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4. Neural effects of propofol-induced unconsciousness and its reversal using thalamic stimulation

Author

André M Bastos, Jacob A Donoghue, Scott L Brincat, Meredith Mahnke, Jorge Yanar, Josefina Correa, Ayan S Waite, Mikael Lundqvist, Jefferson Roy, Emery N Brown, and Earl K Miller

Subjects
general anesthesia, consciousness, cortex, thalamus, neural oscillations, Medicine, Science, Biology (General), QH301-705.5
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.

Published
2021
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5. Closed-Loop Control of Anesthetic State in Non-Human Primates

Author

Jacob A. Donoghue, Earl K. Miller, Ayan S. Waite, Meredith Mahnke, Sourish Chakravarty, Emery N. Brown, and Indie C. Garwood

Subjects
medicine.diagnostic_test, Control theory, Computer science, Continuous monitoring, medicine, Infusion pump, Local field potential, Neurophysiology, Robust control, Electroencephalography, Optimal control, Propofol, medicine.drug
Abstract

Continuous monitoring of electroencephalogram (EEG) recordings in humans under general anesthesia (GA) has demonstrated that changes in EEG dynamics induced by an anesthetic drug are reliably associated with the altered arousal states caused by the drug. This observation suggests that an intelligent, closed-loop anesthesia delivery (CLAD) system operating in real-time could track EEG dynamics and control the infusion rate of a programmable pump to precisely maintain unconsciousness. The United States FDA acknowledges the potential benefits of such automatic physiological closed-loop control devices for patient care. Bringing these devices into clinical practice requires establishing their feasibility in suitable animal models. Therefore, given the close neurophysiological proximity between human and non-human primates (NHPs), we address this problem by developing and validating a propofol CLAD system in rhesus macaques. Our CLAD system has three key components: (1) a data acquisition system that records cortical local field potentials (LFPs) from an NHP in real-time; (2) a computer executing our CLAD algorithm that takes in the LFP signals as input and outputs infusion rates; and (3) a computer-controlled infusion pump that administers intravenous propofol. Our CLAD system controls an empirically-determined LFP marker of unconsciousness (MOU) at a user-prescribed target value by updating every 20 seconds the propofol infusion rate based on real-time processing of the LFP signal. The MOU is the instantaneous power in the 20 to 30 Hz band of the LFP spectrogram. Every cycle (duration ≈ 20 sec), our CLAD algorithm updates the MOU estimate and uses a robust optimal control strategy to adjust the propofol infusion rate based on the instantaneous error. This error is computed as the difference between the current and the user-prescribed target MOU values. Using neural recordings from multiple NHP anesthesia sessions, we first established that our chosen MOU signal was strongly correlated with propofol-induced decreased spiking activity which itself has been shown earlier to be associated with the level of unconsciousness in NHPs. Then we designed robust optimal control strategies that used subject-specific pharmacokinetic-pharmacodynamic models describing the MOU dynamics due to propofol infusion rate changes. Finally, we achieved safe and efficient closed-loop control of level of unconsciousness in 9 CLAD experiments involving 2 NHPs and 2 different 125 min long target MOU profiles with three target MOU changes within a given experiment. Our CLAD system performs stably, accurately and robustly across a total of 1125 min of closed-loop control. The CLAD performance measures, represented as median (25th percentile, 75th percentile), are 3.13 % (2.62%, 3.53%) for inaccuracy, 0.54 %(-0.31%, 0.89%) for bias, -0.02%/min (-0.06%/min, 0.00%/min) for divergence, and 3% (2.49%, 3.59%) for wobble. These performance measures were comparable or superior to previously reported CLAD performance measures from clinical studies (conducted outside USA) as well as rodent-based studies. The key innovations here are: (1) a pre-clinical NHP model for CLAD development and testing, (2) a neuroscience-informed LFP-based MOU for CLAD, (3) parsimonious, pharmacology-informed models to describe MOU dynamics under propofol infusion in rhesus macaques, (4) a novel numerical testing framework for propofol CLAD that incorporates a principled optimal robust control strategy for titrating propofol, and finally (5) experimental findings demonstrating the feasibility of stable, accurate and robust CLAD in the NHP model. Our NHP-based CLAD framework provides a principled pre-clinical research platform that can form the foundation for future clinical studies.

