4.2 Article

Ketamine-Induced Hallucinations

Journal

PSYCHOPATHOLOGY
Volume 48, Issue 6, Pages 376-385

Publisher

KARGER
DOI: 10.1159/000438675

Keywords

Ketamine; Hallucinations; Predictive coding; Psychosis; Computational psychiatry; Prediction; Psychosis

Categories

Funding

  1. NIMH [5R25MH071584-07, 5T32MH19961-14]
  2. Yale Detre Fellowship for Translational Neuroscience
  3. Wellcome Trust
  4. Bernard Wolfe Health Neuroscience fund
  5. Medical Research Council
  6. Connecticut State Department of Mental Health and Addiction Services
  7. IMHRO/Janssen Rising Star Translational Research Award
  8. CTSA from the National Center for Research Resources (NCRR), National Institutes of Health (NIH) [UL1 TR000142]
  9. National Center for Advancing Translational Science (NCATS), National Institutes of Health (NIH)
  10. NIH roadmap for Medical Research

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Background: Ketamine, the NMDA glutamate receptor antagonist drug, is increasingly employed as an experimental model of psychosis in healthy volunteers. At subanesthetic doses, it safely and reversibly causes delusion-like ideas, amotivation and perceptual disruptions reminiscent of the aberrant salience experiences that characterize first-episode psychosis. However, auditory verbal hallucinations, a hallmark symptom of schizophrenia, have not been reported consistently in healthy volunteers even at high doses of ketamine. Sampling and Methods: Here we present data from a set of healthy participants who received moderately dosed, placebo-controlled ketamine infusions in the reduced stimulation environment of the magnetic resonance imaging (MRI) scanner. We highlight the phenomenological experiences of 3 participants who experienced particularly vivid hallucinations. Results: Participants in this series reported auditory verbal and musical hallucinations at a ketamine dose that does not induce auditory hallucination outside of the scanner. Conclusions: We interpret the observation of ketamine-induced auditory verbal hallucinations in the context of the reduced perceptual environment of the MRI scanner and offer an explanation grounded in predictive coding models of perception and psychosis - the brain fills in expected perceptual inputs, and it does so more in situations of altered perceptual input. The altered perceptual input of the MRI scanner creates a mismatch between top-down perceptual expectations and the heightened bottom-up signals induced by ketamine. Such circumstances induce aberrant percepts, including musical and auditory verbal hallucinations. We suggest that these circumstances might rep resent a useful experimental model of auditory verbal hallucinations and highlight the impact of ambient sensory stimuli on psychopathology. (C) 2015 S. Karger AG, Basel

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