I Predict, Therefore I Am: Perturbed Predictive Coding Under Ketamine and in Schizophrenia

  • Philip R. Corlett
    Address correspondence to: Philip Corlett, Ph.D., Abraham Ribicoff Research Facilities, Connecticut Mental Health Center, 34 Park Street, New Haven, CT06511; .
    Department of Psychiatry, Yale University, New Haven, Connecticut
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      Predictive coding involves inferences about current sensations based on past experience. We infer what would need to be present (externally and internally) to cause the sensory information we detect (
      • Friston K.
      • Frith C.
      A duet for one.
      ). The stimuli whose causes are being inferred have transducers (e.g., photoreceptors in the eye, hair cells in the ear) that convert sensory energy into neural activity, which is processed hierarchically within streams that may be relatively encapsulated. However, ultimately these hierarchies converge on a coherent integrated percept (
      • Friston K.
      • Frith C.
      A duet for one.
      ). One crucial complexity, with relevance to the symptoms of psychotic illness, is that we change the sensations we receive from the world when we move through it (
      • Friston K.
      • Frith C.
      A duet for one.
      ). To accurately infer the causes of sensory inputs incident on us, we must take that into account (
      • Friston K.
      • Frith C.
      A duet for one.
      ). We do so by modeling ourselves as agents in the world, predicting and explaining away the sensory consequences of our actions (
      • Friston K.
      • Frith C.
      A duet for one.
      ). Failure to make such predictions can drastically change what we infer about ourselves and the world, manifest ultimately as psychotic symptoms—the profound departures from consensual reality that characterize serious mental illnesses such as schizophrenia (
      • Corlett P.R.
      • Honey G.D.
      • Krystal J.H.
      • Fletcher P.C.
      Glutamatergic model psychoses: Prediction error, learning, and inference.
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      Linked Article

      • Role of N-Methyl-D-Aspartate Receptors in Action-Based Predictive Coding Deficits in Schizophrenia
        Biological PsychiatryVol. 81Issue 6
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          Recent theoretical models of schizophrenia posit that dysfunction of the neural mechanisms subserving predictive coding contributes to symptoms and cognitive deficits, and this dysfunction is further posited to result from N-methyl-D-aspartate glutamate receptor (NMDAR) hypofunction. Previously, by examining auditory cortical responses to self-generated speech sounds, we demonstrated that predictive coding during vocalization is disrupted in schizophrenia. To test the hypothesized contribution of NMDAR hypofunction to this disruption, we examined the effects of the NMDAR antagonist, ketamine, on predictive coding during vocalization in healthy volunteers and compared them with the effects of schizophrenia.
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