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      Complexity of Multi-Dimensional Spontaneous EEG Decreases during Propofol Induced General Anaesthesia

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          Abstract

          Emerging neural theories of consciousness suggest a correlation between a specific type of neural dynamical complexity and the level of consciousness: When awake and aware, causal interactions between brain regions are both integrated (all regions are to a certain extent connected) and differentiated (there is inhomogeneity and variety in the interactions). In support of this, recent work by Casali et al (2013) has shown that Lempel-Ziv complexity correlates strongly with conscious level, when computed on the EEG response to transcranial magnetic stimulation. Here we investigated complexity of spontaneous high-density EEG data during propofol-induced general anaesthesia. We consider three distinct measures: (i) Lempel-Ziv complexity, which is derived from how compressible the data are; (ii) amplitude coalition entropy, which measures the variability in the constitution of the set of active channels; and (iii) the novel synchrony coalition entropy (SCE), which measures the variability in the constitution of the set of synchronous channels. After some simulations on Kuramoto oscillator models which demonstrate that these measures capture distinct ‘flavours’ of complexity, we show that there is a robustly measurable decrease in the complexity of spontaneous EEG during general anaesthesia.

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          Approximate entropy as a measure of system complexity.

          Techniques to determine changing system complexity from data are evaluated. Convergence of a frequently used correlation dimension algorithm to a finite value does not necessarily imply an underlying deterministic model or chaos. Analysis of a recently developed family of formulas and statistics, approximate entropy (ApEn), suggests that ApEn can classify complex systems, given at least 1000 data values in diverse settings that include both deterministic chaotic and stochastic processes. The capability to discern changing complexity from such a relatively small amount of data holds promise for applications of ApEn in a variety of contexts.
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            The entropic brain: a theory of conscious states informed by neuroimaging research with psychedelic drugs

            Entropy is a dimensionless quantity that is used for measuring uncertainty about the state of a system but it can also imply physical qualities, where high entropy is synonymous with high disorder. Entropy is applied here in the context of states of consciousness and their associated neurodynamics, with a particular focus on the psychedelic state. The psychedelic state is considered an exemplar of a primitive or primary state of consciousness that preceded the development of modern, adult, human, normal waking consciousness. Based on neuroimaging data with psilocybin, a classic psychedelic drug, it is argued that the defining feature of “primary states” is elevated entropy in certain aspects of brain function, such as the repertoire of functional connectivity motifs that form and fragment across time. Indeed, since there is a greater repertoire of connectivity motifs in the psychedelic state than in normal waking consciousness, this implies that primary states may exhibit “criticality,” i.e., the property of being poised at a “critical” point in a transition zone between order and disorder where certain phenomena such as power-law scaling appear. Moreover, if primary states are critical, then this suggests that entropy is suppressed in normal waking consciousness, meaning that the brain operates just below criticality. It is argued that this entropy suppression furnishes normal waking consciousness with a constrained quality and associated metacognitive functions, including reality-testing and self-awareness. It is also proposed that entry into primary states depends on a collapse of the normally highly organized activity within the default-mode network (DMN) and a decoupling between the DMN and the medial temporal lobes (which are normally significantly coupled). These hypotheses can be tested by examining brain activity and associated cognition in other candidate primary states such as rapid eye movement (REM) sleep and early psychosis and comparing these with non-primary states such as normal waking consciousness and the anaesthetized state.
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              Controlled sedation with alphaxalone-alphadolone.

              Alphaxalone-alphadolone (Althesin), diluted and administered as a controlled infusion, was used as a sedative for 30 patients in an intensive therapy unit. This technique allowed rapid and accurate control of the level of sedation. It had three particularly useful applications: it provided "light sleep," allowed rapid variation in the level of sedation, and enabled repeated assessment of the central nervous system.Sedation was satisfactory for 86% of the total time, and no serious complications were attributed to the use of the drug. Furthermore, though alphaxalone-alphadolone was given for periods up to 20 days there was no evidence of tachyphylaxis or delay in recovery time.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                2015
                7 August 2015
                : 10
                : 8
                : e0133532
                Affiliations
                [1 ]Sackler Centre for Consciousness Science, Department of Informatics, University of Sussex, Brighton, United Kingdom
                [2 ]Coma Science Group, University of Liège, Liège, Belgium
                [3 ]Department of Neurology, University of Wisconsin, Madison, United States of America
                [4 ]Department of Psychiatry, University of Wisconsin, Madison, United States of America
                [5 ]Department of Clinical Sciences, University of Milan, Milan, Italy
                National Scientific and Technical Research Council (CONICET)., ARGENTINA
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: MS AB. Performed the experiments: MS AB. Analyzed the data: MS. Contributed reagents/materials/analysis tools: MAB QN MB SL. Wrote the paper: AB MS AS QN.

                Article
                PONE-D-15-00798
                10.1371/journal.pone.0133532
                4529106
                26252378
                b81d9ea4-e63e-4722-98d7-331f0859e1e6
                Copyright @ 2015

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

                History
                : 7 January 2015
                : 28 June 2015
                Page count
                Figures: 10, Tables: 2, Pages: 21
                Funding
                MMS is supported by a GTA of the Department of Informatics, University of Sussex. ABB is supported by Engineering and Physical Sciences Research Council fellowship EP/L005131/1. AKS is supported from The Dr. Mortimer and Theresa Sackler Foundation, as part of their support of the Sackler Centre for Consciousness Science. SL is a Belgian Funds for Scientific Research (FRS) Senior Research Associate and MAB, QN and MB are FRS Postdoctoral Researchers. This work was also supported by the European Commission (DECODER), Fondazione Europea di Ricerca Biomedica, McDonnell Foundation, Mind Science Foundation, Public Utility Foundation ‘‘Université Européenne du Travail’’ and the University of Liège. Possible inaccuracies of information are the responsibility of the project team. The text reflects solely the views of its authors. The European Commission is not liable for any use that may be made of the information contained herein. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Custom metadata
                Data are from Murphy et al (Murphy M, Bruno M, Riedner B, et al. (2011) Propofol anesthesia and sleep: a high-density EEG study. Sleep 34:283–291A), whose authors can be contacted at http://www.coma.ulg.ac.be/home/people.html.

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