present an alpha modulation index which characterizes how these patterns track the transition from awake to sedation as a function of increasing dosage. Our study reveals dynamics indices that track the evolution of neurophysiological of propofol on brain circuits. Analyzing the spatiospectral dynamics influenced by propofol provides valuable understanding of the mechanisms of these agents and strategies for monitoring and precisely controlling the level of consciousness in patients under sedation and general anesthesia.
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Affiliation(s)
- Xuan Li
- Department of Anesthesiology, The Fifth Affiliated Hospital, Sun Yat-Sen University, Zhuhai, Guangdong, PR China
| | - Dezhao Liu
- Department of Anesthesiology, The Fifth Affiliated Hospital, Sun Yat-Sen University, Zhuhai, Guangdong, PR China
| | - Zheng Li
- Department of Psychology, Faculty of Arts and Sciences, Center for Cognition and Neuroergonomics, State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University at Zhuhai, Zhuhai, PR China; Beijing Key Laboratory of Applied Experimental Psychology, National Demonstration Center for Experimental Psychology Education (Beijing Normal University), Faculty of Psychology, Beijing Normal University, PR China
| | - Rui Wang
- Department of Psychology, Faculty of Arts and Sciences, Center for Cognition and Neuroergonomics, State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University at Zhuhai, Zhuhai, PR China
| | - Xiaoli Li
- School of Automation Science and Engineering, South China University of Technology, & Pazhou Laboratory, Guangzhou, PR China.
| | - Tianyi Zhou
- Department of Psychology, Faculty of Arts and Sciences, Center for Cognition and Neuroergonomics, State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University at Zhuhai, Zhuhai, PR China; Beijing Key Laboratory of Applied Experimental Psychology, National Demonstration Center for Experimental Psychology Education (Beijing Normal University), Faculty of Psychology, Beijing Normal University, PR China.
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Freedman IG, Boncompte G, Qu JZ, Khawaja ZQ, Turco I, Mueller A, Wiredu K, McKay TB, Westover MB, Pedemonte JC, Akeju O. Anesthesia-induced electroencephalogram oscillations and perioperative outcomes in older adults undergoing cardiac surgery. J Clin Anesth 2025; 102:111770. [PMID: 39921932 PMCID: PMC11953626 DOI: 10.1016/j.jclinane.2025.111770] [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: 01/22/2024] [Revised: 12/07/2024] [Accepted: 01/29/2025] [Indexed: 02/10/2025]
Abstract
BACKGROUND Electroencephalogram oscillations during general anesthesia may change as a function of cognitive and physical health. This study aimed to characterize associations between anesthesia-induced oscillations and postoperative outcomes in cardiac surgery patients over 60 years. METHODS This was a prespecified secondary data analysis from the Minimizing Intensive Care Unit Dysfunction with Dexmedetomidine-induced Sleep (MINDDS) study. Participants were admitted from home for elective cardiac surgery with cardiopulmonary bypass. The primary outcome was postoperative delirium obtained using the Confusion Assessment Method. Secondary outcomes were non-home discharge and 30-day readmission. The exposure of interest was alpha power measured during the maintenance phase of isoflurane-general anesthesia. Confounding cognitive and physical health variables were collected. RESULTS Of 394 participants in the MINDDS study, 302 had analyzable electroencephalograms. The incidence of postoperative delirium was 11.1 %. Odds of postoperative delirium decreased by 14 % for every decibel increase in alpha power (OR 0.86, 95 % CI: 0.78 to 0.95; P = 0.004). This finding was not significant in adjusted analysis (ORadj 0.92, 95 % CI: 0.81 to 1.03; P = 0.154). Non-home discharge setting findings were not associated with alpha power. The odds of 30-day readmission decreased by 20 % for every decibel increase in alpha power (ORadj 0.80, 95 % CI: 0.71 to 0.91; P < 0.001). Findings were conserved in exploratory and sensitivity analyses. CONCLUSIONS In this study anesthesia-induced oscillations were associated with postoperative outcomes; however, these were not independently associated with delirium or discharge disposition after considering preoperative cognitive and physical health. These oscillations were robustly associated with 30-day readmission however, which may help anesthesiologists identify high-risk patients, offering benefits beyond the operating room. CLINICAL TRIAL REGISTRATION Registration Number: NCT02856594.
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Affiliation(s)
- Isaac G Freedman
- Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
| | - Gonzalo Boncompte
- Neurodynamics of Cognition Laboratory, Department of Psychiatry, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile; División de Anestesiología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Jason Z Qu
- Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Zain Q Khawaja
- Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Case Western Reserve University School of Medicine, Cleveland, OH, USA
| | - Isabella Turco
- Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Ariel Mueller
- Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Kwame Wiredu
- Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Tina B McKay
- Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - M Brandon Westover
- Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA, USA
| | - Juan C Pedemonte
- División de Anestesiología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile; Programa de Farmacología y Toxicología, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Oluwaseun Akeju
- Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
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Ostertag J, Zanner R, Schneider G, Kreuzer M. Permutation Entropy Does Not Track the Electroencephalogram-Related Manifestations of Paradoxical Excitation During Propofol-Induced Loss of Responsiveness: Results From a Prospective Observational Cohort Study. Anesth Analg 2025; 140:136-144. [PMID: 38412114 DOI: 10.1213/ane.0000000000006919] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/29/2024]
Abstract
BACKGROUND During the anesthetic-induced loss of responsiveness (LOR), a "paradoxical excitation" with activation of β-frequencies in the electroencephalogram (EEG) can be observed. Thus, spectral parameters-as widely used in commercial anesthesia monitoring devices-may mistakenly indicate that patients are awake when they are actually losing responsiveness. Nonlinear time-domain parameters such as permutation entropy (PeEn) may analyze additional EEG information and appropriately reflect the change in cognitive state during the transition. Determining which parameters correctly track the level of anesthesia is essential for designing monitoring algorithms but may also give valuable insight regarding the signal characteristics during state transitions. METHODS EEG data from 60 patients who underwent general anesthesia were extracted and analyzed around LOR. We derived the following information from the power spectrum: (i) spectral band power, (ii) the spectral edge frequency as well as 2 parameters known to be incorporated in monitoring systems, (iii) beta ratio, and (iv) spectral entropy. We also calculated (v) PeEn as a time-domain parameter. We used Friedman's test and Bonferroni correction to track how the parameters change over time and the area under the receiver operating curve to separate the power spectra between time points. RESULTS Within our patient collective, we observed a "paradoxical excitation" around the time of LOR as indicated by increasing beta-band power. Spectral edge frequency and spectral entropy values increased from 19.78 [10.25-34.18] Hz to 25.39 [22.46-30.27] Hz ( P = .0122) and from 0.61 [0.54-0.75] to 0.77 [0.64-0.81] ( P < .0001), respectively, before LOR, indicating a (paradoxically) higher level of high-frequency activity. PeEn and beta ratio values decrease from 0.78 [0.77-0.82] to 0.76 [0.73-0.81] ( P < .0001) and from -0.74 [-1.14 to -0.09] to -2.58 [-2.83 to -1.77] ( P < .0001), respectively, better reflecting the state transition into anesthesia. CONCLUSIONS PeEn and beta ratio seem suitable parameters to monitor the state transition during anesthesia induction. The decreasing PeEn values suggest a reduction of signal complexity and information content, which may very well describe the clinical situation at LOR. The beta ratio mainly focuses on the loss of power in the gamma-band. PeEn, in particular, may present a single parameter capable of tracking the LOR transition without being affected by paradoxical excitation.
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Affiliation(s)
- Julian Ostertag
- From the Department of Anesthesiology & Intensive Care, School of Medicine, Technical University of Munich, Munich, Germany
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Vedururu Srinivas A, Canavier CC. Existence and stability criteria for global synchrony and for synchrony in two alternating clusters of pulse-coupled oscillators updated to include conduction delays. Math Biosci 2024; 378:109335. [PMID: 39491588 PMCID: PMC11614676 DOI: 10.1016/j.mbs.2024.109335] [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: 08/26/2024] [Revised: 10/22/2024] [Accepted: 10/25/2024] [Indexed: 11/05/2024]
Abstract
Phase Response Curves (PRCs) have been useful in determining and analyzing various phase-locking modes in networks of oscillators under pulse-coupling assumptions, as reviewed in Mathematical Biosciences, 226:77-96, 2010. Here, we update that review to include progress since 2010 on pulse coupled oscillators with conduction delays. We then present original results that extend the derivation of the criteria for stability of global synchrony in networks of pulse-coupled oscillators to include conduction delays. We also incorporate conduction delays to extend previous studies that showed how an alternating firing pattern between two synchronized clusters could enforce within-cluster synchrony, even for clusters unable to synchronize themselves in isolation. To obtain these results, we used self-connected neurons to represent clusters. These results greatly extend the applicability of the stability analyses to networks of pulse-coupled oscillators since conduction delays are ubiquitous and strongly impact the stability of synchrony. Although these analyses only strictly apply to identical oscillators with identical connections to other oscillators, the principles are general and suggest how to promote or impede synchrony in physiological networks of neurons, for example. Heterogeneity can be interpreted as a form of frozen noise, and approximate synchrony can be sustained despite heterogeneity. The pulse-coupled oscillator model can not only be used to describe biological neuronal networks but also cardiac pacemakers, lasers, fireflies, artificial neural networks, social self-organization, and wireless sensor networks.
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Affiliation(s)
- Ananth Vedururu Srinivas
- Louisiana State University Health Sciences Center, Department of Cell Biology and Anatomy, New Orleans, LA, 70112, USA
| | - Carmen C Canavier
- Louisiana State University Health Sciences Center, Department of Cell Biology and Anatomy, New Orleans, LA, 70112, USA.
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Wilkinson CL, Yankowitz LD, Chao JY, Gutiérrez R, Rhoades JL, Shinnar S, Purdon PL, Nelson CA. Developmental trajectories of EEG aperiodic and periodic components in children 2-44 months of age. Nat Commun 2024; 15:5788. [PMID: 38987558 PMCID: PMC11237135 DOI: 10.1038/s41467-024-50204-4] [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: 08/11/2023] [Accepted: 07/02/2024] [Indexed: 07/12/2024] Open
Abstract
The development of neural circuits has long-lasting effects on brain function, yet our understanding of early circuit development in humans remains limited. Here, periodic EEG power features and aperiodic components were examined from longitudinal EEGs collected from 592 healthy 2-44 month-old infants, revealing age-dependent nonlinear changes suggestive of distinct milestones in early brain maturation. Developmental changes in periodic peaks include (1) the presence and then absence of a 9-10 Hz alpha peak between 2-6 months, (2) nonlinear changes in high beta peaks (20-30 Hz) between 4-18 months, and (3) the emergence of a low beta peak (12-20 Hz) in some infants after six months of age. We hypothesized that the emergence of the low beta peak may reflect maturation of thalamocortical network development. Infant anesthesia studies observe that GABA-modulating anesthetics do not induce thalamocortical mediated frontal alpha coherence until 10-12 months of age. Using a small cohort of infants (n = 23) with EEG before and during GABA-modulating anesthesia, we provide preliminary evidence that infants with a low beta peak have higher anesthesia-induced alpha coherence compared to those without a low beta peak.
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Affiliation(s)
- Carol L Wilkinson
- Division of Developmental Medicine, Boston Children's Hospital, Boston, MA, USA.
- Harvard Medical School, Boston, MA, USA.
| | - Lisa D Yankowitz
- Division of Developmental Medicine, Boston Children's Hospital, Boston, MA, USA
- Harvard Medical School, Boston, MA, USA
| | - Jerry Y Chao
- Department of Anesthesiology, Montefiore Medical Center, Children's Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, NY, USA
| | - Rodrigo Gutiérrez
- Departamento de Anestesia y Medicina Perioperatoria, Hospital Clínico de la Universidad de Chile, Santiago, Chile
- Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA, USA
| | - Jeff L Rhoades
- Department of Neurobiology, Harvard Medical School, Boston, MA, USA
- Program in Neuroscience, Division of Medical Sciences, Graduate School of Arts and Sciences, Harvard University, Cambridge, MA, USA
| | - Shlomo Shinnar
- The Saul R. Korey Department of Neurology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA
- Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA
| | - Patrick L Purdon
- Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA, USA
| | - Charles A Nelson
- Division of Developmental Medicine, Boston Children's Hospital, Boston, MA, USA
- Harvard Medical School, Boston, MA, USA
- Harvard Graduate School of Education, Cambridge, MA, USA
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Thum JA, Malekmohammadi M, Toker D, Sparks H, Alijanpourotaghsara A, Choi JW, Hudson AE, Monti MM, Pouratian N. Globus pallidus externus drives increase in network-wide alpha power with propofol-induced loss-of-consciousness in humans. Cereb Cortex 2024; 34:bhae243. [PMID: 38850214 PMCID: PMC11161864 DOI: 10.1093/cercor/bhae243] [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: 10/19/2023] [Revised: 05/16/2024] [Accepted: 05/29/2024] [Indexed: 06/10/2024] Open
Abstract
States of consciousness are likely mediated by multiple parallel yet interacting cortico-subcortical recurrent networks. Although the mesocircuit model has implicated the pallidocortical circuit as one such network, this circuit has not been extensively evaluated to identify network-level electrophysiological changes related to loss of consciousness (LOC). We characterize changes in the mesocircuit in awake versus propofol-induced LOC in humans by directly simultaneously recording from sensorimotor cortices (S1/M1) and globus pallidus interna and externa (GPi/GPe) in 12 patients with Parkinson disease undergoing deep brain stimulator implantation. Propofol-induced LOC is associated with increases in local power up to 20 Hz in GPi, 35 Hz in GPe, and 100 Hz in S1/M1. LOC is likewise marked by increased pallidocortical alpha synchrony across all nodes, with increased alpha/low beta Granger causal (GC) flow from GPe to all other nodes. In contrast, LOC is associated with decreased network-wide beta coupling and beta GC from M1 to the rest of the network. Results implicate an important and possibly central role of GPe in mediating LOC-related increases in alpha power, supporting a significant role of the GPe in modulating cortico-subcortical circuits for consciousness. Simultaneous LOC-related suppression of beta synchrony highlights that distinct oscillatory frequencies act independently, conveying unique network activity.