Published
2021
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7. A hidden Markov model reliably characterizes ketamine-induced spectral dynamics in macaque LFP and human EEG

Author

Shubham Chamadia, Emery N. Brown, Jacob A. Donoghue, Oluwaseun Akeju, Earl K. Miller, Sourish Chakravarty, Indie C. Garwood, and Pegah Kahali

Subjects
Physics, medicine.diagnostic_test, Markov chain, Oscillation, Anesthetic, Trajectory, medicine, Probability distribution, Statistical physics, Local field potential, Electroencephalography, Hidden Markov model, medicine.drug
Abstract

Ketamine is an NMDA receptor antagonist commonly used to maintain general anesthesia. At anesthetic doses, ketamine causes bursts of 30-50 Hz oscillations alternating with 0.1 to 10 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 10 Hz 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. Together, the estimated beta-HMM parameters and optimal state trajectory revealed an alternating pattern of states characterized primarily by gamma burst and slow oscillation activity, as well as intermediate states in between. The mean duration of the gamma burst state was 2.5s([1.9,3.4]s) and 1.2s([0.9,1.5]s) for the two NHPs, and 2.7s([1.9,3.8]s) for the human subjects. The mean duration of the slow oscillation state was 1.6s([1.1,2.5]s) and 0.7s([0.6,0.9]s) for the two NHPs, and 2.8s([1.9,4.3]s) for the human subjects. Our beta-HMM framework provides a useful tool for experimental data analysis. Our characterizations of the gamma-burst process offer detailed, quantitative constraints that 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.

Published
2020
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8. Interhemispheric transfer of working memories

Author

Earl K. Miller, Mikael Lundqvist, Simon Kornblith, Scott L. Brincat, Meredith Mahnke, and Jacob A. Donoghue

Subjects
Neural activity, Working memory, Transfer (computing), Saccade, Laterality, Directionality, Engram, Psychology, Neuroscience, Lateralization of brain function
Abstract

SUMMARYVisual working memory (WM) storage is largely independent between the left and right visual hemifields/cerebral hemispheres, yet somehow WM feels seamless. We studied how WM is integrated across hemifields by recording neural activity bilaterally from lateral prefrontal cortex. An instructed saccade during the WM delay shifted the remembered location from one hemifield to the other. Before the shift, spike rates and oscillatory power showed clear signatures of memory laterality. After the shift, the lateralization inverted, consistent with transfer of the memory trace from one hemisphere to the other. Transferred traces initially used different neural ensembles from feedforward-induced ones but they converged at the end of the delay. Around the time of transfer, synchrony between the two prefrontal hemispheres peaked in theta and beta frequencies, with a directionality consistent with memory trace transfer. This illustrates how dynamics between the two cortical hemispheres can stitch together WM traces across visual hemifields.

Published
2020
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9. Neural effects of propofol-induced unconsciousness and its reversal using thalamic stimulation

Author

Meredith Mahnke, Scott L. Brincat, André M. Bastos, Jacob A. Donoghue, Jorge Yanar, Emery N. Brown, Earl K. Miller, Ayan S. Waite, Jefferson E. Roy, Mikael Lundqvist, and Josefina Correa

Subjects
Male, 0301 basic medicine, QH301-705.5, Science, neural oscillations, Thalamus, Unconsciousness, Local field potential, consciousness, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Neural activity, 0302 clinical medicine, Rhesus macaque, medicine, Animals, Hypnotics and Sedatives, Biology (General), Propofol, Thalamic stimulator, Cerebral Cortex, General Immunology and Microbiology, Chemistry, General Neuroscience, Recovery of Function, General Medicine, general anesthesia, Macaca mulatta, Entrainment (biomusicology), Cortex (botany), cortex, 030104 developmental biology, Anesthetic, Medicine, Female, medicine.symptom, Neuroscience, Anesthetics, Intravenous, 030217 neurology & neurosurgery, Temporal Cortices, Research Article, medicine.drug
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 spiking, 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.

