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REBUS and the Anarchic Brain: Toward a Unified Model of the Brain Action of Psychedelics

R. L. Carhart-Harris and K. J. Friston
Eric L. Barker, ASSOCIATE EDITOR
Pharmacological Reviews July 2019, 71 (3) 316-344; DOI: https://doi.org/10.1124/pr.118.017160
R. L. Carhart-Harris
Centre for Psychedelic Research, Division of Brain Sciences, Imperial College London, London, United Kingdom (R.L.C.-H.); and Institute of Neurology, Wellcome Trust Centre for Neuroimaging, University College London, London, United Kingdom (K.J.F.)
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K. J. Friston
Centre for Psychedelic Research, Division of Brain Sciences, Imperial College London, London, United Kingdom (R.L.C.-H.); and Institute of Neurology, Wellcome Trust Centre for Neuroimaging, University College London, London, United Kingdom (K.J.F.)
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Eric L. Barker
Roles: ASSOCIATE EDITOR
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    Fig. 1.

    This schematic illustrates the proposed effects of psychedelics on hierarchical predictive coding, a predominant process theory for Bayesian inference and variational free-energy minimization in the brain. Under these computational architectures, sensory input arrives at the sensory epithelia and is compared with descending predictions. The ensuing prediction error (blue circles; e.g., neuronal populations of superficial pyramidal cells) is then passed forward into hierarchies, to update expectations at higher levels (blue arrows). These posterior expectations (teal circles; e.g., deep pyramidal cells) then generate predictions of the representations in lower levels, via descending predictions (teal arrows). The recurrent neuronal message passing (i.e., neuronal dynamics) tries to minimize the amplitude of prediction errors at each and every level of the hierarchy, thereby furnishing the best explanation for sensory input at multiple levels of hierarchal abstraction. Crucially, this process depends upon the precision (ascribed importance or salience) afforded to the ascending prediction errors (surprise) and the precision (felt confidence) of posterior beliefs. The basic idea—pursued in this article—is that psychedelics act preferentially via stimulating 5-HT2ARs on deep pyramidal cells within the visual cortex as well as at higher levels of the cortical hierarchy. Deep-layer pyramidal neurons are thought to encode posterior expectations, priors, or beliefs. The resulting disinhibition or sensitization of these units lightens to precision of higher-level expectations so that (by implication of the model) they are more sensitive to ascending prediction errors (surprise/ascending information), as indicated by the thick blue arrow in the lower panel. Computationally, this process corresponds to reducing the precision of higher-level prior beliefs and an implicit reduction in the curvature of the free-energy landscape that contains neuronal dynamics. Effectively, this can be thought of as a flattening of local minima, enabling neuronal dynamics to escape their basins of attraction and—when in flat minima—express long-range correlations and desynchronized activity. This schematic uses the format in Bastos et al. (2012), to which the reader is referred for details.

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    Fig. 2.

    These schematics depict: on the top row, brain organization in psychopathologies such as depression in which high-level priors (e.g., instantiated by the DMN) are overweighted (thick top-down arrow), causing a suppression of and insensitivity to bottom-up signaling (e.g., stemming from the limbic system). In this figure, we show compromised bottom-up signaling via a thin arrow with a red cross over its center. The graphic on the top right depicts a pathologically rigid or frozen system, insensitive to perturbation, represented in this figure as a heavy ball dropped on a solid surface having a minimal effect on the system, i.e., the ball lands with an uneventful thud. The bottom row depicts brain organization under a psychedelic. In this figure, the top-down arrow has been made translucent to reflect a deweighting or relaxation of high-level priors or beliefs (this component of the model is referred to by the acronym REBUS). The effect of this deweighting is to enable bottom-up information intrinsic to the system, to travel up the hierarchy with greater latitude and compass. We refer to this component of the model as the anarchic brain. That the two brains on the bottom row are on the same level and of the same size is intended to reflect a generalized decrease in hierarchical constraints under the psychedelic. The graphic on the bottom right represents a phenomenon known as critical slowing, i.e., systems at criticality display maximal sensitivity to perturbation. In this figure, one can see ripples appearing after a heavy ball is dropped into a liquid surface, reflecting how, in this particular system, and unlike its frozen counterpart above, there will be a slow recovery to the same perturbation. Illustrations by Pedro Oliveira, courtesy of Favo Studio.

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Pharmacological Reviews: 71 (3)
Pharmacological Reviews
Vol. 71, Issue 3
1 Jul 2019
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Review ArticleReview Article

REBUS and the Anarchic Brain

R. L. Carhart-Harris and K. J. Friston
Pharmacological Reviews July 1, 2019, 71 (3) 316-344; DOI: https://doi.org/10.1124/pr.118.017160

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Review ArticleReview Article

REBUS and the Anarchic Brain

R. L. Carhart-Harris and K. J. Friston
Pharmacological Reviews July 1, 2019, 71 (3) 316-344; DOI: https://doi.org/10.1124/pr.118.017160
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