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Affiliation(s)
- Jasmine A Thum
- Department of Neurosurgery, University of California Los Angeles, 300 Stein Plaza, Suite 540, Los Angeles, CA 90095, United States
| | - Mahsa Malekmohammadi
- Department of Neurosurgery, University of California Los Angeles, 300 Stein Plaza, Suite 540, Los Angeles, CA 90095, United States
| | - Daniel Toker
- Department of Psychology, University of California, Los Angeles, 6522 Pritzker Hall, Los Angeles, CA 90095, United States
| | - Hiro Sparks
- Department of Neurosurgery, University of California Los Angeles, 300 Stein Plaza, Suite 540, Los Angeles, CA 90095, United States
| | - Amirreza Alijanpourotaghsara
- Department of Neurological Surgery, UT Southwestern Medical Center, 5323 Harry Hines Blvd MC8855, Dallas, TX 75390, United States
| | - Jeong Woo Choi
- Department of Neurological Surgery, UT Southwestern Medical Center, 5323 Harry Hines Blvd MC8855, Dallas, TX 75390, United States
| | - Andrew E Hudson
- Department of Anesthesiology, University of California, Los Angeles, 747 Westwood Plaza, Los Angeles, CA 90095, United States
| | - Martin M Monti
- Department of Neurosurgery, University of California Los Angeles, 300 Stein Plaza, Suite 540, Los Angeles, CA 90095, United States
- Department of Psychology, University of California, Los Angeles, 6522 Pritzker Hall, Los Angeles, CA 90095, United States
| | - Nader Pouratian
- Department of Neurological Surgery, UT Southwestern Medical Center, 5323 Harry Hines Blvd MC8855, Dallas, TX 75390, United States
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Obert DP, Killing D, Happe T, Tamas P, Altunkaya A, Dragovic SZ, Kreuzer M, Schneider G, Fenzl T. Substance specific EEG patterns in mice undergoing slow anesthesia induction. BMC Anesthesiol 2024; 24:167. [PMID: 38702608 PMCID: PMC11067159 DOI: 10.1186/s12871-024-02552-3] [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: 03/06/2024] [Accepted: 04/26/2024] [Indexed: 05/06/2024] Open
Abstract
The exact mechanisms and the neural circuits involved in anesthesia induced unconsciousness are still not fully understood. To elucidate them valid animal models are necessary. Since the most commonly used species in neuroscience are mice, we established a murine model for commonly used anesthetics/sedatives and evaluated the epidural electroencephalographic (EEG) patterns during slow anesthesia induction and emergence. Forty-four mice underwent surgery in which we inserted a central venous catheter and implanted nine intracranial electrodes above the prefrontal, motor, sensory, and visual cortex. After at least one week of recovery, mice were anesthetized either by inhalational sevoflurane or intravenous propofol, ketamine, or dexmedetomidine. We evaluated the loss and return of righting reflex (LORR/RORR) and recorded the electrocorticogram. For spectral analysis we focused on the prefrontal and visual cortex. In addition to analyzing the power spectral density at specific time points we evaluated the changes in the spectral power distribution longitudinally. The median time to LORR after start anesthesia ranged from 1080 [1st quartile: 960; 3rd quartile: 1080]s under sevoflurane anesthesia to 1541 [1455; 1890]s with ketamine. Around LORR sevoflurane as well as propofol induced a decrease in the theta/alpha band and an increase in the beta/gamma band. Dexmedetomidine infusion resulted in a shift towards lower frequencies with an increase in the delta range. Ketamine induced stronger activity in the higher frequencies. Our results showed substance-specific changes in EEG patterns during slow anesthesia induction. These patterns were partially identical to previous observations in humans, but also included significant differences, especially in the low frequencies. Our study emphasizes strengths and limitations of murine models in neuroscience and provides an important basis for future studies investigating complex neurophysiological mechanisms.
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Affiliation(s)
- David P Obert
- School of Medicine and Health, Department of Anesthesiology and Intensive Care, Technical University of Munich, 81675, Munich, Germany
- Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts's General Hospital, Boston, MA, 02114, USA
- Harvard Medical School, Boston, MA, 02115, USA
| | - David Killing
- School of Medicine and Health, Department of Anesthesiology and Intensive Care, Technical University of Munich, 81675, Munich, Germany
| | - Tom Happe
- School of Medicine and Health, Department of Anesthesiology and Intensive Care, Technical University of Munich, 81675, Munich, Germany
| | - Philipp Tamas
- School of Medicine and Health, Department of Anesthesiology and Intensive Care, Technical University of Munich, 81675, Munich, Germany
| | - Alp Altunkaya
- School of Medicine and Health, Department of Anesthesiology and Intensive Care, Technical University of Munich, 81675, Munich, Germany
| | - Srdjan Z Dragovic
- School of Medicine and Health, Department of Anesthesiology and Intensive Care, Technical University of Munich, 81675, Munich, Germany
| | - Matthias Kreuzer
- School of Medicine and Health, Department of Anesthesiology and Intensive Care, Technical University of Munich, 81675, Munich, Germany
| | - Gerhard Schneider
- School of Medicine and Health, Department of Anesthesiology and Intensive Care, Technical University of Munich, 81675, Munich, Germany
| | - Thomas Fenzl
- School of Medicine and Health, Department of Anesthesiology and Intensive Care, Technical University of Munich, 81675, Munich, Germany.
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Adam E, Kowalski M, Akeju O, Miller EK, Brown EN, McCarthy MM, Kopell N. Ketamine can produce oscillatory dynamics by engaging mechanisms dependent on the kinetics of NMDA receptors. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2024:2024.04.03.587998. [PMID: 38617266 PMCID: PMC11014619 DOI: 10.1101/2024.04.03.587998] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/16/2024]
Abstract
Ketamine is an NMDA-receptor antagonist that produces sedation, analgesia and dissociation at low doses and profound unconsciousness with antinociception at high doses. At high and low doses, ketamine can generate gamma oscillations (>25 Hz) in the electroencephalogram (EEG). The gamma oscillations are interrupted by slow-delta oscillations (0.1-4 Hz) at high doses. Ketamine's primary molecular targets and its oscillatory dynamics have been characterized. However, how the actions of ketamine at the subcellular level give rise to the oscillatory dynamics observed at the network level remains unknown. By developing a biophysical model of cortical circuits, we demonstrate how NMDA-receptor antagonism by ketamine can produce the oscillatory dynamics observed in human EEG recordings and non-human primate local field potential recordings. We have discovered how impaired NMDA-receptor kinetics can cause disinhibition in neuronal circuits and how a disinhibited interaction between NMDA-receptor-mediated excitation and GABA-receptor-mediated inhibition can produce gamma oscillations at high and low doses, and slow-delta oscillations at high doses. Our work uncovers general mechanisms for generating oscillatory brain dynamics that differs from ones previously reported, and provides important insights into ketamine's mechanisms of action as an anesthetic and as a therapy for treatment-resistant depression.
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Affiliation(s)
- Elie Adam
- Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139
- Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA 02114
| | - Marek Kowalski
- Department of Mathematics and Statistics, Boston University, Boston, MA 02215
| | - Oluwaseun Akeju
- Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA 02114
- Department of Anesthesia, Harvard Medical School, Boston, MA 02215
| | - Earl K. Miller
- Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139
| | - Emery N. Brown
- Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139
- Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA 02114
- Department of Anesthesia, Harvard Medical School, Boston, MA 02215
| | | | - Nancy Kopell
- Department of Mathematics and Statistics, Boston University, Boston, MA 02215
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11
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Wilkinson CL, Yankowitz L, Chao JY, Gutiérrez R, Rhoades JL, Shinnar S, Purdon PL, Nelson CA. Developmental trajectories of EEG aperiodic and periodic components: Implications for understanding thalamocortical development during infancy. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2024:2023.07.21.550114. [PMID: 37546863 PMCID: PMC10401947 DOI: 10.1101/2023.07.21.550114] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 08/08/2023]
Abstract
The development of neural circuits has long-lasting effects on brain function, yet our understanding of early circuit development in humans remains limited. Here, periodic EEG power features and aperiodic components were examined from longitudinal EEGs collected from 592 healthy 2-44 month-old infants, revealing age-dependent nonlinear changes suggestive of distinct milestones in early brain maturation. Consistent with the transient developmental progression of thalamocortical circuitry, we observe the presence and then absence of periodic alpha and high beta peaks across the three-year period, as well as the emergence of a low beta peak (12-20Hz) after six months of age. We present preliminary evidence that the emergence of the low beta peak is associated with higher thalamocortical-dependent, anesthesia-induced alpha coherence. Together, these findings suggest that early age-dependent changes in alpha and beta periodic peaks may reflect the state of thalamocortical network development.
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Affiliation(s)
- Carol L Wilkinson
- Division of Developmental Medicine, Boston Children's Hospital, Boston, MA, United States
- Harvard Medical School, Boston, MA, USA
| | - Lisa Yankowitz
- Division of Developmental Medicine, Boston Children's Hospital, Boston, MA, United States
| | - Jerry Y Chao
- Department of Anesthesiology, Montefiore Medical Center, Children's Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, NY, USA
| | - Rodrigo Gutiérrez
- Departamento de Anestesia y Medicina Perioperatoria, Hospital Clínico de la Universidad de Chile, Santiago, Chile
- Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA, United States
| | - Jeff L Rhoades
- Department of Neurobiology, Harvard Medical School, Boston, MA, USA
- Program in Neuroscience, Division of Medical Sciences, Graduate School of Arts and Sciences, Harvard University, Cambridge, MA, USA
| | - Shlomo Shinnar
- The Saul R. Korey Department of Neurology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA
- Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA
| | - Patrick L Purdon
- Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA, United States
| | - Charles A Nelson
- Division of Developmental Medicine, Boston Children's Hospital, Boston, MA, United States
- Harvard Medical School, Boston, MA, USA
- Harvard Graduate School of Education, Cambridge, MA, United States
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12
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Zhang Q, Lu H, Wang J, Yang T, Bi W, Zeng Y, Yu B. Hierarchical rhythmic propagation of corticothalamic interactions for consciousness: A computational study. Comput Biol Med 2024; 169:107843. [PMID: 38141448 DOI: 10.1016/j.compbiomed.2023.107843] [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: 03/29/2023] [Revised: 11/22/2023] [Accepted: 12/11/2023] [Indexed: 12/25/2023]
Abstract
Clarifying the mechanisms of loss and recovery of consciousness in the brain is a major challenge in neuroscience, and research on the spatiotemporal organization of rhythms at the brain region scale at different levels of consciousness remains scarce. By applying computational neuroscience, an extended corticothalamic network model was developed in this study to simulate the altered states of consciousness induced by different concentration levels of propofol. The cortex area containing oscillation spread from posterior to anterior in four successive time stages, defining four groups of brain regions. A quantitative analysis showed that hierarchical rhythm propagation was mainly due to heterogeneity in the inter-brain region connections. These results indicate that the proposed model is an anatomically data-driven testbed and a simulation platform with millisecond resolution. It facilitates understanding of activity coordination across multiple areas of the conscious brain and the mechanisms of action of anesthetics in terms of brain regions.
