Enhanced predictive signalling in schizophrenia

Positive symptoms of schizophrenia such as delusions and hallucinations are thought to arise from an alteration in predictive mechanisms of the brain. Here, we empirically tested the hypothesis that schizophrenia is associated with an enhanced signalling of higher‐level predictions that shape perception into conformity with acquired beliefs. Twenty‐one patients with schizophrenia and twenty‐eight healthy controls matched for age and gender took part in a functional magnetic resonance imaging (fMRI) experiment that assessed the effect of an experimental manipulation of cognitive beliefs on the perception of an ambiguous visual motion stimulus. At the behavioural level, there was a generally weaker effect of experimentally induced beliefs on perception in schizophrenia patients compared with controls, but a positive correlation between the effect of beliefs on perception and the severity of positive symptoms. At the neural level, belief‐related connectivity between a region encoding beliefs in the orbitofrontal cortex (OFC) and a region encoding visual motion in the visual cortex (V5) was higher in patients compared with controls, indicating a stronger impact of cognitive beliefs on visual processing in schizophrenia. We suggest that schizophrenia might be associated with a generally weaker acquisition of externally generated beliefs and a compensatory increase in the effect of beliefs on sensory processing. Our current results are in line with the notion that enhanced signalling of higher‐level predictions that shape perception into conformity with acquired beliefs might underlie positive symptoms in schizophrenia. Hum Brain Mapp 38:1767–1779, 2017. © 2017 Wiley Periodicals, Inc.

[1]  H. M. Emrich,et al.  Reduced binocular depth inversion in schizophrenic patients , 2002, Schizophrenia Research.

[2]  Philipp Sterzer,et al.  Altered Contextual Modulation of Primary Visual Cortex Responses in Schizophrenia , 2013, Neuropsychopharmacology.

[3]  Xiao-Jing Wang,et al.  Toward a neurobiology of delusions , 2010, Progress in Neurobiology.

[4]  John M. Davis,et al.  Dose Equivalents for Antipsychotic Drugs: The DDD Method. , 2016, Schizophrenia bulletin.

[5]  P. Petrovic,et al.  Placebo and Opioid Analgesia-- Imaging a Shared Neuronal Network , 2002, Science.

[6]  Steven Warach,et al.  Schizophrenic subjects activate dorsolateral prefrontal cortex during a working memory task, as measured by fMRI , 1999, Biological Psychiatry.

[7]  P. Petrovic,et al.  Delusions and the Role of Beliefs in Perceptual Inference , 2013, The Journal of Neuroscience.

[8]  D. Hemsley,et al.  The schizophrenic experience: taken out of context? , 2005, Schizophrenia bulletin.

[9]  S. Kapur.  Psychosis as a state of aberrant salience: a framework linking biology, phenomenology, and pharmacology in schizophrenia. , 2003, The American journal of psychiatry.

[10]  L. Muckli,et al.  Detection of visual events along the apparent motion trace in patients with paranoid schizophrenia , 2012, Psychiatry Research.

[11]  D Mumford,et al.  On the computational architecture of the neocortex. II. The role of cortico-cortical loops. , 1992, Biological cybernetics.

[12]  Philipp Sterzer,et al.  Perceptual instability in schizophrenia: Probing predictive coding accounts of delusions with ambiguous stimuli , 2015, Schizophrenia Research: Cognition.

[13]  A. Heinz,et al.  Dopaminergic dysfunction in alcoholism and schizophrenia – psychopathological and behavioral correlates , 2002, European Psychiatry.

[14]  Aaron Schurger.  A very inexpensive MRI-compatible method for dichoptic visual stimulation , 2009, Journal of Neuroscience Methods.

[15]  A. Yuille,et al.  Object perception as Bayesian inference. , 2004, Annual review of psychology.

[16]  D. Mumford.  On the computational architecture of the neocortex , 2004, Biological Cybernetics.

[17]  Josiah R. Boivin,et al.  A Causal Link Between Prediction Errors, Dopamine Neurons and Learning , 2013, Nature Neuroscience.

[18]  ChrisD . Frith,et al.  Perceiving is believing: a Bayesian approach to explaining the positive symptoms of schizophrenia , 2009, Nature Reviews Neuroscience.

[19]  Heinrich Lanfermann,et al.  Understanding why patients with schizophrenia do not perceive the hollow-mask illusion using dynamic causal modelling , 2009, NeuroImage.

[20]  W. A. Phillips,et al.  Evidence for impaired visual context processing in schizotypy with thought disorder , 2004, Schizophrenia Research.

[21]  Karl J. Friston,et al.  Psychophysiological and Modulatory Interactions in Neuroimaging , 1997, NeuroImage.

[22]  Karl J. Friston,et al.  A theory of cortical responses , 2005, Philosophical Transactions of the Royal Society B: Biological Sciences.

[23]  Karl J. Friston,et al.  The Computational Anatomy of Psychosis , 2013, Front. Psychiatry.

[24]  Philip R Corlett,et al.  Hallucinations as top-down effects on perception. , 2016, Biological psychiatry. Cognitive neuroscience and neuroimaging.

[25]  Renaud Jardri,et al.  What visual illusions teach us about schizophrenia , 2014, Front. Integr. Neurosci..

[26]  P. Petrovic,et al.  Believing is seeing: expectations alter visual awareness , 2008, Current Biology.

[27]  Christoph Teufel,et al.  Shift toward prior knowledge confers a perceptual advantage in early psychosis and psychosis-prone healthy individuals , 2015, Proceedings of the National Academy of Sciences.

[28]  S. Dakin,et al.  Weak suppression of visual context in chronic schizophrenia , 2005, Current Biology.

[29]  C. Frith,et al.  From drugs to deprivation: a Bayesian framework for understanding models of psychosis , 2009, Psychopharmacology.

[30]  C. Summerfield,et al.  A Neural Representation of Prior Information during Perceptual Inference , 2008, Neuron.

[31]  Karl J. Friston,et al.  Modeling regional and psychophysiologic interactions in fMRI: the importance of hemodynamic deconvolution , 2003, NeuroImage.

[32]  Andreas Heinz,et al.  Reinforcement Learning and Dopamine in Schizophrenia: Dimensions of Symptoms or Specific Features of a Disease Group? , 2013, Front. Psychiatry.