Journal
PSYCHOPATHOLOGY
Volume 48, Issue 6, Pages 376-385Publisher
KARGER
DOI: 10.1159/000438675
Keywords
Ketamine; Hallucinations; Predictive coding; Psychosis; Computational psychiatry; Prediction; Psychosis
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Funding
- NIMH [5R25MH071584-07, 5T32MH19961-14]
- Yale Detre Fellowship for Translational Neuroscience
- Wellcome Trust
- Bernard Wolfe Health Neuroscience fund
- Medical Research Council
- Connecticut State Department of Mental Health and Addiction Services
- IMHRO/Janssen Rising Star Translational Research Award
- CTSA from the National Center for Research Resources (NCRR), National Institutes of Health (NIH) [UL1 TR000142]
- National Center for Advancing Translational Science (NCATS), National Institutes of Health (NIH)
- 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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