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Affiliation(s)
- Qian Zhang
- Brain-inspired Cognitive Intelligence Lab, Institute of Automation, Chinese Academy of Sciences, Beijing, 100190, China; School of Artificial Intelligence, University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Han Lu
- Department of Anesthesiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
| | - Jihang Wang
- Brain-inspired Cognitive Intelligence Lab, Institute of Automation, Chinese Academy of Sciences, Beijing, 100190, China; School of Artificial Intelligence, University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Taoyi Yang
- Brain-inspired Cognitive Intelligence Lab, Institute of Automation, Chinese Academy of Sciences, Beijing, 100190, China
| | - Weida Bi
- Brain-inspired Cognitive Intelligence Lab, Institute of Automation, Chinese Academy of Sciences, Beijing, 100190, China
| | - Yi Zeng
- Brain-inspired Cognitive Intelligence Lab, Institute of Automation, Chinese Academy of Sciences, Beijing, 100190, China; School of Artificial Intelligence, University of Chinese Academy of Sciences, Beijing, 100049, China; Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, 200031, China.
| | - Buwei Yu
- Department of Anesthesiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
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13
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Zhang Y, Wang Y, Cheng H, Yan F, Li D, Song D, Wang Q, Huang L. EEG spectral slope: A reliable indicator for continuous evaluation of consciousness levels during propofol anesthesia. Neuroimage 2023; 283:120426. [PMID: 37898378 DOI: 10.1016/j.neuroimage.2023.120426] [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: 07/11/2023] [Revised: 10/17/2023] [Accepted: 10/25/2023] [Indexed: 10/30/2023] Open
Abstract
The level of consciousness undergoes continuous alterations during anesthesia. Prior to the onset of propofol-induced complete unconsciousness, degraded levels of behavioral responsiveness can be observed. However, a reliable index to monitor altered consciousness levels during anesthesia has not been sufficiently investigated. In this study, we obtained 60-channel EEG data from 24 healthy participants during an ultra-slow propofol infusion protocol starting with an initial concentration of 1 μg/ml and a stepwise increase of 0.2 μg/ml in concentration. Consecutive auditory stimuli were delivered every 5 to 6 s, and the response time to the stimuli was used to assess the responsiveness levels. We calculated the spectral slope in a time-resolved manner by extracting 5-second EEG segments at each auditory stimulus and estimated their correlation with the corresponding response time. Our results demonstrated that during slow propofol infusion, the response time to external stimuli increased, while the EEG spectral slope, fitted at 15-45 Hz, became steeper, and a significant negative correlation was observed between them. Moreover, the spectral slope further steepened at deeper anesthetic levels and became flatter during anesthesia recovery. We verified these findings using an external dataset. Additionally, we found that the spectral slope of frontal electrodes over the prefrontal lobe had the best performance in predicting the response time. Overall, this study used a time-resolved analysis to suggest that the EEG spectral slope could reliably track continuously altered consciousness levels during propofol anesthesia. Furthermore, the frontal spectral slope may be a promising index for clinical monitoring of anesthesia depth.
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Affiliation(s)
- Yun Zhang
- School of Life Science and Technology, Xidian University, No.2 TaiBai South Road, Xi'an 710061, China
| | - Yubo Wang
- School of Life Science and Technology, Xidian University, No.2 TaiBai South Road, Xi'an 710061, China
| | - Huanhuan Cheng
- School of Life Science and Technology, Xidian University, No.2 TaiBai South Road, Xi'an 710061, China
| | - Fei Yan
- Department of Anesthesiology & Center for Brain Science, the First Affiliated Hospital of Xi'an Jiaotong University, No. 277 Yanta West Road, Xi'an 710061, China
| | - Dingning Li
- School of Life Science and Technology, Xidian University, No.2 TaiBai South Road, Xi'an 710061, China
| | - Dawei Song
- Department of Anesthesiology & Center for Brain Science, the First Affiliated Hospital of Xi'an Jiaotong University, No. 277 Yanta West Road, Xi'an 710061, China
| | - Qiang Wang
- Department of Anesthesiology & Center for Brain Science, the First Affiliated Hospital of Xi'an Jiaotong University, No. 277 Yanta West Road, Xi'an 710061, China.
| | - Liyu Huang
- School of Life Science and Technology, Xidian University, No.2 TaiBai South Road, Xi'an 710061, China.
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14
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Qin X, Chen X, Wang B, Zhao X, Tang Y, Yao L, Liang Z, He J, Li X. EEG Changes during Propofol Anesthesia Induction in Vegetative State Patients Undergoing Spinal Cord Stimulation Implantation Surgery. Brain Sci 2023; 13:1608. [PMID: 38002567 PMCID: PMC10669685 DOI: 10.3390/brainsci13111608] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2023] [Revised: 11/07/2023] [Accepted: 11/17/2023] [Indexed: 11/26/2023] Open
Abstract
OBJECTIVE To compare the EEG changes in vegetative state (VS) patients and non-craniotomy, non-vegetative state (NVS) patients during general anesthesia with low-dose propofol and to find whether it affects the arousal rate of VS patients. METHODS Seven vegetative state patients (VS group: five with traumatic brain injury, two with ischemic-hypoxic VS) and five non-craniotomy, non-vegetative state patients (NVS group) treated in the Department of Neurosurgery, Peking University International Hospital from January to May 2022 were selected. All patients were induced with 0.5 mg/kg propofol, and the Bispectral Index (BIS) changes within 5 min after administration were observed. Raw EEG signals and perioperative EEG signals were collected and analyzed using EEGLAB in the MATLAB software environment, time-frequency spectrums were calculated, and EEG changes were analyzed using power spectrums. RESULTS There was no significant difference in the general data before surgery between the two groups (p > 0.05); the BIS reduction in the VS group was significantly greater than that in the NVS group at 1 min, 2 min, 3 min, 4 min, and 5 min after 0.5 mg/kg propofol induction (p < 0.05). Time-frequency spectrum analysis showed the following: prominent α band energy around 10 Hz and decreased high-frequency energy in the NVS group, decreased high-frequency energy and main energy concentrated below 10 Hz in traumatic brain injury VS patients, higher energy in the 10-20 Hz band in ischemic-hypoxic VS patients. The power spectrum showed that the brain electrical energy of the NVS group was weakened R5 min after anesthesia induction compared with 5 min before induction, mainly concentrated in the small wave peak after 10 Hz, i.e., the α band peak; the energy of traumatic brain injury VS patients was weakened after anesthesia induction, but no α band peak appeared; and in ischemic-hypoxic VS patients, there was no significant change in low-frequency energy after anesthesia induction, high-frequency energy was significantly weakened, and a clear α band peak appeared slightly after 10 Hz. Three months after the operation, follow-up visits were made to the VS group patients who had undergone SCS surgery. One patient with traumatic brain injury VS was diagnosed with MCS-, one patient with ischemic-hypoxic VS had increased their CRS-R score by 1 point, and the remaining five patients had no change in their CRS scores. CONCLUSIONS Low doses of propofol cause great differences in the EEG of different types of VS patients, which may be the unique response of damaged nerve cell residual function to propofol, and these weak responses may also be the basis of brain recovery.
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Affiliation(s)
- Xuewei Qin
- Department of Anesthesiology, Peking University International Hospital, Beijing 102206, China; (X.Q.); (X.Z.)
| | - Xuanling Chen
- Department of Anesthesiology, Peking University International Hospital, Beijing 102206, China; (X.Q.); (X.Z.)
| | - Bo Wang
- Department of Anesthesiology, Peking University International Hospital, Beijing 102206, China; (X.Q.); (X.Z.)
| | - Xin Zhao
- Department of Anesthesiology, Peking University International Hospital, Beijing 102206, China; (X.Q.); (X.Z.)
| | - Yi Tang
- Department of Anesthesiology, Peking University International Hospital, Beijing 102206, China; (X.Q.); (X.Z.)
| | - Lan Yao
- Department of Anesthesiology, Peking University International Hospital, Beijing 102206, China; (X.Q.); (X.Z.)
| | - Zhenhu Liang
- Institute of Electrical Engineering, Yanshan University, Qinhuangdao 066004, China;
| | - Jianghong He
- Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China;
| | - Xiaoli Li
- State Key Laboratory of Cognitive Neuroscience and Learning, IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing 100875, China;
- Center for Collaboration and Innovation in Brain and Learning Sciences, Beijing Normal University, Beijing 100875, China
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15
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Wilkinson CL, Yankowitz L, Chao JY, Gutiérrez R, Rhoades JL, Shinnar S, Purdon PL, Nelson CA. Developmental trajectories of EEG aperiodic and periodic power: Implications for understanding the timing of thalamocortical development during infancy. RESEARCH SQUARE 2023:rs.3.rs-3215728. [PMID: 37790544 PMCID: PMC10543027 DOI: 10.21203/rs.3.rs-3215728/v1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/05/2023]
Abstract
The development of neural circuits over the first years of life has long-lasting effects on brain function, yet our understanding of early circuit development in humans remains limited. Here, aperiodic and periodic EEG power features were examined from longitudinal EEGs collected from 592 healthy 2-44 month-old infants, revealing age-dependent nonlinear changes suggestive of distinct milestones in early brain maturation. Consistent with the transient developmental progression of thalamocortical circuitry, we observe the presence and then absence of periodic alpha and high beta peaks across the three-year period, as well as the emergence of a low beta peak (12-20Hz) after six months of age. We present preliminary evidence that the emergence of the low beta peak is associated with thalamocortical connectivity sufficient for anesthesia-induced alpha coherence. Together, these findings suggest that early age-dependent changes in alpha and beta periodic peaks may reflect the state of thalamocortical network development.
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Affiliation(s)
- Carol L Wilkinson
- Division of Developmental Medicine, Boston Children's Hospital, Boston, MA, United States
- Harvard Medical School, Boston, MA, USA
| | - Lisa Yankowitz
- Division of Developmental Medicine, Boston Children's Hospital, Boston, MA, United States
| | - Jerry Y Chao
- Department of Anesthesiology, Montefiore Medical Center, Children's Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, NY, USA
| | - Rodrigo Gutiérrez
- Centro de Investigación Clínica Avanzada, Hospital Clínico de la Universidad de Chile, Santiago, Chile
- Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA, United States
| | - Jeff L Rhoades
- Department of Neurobiology, Harvard Medical School, Boston, MA, USA
- Program in Neuroscience, Division of Medical Sciences, Graduate School of Arts and Sciences, Harvard University, Cambridge, MA, USA
| | - Shlomo Shinnar
- The Saul R. Korey Department of Neurology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA
- Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA
| | - Patrick L Purdon
- Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA, United States
| | - Charles A Nelson
- Division of Developmental Medicine, Boston Children's Hospital, Boston, MA, United States
- Harvard Medical School, Boston, MA, USA
- Harvard Graduate School of Education, Cambridge, MA, United States
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16
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Soplata AE, Adam E, Brown EN, Purdon PL, McCarthy MM, Kopell N. Rapid thalamocortical network switching mediated by cortical synchronization underlies propofol-induced EEG signatures: a biophysical model. J Neurophysiol 2023; 130:86-103. [PMID: 37314079 PMCID: PMC10312318 DOI: 10.1152/jn.00068.2022] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2022] [Revised: 06/08/2023] [Accepted: 06/08/2023] [Indexed: 06/15/2023] Open
Abstract
Propofol-mediated unconsciousness elicits strong alpha/low-beta and slow oscillations in the electroencephalogram (EEG) of patients. As anesthetic dose increases, the EEG signal changes in ways that give clues to the level of unconsciousness; the network mechanisms of these changes are only partially understood. Here, we construct a biophysical thalamocortical network involving brain stem influences that reproduces transitions in dynamics seen in the EEG involving the evolution of the power and frequency of alpha/low-beta and slow rhythm, as well as their interactions. Our model suggests that propofol engages thalamic spindle and cortical sleep mechanisms to elicit persistent alpha/low-beta and slow rhythms, respectively. The thalamocortical network fluctuates between two mutually exclusive states on the timescale of seconds. One state is characterized by continuous alpha/low-beta-frequency spiking in thalamus (C-state), whereas in the other, thalamic alpha spiking is interrupted by periods of co-occurring thalamic and cortical silence (I-state). In the I-state, alpha colocalizes to the peak of the slow oscillation; in the C-state, there is a variable relationship between an alpha/beta rhythm and the slow oscillation. The C-state predominates near loss of consciousness; with increasing dose, the proportion of time spent in the I-state increases, recapitulating EEG phenomenology. Cortical synchrony drives the switch to the I-state by changing the nature of the thalamocortical feedback. Brain stem influence on the strength of thalamocortical feedback mediates the amount of cortical synchrony. Our model implicates loss of low-beta, cortical synchrony, and coordinated thalamocortical silent periods as contributing to the unconscious state.NEW & NOTEWORTHY GABAergic anesthetics induce alpha/low-beta and slow oscillations in the EEG, which interact in dose-dependent ways. We constructed a thalamocortical model to investigate how these interdependent oscillations change with propofol dose. We find two dynamic states of thalamocortical coordination, which change on the timescale of seconds and dose-dependently mirror known changes in EEG. Thalamocortical feedback determines the oscillatory coupling and power seen in each state, and this is primarily driven by cortical synchrony and brain stem neuromodulation.