Published
2020
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10. Neural signatures of loss of consciousness and its recovery by thalamic stimulation

Author

Emery N. Brown, Earl K. Miller, Jorge Yanar, Meredith Mahnke, André M. Bastos, Jacob A. Donoghue, and Simon Kornblith

Subjects
0303 health sciences, business.industry, media_common.quotation_subject, Unconsciousness, Thalamus, Stimulation, Local field potential, 03 medical and health sciences, 0302 clinical medicine, medicine, medicine.symptom, Consciousness, Propofol, business, Thalamic stimulator, Neuroscience, 030217 neurology & neurosurgery, Cortical rhythms, 030304 developmental biology, medicine.drug, media_common
Abstract

We know that general anesthesia produces unconsciousness but not quite how. We recorded neural activity from the frontal, parietal, and temporal cortices and thalamus while maintaining unconsciousness in non-human primates (NHPs) with propofol. Unconsciousness was marked by slow frequency (∼1 Hz) oscillations in local field potentials, entraining local spiking to Up states alternating with Down states of little spiking, and decreased higher frequency (>4 Hz) coherence. The thalamus contributed to cortical rhythms. Its stimulation “awakened” anesthetized NHPs and reversed the electrophysiologic features of unconsciousness. Unconsciousness thus resulted from slow frequency hypersynchrony and loss of high-frequency dynamics, partly mediated by the thalamus, that disrupts cortical communication/integration.

Published
2019
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11. Interhemispheric transfer of working memories

Author

Mikael Lundqvist, Simon Kornblith, Scott L. Brincat, Earl K. Miller, Jacob A. Donoghue, Meredith Mahnke, and Picower Institute for Learning and Memory

Subjects
Male, 0301 basic medicine, genetic structures, Working memory, General Neuroscience, Prefrontal Cortex, Cognition, Engram, Macaca mulatta, Functional Laterality, Lateralization of brain function, 03 medical and health sciences, Memory, Short-Term, 030104 developmental biology, 0302 clinical medicine, Laterality, Saccade, Visual Perception, Animals, Directionality, Female, Prefrontal cortex, Psychology, Neuroscience, 030217 neurology & neurosurgery
Abstract

Visual working memory (WM) storage is largely independent between the left and right visual hemifields/cerebral hemispheres, yet somehow WM feels seamless. We studied how WM is integrated across hemifields by recording neural activity bilaterally from lateral prefrontal cortex. An instructed saccade during the WM delay shifted the remembered location from one hemifield to the other. Before the shift, spike rates and oscillatory power showed clear signatures of memory laterality. After the shift, the lateralization inverted, consistent with transfer of the memory trace from one hemisphere to the other. Transferred traces initially used different neural ensembles from feedforward-induced ones, but they converged at the end of the delay. Around the time of transfer, synchrony between the two prefrontal hemispheres peaked in theta and beta frequencies, with a directionality consistent with memory trace transfer. This illustrates how dynamics between the two cortical hemispheres can stitch together WM traces across visual hemifields.Brincat et al. use bilateral recording to show working memories transferring between the right and left prefrontal cortex. Transferred memories engage different ensembles than feedforward-induced memory traces. Trace transfer is accompanied by directed interhemispheric theta/beta synchrony., NIMH (Grant R37MH087027), ONR (Grant MURI N00014-16-1-2832), NIGMS (Grant T32GM007753)

Published
2021
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12. Different Levels of Category Abstraction by Different Dynamics in Different Prefrontal Areas

Author

Andreas Wutz, Roman Loonis, Jefferson E. Roy, Earl K. Miller, and Jacob A. Donoghue

Subjects
Male, 0301 basic medicine, Ventrolateral prefrontal cortex, Computer science, Prototype pattern, Prefrontal Cortex, Sensory system, Article, 03 medical and health sciences, 0302 clinical medicine, medicine, Animals, Gamma Rhythm, Beta Rhythm, Abstraction, Prefrontal cortex, Neurons, business.industry, General Neuroscience, Recognition, Psychology, Pattern recognition, Macaca mulatta, Dorsolateral prefrontal cortex, 030104 developmental biology, medicine.anatomical_structure, Pattern Recognition, Visual, Categorization, Female, Artificial intelligence, business, Photic Stimulation, 030217 neurology & neurosurgery
Abstract

