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      DMT alters cortical travelling waves

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          Abstract

          Psychedelic drugs are potent modulators of conscious states and therefore powerful tools for investigating their neurobiology. N,N, Dimethyltryptamine (DMT) can rapidly induce an extremely immersive state of consciousness characterized by vivid and elaborate visual imagery. Here, we investigated the electrophysiological correlates of the DMT-induced altered state from a pool of participants receiving DMT and (separately) placebo (saline) while instructed to keep their eyes closed. Consistent with our hypotheses, results revealed a spatio-temporal pattern of cortical activation (i.e. travelling waves) similar to that elicited by visual stimulation. Moreover, the typical top-down alpha-band rhythms of closed-eyes rest were significantly decreased, while the bottom-up forward wave was significantly increased. These results support a recent model proposing that psychedelics reduce the ‘precision-weighting of priors’, thus altering the balance of top-down versus bottom-up information passing. The robust hypothesis-confirming nature of these findings imply the discovery of an important mechanistic principle underpinning psychedelic-induced altered states.

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          Most cited references52

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          FieldTrip: Open Source Software for Advanced Analysis of MEG, EEG, and Invasive Electrophysiological Data

          This paper describes FieldTrip, an open source software package that we developed for the analysis of MEG, EEG, and other electrophysiological data. The software is implemented as a MATLAB toolbox and includes a complete set of consistent and user-friendly high-level functions that allow experimental neuroscientists to analyze experimental data. It includes algorithms for simple and advanced analysis, such as time-frequency analysis using multitapers, source reconstruction using dipoles, distributed sources and beamformers, connectivity analysis, and nonparametric statistical permutation tests at the channel and source level. The implementation as toolbox allows the user to perform elaborate and structured analyses of large data sets using the MATLAB command line and batch scripting. Furthermore, users and developers can easily extend the functionality and implement new algorithms. The modular design facilitates the reuse in other software packages.
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            Psychedelics.

            Psychedelics (serotonergic hallucinogens) are powerful psychoactive substances that alter perception and mood and affect numerous cognitive processes. They are generally considered physiologically safe and do not lead to dependence or addiction. Their origin predates written history, and they were employed by early cultures in many sociocultural and ritual contexts. After the virtually contemporaneous discovery of (5R,8R)-(+)-lysergic acid-N,N-diethylamide (LSD)-25 and the identification of serotonin in the brain, early research focused intensively on the possibility that LSD and other psychedelics had a serotonergic basis for their action. Today there is a consensus that psychedelics are agonists or partial agonists at brain serotonin 5-hydroxytryptamine 2A receptors, with particular importance on those expressed on apical dendrites of neocortical pyramidal cells in layer V. Several useful rodent models have been developed over the years to help unravel the neurochemical correlates of serotonin 5-hydroxytryptamine 2A receptor activation in the brain, and a variety of imaging techniques have been employed to identify key brain areas that are directly affected by psychedelics. Recent and exciting developments in the field have occurred in clinical research, where several double-blind placebo-controlled phase 2 studies of psilocybin-assisted psychotherapy in patients with cancer-related psychosocial distress have demonstrated unprecedented positive relief of anxiety and depression. Two small pilot studies of psilocybin-assisted psychotherapy also have shown positive benefit in treating both alcohol and nicotine addiction. Recently, blood oxygen level-dependent functional magnetic resonance imaging and magnetoencephalography have been employed for in vivo brain imaging in humans after administration of a psychedelic, and results indicate that intravenously administered psilocybin and LSD produce decreases in oscillatory power in areas of the brain's default mode network.
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              REBUS and the Anarchic Brain: Toward a Unified Model of the Brain Action of Psychedelics

              This paper formulates the action of psychedelics by integrating the free-energy principle and entropic brain hypothesis. We call this formulation relaxed beliefs under psychedelics (REBUS) and the anarchic brain, founded on the principle that—via their entropic effect on spontaneous cortical activity—psychedelics work to relax the precision of high-level priors or beliefs, thereby liberating bottom-up information flow, particularly via intrinsic sources such as the limbic system. We assemble evidence for this model and show how it can explain a broad range of phenomena associated with the psychedelic experience. With regard to their potential therapeutic use, we propose that psychedelics work to relax the precision weighting of pathologically overweighted priors underpinning various expressions of mental illness. We propose that this process entails an increased sensitization of high-level priors to bottom-up signaling (stemming from intrinsic sources), and that this heightened sensitivity enables the potential revision and deweighting of overweighted priors. We end by discussing further implications of the model, such as that psychedelics can bring about the revision of other heavily weighted high-level priors, not directly related to mental health, such as those underlying partisan and/or overly-confident political, religious, and/or philosophical perspectives. Significance Statement Psychedelics are capturing interest, with efforts underway to bring psilocybin therapy to marketing authorisation and legal access within a decade, spearheaded by the findings of a series of phase 2 trials. In this climate, a compelling unified model of how psychedelics alter brain function to alter consciousness would have appeal. Towards this end, we have sought to integrate a leading model of global brain function, hierarchical predictive coding, with an often-cited model of the acute action of psychedelics, the entropic brain hypothesis. The resulting synthesis states that psychedelics work to relax high-level priors, sensitising them to liberated bottom-up information flow, which, with the right intention, care provision and context, can help guide and cultivate the revision of entrenched pathological priors.
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                Author and article information

                Contributors
                Role: Reviewing Editor
                Role: Senior Editor
                Journal
                eLife
                Elife
                eLife
                eLife
                eLife Sciences Publications, Ltd
                2050-084X
                12 October 2020
                2020
                : 9
                : e59784
                Affiliations
                [1 ]Cerco, CNRS Université de Toulouse ToulouseFrance
                [2 ]Computational, Cognitive and Clinical Neuroscience Laboratory (C3NL), Faculty of Medicine, Imperial College LondonUnited Kingdom
                [3 ]Centre for Psychedelic Research, Division of Psychiatry, Department of Brain Sciences, Imperial College London LondonUnited Kingdom
                [4 ]Artificial and Natural Intelligence Toulouse Institute (ANITI) ToulouseFrance
                CEA, DRF/I2BM, NeuroSpin; INSERM, U992, Cognitive Neuroimaging Unit France
                University of Oxford United Kingdom
                CEA, DRF/I2BM, NeuroSpin; INSERM, U992, Cognitive Neuroimaging Unit France
                KU Leuven Belgium
                Author notes
                [†]

                These authors contributed equally to this work.

                Author information
                https://orcid.org/0000-0001-9826-2161
                https://orcid.org/0000-0002-2281-377X
                https://orcid.org/0000-0002-3611-7716
                Article
                59784
                10.7554/eLife.59784
                7577737
                33043883
                47b50f65-5e86-4575-ac91-cd335614736c
                © 2020, Alamia et al

                This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.

                History
                : 08 June 2020
                : 11 October 2020
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/100015904, Alexander Mosley Charitable Trust;
                Award Recipient :
                Funded by: Ad Astra Chandaria Foundation;
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/100015904, CRCNS ANR-NSF;
                Award ID: ANR-19-NEUC-0004
                Award Recipient :
                Funded by: Comision Nacional de Investigacion Cientifica y Tecnologica de Chile;
                Award Recipient :
                The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
                Categories
                Research Article
                Neuroscience
                Custom metadata
                Psychedelics induce a pattern of cortical activity very similar to the one observed during visual perception, despite participants had shut eyes.

                Life sciences
                n,n, dimethyltryptamine,dmt,travelling waves,eeg oscillations,visual hallucinations,conscious perception,human

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