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Affiliation(s)
- Austin E Soplata
- Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States
- Department of Mathematics and Statistics, Boston University, Boston, Massachusetts, United States
| | - Elie Adam
- Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States
- Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States
| | - Emery N Brown
- Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States
- Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States
- Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States
- Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States
| | - Patrick L Purdon
- Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States
| | - Michelle M McCarthy
- Department of Mathematics and Statistics, Boston University, Boston, Massachusetts, United States
| | - Nancy Kopell
- Department of Mathematics and Statistics, Boston University, Boston, Massachusetts, United States
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17
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Codianni MG, Rubin JE. A spiking computational model for striatal cholinergic interneurons. Brain Struct Funct 2023; 228:589-611. [PMID: 36653544 DOI: 10.1007/s00429-022-02604-9] [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: 03/28/2022] [Accepted: 12/14/2022] [Indexed: 01/19/2023]
Abstract
Cholinergic interneurons in the striatum, also known as tonically active interneurons or TANs, are thought to have a strong effect on corticostriatal plasticity and on striatal activity and outputs, which in turn play a critical role in modulating downstream basal ganglia activity and movement. Striatal TANs can exhibit a variety of firing patterns and responses to synaptic inputs; furthermore, they have been found to display various surges and pauses in activity associated with sensory cues and reward delivery in learning as well as with motor tic production. To help explain the factors that contribute to TAN activity patterns and to provide a resource for future studies, we present a novel conductance-based computational model of a striatal TAN. We show that this model produces the various characteristic firing patterns observed in recordings of TANs. With a single baseline tuning associated with tonic firing, the model also captures a wide range of TAN behaviors found in previous experiments involving a variety of manipulations. In addition to demonstrating these results, we explain how various ionic currents in the model contribute to them. Finally, we use this model to explore the contributions of the acetylcholine released by TANs to the production of surges and pauses in TAN activity in response to strong excitatory inputs. These results provide predictions for future experimental testing that may help with efforts to advance our understanding of the role of TANs in reinforcement learning and in motor disorders such as Tourette's syndrome.
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Affiliation(s)
- Marcello G Codianni
- Department of Mathematics, University of Pittsburgh, Pittsburgh, PA, 15260, USA
| | - Jonathan E Rubin
- Department of Mathematics, University of Pittsburgh, Pittsburgh, PA, 15260, USA. .,Center for the Neural Basis of Cognition, Pittsburgh, PA, 15260, USA.
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18
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Murillo C, Weil AB, Moore GE, Kreuzer M, Ko JC. Electroencephalographic and Cardiovascular Changes Associated with Propofol Constant Rate of Infusion Anesthesia in Young Healthy Dogs. Animals (Basel) 2023; 13:664. [PMID: 36830451 PMCID: PMC9951736 DOI: 10.3390/ani13040664] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2023] [Revised: 02/10/2023] [Accepted: 02/13/2023] [Indexed: 02/17/2023] Open
Abstract
This study aimed to evaluate electroencephalography (EEG) and cardiovascular changes associated with propofol constant rate of infusion (CRI) anesthesia in dogs. Six dogs were each given propofol CRI to induce different anesthetic phases including induction (1 mg/kg/min for 10 min), and decremental maintenance doses of 2.4 mg per kg per min, 1.6 mg per kg per min, and 0.8 mg per kg per minute over 45 min. Processed EEG indices including patient state index (PSI), (burst) suppression ratio (SR), and spectral edge frequency (95%) were obtained continuously until the dogs recovered to sternal recumbency. The dogs were intubated and ventilated. Cardiovascular and EEG index values were compared between anesthetic phases. The PSI, SR, mean arterial blood pressure, and subjective anesthetic depth scores were highly correlated throughout anesthetic depth changes. The PSI decreased from 85.0 ± 17.3 at awake to 66.0 ± 29.0 at induction, and then sharply reduced to 19.7 ± 23.6 during maintenance and returned to 61.5 ± 19.2 at extubation. The SR increased from 15.4 ± 30.9% at induction to 70.9 ± 39.8% during maintenance and decreased to 3.4 ± 8.9% at extubation. We concluded that EEG indices can be used to aid in tracking ongoing brain state changes during propofol anesthesia in dogs.
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Affiliation(s)
- Carla Murillo
- Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Purdue University, West Lafayette, IN 47907, USA
| | - Ann B. Weil
- Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Purdue University, West Lafayette, IN 47907, USA
| | - George E. Moore
- Department of Veterinary Administration, College of Veterinary Medicine, Purdue University, West Lafayette, IN 47907, USA
| | - Matthias Kreuzer
- Department of Anesthesiology and Intensive Care, School of Medicine, Technical University of Munich, 80333 München, Germany
| | - Jeff C. Ko
- Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Purdue University, West Lafayette, IN 47907, USA
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19
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Artoni F, Maillard J, Britz J, Seeber M, Lysakowski C, Bréchet L, Tramèr MR, Michel CM. EEG microstate dynamics indicate a U-shaped path to propofol-induced loss of consciousness. Neuroimage 2022; 256:119156. [PMID: 35364276 DOI: 10.1016/j.neuroimage.2022.119156] [Citation(s) in RCA: 29] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2021] [Revised: 03/22/2022] [Accepted: 03/27/2022] [Indexed: 11/16/2022] Open
Abstract
Evidence suggests that the stream of consciousness is parsed into transient brain states manifesting themselves as discrete spatiotemporal patterns of global neuronal activity. Electroencephalographical (EEG) microstates are proposed as the neurophysiological correlates of these transiently stable brain states that last for fractions of seconds. To further understand the link between EEG microstate dynamics and consciousness, we continuously recorded high-density EEG in 23 surgical patients from their awake state to unconsciousness, induced by step-wise increasing concentrations of the intravenous anesthetic propofol. Besides the conventional parameters of microstate dynamics, we introduce a new implementation of a method to estimate the complexity of microstate sequences. The brain activity under the surgical anesthesia showed a decreased sequence complexity of the stereotypical microstates, which became sparser and longer-lasting. However, we observed an initial increase in microstates' temporal dynamics and complexity with increasing depth of sedation leading to a distinctive "U-shape" that may be linked to the paradoxical excitation induced by moderate levels of propofol. Our results support the idea that the brain is in a metastable state under normal conditions, balancing between order and chaos in order to flexibly switch from one state to another. The temporal dynamics of EEG microstates indicate changes of this critical balance between stability and transition that lead to altered states of consciousness.
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Affiliation(s)
- Fiorenzo Artoni
- Functional Brain Mapping Laboratory, Department of Basic Neurosciences, University of Geneva, Campus Biotech, Switzerland.
| | - Julien Maillard
- Division of Anesthesiology, Department of Anesthesiology, Clinical Pharmacology, Intensive Care and Emergency Medicine, Geneva University Hospitals, Geneva, Switzerland
| | - Juliane Britz
- Department of Psychology, University of Fribourg, Fribourg, Switzerland; CIBM Center for Biomedical Imaging, Lausanne, Geneva, Switzerland
| | - Martin Seeber
- Functional Brain Mapping Laboratory, Department of Basic Neurosciences, University of Geneva, Campus Biotech, Switzerland
| | - Christopher Lysakowski
- Division of Anesthesiology, Department of Anesthesiology, Clinical Pharmacology, Intensive Care and Emergency Medicine, Geneva University Hospitals, Geneva, Switzerland
| | - Lucie Bréchet
- CIBM Center for Biomedical Imaging, Lausanne, Geneva, Switzerland; Functional Brain Mapping Laboratory, Department of Basic Neurosciences, University of Geneva, Campus Biotech, Switzerland
| | - Martin R Tramèr
- Division of Anesthesiology, Department of Anesthesiology, Clinical Pharmacology, Intensive Care and Emergency Medicine, Geneva University Hospitals, Geneva, Switzerland
| | - Christoph M Michel
- Functional Brain Mapping Laboratory, Department of Basic Neurosciences, University of Geneva, Campus Biotech, Switzerland; CIBM Center for Biomedical Imaging, Lausanne, Geneva, Switzerland.
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Fridman EA, Schiff ND. Organizing a Rational Approach to Treatments of Disorders of Consciousness Using the Anterior Forebrain Mesocircuit Model. J Clin Neurophysiol 2022; 39:40-48. [PMID: 34474427 PMCID: PMC8900660 DOI: 10.1097/wnp.0000000000000729] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Abstract
SUMMARY Organizing a rational treatment strategy for patients with multifocal structural brain injuries and disorders of consciousness (DOC) is an important and challenging clinical goal. Among potential clinical end points, restoring elements of communication to DOC patients can support improved patient care, caregiver satisfaction, and patients' quality of life. Over the past decade, several studies have considered the use of the anterior forebrain mesocircuit model to approach this problem because this model proposes a supervening circuit-level impairment arising across DOC of varying etiologies. We review both the conceptual foundation of the mesocircuit model and studies of mechanisms underlying DOC that test predictions of this model. We consider how this model can guide therapeutic interventions and discuss a proposed treatment algorithm based on these ideas. Although the approach reviewed originates in the evaluation of patients with chronic DOC, we consider some emerging implications for patients in acute and subacute settings.
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Affiliation(s)
- Esteban A Fridman
- Brain and Mind Research Institute, Weill Cornell Medicine, New York, New York, U.S.A
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21
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Félix L, Correia R, Sequeira R, Ribeiro C, Monteiro S, Antunes L, Silva J, Venâncio C, Valentim A. MS-222 and Propofol Sedation during and after the Simulated Transport of Nile tilapia ( Oreochromis niloticus). BIOLOGY 2021; 10:1309. [PMID: 34943224 PMCID: PMC8698739 DOI: 10.3390/biology10121309] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/15/2021] [Revised: 12/02/2021] [Accepted: 12/06/2021] [Indexed: 01/18/2023]
Abstract
The use of anesthetics has been suggested as a strategy to hamper live fish transport-induced stress. Still, there is insufficient data available on the use of alternative anesthetics to MS-222. This study investigated the use of propofol to mitigate stress in Nile tilapia (Oreochromis niloticus, 143.8 ± 20.9 g and 20.4 ± 0.9 cm) during a 6 h simulated transport. Individuals (n = 7) were divided into three groups: control, 40 mg L-1 MS-222, and 0.8 mg L-1 propofol. A naïve group non-transported was also considered. During the 6 h transport and 24 h after, the response to external stimuli, opercular movements, water quality parameters, behavior, blood hematology and other physiological values, the histopathology of the gills, the quality of the fillet, and oxidative-stress changes in gills, muscle, brain, and liver were evaluated. Propofol increased swimming activity of fish but decreased opercular movements and responses to external stimuli, indicating oscillations of the sedation depth. Water pH and glucose levels increased, while hematocrit (HCT) and lactate decreased in propofol groups at 6 h. At this time-point, MS-222 also induced a decrease in the HCT and lactate levels while increasing cortisol levels. Despite these effects, the stress-related behaviors lessened with anesthetics compared to the control group. After the recovery period, physiological responses normalized in animals from both anesthetic groups, but the control still had high cortisol levels. Overall, propofol is a good alternative for the transportation of this species, showing efficient sedation without compromising health or fillet quality. However, further pharmacodynamics and pharmacokinetics knowledge is required to support its use in aquaculture settings.
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Affiliation(s)
- Luís Félix
- Instituto de Investigação e Inovação em Saúde (i3s), Universidade of Porto, 4200-135 Porto, Portugal
- Laboratory Animal Science, Instituto de Biologia Molecular e Celular (IBMC), Universidade do Porto, 4200-135 Porto, Portugal
- Centre for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB), University of Trás-os-Montes and Alto Douro (UTAD), 5000-801 Vila Real, Portugal; (S.M.); (L.A.); (C.V.)
- Institute for Innovation, Capacity Building and Sustainability of Agri-Food Production (Inov4Agro), University of Trás-os-Montes and Alto Douro (UTAD), 5000-801 Vila Real, Portugal
| | - Rita Correia
- School of Agrarian and Veterinary Sciences (ECAV), University of Trás-os-Montes and Alto Douro (UTAD), 5000-801 Vila Real, Portugal; (R.C.); (J.S.)
| | - Rita Sequeira
- School of Life and Environmental Sciences (ECVA), University of Trás-os-Montes and Alto Douro (UTAD), 5000-801 Vila Real, Portugal; (R.S.); (C.R.)
| | - Cristiana Ribeiro
- School of Life and Environmental Sciences (ECVA), University of Trás-os-Montes and Alto Douro (UTAD), 5000-801 Vila Real, Portugal; (R.S.); (C.R.)
| | - Sandra Monteiro
- Centre for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB), University of Trás-os-Montes and Alto Douro (UTAD), 5000-801 Vila Real, Portugal; (S.M.); (L.A.); (C.V.)
- Institute for Innovation, Capacity Building and Sustainability of Agri-Food Production (Inov4Agro), University of Trás-os-Montes and Alto Douro (UTAD), 5000-801 Vila Real, Portugal
- School of Life and Environmental Sciences (ECVA), University of Trás-os-Montes and Alto Douro (UTAD), 5000-801 Vila Real, Portugal; (R.S.); (C.R.)
| | - Luís Antunes
- Centre for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB), University of Trás-os-Montes and Alto Douro (UTAD), 5000-801 Vila Real, Portugal; (S.M.); (L.A.); (C.V.)