© 2018 Elsevier Inc. Categories can be grouped by shared sensory attributes (i.e., cats) or a more abstract rule (i.e., animals). We explored the neural basis of abstraction by recording from multi-electrode arrays in prefrontal cortex (PFC) while monkeys performed a dot-pattern categorization task. Category abstraction was varied by the degree of exemplar distortion from the prototype pattern. Different dynamics in different PFC regions processed different levels of category abstraction. Bottom-up dynamics (stimulus-locked gamma power and spiking) in the ventral PFC processed more low-level abstractions, whereas top-down dynamics (beta power and beta spike-LFP coherence) in the dorsal PFC processed more high-level abstractions. Our results suggest a two-stage, rhythm-based model for abstracting categories. Wutz et al. show that different levels of category abstraction engage different oscillatory dynamics in different prefrontal cortex (PFC) areas. This suggests a functional specialization within PFC for low-level, stimulus-based categories (e.g., cats) and high-level, rule-based categories (e.g., animals).

Published
2018
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13. Colonic tuberculosis in an immunocompetent patient

Author

Juan Del Castillo-Calcáneo, Eduardo Villanueva-Saenz, Jacob A. Donoghue, Carlos Gonzalez-Sanchez, Gregorio Zubieta-O’Farrill, Harvard University--MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences, and Donoghue, Jacob Alexander

Subjects
education.field_of_study, medicine.medical_specialty, Tuberculosis, business.industry, Extrapulmonary tuberculosis, Population, MEDLINE, Disease, medicine.disease, Dermatology, Article, Tuberculosis in immunocompetent subjects, Colonic tuberculosis, Immunology, Medicine, Surgery, Presentation (obstetrics), education, business, Colonoscopy in tuberculosis
Abstract

INTRODUCTION: One-third of the world's population is infected with tuberculosis (TB), with intestinal TB representing the sixth most common presentation of extrapulmonary TB. The diagnosis of intestinal TB is a challenge for physicians due to its diverse clinical manifestations that mimic other infectious, autoimmune, and neoplastic disorders, and is thus rarely considered as the causative agent of disease. PRESENTATION OF CASE: We present a 55-year-old male with no relevant familial history, who presented due to a loss of 10 kg of weight in 2 months accompanied by nocturnal diaphoresis and continuous abdominal distension. DISCUSSION: The incidence and the severity of intestinal TB are increased in immunosuppressed patients and more rapidly progress due to deficient immune response. However, our immunocompetent had severe progression resulting in surgery less than a month after the diagnosis was made. CONCLUSION: While the diagnosis of intestinal TB, and specifically colonic TB, is difficult and is almost never the first diagnosis entertained outside the immunocompromised population, we present a rare case in which the disease presents in an immunocompetent patient., National Institute of General Medical Sciences (U.S.) (Award T32GM007753)

Published
2013

14. Rapid fragmentation of neuronal networks at the onset of propofol-induced unconsciousness

Author

Leigh R. Hochberg, Joseph R. Madsen, Jacob A. Donoghue, Patrick L. Purdon, Eran A. Mukamel, William S. Anderson, Veronica S. Weiner, Emery N. Brown, Sydney S. Cash, Emad N. Eskandar, and Laura D. Lewis

Subjects
Multidisciplinary, Nerve net, Unconsciousness, Local field potential, Biology, Electrophysiology, medicine.anatomical_structure, Cerebral cortex, Cortex (anatomy), Anesthetic, medicine, Biological neural network, medicine.symptom, Neuroscience, medicine.drug
Abstract

The neurophysiological mechanisms by which anesthetic drugs cause loss of consciousness are poorly understood. Anesthetic actions at the molecular, cellular, and systems levels have been studied in detail at steady states of deep general anesthesia. However, little is known about how anesthetics alter neural activity during the transition into unconsciousness. We recorded simultaneous multiscale neural activity from human cortex, including ensembles of single neurons, local field potentials, and intracranial electrocorticograms, during induction of general anesthesia. We analyzed local and global neuronal network changes that occurred simultaneously with loss of consciousness. We show that propofol-induced unconsciousness occurs within seconds of the abrupt onset of a slow (

