N-methyl-d-aspartate receptor hypofunction causes recurrent and transient failures of perceptual inference.
Brain : a journal of neurology – May 13, 2025
Source: PubMed
Summary
Our brains constantly balance sensory input with stored knowledge to make sense of the world. New research reveals how ketamine disrupts this delicate process, offering insights into visual perception and psychosis. Scientists found that ketamine temporarily prevents the brain from properly integrating past experiences with current sensory information. This mirrors patterns seen in schizophrenia, where patients often struggle with bistable perception - the ability to switch between different interpretations of ambiguous visual scenes.
Abstract
Perception integrates external sensory signals with internal predictions that reflect prior knowledge about the world. Previous research suggests that this integration is governed by slow alternations between an external mode, driven by sensory signals, and an internal mode, shaped by prior knowledge. Using a double-blind, placebo-controlled, cross-over experiment in healthy human participants, we investigated the effects of the N-methyl-D-aspartate receptor (NMDAR) antagonist S-ketamine on the balance between external and internal modes. We found that S-ketamine causes a shift of perception towards the external mode. A case-control study revealed that individuals with paranoid schizophrenia, a disorder repeatedly associated with NMDAR hypofunction, spend more time in the external mode. This NMDAR-dependent increase in the external mode suggests that the symptoms of schizophrenia are caused by recurring dissociations of perception from prior knowledge about the world.