- Institute for Innovation, Capacity Building and Sustainability of Agri-Food Production (Inov4Agro), University of Trás-os-Montes and Alto Douro (UTAD), 5000-801 Vila Real, Portugal
- School of Agrarian and Veterinary Sciences (ECAV), University of Trás-os-Montes and Alto Douro (UTAD), 5000-801 Vila Real, Portugal; (R.C.); (J.S.)
| | - José Silva
- School of Agrarian and Veterinary Sciences (ECAV), University of Trás-os-Montes and Alto Douro (UTAD), 5000-801 Vila Real, Portugal; (R.C.); (J.S.)
- Animal and Veterinary Research Centre (CECAV), University of Trás-os-Montes and Alto Douro (UTAD), 5000-801 Vila Real, Portugal
| | - Carlos Venâncio
- Centre for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB), University of Trás-os-Montes and Alto Douro (UTAD), 5000-801 Vila Real, Portugal; (S.M.); (L.A.); (C.V.)
- Institute for Innovation, Capacity Building and Sustainability of Agri-Food Production (Inov4Agro), University of Trás-os-Montes and Alto Douro (UTAD), 5000-801 Vila Real, Portugal
- School of Agrarian and Veterinary Sciences (ECAV), University of Trás-os-Montes and Alto Douro (UTAD), 5000-801 Vila Real, Portugal; (R.C.); (J.S.)
- Animal and Veterinary Research Centre (CECAV), University of Trás-os-Montes and Alto Douro (UTAD), 5000-801 Vila Real, Portugal
| | - Ana Valentim
- Instituto de Investigação e Inovação em Saúde (i3s), Universidade of Porto, 4200-135 Porto, Portugal
- Laboratory Animal Science, Instituto de Biologia Molecular e Celular (IBMC), Universidade do Porto, 4200-135 Porto, Portugal
- Centre for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB), University of Trás-os-Montes and Alto Douro (UTAD), 5000-801 Vila Real, Portugal; (S.M.); (L.A.); (C.V.)
- Institute for Innovation, Capacity Building and Sustainability of Agri-Food Production (Inov4Agro), University of Trás-os-Montes and Alto Douro (UTAD), 5000-801 Vila Real, Portugal
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Neurophysiologic Complexity in Children Increases with Developmental Age and Is Reduced by General Anesthesia. Anesthesiology 2021; 135:813-828. [PMID: 34491305 DOI: 10.1097/aln.0000000000003929] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND Neurophysiologic complexity in the cortex has been shown to reflect changes in the level of consciousness in adults but remains incompletely understood in the developing brain. This study aimed to address changes in cortical complexity related to age and anesthetic state transitions. This study tested the hypotheses that cortical complexity would (1) increase with developmental age and (2) decrease during general anesthesia. METHODS This was a single-center, prospective, cross-sectional study of healthy (American Society of Anesthesiologists physical status I or II) children (n = 50) of age 8 to 16 undergoing surgery with general anesthesia at Michigan Medicine. This age range was chosen because it reflects a period of substantial brain network maturation. Whole scalp (16-channel), wireless electroencephalographic data were collected from the preoperative period through the recovery of consciousness. Cortical complexity was measured using the Lempel-Ziv algorithm and analyzed during the baseline, premedication, maintenance of general anesthesia, and clinical recovery periods. The effect of spectral power on Lempel-Ziv complexity was analyzed by comparing the original complexity value with those of surrogate time series generated through phase randomization that preserves power spectrum. RESULTS Baseline spatiotemporal Lempel-Ziv complexity increased with age (yr; slope [95% CI], 0.010 [0.004, 0.016]; P < 0.001); when normalized to account for spectral power, there was no significant age effect on cortical complexity (0.001 [-0.004, 0.005]; P = 0.737). General anesthesia was associated with a significant decrease in spatiotemporal complexity (median [25th, 75th]; baseline, 0.660 [0.620, 0.690] vs. maintenance, 0.459 [0.402, 0.527]; P < 0.001), and spatiotemporal complexity exceeded baseline levels during postoperative recovery (0.704 [0.642, 0.745]; P = 0.009). When normalized, there was a similar reduction in complexity during general anesthesia (baseline, 0.913 [0.887, 0.923] vs. maintenance 0.851 [0.823, 0.877]; P < 0.001), but complexity remained significantly reduced during recovery (0.873 [0.840, 0.902], P < 0.001). CONCLUSIONS Cortical complexity increased with developmental age and decreased during general anesthesia. This association remained significant when controlling for spectral changes during anesthetic-induced perturbations in consciousness but not with developmental age. EDITOR’S PERSPECTIVE
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23
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Progress in modelling of brain dynamics during anaesthesia and the role of sleep-wake circuitry. Biochem Pharmacol 2021; 191:114388. [DOI: 10.1016/j.bcp.2020.114388] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2020] [Revised: 12/16/2020] [Accepted: 12/17/2020] [Indexed: 12/28/2022]
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Garwood IC, Chakravarty S, Donoghue J, Mahnke M, Kahali P, Chamadia S, Akeju O, Miller EK, Brown EN. A hidden Markov model reliably characterizes ketamine-induced spectral dynamics in macaque local field potentials and human electroencephalograms. PLoS Comput Biol 2021; 17:e1009280. [PMID: 34407069 PMCID: PMC8405019 DOI: 10.1371/journal.pcbi.1009280] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2020] [Revised: 08/30/2021] [Accepted: 07/15/2021] [Indexed: 11/18/2022] Open
Abstract
Ketamine is an NMDA receptor antagonist commonly used to maintain general anesthesia. At anesthetic doses, ketamine causes high power gamma (25-50 Hz) oscillations alternating with slow-delta (0.1-4 Hz) oscillations. These dynamics are readily observed in local field potentials (LFPs) of non-human primates (NHPs) and electroencephalogram (EEG) recordings from human subjects. However, a detailed statistical analysis of these dynamics has not been reported. We characterize ketamine's neural dynamics using a hidden Markov model (HMM). The HMM observations are sequences of spectral power in seven canonical frequency bands between 0 to 50 Hz, where power is averaged within each band and scaled between 0 and 1. We model the observations as realizations of multivariate beta probability distributions that depend on a discrete-valued latent state process whose state transitions obey Markov dynamics. Using an expectation-maximization algorithm, we fit this beta-HMM to LFP recordings from 2 NHPs, and separately, to EEG recordings from 9 human subjects who received anesthetic doses of ketamine. Our beta-HMM framework provides a useful tool for experimental data analysis. Together, the estimated beta-HMM parameters and optimal state trajectory revealed an alternating pattern of states characterized primarily by gamma and slow-delta activities. The mean duration of the gamma activity was 2.2s([1.7,2.8]s) and 1.2s([0.9,1.5]s) for the two NHPs, and 2.5s([1.7,3.6]s) for the human subjects. The mean duration of the slow-delta activity was 1.6s([1.2,2.0]s) and 1.0s([0.8,1.2]s) for the two NHPs, and 1.8s([1.3,2.4]s) for the human subjects. Our characterizations of the alternating gamma slow-delta activities revealed five sub-states that show regular sequential transitions. These quantitative insights can inform the development of rhythm-generating neuronal circuit models that give mechanistic insights into this phenomenon and how ketamine produces altered states of arousal.
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Affiliation(s)
- Indie C. Garwood
- Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America
- The Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America
- Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America
| | - Sourish Chakravarty
- The Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America
- Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, Boston, Massachusetts, United States of America
| | - Jacob Donoghue
- Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America
- The Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America
- Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America
| | - Meredith Mahnke
- The Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America
| | - Pegah Kahali
- The Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America
- Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, Boston, Massachusetts, United States of America
| | - Shubham Chamadia
- Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, Boston, Massachusetts, United States of America
| | - Oluwaseun Akeju
- Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, Boston, Massachusetts, United States of America
| | - Earl K. Miller
- The Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America
- Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America
| | - Emery N. Brown
- Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America
- The Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America
- Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America
- Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, Boston, Massachusetts, United States of America
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25
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Bhattacharya S, Cauchois MBL, Iglesias PA, Chen ZS. The impact of a closed-loop thalamocortical model on the spatiotemporal dynamics of cortical and thalamic traveling waves. Sci Rep 2021; 11:14359. [PMID: 34257333 PMCID: PMC8277909 DOI: 10.1038/s41598-021-93618-6] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2021] [Accepted: 06/21/2021] [Indexed: 12/23/2022] Open
Abstract
Propagation of activity in spatially structured neuronal networks has been observed in awake, anesthetized, and sleeping brains. How these wave patterns emerge and organize across brain structures, and how network connectivity affects spatiotemporal neural activity remains unclear. Here, we develop a computational model of a two-dimensional thalamocortical network, which gives rise to emergent traveling waves similar to those observed experimentally. We illustrate how spontaneous and evoked oscillatory activity in space and time emerge using a closed-loop thalamocortical architecture, sustaining smooth waves in the cortex and staggered waves in the thalamus. We further show that intracortical and thalamocortical network connectivity, cortical excitation/inhibition balance, and thalamocortical or corticothalamic delay can independently or jointly change the spatiotemporal patterns (radial, planar and rotating waves) and characteristics (speed, direction, and frequency) of cortical and thalamic traveling waves. Computer simulations predict that increased thalamic inhibition induces slower cortical frequencies and that enhanced cortical excitation increases traveling wave speed and frequency. Overall, our results provide insight into the genesis and sustainability of thalamocortical spatiotemporal patterns, showing how simple synaptic alterations cause varied spontaneous and evoked wave patterns. Our model and simulations highlight the need for spatially spread neural recordings to uncover critical circuit mechanisms for brain functions.
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Affiliation(s)
- Sayak Bhattacharya
- Department of Electrical and Computer Engineering, Whiting School of Engineering, Johns Hopkins University, Baltimore, MD, 21218, USA
| | - Matthieu B L Cauchois
- Department of Mechanical Engineering, Whiting School of Engineering, Johns Hopkins University, Baltimore, MD, 21218, USA
| | - Pablo A Iglesias
- Department of Electrical and Computer Engineering, Whiting School of Engineering, Johns Hopkins University, Baltimore, MD, 21218, USA.
| | - Zhe Sage Chen
- Department of Psychiatry, Department of Neuroscience and Physiology, Neuroscience Institute, New York University Grossman School of Medicine, New York, NY, 10016, USA.
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26
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27
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Boncompte G, Medel V, Cortínez LI, Ossandón T. Brain activity complexity has a nonlinear relation to the level of propofol sedation. Br J Anaesth 2021; 127:254-263. [PMID: 34099242 DOI: 10.1016/j.bja.2021.04.023] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2020] [Revised: 03/29/2021] [Accepted: 04/16/2021] [Indexed: 10/21/2022] Open
Abstract
BACKGROUND Brain activity complexity is a promising correlate of states of consciousness. Previous studies have shown higher complexity for awake compared with deep anaesthesia states. However, little attention has been paid to complexity in intermediate states of sedation. METHODS We analysed the Lempel-Ziv complexity of EEG signals from subjects undergoing moderate propofol sedation, from an open access database, and related it to behavioural performance as a continuous marker of the level of sedation and to plasma propofol concentrations. We explored its relation to spectral properties, to propofol susceptibility, and its topographical distribution. RESULTS Subjects who retained behavioural performance despite propofol sedation showed increased brain activity complexity compared with baseline (M=13.9%, 95% confidence interval=7.5-20.3). This was not the case for subjects who lost behavioural performance. The increase was most prominent in frontal electrodes, and correlated with behavioural performance and propofol susceptibility. This effect was positively correlated with high-frequency activity. However, abolishing specific frequency ranges (e.g. alpha or gamma) did not reduce the propofol-induced increase in Lempel-Ziv complexity. CONCLUSIONS Brain activity complexity can increase in response to propofol, particularly during low-dose sedation. Propofol-mediated Lempel-Ziv complexity increase was independent of frequency-specific spectral power manipulations, and most prominent in frontal areas. Taken together, these results advance our understanding of brain activity complexity and anaesthetics. They do not support models of consciousness that propose a direct relation between brain activity complexity and states of consciousness.
