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      The Computational Anatomy of Psychosis

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          Abstract

          This paper considers psychotic symptoms in terms of false inferences or beliefs. It is based on the notion that the brain is an inference machine that actively constructs hypotheses to explain or predict its sensations. This perspective provides a normative (Bayes-optimal) account of action and perception that emphasizes probabilistic representations; in particular, the confidence or precision of beliefs about the world. We will consider hallucinosis, abnormal eye movements, sensory attenuation deficits, catatonia, and delusions as various expressions of the same core pathology: namely, an aberrant encoding of precision. From a cognitive perspective, this represents a pernicious failure of metacognition (beliefs about beliefs) that can confound perceptual inference. In the embodied setting of active (Bayesian) inference, it can lead to behaviors that are paradoxically more accurate than Bayes-optimal behavior. Crucially, this normative account is accompanied by a neuronally plausible process theory based upon hierarchical predictive coding. In predictive coding, precision is thought to be encoded by the post-synaptic gain of neurons reporting prediction error. This suggests that both pervasive trait abnormalities and florid failures of inference in the psychotic state can be linked to factors controlling post-synaptic gain – such as NMDA receptor function and (dopaminergic) neuromodulation. We illustrate these points using biologically plausible simulations of perceptual synthesis, smooth pursuit eye movements and attribution of agency – that all use the same predictive coding scheme and pathology: namely, a reduction in the precision of prior beliefs, relative to sensory evidence.

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          Most cited references119

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          Dynamic causal modelling.

          In this paper we present an approach to the identification of nonlinear input-state-output systems. By using a bilinear approximation to the dynamics of interactions among states, the parameters of the implicit causal model reduce to three sets. These comprise (1) parameters that mediate the influence of extrinsic inputs on the states, (2) parameters that mediate intrinsic coupling among the states, and (3) [bilinear] parameters that allow the inputs to modulate that coupling. Identification proceeds in a Bayesian framework given known, deterministic inputs and the observed responses of the system. We developed this approach for the analysis of effective connectivity using experimentally designed inputs and fMRI responses. In this context, the coupling parameters correspond to effective connectivity and the bilinear parameters reflect the changes in connectivity induced by inputs. The ensuing framework allows one to characterise fMRI experiments, conceptually, as an experimental manipulation of integration among brain regions (by contextual or trial-free inputs, like time or attentional set) that is revealed using evoked responses (to perturbations or trial-bound inputs, like stimuli). As with previous analyses of effective connectivity, the focus is on experimentally induced changes in coupling (cf., psychophysiologic interactions). However, unlike previous approaches in neuroimaging, the causal model ascribes responses to designed deterministic inputs, as opposed to treating inputs as unknown and stochastic.
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            The free-energy principle: a rough guide to the brain?

            This article reviews a free-energy formulation that advances Helmholtz's agenda to find principles of brain function based on conservation laws and neuronal energy. It rests on advances in statistical physics, theoretical biology and machine learning to explain a remarkable range of facts about brain structure and function. We could have just scratched the surface of what this formulation offers; for example, it is becoming clear that the Bayesian brain is just one facet of the free-energy principle and that perception is an inevitable consequence of active exchange with the environment. Furthermore, one can see easily how constructs like memory, attention, value, reinforcement and salience might disclose their simple relationships within this framework.
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              Psychosis as a state of aberrant salience: a framework linking biology, phenomenology, and pharmacology in schizophrenia.

              The clinical hallmark of schizophrenia is psychosis. The objective of this overview is to link the neurobiology (brain), the phenomenological experience (mind), and pharmacological aspects of psychosis-in-schizophrenia into a unitary framework. Current ideas regarding the neurobiology and phenomenology of psychosis and schizophrenia, the role of dopamine, and the mechanism of action of antipsychotic medication were integrated to develop this framework. A central role of dopamine is to mediate the "salience" of environmental events and internal representations. It is proposed that a dysregulated, hyperdopaminergic state, at a "brain" level of description and analysis, leads to an aberrant assignment of salience to the elements of one's experience, at a "mind" level. Delusions are a cognitive effort by the patient to make sense of these aberrantly salient experiences, whereas hallucinations reflect a direct experience of the aberrant salience of internal representations. Antipsychotics "dampen the salience" of these abnormal experiences and by doing so permit the resolution of symptoms. The antipsychotics do not erase the symptoms but provide the platform for a process of psychological resolution. However, if antipsychotic treatment is stopped, the dysregulated neurochemistry returns, the dormant ideas and experiences become reinvested with aberrant salience, and a relapse occurs. The article provides a heuristic framework for linking the psychological and biological in psychosis. Predictions of this hypothesis, particularly regarding the possibility of synergy between psychological and pharmacological therapies, are presented. The author describes how the hypothesis is complementary to other ideas about psychosis and also discusses its limitations.
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                Author and article information

                Journal
                Front Psychiatry
                Front Psychiatry
                Front. Psychiatry
                Frontiers in Psychiatry
                Frontiers Media S.A.
                1664-0640
                25 April 2013
                30 May 2013
                2013
                : 4
                : 47
                Affiliations
                [1] 1Wellcome Trust Centre for Neuroimaging, Institute of Neurology, University College London , London, UK.
                [2] 2Translational Neuromodeling Unit, Institute for Biomedical Engineering, University of Zurich , ETH Zurich, Zurich, Switzerland
                [3] 3Laboratory for Social and Neural Systems Research, University of Zurich , Zurich, Switzerland
                Author notes

                Edited by: Stefan Borgwardt, University of Basel, Switzerland

                Reviewed by: Andrea Mechelli, King’s College London, UK; Christian G. Huber, Universitäre Psychiatrische Kliniken Basel, Switzerland

                *Correspondence: Rick A. Adams, Wellcome Trust Centre for Neuroimaging, 12 Queen Square, London WC1N 3BG, UK e-mail: rick.adams@ 123456ucl.ac.uk

                This article was submitted to Frontiers in Schizophrenia, a specialty of Frontiers in Psychiatry.

                Article
                10.3389/fpsyt.2013.00047
                3667557
                23750138
                1a41a2ea-2641-4fa8-bf40-a1698daf4568
                Copyright © 2013 Adams, Stephan, Brown, Frith and Friston.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc.

                History
                : 15 April 2013
                : 16 May 2013
                Page count
                Figures: 13, Tables: 0, Equations: 5, References: 149, Pages: 26, Words: 20553
                Categories
                Psychiatry
                Review Article

                Clinical Psychology & Psychiatry
                free energy,active inference,precision,sensory attenuation,illusions,psychosis,schizophrenia

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