Published
2012
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15. Spatiotemporal dynamics of neocortical excitation and inhibition during human sleep

Author

Alain Destexhe, Jacob A. Donoghue, Joseph R. Madsen, Eric Halgren, Emad N. Eskandar, Adrien Peyrache, Sydney S. Cash, Leigh R. Hochberg, Nima Dehghani, William S. Anderson, Unité de Neurosciences Information et Complexité [Gif sur Yvette] (UNIC), Centre National de la Recherche Scientifique (CNRS), Institut de Neurobiologie Alfred Fessard (INAF), Center for Molecular and Behavioral Neuroscience, Rutgers, The State University of New Jersey [New Brunswick] (RU), Rutgers University System (Rutgers)-Rutgers University System (Rutgers), Department Neurology, Department of Neurosurgery, MGH, Harvard University [Cambridge], Nayef Al-Rodhan Laboratories for Cellular Neurosurgery and Neurosurgical Technology, Harvard Medical School [Boston] (HMS)-Massachusetts General Hospital [Boston], Department of Neurosurgery [Boston], Brigham and Women's Hospital [Boston], Multimodal Imaging Laboratory, Department Radiology and Neurosciences (UCSD), University of California [San Diego] (UC San Diego), and University of California-University of California

Subjects
Action Potentials, Neocortex, Electroencephalography, Inhibitory postsynaptic potential, 03 medical and health sciences, Bursting, 0302 clinical medicine, medicine, Premovement neuronal activity, Humans, 030304 developmental biology, Neurons, 0303 health sciences, Multidisciplinary, medicine.diagnostic_test, Chemistry, Dynamics (mechanics), Biological Sciences, Sleep in non-human animals, medicine.anatomical_structure, Excitatory postsynaptic potential, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Sleep, Neuroscience, 030217 neurology & neurosurgery
Abstract

International audience; Intracranial recording is an important diagnostic method routinely used in a number of neurological monitoring scenarios. In recent years, advancements in such recordings have been extended to include unit activity of an ensemble of neurons. However, a detailed functional characterization of excitatory and inhibitory cells has not been attempted in human neocortex, particularly during the sleep state. Here, we report that such feature discrimination is possible from high-density recordings in the neocortex by using 2D multielectrode arrays. Successful separation of regular-spiking neurons (or bursting cells) from fast-spiking cells resulted in well-defined clusters that each showed unique intrinsic firing properties. The high density of the array, which allowed recording from a large number of cells (up to 90), helped us to identify apparent monosynaptic connections, confirming the excitatory and inhibitory nature of regular-spiking and fast-spiking cells, thus categorized as putative pyramidal cells and interneurons, respectively. Finally, we investigated the dynamics of correlations within each class. A marked exponential decay with distance was observed in the case of excitatory but not for inhibitory cells. Although the amplitude of that decline depended on the timescale at which the correlations were computed, the spatial constant did not. Furthermore, this spatial constant is compatible with the typical size of human columnar organization. These findings provide a detailed characterization of neuronal activity, functional connectivity at the microcircuit level, and the interplay of excitation and inhibition in the human neocortex.

Published
2012
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17. Contributors