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Affiliation(s)
- Gonzalo Boncompte
- Neurodynamics of Cognition Laboratory, Departamento de Psiquiatría, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile.
| | - Vicente Medel
- Neurodynamics of Cognition Laboratory, Departamento de Psiquiatría, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Luis I Cortínez
- División de Anestesiología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Tomás Ossandón
- Neurodynamics of Cognition Laboratory, Departamento de Psiquiatría, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile; Institute for Biological and Medical Engineering, Schools of Engineering, Medicine and Biological Sciences, Pontificia Universidad Católica de Chile, Chile
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28
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Kaiser HA, Knapp J, Sleigh J, Avidan MS, Stüber F, Hight D. [The quantitative EEG in electroencephalogram-based brain monitoring during general anesthesia]. Anaesthesist 2021; 70:531-547. [PMID: 33970302 PMCID: PMC8108440 DOI: 10.1007/s00101-021-00960-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/06/2021] [Indexed: 11/12/2022]
Abstract
The electroencephalogram (EEG) is increasingly being used in the clinical routine of anesthesia in German-speaking countries. In over 90% of patients the frontal EEG changes somewhat predictably in response to administration of the normally used anesthetic agents (propofol and volatile gasses). An adequate depth of anesthesia and appropriate concentrations of anesthetics in the brain generate mostly frontal oscillations between 8 and 12 Hz as well as slow delta waves between 0.5 and 4 Hz. The frontal EEG channel is well-suited for avoidance of insufficient depth of anesthesia and excessive administration of anesthetics. This article explains the clinical interpretation of the most important EEG patterns and the biophysical background. Also discussed are important limitations and pitfalls for the clinical routine, which the anesthetist should know in order to utilize the EEG as an admittedly incomplete but clinically extremely important parameter for the level of consciousness.
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Affiliation(s)
- H A Kaiser
- Universitätsklinik für Anästhesiologie und Schmerztherapie, Inselspital, Universitätsspital Bern, Freiburgstr., 3010, Bern, Schweiz.
| | - J Knapp
- Universitätsklinik für Anästhesiologie und Schmerztherapie, Inselspital, Universitätsspital Bern, Freiburgstr., 3010, Bern, Schweiz
| | - J Sleigh
- Department of Anaesthesia, Waikato Clinical School, University of Auckland, Hamilton, Neuseeland
| | - M S Avidan
- Department of Anesthesiology, Washington University School of Medicine, 660 S. Euclid Ave., MO 63110, St. Louis, USA
| | - F Stüber
- Universitätsklinik für Anästhesiologie und Schmerztherapie, Inselspital, Universitätsspital Bern, Freiburgstr., 3010, Bern, Schweiz
| | - D Hight
- Universitätsklinik für Anästhesiologie und Schmerztherapie, Inselspital, Universitätsspital Bern, Freiburgstr., 3010, Bern, Schweiz
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29
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Bastos AM, Donoghue JA, Brincat SL, Mahnke M, Yanar J, Correa J, Waite AS, Lundqvist M, Roy J, Brown EN, Miller EK. Neural effects of propofol-induced unconsciousness and its reversal using thalamic stimulation. eLife 2021; 10:60824. [PMID: 33904411 PMCID: PMC8079153 DOI: 10.7554/elife.60824] [Citation(s) in RCA: 84] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2020] [Accepted: 03/28/2021] [Indexed: 01/05/2023] Open
Abstract
The specific circuit mechanisms through which anesthetics induce unconsciousness have not been completely characterized. We recorded neural activity from the frontal, parietal, and temporal cortices and thalamus while maintaining unconsciousness in non-human primates (NHPs) with the anesthetic propofol. Unconsciousness was marked by slow frequency (~1 Hz) oscillations in local field potentials, entrainment of local spiking to Up states alternating with Down states of little or no spiking activity, and decreased coherence in frequencies above 4 Hz. Thalamic stimulation ‘awakened’ anesthetized NHPs and reversed the electrophysiologic features of unconsciousness. Unconsciousness is linked to cortical and thalamic slow frequency synchrony coupled with decreased spiking, and loss of higher-frequency dynamics. This may disrupt cortical communication/integration.
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Affiliation(s)
- André M Bastos
- The Picower Institute for Learning and Memory and Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, United States
| | - Jacob A Donoghue
- The Picower Institute for Learning and Memory and Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, United States
| | - Scott L Brincat
- The Picower Institute for Learning and Memory and Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, United States
| | - Meredith Mahnke
- The Picower Institute for Learning and Memory and Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, United States
| | - Jorge Yanar
- The Picower Institute for Learning and Memory and Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, United States
| | - Josefina Correa
- The Picower Institute for Learning and Memory and Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, United States
| | - Ayan S Waite
- The Picower Institute for Learning and Memory and Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, United States
| | - Mikael Lundqvist
- The Picower Institute for Learning and Memory and Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, United States
| | - Jefferson Roy
- The Picower Institute for Learning and Memory and Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, United States
| | - Emery N Brown
- The Picower Institute for Learning and Memory and Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, United States.,The Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital/Harvard Medical School, Boston, United States.,The Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, United States
| | - Earl K Miller
- The Picower Institute for Learning and Memory and Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, United States
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Glomb K, Cabral J, Cattani A, Mazzoni A, Raj A, Franceschiello B. Computational Models in Electroencephalography. Brain Topogr 2021; 35:142-161. [PMID: 33779888 PMCID: PMC8813814 DOI: 10.1007/s10548-021-00828-2] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2020] [Accepted: 02/19/2021] [Indexed: 12/17/2022]
Abstract
Computational models lie at the intersection of basic neuroscience and healthcare applications because they allow researchers to test hypotheses in silico and predict the outcome of experiments and interactions that are very hard to test in reality. Yet, what is meant by “computational model” is understood in many different ways by researchers in different fields of neuroscience and psychology, hindering communication and collaboration. In this review, we point out the state of the art of computational modeling in Electroencephalography (EEG) and outline how these models can be used to integrate findings from electrophysiology, network-level models, and behavior. On the one hand, computational models serve to investigate the mechanisms that generate brain activity, for example measured with EEG, such as the transient emergence of oscillations at different frequency bands and/or with different spatial topographies. On the other hand, computational models serve to design experiments and test hypotheses in silico. The final purpose of computational models of EEG is to obtain a comprehensive understanding of the mechanisms that underlie the EEG signal. This is crucial for an accurate interpretation of EEG measurements that may ultimately serve in the development of novel clinical applications.
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Affiliation(s)
- Katharina Glomb
- Connectomics Lab, Department of Radiology, Lausanne University Hospital and University of Lausanne (CHUV-UNIL), Lausanne, Switzerland.
| | - Joana Cabral
- Life and Health Sciences Research Institute (ICVS), University of Minho, Braga, Portugal
| | - Anna Cattani
- Department of Psychiatry, University of Wisconsin-Madison, Madison, USA.,Department of Biomedical and Clinical Sciences 'Luigi Sacco', University of Milan, Milan, Italy
| | - Alberto Mazzoni
- The BioRobotics Institute, Scuola Superiore Sant'Anna, Pisa, Italy
| | - Ashish Raj
- School of Medicine, UCSF, San Francisco, USA
| | - Benedetta Franceschiello
- Department of Ophthalmology, Hopital Ophthalmic Jules Gonin, FAA, Lausanne, Switzerland.,CIBM Centre for Biomedical Imaging, EEG Section CHUV-UNIL, Lausanne, Switzerland.,Laboratory for Investigative Neurophysiology, Department of Radiology, Lausanne University Hospital and University of Lausanne (CHUV-UNIL), Lausanne, Switzerland
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Xiao J, Chen Z, Yu B. A Potential Mechanism of Sodium Channel Mediating the General Anesthesia Induced by Propofol. Front Cell Neurosci 2020; 14:593050. [PMID: 33343303 PMCID: PMC7746837 DOI: 10.3389/fncel.2020.593050] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2020] [Accepted: 11/10/2020] [Indexed: 12/19/2022] Open
Abstract
General anesthesia has revolutionized healthcare over the past 200 years and continues to show advancements. However, many phenomena induced by general anesthetics including paradoxical excitation are still poorly understood. Voltage-gated sodium channels (NaV) were believed to be one of the proteins targeted during general anesthesia. Based on electrophysiological measurements before and after propofol treatments of different concentrations, we mathematically modified the Hodgkin–Huxley sodium channel formulations and constructed a thalamocortical model to investigate the potential roles of NaV. The ion channels of individual neurons were modeled using the Hodgkin–Huxley type equations. The enhancement of propofol-induced GABAa current was simulated by increasing the maximal conductance and the time-constant of decay. Electroencephalogram (EEG) was evaluated as the post-synaptic potential from pyramidal (PY) cells. We found that a left shift in activation of NaV was induced primarily by a low concentration of propofol (0.3–10 μM), while a left shift in inactivation of NaV was induced by an increasing concentration (0.3–30 μM). Mathematical simulation indicated that a left shift of NaV activation produced a Hopf bifurcation, leading to cell oscillations. Left shift of NaV activation around a value of 5.5 mV in the thalamocortical models suppressed normal bursting of thalamocortical (TC) cells by triggering its chaotic oscillations. This led to irregular spiking of PY cells and an increased frequency in EEG readings. This observation suggests a mechanism leading to paradoxical excitation during general anesthesia. While a left shift in inactivation led to light hyperpolarization in individual cells, it inhibited the activity of the thalamocortical model after a certain depth of anesthesia. This finding implies that high doses of propofol inhibit the network partly by accelerating NaV toward inactivation. Additionally, this result explains why the application of sodium channel blockers decreases the requirement for general anesthetics. Our study provides an insight into the roles that NaV plays in the mechanism of general anesthesia. Since the activation and inactivation of NaV are structurally independent, it should be possible to avoid side effects by state-dependent binding to the NaV to achieve precision medicine in the future.
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Affiliation(s)
- Jinglei Xiao
- Department of Anesthesiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Zhengguo Chen
- College of Computer, National University of Defence Technology, Changsha, China
| | - Buwei Yu
- Department of Anesthesiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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Continuing professional development module : An updated introduction to electroencephalogram-based brain monitoring during intended general anesthesia. Can J Anaesth 2020; 67:1858-1878. [PMID: 33190217 PMCID: PMC7666718 DOI: 10.1007/s12630-020-01820-3] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2019] [Revised: 07/25/2019] [Accepted: 07/13/2020] [Indexed: 10/27/2022] Open
Abstract
The electroencephalogram (EEG) provides a reliable reflection of the brain's electrical state, so it can reassure us that the anesthetic agents are actually reaching the patient's brain, and are having the desired effect. In most patients, the EEG changes somewhat predictably in response to propofol and volatile agents, so a frontal EEG channel can guide avoidance of insufficient and excessive administration of general anesthesia. Persistent alpha-spindles (around 10 Hz) phase-amplitude coupled with slow delta waves (around 1 Hz) are commonly seen during an "appropriate hypnotic state of general anesthesia". Such patterns can be appreciated from the EEG waveform or from the spectrogram (a colour-coded display of how the power in the various EEG frequencies changes with time). Nevertheless, there are exceptions to this. For example, administration of ketamine and nitrous oxide is generally not associated with the aforementioned alpha-spindle coupled with delta wave pattern. Also, some patients, including older adults and those with neurodegenerative disorders, are less predisposed to generate a strong electroencephalographic "alpha-spindle" pattern during general anesthesia. There might also be some rare instances when the frontal EEG shows a pattern suggestive of general anesthesia, while the patient has some awareness and is able to follow simple commands, albeit this is typically without obvious distress or memory formation. Thus, the frontal EEG alone, as currently analyzed, is an imperfect but clinically useful mirror, and more scientific insights will be needed before we can claim to have a reliable readout of brain "function" during general anesthesia.
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The influence of induction speed on the frontal (processed) EEG. Sci Rep 2020; 10:19444. [PMID: 33173114 PMCID: PMC7655958 DOI: 10.1038/s41598-020-76323-8] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2020] [Accepted: 10/27/2020] [Indexed: 12/12/2022] Open
Abstract
The intravenous injection of the anaesthetic propofol is clinical routine to induce loss of responsiveness (LOR). However, there are only a few studies investigating the influence of the injection rate on the frontal electroencephalogram (EEG) during LOR. Therefore, we focused on changes of the frontal EEG especially during this period. We included 18 patients which were randomly assigned to a slow or fast induction group and recorded the frontal EEG. Based on this data, we calculated the power spectral density, the band powers and band ratios. To analyse the behaviour of processed EEG parameters we calculated the beta ratio, the spectral entropy, and the spectral edge frequency. Due to the prolonged induction period in the slow injection group we were able to distinguish loss of responsiveness to verbal command (LOvR) from loss of responsiveness to painful stimulus (LOpR) whereas in the fast induction group we could not. At LOpR, we observed a higher relative alpha and beta power in the slow induction group while the relative power in the delta range was lower than in the fast induction group. When concentrating on the slow induction group the increase in relative alpha power pre-LOpR and even before LOvR indicated that frontal EEG patterns, which have been suggested as an indicator of unconsciousness, can develop before LOR. Further, LOvR was best reflected by an increase of the alpha to delta ratio, and LOpR was indicated by a decrease of the beta to alpha ratio. These findings highlight the different spectral properties of the EEG at various levels of responsiveness and underline the influence of the propofol injection rate on the frontal EEG during induction of general anesthesia.
