Perception normally balances external sensory signals with internal predictions based on prior knowledge. In a double-blind, placebo-controlled, cross-over experiment with healthy participants, the N-methyl-D-aspartate receptor (NMDAR) antagonist S-ketamine shifted perception toward the external mode, favoring sensory input over prior knowledge. A case-control study found that people with paranoid schizophrenia, a condition linked to NMDAR hypofunction, also spend more time in the external mode. This NMDAR-dependent shift suggests that schizophrenia symptoms may arise from recurring disconnections between perception and prior knowledge about the world.
The brain resolves ambiguous sensory signals by using recent perceptual history as a predictive context. When sensory input violates this temporal context, perceptual prediction errors arise and drive spontaneous switches between alternative interpretations. Using fMRI and a bistable structure-from-motion paradigm with 26 participants, the study compared neural responses to perceptual conflicts induced by violations of temporal context versus spatial context. Only the anterior insula bilaterally showed activation for both types of conflict. Approximate prediction-error signals also appeared in the right inferior frontal gyrus and right inferior parietal lobe. These results suggest the anterior insular cortex plays a key role in detecting perceptual conflicts and constructing unambiguous conscious experiences.