Author

Bizhan Aarabi, Rick Abbott, Saleem I. Abdulrauf, Frank L. Acosta, John R. Adler, Nzhde Agazaryan, Manish Aghi, Edward S. Ahn, Ali Alaraj, Gregory W. Albert, Leland Albright, Felipe C. Albuquerque, Tord D. Alden, Michael J. Alexander, Andrei V. Alexandrov, Ossama Al-Mefty, Ron L. Alterman, Lázaro Álvarez, Nduka M. Amankulor, Peter S. Amenta, Christopher P. Ames, Sepideh Amin-Hanjani, Mario Ammirati, Carryn Anderson, Richard C.E. Anderson, William S. Anderson, Peter D. Angevine, Hiba Arif, Jeffrey E. Arle, Rocco Armonda, Paul M. Arnold, Kaveh Asadi-Moghaddam, Ferhan A. Asghar, William W. Ashley, Sabri Aydin, Nafi Aygun, Joachim M. Baehring, Jacob H. Bagley, Diaa Bahgat, Julian E. Bailes, Jonathon R. Ball, Gordon H. Baltuch, Nicholas C. Bambakidis, Scott C. Baraban, Igor J. Barani, Nicholas M. Barbaro, Frederick G. Barker, Gene H. Barnett, Stanley L. Barnwell, Constance M. Barone, Daniel L. Barrow, Fabrice Bartolomei, Juan Bartolomei, Tracy T. Batchelor, H. Hunt Batjer, Andrew M. Bauer, Joel A. Bauman, Thomas K. Baumann, James E. Baumgartner, John Bayouth, Andrew Beaumont, Joshua B. Bederson, Rudolf Beisse, Randy S. Bell, Allan Belzberg, Alim Louis Benabid, Eduardo E. Benarroch, Abdelhamid Benazzouz, Bernard R. Bendok, Edward C. Benzel, Alejandro Berenstein, Mitchel S. Berger, Marvin Bergsneider, Helmut Bertalanffy, Tarun Bhalla, Dani S. Bidros, José Biller, Mark H. Bilsky, Devin K. Binder, William Bingaman, Rolfe Birch, Allen T. Bishop, Peter M. Black, Jeffrey P. Blount, Peter C. Blumbergs, Leif-Erik Bohman, Zackary E. Boomsaad, Frederick A. Boop, Pascal Bou-Haidar, Daniel R. Boué, Blaise F.D. Bourgeois, Robin M. Bowman, Oliver Bozinov, Helen M. Bramlett, Henry Brem, Steven Brem, Gavin W. Britz, Douglas L. Brockmeyer, David J. Brooks, Samuel R. Browd, Paul D. Brown, Robert D. Brown, Jeffrey N. Bruce, Janice E. Brunstrom-Hernandez, John Buatti, M. Ross Bullock, Kim J. Burchiel, Peter C. Burger, Marc R. Bussière, Mohamad Bydon, Richard W. Byrne, Maria Elisa Calcagnotto, Victoria A. Campbell, William Campbell, George M. Cannon, Louis P. Caragine, Benjamin S. Carson, Gregory D. Cascino, Ethan Cascio, Frédéric Castinetti, C. Michael Cawley, Justin S. Cetas, Stéphan Chabardès, Edward F. Chang, Eric C. Chang, Eric L. Chang, Steven D. Chang, Steven W. Chang, Susan M. Chang, Kevin Chao, Paul H. Chapman, Fady T. Charbel, Patrick Chauvel, Grace Chen, Boyle C. Cheng, Joseph S. Cheng, Joshua J. Chern, E. Antonio Chiocca, Ondrej Choutka, Shakeel A. Chowdhry, Cindy W. Christian, Kathy Chuang, Jan Claassen, Richard E. Clatterbuck, Elizabeth B. Claus, Daniel R. Cleary, Robert J. Coffey, Alan R. Cohen, Andrew J. Cole, E. Sander Connolly, Patrick J. Connolly, Anne G. Copay, Jeroen R. Coppens, James J. Corbett, Daniel M. Corcos, Domagoj Coric, Garth Rees Cosgrove, William T. Couldwell, Stirling Craig, Neil R. Crawford, Peter B. Crino, R. Webster Crowley, Bradford A. Curt, Marek Czosnyka, Zofia Czosnyka, Vladimir Y. Dadashev, Andrew T. Dailey, Deepa Danan, Shabbar F. Danish, Shervin R. Dashti, Carlos A. David, David J. David, Arthur L. Day, Antonio A.F. De Salles, Amir R. Dehdashti, Oscar H. Del Brutto, Johnny B. Delashaw, Bradley Delman, Mahlon R. DeLong, Franco DeMonte, Sanjay S. Dhall, Mark S. Dias, Curtis A. Dickman, W. Dalton Dietrich, Michael L. DiLuna, Francesco Di Meco, Peter Dirks, C. Edward Dixon, Jacob A. Donoghue, Ian G. Dorward, Amish H. Doshi, James Drake, Dan Drzymalski, Rose Du, Andrew Ducruet, Ann-Christine Duhaime, Aaron S. Dumont, Christopher D. Duntsch, Joshua R. Dusick, Suzan Dyve, James Eberwine, Paula Eboli, Robert D. Ecker, Richard J. Edwards, Marc E. Eichler, Doortje C. Engel, Nancy E. Epstein, Matthew G. Ewend, Hamad Farhat, Christopher J. Farrell, Michael G. Fehlings, Iman Feiz-Erfan, Neil A. Feldstein, Richard G. Fessler, Juan J. Figueroa, Aaron G. Filler, J. Max Findlay, Michael A. Finn, David J. Fiorella, James L. Fisher, Robert S. Fisher, Eugene S. Flamm, James D. Fleck, Kelly D. Flemming, John C. Flickinger, Laura Flores-Sarnat, Kenneth A. Follett, Kelly D. Foote, Daryl R. Fourney, Valerie