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Theilmann W, Rosenholm M, Hampel P, Löscher W, Rantamäki T. Lack of antidepressant effects of burst-suppressing isoflurane anesthesia in adult male Wistar outbred rats subjected to chronic mild stress. PLoS One 2020; 15:e0235046. [PMID: 32579566 PMCID: PMC7313995 DOI: 10.1371/journal.pone.0235046] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2020] [Accepted: 05/04/2020] [Indexed: 11/30/2022] Open
Abstract
Post-ictal emergence of slow wave EEG (electroencephalogram) activity and burst-suppression has been associated with the therapeutic effects of the electroconvulsive therapy (ECT), indicating that mere “cerebral silence” may elicit antidepressant actions. Indeed, brief exposures to burst-suppressing anesthesia has been reported to elicit antidepressant effects in a subset of patients, and produce behavioral and molecular alterations, such as increased expression of brain-derived neurotrophic factor (BDNF), connected with antidepressant responses in rodents. Here, we have further tested the cerebral silence hypothesis by determining whether repeated exposures to isoflurane anesthesia reduce depressive-like symptoms or influence BDNF expression in male Wistar outbred rats (Crl:WI(Han)) subjected to chronic mild stress (CMS), a model which is responsive to repeated electroconvulsive shocks (ECS, a model of ECT). Stress-susceptible, stress-resilient, and unstressed rats were exposed to 5 doses of isoflurane over a 15-day time period, with administrations occurring every third day. Isoflurane dosing is known to reliably produce rapid EEG burst-suppression (4% induction, 2% maintenance; 15 min). Antidepressant and anxiolytic effects of isoflurane were assessed after the first, third, and fifth drug exposure by measuring sucrose consumption, as well as performance on the open field and the elevated plus maze tasks. Tissue samples from the medial prefrontal cortex and hippocampus were collected, and levels of BDNF (brain-derived neurotrophic factor) protein were assessed. We find that isoflurane anesthesia had no impact on the behavior of stress-resilient or anhedonic rats in selected tests; findings which were consistent—perhaps inherently related—with unchanged levels of BDNF.
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Affiliation(s)
- Wiebke Theilmann
- Department of Pharmacology, Toxicology and Pharmacy, University of Veterinary Medicine Hannover, Hannover, Germany
| | - Marko Rosenholm
- Division of Pharmacology and Pharmacotherapy, Faculty of Pharmacy, Laboratory of Neurotherapeutics, Drug Research Program, University of Helsinki, Helsinki, Finland
- SleepWell Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland
| | - Philip Hampel
- Department of Pharmacology, Toxicology and Pharmacy, University of Veterinary Medicine Hannover, Hannover, Germany
| | - Wolfgang Löscher
- Department of Pharmacology, Toxicology and Pharmacy, University of Veterinary Medicine Hannover, Hannover, Germany
| | - Tomi Rantamäki
- Division of Pharmacology and Pharmacotherapy, Faculty of Pharmacy, Laboratory of Neurotherapeutics, Drug Research Program, University of Helsinki, Helsinki, Finland
- SleepWell Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland
- * E-mail:
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Sun Y, Wei C, Cui V, Xiu M, Wu A. Electroencephalography: Clinical Applications During the Perioperative Period. Front Med (Lausanne) 2020; 7:251. [PMID: 32582735 PMCID: PMC7296088 DOI: 10.3389/fmed.2020.00251] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2019] [Accepted: 05/11/2020] [Indexed: 12/28/2022] Open
Abstract
Electroencephalography (EEG) monitoring has become technically feasible in daily clinical anesthesia practice. EEG is a sensitive method for detecting neurophysiological changes in the brain and represents an important frontier in the monitoring and treatment of patients in the perioperative period. In this review, we briefly introduce the essential principles of EEG. We review EEG application during anesthesia practice in the operating room, including the use of processed EEG in depth of anesthesia assessment, raw EEG monitoring in recognizing brain states under different anesthetic agents, the use of EEG in the prevention of perioperative neurocognitive disorders and detection of cerebral ischemia. We then discuss EEG utilization in the intensive care units, including the use of EEG in sedative level titration and prognostication of clinical outcomes. Existing literature provides insight into both the advances and challenges of the clinical applications of EEG. Future study is clearly needed to elucidate the precise EEG features that can reliably optimize perioperative care for individual patients.
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Affiliation(s)
- Yi Sun
- Department of Anesthesiology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China
| | - Changwei Wei
- Department of Anesthesiology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China
| | - Victoria Cui
- Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO, United States
| | - Meihong Xiu
- Peking University HuiLongGuan Clinical Medical School, Beijing HuiLongGuan Hospital, Beijing, China
| | - Anshi Wu
- Department of Anesthesiology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China
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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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Kim M, Fricchione G, Brown E, Akeju O. Role of electroencephalogram oscillations and the spectrogram in monitoring anaesthesia. BJA Educ 2020; 20:166-172. [DOI: 10.1016/j.bjae.2020.01.004] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/20/2020] [Indexed: 12/20/2022] Open
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Standage D, Paré M, Blohm G. Hierarchical recruitment of competition alleviates working memory overload in a frontoparietal model. J Vis 2019; 19:8. [PMID: 31621817 DOI: 10.1167/19.12.8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022] Open
Abstract
The storage limitations of visual working memory have been the subject of intense research interest for several decades, but few studies have systematically investigated the dependence of these limitations on memory load that exceeds our retention abilities. Under this real-world scenario, performance typically declines beyond a critical load among low-performing subjects, a phenomenon known as working memory overload. We used a frontoparietal cortical model to test the hypothesis that high-performing subjects select a manageable number of items for storage, thereby avoiding overload. The model accounts for behavioral and electrophysiological data from high-performing subjects in a parameter regime where competitive encoding in its prefrontal network selects items for storage, interareal projections sustain their representations after stimulus offset, and weak dynamics in its parietal network limit their mutual interference. Violation of these principles accounts for these data among low-performing subjects, implying that poor visual working memory performance reflects poor control over frontoparietal circuitry, making testable predictions for experiments.
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Affiliation(s)
- Dominic Standage
- Centre for Neuroscience Studies, Queen's University, Kingston, Ontario, Canada.,School of Psychology, University of Birmingham, Birmingham, UK
| | - Martin Paré
- Centre for Neuroscience Studies, Queen's University, Kingston, Ontario, Canada
| | - Gunnar Blohm
- Centre for Neuroscience Studies, Queen's University, Kingston, Ontario, Canada
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Zebrafish behavioural profiling identifies GABA and serotonin receptor ligands related to sedation and paradoxical excitation. Nat Commun 2019; 10:4078. [PMID: 31501447 PMCID: PMC6733874 DOI: 10.1038/s41467-019-11936-w] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2019] [Accepted: 08/13/2019] [Indexed: 02/08/2023] Open
Abstract
Anesthetics are generally associated with sedation, but some anesthetics can also increase brain and motor activity—a phenomenon known as paradoxical excitation. Previous studies have identified GABAA receptors as the primary targets of most anesthetic drugs, but how these compounds produce paradoxical excitation is poorly understood. To identify and understand such compounds, we applied a behavior-based drug profiling approach. Here, we show that a subset of central nervous system depressants cause paradoxical excitation in zebrafish. Using this behavior as a readout, we screened thousands of compounds and identified dozens of hits that caused paradoxical excitation. Many hit compounds modulated human GABAA receptors, while others appeared to modulate different neuronal targets, including the human serotonin-6 receptor. Ligands at these receptors generally decreased neuronal activity, but paradoxically increased activity in the caudal hindbrain. Together, these studies identify ligands, targets, and neurons affecting sedation and paradoxical excitation in vivo in zebrafish. Some anesthetics despite being generally associated with sedation, can also increase brain activity—a phenomenon called paradoxical excitation. The authors identified dozens of compounds that generally decrease neuronal activity, but increase activity in the caudal hindbrain of zebrafish.
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Influence of midazolam premedication on intraoperative EEG signatures in elderly patients. Clin Neurophysiol 2019; 130:1673-1681. [PMID: 31351371 DOI: 10.1016/j.clinph.2019.05.035] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2018] [Revised: 04/23/2019] [Accepted: 05/30/2019] [Indexed: 12/25/2022]
Abstract
OBJECTIVE To investigate the influence of midazolam premedication on the EEG-spectrum before and during general anesthesia in elderly patients. METHODS Patients aged ≥65 years, undergoing elective surgery were included in this prospective observational study. A continuous pre- and intraoperative frontal EEG was recorded in patients who received premedication with midazolam (Mid, n = 15) and patients who did not (noMid, n = 30). Absolute power within the delta (0.5-4 Hz), theta (4-8 Hz), alpha (8-12 Hz), and beta (12-25 Hz) frequency-bands was analyzed in EEG-sections before (pre-induction), and after induction of anesthesia with propofol (post-induction), as well as during general anesthesia with either propofol or volatile-anesthetics (intra-operative). RESULTS Pre-induction, α-power of Mid patients was lower compared with noMid-patients (α-power: Mid: -10.75 dB vs. noMid: -9.20 dB; p = 0.036). After induction of anesthesia Mid-patients displayed a stronger increase of frontal α-power resulting in higher absolute α-power at post-induction state, (α-power: Mid -3.56 dB vs. noMid: -6.69 dB; p = 0.004), which remained higher intraoperatively (α-power: Mid: -2.12 dB vs. noMid: -6.10 dB; p = 0.024). CONCLUSION Midazolam premedication alters the intraoperative EEG-spectrum in elderly patients. SIGNIFICANCE This finding provides further evidence for the role of GABAergic activation in the induction of elevated, frontal α-power during general anesthesia. TRIAL REGISTRY NUMBER NCT02265263. 23 September 2014. Principal investigator: Prof. Dr. med. Claudia Spies. (https://clinicaltrials.gov/ct2/show/NCT02265263).
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41
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Role of cerebellar GABAergic dysfunctions in the origins of essential tremor. Proc Natl Acad Sci U S A 2019; 116:13592-13601. [PMID: 31209041 DOI: 10.1073/pnas.1817689116] [Citation(s) in RCA: 45] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023] Open
Abstract
Essential tremor (ET) is among the most prevalent movement disorders, but its origins are elusive. The inferior olivary nucleus (ION) has been hypothesized as the prime generator of tremor because of the pacemaker properties of ION neurons, but structural and functional changes in ION are unlikely under ET. Abnormalities have instead been reported in the cerebello-thalamo-cortical network, including dysfunctions of the GABAergic projections from the cerebellar cortex to the dentate nucleus. It remains unclear, though, how tremor would relate to a dysfunction of cerebellar connectivity. To address this question, we built a computational model of the cortico-cerebello-thalamo-cortical loop. We simulated the effects of a progressive loss of GABAA α1-receptor subunits and up-regulation of α2/3-receptor subunits in the dentate nucleus, and correspondingly, we studied the evolution of the firing patterns along the loop. The model closely reproduced experimental evidence for each structure in the loop. It showed that an alteration of amplitudes and decay times of the GABAergic currents to the dentate nucleus can facilitate sustained oscillatory activity at tremor frequency throughout the network as well as a robust bursting activity in the thalamus, which is consistent with observations of thalamic tremor cells in ET patients. Tremor-related oscillations initiated in small neural populations and spread to a larger network as the synaptic dysfunction increased, while thalamic high-frequency stimulation suppressed tremor-related activity in thalamus but increased the oscillation frequency in the olivocerebellar loop. These results suggest a mechanism for tremor generation under cerebellar dysfunction, which may explain the origin of ET.
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Abstract
PURPOSE OF REVIEW To summarize recent recommendations on intraoperative electroencephalogram (EEG) neuromonitoring in the elderly aimed at the prevention of postoperative delirium and long-term neurocognitive decline. We discuss recent perioperative EEG investigations relating to aging and cognitive dysfunction, and their implications on intraoperative EEG neuromonitoring in elderly patients. RECENT FINDINGS The incidence of postoperative delirium in elderly can be reduced by monitoring depth of anesthesia, using an index number (0-100) derived from processed frontal EEG readings. The recently published European Society of Anaesthesiology guideline on postoperative delirium in elderly now recommends guiding general anesthesia with such indices (Level A). However, intraoperative EEG signatures are heavily influenced by age, cognitive function, and choice of anesthetic agents. Detailed spectral EEG analysis and research on EEG-based functional connectivity provide new insights into the pathophysiology of neuronal excitability, which is seen in elderly patients with postoperative delirium. SUMMARY Anesthesiologists should become acquainted with intraoperative EEG signatures and their relation to age, anesthetic agents, and the risk of postoperative cognitive complications. A working knowledge would allow an optimized and individualized provision of general anesthesia for the elderly.