Fraix, James L. Frazier, Itzhak Fried, Allan H. Friedman, William A. Friedman, Gerhard M. Friehs, Donald E. Fry, Gregory N. Fuller, Hector H. Garcia, Paul A. Gardner, Mark Garrett, Hugh Garton, Cormac G. Gavin, Alisa D. Gean, Thomas A. Gennarelli, Venelin Gerganov, Anand V. Germanwala, Massimo Gerosa, Elizabeth R. Gerstner, Peter C. Gerszten, Saadi Ghatan, Samer Ghostine, Steven Giannotta, Paul R. Gigante, Frank Gilliam, Holly Gilmer-Hill, Albert Gjedde, Roberta P. Glick, Ziya L. Gokaslan, Yakov Gologorsky, Kiarash Golshani, Nestor R. Gonzalez, James Tait Goodrich, Tessa Gordon, Alessandra A. Gorgulho, Liliana C. Goumnerova, M. Sean Grady, Jordan Grafman, Sylvie Grand, Gerald A. Grant, Gregory P. Graziano, Benjamin Greenberg, James Guest, Abhijit Guha, Murat Günel, Gaurav Gupta, Nalin Gupta, Jorge Guridi, Barton L. Guthrie, Georges F. Haddad, Michael M. Haglund, Regis W. Haid, Stephen J. Haines, Clement Hamani, Bronwyn E. Hamilton, D. Kojo Hamilton, Todd C. Hankinson, Leo T. Happel, Ihtsham Ul Haq, Raqeeb Haque, Robert E. Harbaugh, Ciara D. Harraher, Leo Harris, James S. Harrop, Wael Hassaneen, Cynthia Hawkins, Gregory W.J. Hawryluk, Neal G. Haynes, Robert F. Heary, Amy B. Heimberger, Mary M. Heinricher, Thomas M. Hemmen, Jaimie M. Henderson, Roberto C. Heros, Karl Herrup, Shawn L. Hervey-Jumper, Gregory G. Heuer, Lawrence J. Hirsch, Robert Hirschl, Brian L. Hoh, Daniel J. Hoh, Eric C. Holland, Paul E. Holtzheimer, L. Nelson Hopkins, Philip J. Horner, David A. Hovda, Matthew A. Howard, Patrick Hsieh, Yin C. Hu, Sherwin E. Hua, Jason H. Huang, Judy Huang, Samuel A. Hughes, Thierry A.G.M. Huisman, Matthew A. Hunt, R. John Hurlbert, Robert W. Hurst, Anita Huttner, Steven W. Hwang, Ioannis U. Isaias, Bermans J. Iskandar, Arun Jacob, Kurt A. Jaeckle, Jay Jagannathan, Regina I. Jakacki, George I. Jallo, John A. Jane, Ryan Janicki, Damir Janigro, N u Owase Jeelani, Kurt A. Jellinger, Arthur L. Jenkins, Sarah Jernigan, David F. Jimenez, Conrad E. Johanson, J. Patrick Johnson, Matthew D. Johnson, G. Alexander Jones, Rajni K. Jutla, Koijan Singh Kainth, Michael G. Kaiser, U. Kumar Kakarla, Iain H. Kalfas, Aleksandrs Uldis Kalnins, Hideyuki Kano, Yucel Kanpolat, Adam S. Kanter, Reza J. Karimi, Amin B. Kassam, Bruce A. Kaufman, Christian B. Kaufman, Hiroto Kawasaki, Brian C. Kelley, Christopher P. Kellner, Nicole C. Keong, John R.W. Kestle, Alexander A. Khalessi, Nadia Khan, Vini G. Khurana, Daniel H. Kim, Dong Gyu Kim, Dong H. Kim, Jong Hyun Kim, Louis J. Kim, Paul K. Kim, Thomas Aquinas Kim, Won Kim, James A.J. King, Ryan S. Kitagawa, Neil D. Kitchen, Paul Klimo, David G. Kline, Kazutaka Kobayashi, Patrick M. Kochanek, Douglas Kondziolka, Paul N. Kongkham, Tyler R. Koski, Thomas Kosztowski, Paul Krack, Joachim K. Krauss, Michael A. Kraut, Niklaus Krayenbühl, Thomas Kretschmer, Ajit Krishnaney, Charles Kuntz, Jeffrey V. Kuo, Brian K. Kwon, Nadia N. Issa Laack, Shivanand P. Lad, Alim M. Ladha, Amos K. Ladouceur, Arthur M. Lam, Frederick F. Lang, Giuseppe Lanzino, Sean D. Lavine, Edward R. Laws, Michael T. Lawton, Adrian W. Laxton, Tuong H. Le, Jean François LeBas, Brett D. Lebed, Richard L. Lebow, Amy Lee, Ian Lee, Seon-Kyu Lee, Emily Lehmann, James W. Leiphart, Gregory P. Lekovic, Frederick A. Lenz, Jeffrey R. Leonard, Peter D. LeRoux, Marc Lévêque, Allan D. Levi, Elad I. Levy, Linda M. Liau, Jason Liauw, Roger Lichtenbaum, Terry Lichtor, David D. Limbrick, Hester Lingsma, Michael J. Link, Mark E. Linskey, Brian Litt, Zachary N. Litvack, James K.C. Liu, Kenneth C. Liu, Jay S. Loeffler, Christopher M. Loftus, Russell R. Lonser, Angeliki Louvi, Andres M. Lozano, Daniel C. Lu, Rimas V. Lukas, L. Dade Lunsford, Neal Luther, Pedro Lylyk, Andrew I.R. Maas, R. Loch Macdonald, Andre Machado, Raul Macias, Robert J. 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Yousem, Eric C. Yuen, Joseph M. Zabramski, Andrew C. Zacest, J. Christopher Zacko, Gabriel Zada, Ross Zafonte, Eric L. Zager, Hasan A. Zaidi, Hekmat Zarzour, Vasilios A. Zerris, Justin A. Zivin, John G. Zovickian, Alexander Y. Zubkov, and Marike Zwienenberg-Lee