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Lee SH, Lee GM, Lee DR, Lee JU. Factors related to paradoxical reactions during propofol-induced sedated endoscopy. Scand J Gastroenterol 2019; 54:371-376. [PMID: 30931652 DOI: 10.1080/00365521.2019.1585938] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Objective: The factors related to paradoxical excitement during propofol-induced sedation remain unclear. We aimed to investigate this issue during sedated upper endoscopy. Material and methods: Among the health examinees scheduled for sedated upper endoscopy from June 2017 to December 2017, 421 participated in the study. Endoscopists were blinded to the information about the examinees and evaluated the development of paradoxical reactions. Propofol was exclusively used as the sedative agent via intermittent bolus injection. A multiple logistic regression analysis was performed to investigate the factors associated with paradoxical reactions. Results: The incidence of paradoxical reactions was 16.1%. Anxiety (adjusted odds ratio: 2.76; 95% confidence interval: 1.46 - 5.27; p = .002) and age (odds ratio: 0.92; 95% confidence interval: 0.89 - 0.96; p < .001) were significantly associated with paradoxical reactions. Of the nine items of the anxiety questionnaire, four had independent and significant associations with paradoxical reactions (i.e., excess worry, sleeping problems, somatic symptoms, and health concerns; odds ratios: 2.38, 2.71, 2.27 and 2.39, respectively). Conclusion: Propofol-induced paradoxical reactions tend to occur when an individual has anxiety and is of a young age. Further large population-based studies should be performed to confirm this phenomenon.
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Affiliation(s)
- Seung Hwa Lee
- a Center for Health Promotion and Endoscopy, Seohae Hospital , Seocheon , South Korea
| | - Gyu Min Lee
- b Center for Health Promotion and Endoscopy, Wonkwang University School of Medicine , Gunpo , South Korea
| | - Dong Ryul Lee
- b Center for Health Promotion and Endoscopy, Wonkwang University School of Medicine , Gunpo , South Korea
| | - Jung Un Lee
- b Center for Health Promotion and Endoscopy, Wonkwang University School of Medicine , Gunpo , South Korea
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Finley J. Cellular stress and AMPK links metformin and diverse compounds with accelerated emergence from anesthesia and potential recovery from disorders of consciousness. Med Hypotheses 2019; 124:42-52. [PMID: 30798915 DOI: 10.1016/j.mehy.2019.01.014] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2018] [Accepted: 01/19/2019] [Indexed: 01/23/2023]
Abstract
The neural correlates of consciousness and the mechanisms by which general anesthesia (GA) modulate such correlates to induce loss of consciousness (LOC) has been described as one of the biggest mysteries of modern medicine. Several cellular targets and neural circuits have been identified that play a critical role in LOC induced by GA, including the GABAA receptor and ascending arousal nuclei located in the basal forebrain, hypothalamus, and brain stem. General anesthetics (GAs) including propofol and inhalational agents induce LOC in part by potentiating chloride influx through the GABAA receptor, leading to neural inhibition and LOC. Interestingly, nearly all GAs used clinically may also induce paradoxical excitation, a phenomenon in which GAs promote neuronal excitation at low doses before inducing unconsciousness. Additionally, emergence from GA, a passive process that occurs after anesthetic removal, is associated with lower anesthetic concentrations in the brain compared to doses associated with induction of GA. AMPK, an evolutionarily conserved kinase activated by cellular stress (e.g. increases in calcium [Ca2+] and/or reactive oxygen species [ROS], etc.) increases lifespan and healthspan in several model organisms. AMPK is located throughout the mammalian brain, including in neurons of the thalamus, hypothalamus, and striatum as well as in pyramidal neurons in the hippocampus and cortex. Increases in ROS and Ca2+ play critical roles in neuronal excitation and glutamate, the primary excitatory neurotransmitter in the human brain, activates AMPK in cortical neurons. Nearly every neurotransmitter released from ascending arousal circuits that promote wakefulness, arousal, and consciousness activates AMPK, including acetylcholine, histamine, orexin-A, dopamine, and norepinephrine. Several GAs that are commonly used to induce LOC in human patients also activate AMPK (e.g. propofol, sevoflurane, isoflurane, dexmedetomidine, ketamine, midazolam). Various compounds that accelerate emergence from anesthesia, thus mitigating problematic effects associated with delayed emergence such as delirium, also activate AMPK (e.g. nicotine, caffeine, forskolin, carbachol). GAs and neurotransmitters also act as preconditioning agents and the GABAA receptor inhibitor bicuculline, which reverses propofol anesthesia, also activates AMPK in cortical neurons. We propose the novel hypothesis that cellular stress-induced AMPK activation links wakefulness, arousal, and consciousness with paradoxical excitation and accelerated emergence from anesthesia. Because AMPK activators including metformin and nicotine promote proliferation and differentiation of neural stem cells located in the subventricular zone and the dentate gyrus, AMPK activation may also enhance brain repair and promote potential recovery from disorders of consciousness (i.e. minimally conscious state, vegetative state, coma).
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Tikidji-Hamburyan RA, Leonik CA, Canavier CC. Phase response theory explains cluster formation in sparsely but strongly connected inhibitory neural networks and effects of jitter due to sparse connectivity. J Neurophysiol 2019; 121:1125-1142. [PMID: 30726155 DOI: 10.1152/jn.00728.2018] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
We show how to predict whether a neural network will exhibit global synchrony (a one-cluster state) or a two-cluster state based on the assumption of pulsatile coupling and critically dependent upon the phase response curve (PRC) generated by the appropriate perturbation from a partner cluster. Our results hold for a monotonically increasing (meaning longer delays as the phase increases) PRC, which likely characterizes inhibitory fast-spiking basket and cortical low-threshold-spiking interneurons in response to strong inhibition. Conduction delays stabilize synchrony for this PRC shape, whereas they destroy two-cluster states, the former by avoiding a destabilizing discontinuity and the latter by approaching it. With conduction delays, stronger coupling strength can promote a one-cluster state, so the weak coupling limit is not applicable here. We show how jitter can destabilize global synchrony but not a two-cluster state. Local stability of global synchrony in an all-to-all network does not guarantee that global synchrony can be observed in an appropriately scaled sparsely connected network; the basin of attraction can be inferred from the PRC and must be sufficiently large. Two-cluster synchrony is not obviously different from one-cluster synchrony in the presence of noise and may be the actual substrate for oscillations observed in the local field potential (LFP) and the electroencephalogram (EEG) in situations where global synchrony is not possible. Transitions between cluster states may change the frequency of the rhythms observed in the LFP or EEG. Transitions between cluster states within an inhibitory subnetwork may allow more effective recruitment of pyramidal neurons into the network rhythm. NEW & NOTEWORTHY We show that jitter induced by sparse connectivity can destabilize global synchrony but not a two-cluster state with two smaller clusters firing alternately. On the other hand, conduction delays stabilize synchrony and destroy two-cluster states. These results hold if each cluster exhibits a phase response curve similar to one that characterizes fast-spiking basket and cortical low-threshold-spiking cells for strong inhibition. Either a two-cluster or a one-cluster state might provide the oscillatory substrate for neural computations.
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Affiliation(s)
- Ruben A Tikidji-Hamburyan
- Department of Cell Biology and Anatomy, Louisiana State University Health Sciences Center , New Orleans, Louisiana
| | - Conrad A Leonik
- Department of Cell Biology and Anatomy, Louisiana State University Health Sciences Center , New Orleans, Louisiana
| | - Carmen C Canavier
- Department of Cell Biology and Anatomy, Louisiana State University Health Sciences Center , New Orleans, Louisiana
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Differentiating Drug-related and State-related Effects of Dexmedetomidine and Propofol on the Electroencephalogram. Anesthesiology 2019; 129:22-36. [PMID: 29642080 DOI: 10.1097/aln.0000000000002192] [Citation(s) in RCA: 43] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Abstract
BACKGROUND Differentiating drug-related changes and state-related changes on the electroencephalogram during anesthetic-induced unconsciousness has remained a challenge. To distinguish these, we designed a rigorous experimental protocol with two drugs known to have distinct molecular mechanisms of action. We hypothesized that drug- and state-related changes can be separated. METHODS Forty-seven healthy participants were randomized to receive dexmedetomidine (n = 23) or propofol (n = 24) as target-controlled infusions until loss of responsiveness. Then, an attempt was made to arouse the participant to regain responsiveness while keeping the drug infusion constant. Finally, the concentration was increased 1.5-fold to achieve presumable loss of consciousness. We conducted statistical comparisons between the drugs and different states of consciousness for spectral bandwidths, and observed how drug-induced electroencephalogram patterns reversed upon awakening. Cross-frequency coupling was also analyzed between slow-wave phase and alpha power. RESULTS Eighteen (78%) and 10 (42%) subjects were arousable during the constant drug infusion in the dexmedetomidine and propofol groups, respectively (P = 0.011 between the drugs). Corresponding with deepening anesthetic level, slow-wave power increased, and a state-dependent alpha anteriorization was detected with both drugs, especially with propofol. The slow-wave and frontal alpha activities were momentarily disrupted as the subjects regained responsiveness at awakening. Negative phase-amplitude coupling before and during loss of responsiveness frontally and positive coupling during the highest drug concentration posteriorly were observed in the propofol but not in the dexmedetomidine group. CONCLUSIONS Electroencephalogram effects of dexmedetomidine and propofol are strongly drug- and state-dependent. Changes in slow-wave and alpha activity seemed to best detect different states of consciousness.
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γ-Aminobutyric Acid Type A Receptor Potentiation Inhibits Learning in a Computational Network Model. Anesthesiology 2019; 129:106-117. [PMID: 29664887 DOI: 10.1097/aln.0000000000002230] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
BACKGROUND Propofol produces memory impairment at concentrations well below those abolishing consciousness. Episodic memory, mediated by the hippocampus, is most sensitive. Two potentially overlapping scenarios may explain how γ-aminobutyric acid receptor type A (GABAA) potentiation by propofol disrupts episodic memory-the first mediated by shifting the balance from excitation to inhibition while the second involves disruption of rhythmic oscillations. We use a hippocampal network model to explore these scenarios. The basis for these experiments is the proposal that the brain represents memories as groups of anatomically dispersed strongly connected neurons. METHODS A neuronal network with connections modified by synaptic plasticity was exposed to patterned stimuli, after which spiking output demonstrated evidence of stimulus-related neuronal group development analogous to memory formation. The effect of GABAA potentiation on this memory model was studied in 100 unique networks. RESULTS GABAA potentiation consistent with moderate propofol effects reduced neuronal group size formed in response to a patterned stimulus by around 70%. Concurrently, accuracy of a Bayesian classifier in identifying learned patterns in the network output was reduced. Greater potentiation led to near total failure of group formation. Theta rhythm variations had no effect on group size or classifier accuracy. CONCLUSIONS Memory formation is widely thought to depend on changes in neuronal connection strengths during learning that enable neuronal groups to respond with greater facility to familiar stimuli. This experiment suggests the ability to form such groups is sensitive to alteration in the balance between excitation and inhibition such as that resulting from administration of a γ-aminobutyric acid-mediated anesthetic agent.
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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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Plummer GS, Ibala R, Hahm E, An J, Gitlin J, Deng H, Shelton KT, Solt K, Qu JZ, Akeju O. Electroencephalogram dynamics during general anesthesia predict the later incidence and duration of burst-suppression during cardiopulmonary bypass. Clin Neurophysiol 2018; 130:55-60. [PMID: 30476711 DOI: 10.1016/j.clinph.2018.11.003] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2018] [Revised: 10/18/2018] [Accepted: 11/06/2018] [Indexed: 01/11/2023]
Abstract
OBJECTIVE Electroencephalogram burst-suppression during general anesthesia is associated with post-operative delirium (POD). Whether burst-suppression causes POD or merely reflects susceptibility to POD is unclear. We hypothesized decreased intraoperative alpha (8-12 Hz) and beta (13-33 Hz) power prior to the occurrence of burst-suppression in susceptible patients. METHODS We analyzed intraoperative electroencephalogram data of cardiac surgical patients undergoing cardiopulmonary bypass (CPB). We detected the incidence and duration of CPB burst-suppression with an automated burst-suppression detection algorithm. We analyzed EEG data with multitaper spectral estimation methods. We assessed associations between patient characteristics and burst-suppression using Binomial and Zero-inflated Poisson Regression Models. RESULTS We found significantly decreased alpha and beta power (7.8-22.95 Hz) in the CPB burst-suppression cohort. The odds ratio for the association between point estimates for alpha and beta power (7.8-22.95 Hz) and the incidence of burst-suppression was 0.88 (95% CI: 0.79-0.98). The incidence rate ratio for the association between point estimates for power between the alpha and beta range and the duration of burst-suppression was 0.89 (95% CI: 0.84-0.93). CONCLUSION Decreased intra-operative power within the alpha and beta range was associated with susceptibility to burst-suppression during CPB. SIGNIFICANCE This dynamic may be used to develop principled neurophysiological-based approaches to aid the preemptive identification and targeted care of POD vulnerable patients.
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Affiliation(s)
- George S Plummer
- Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Tufts University School of Medicine, Boston, MA, USA
| | - Reine Ibala
- Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Eunice Hahm
- Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Jingzhi An
- Department of Brain and Cognitive Science, Massachusetts Institute of Technology, Cambridge, MA, USA
| | - Jacob Gitlin
- Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Hao Deng
- Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Kenneth T Shelton
- Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Ken Solt
- Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Jason Z Qu
- Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Oluwaseun Akeju
- Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
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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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