Published
2011
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18. Single-neuron dynamics in human focal epilepsy

Author

Joseph R. Madsen, Wilson Truccolo, Leigh R. Hochberg, Eric Halgren, Emad N. Eskandar, Sydney S. Cash, Jacob A. Donoghue, William S. Anderson, and Emery N. Brown

Subjects
Adult, Male, Spike train, Action Potentials, Electroencephalography, Article, Temporal lobe, Epilepsy, Young Adult, medicine, Premovement neuronal activity, Humans, Neurons, medicine.diagnostic_test, General Neuroscience, Middle Aged, medicine.disease, Temporal Lobe, medicine.anatomical_structure, Nonlinear Dynamics, Female, Neuron, Epilepsies, Partial, Psychology, Neuroscience
Abstract

Epileptic seizures are traditionally characterized as the ultimate expression of monolithic, hypersynchronous neuronal activity arising from unbalanced runaway excitation. Here we report the first examination of spike train patterns in large ensembles of single neurons during seizures in persons with epilepsy. Contrary to the traditional view, neuronal spiking activity during seizure initiation and spread was highly heterogeneous, not hypersynchronous, suggesting complex interactions among different neuronal groups even at the spatial scale of small cortical patches. In contrast to earlier stages, seizure termination is a nearly homogenous phenomenon followed by an almost complete cessation of spiking across recorded neuronal ensembles. Notably, even neurons outside the region of seizure onset showed significant changes in activity minutes before the seizure. These findings suggest a revision of current thinking about seizure mechanisms and point to the possibility of seizure prevention based on spiking activity in neocortical neurons.

Published
2010

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