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.
Inferior frontal cortex plays a causal role in resolving perceptual ambiguities, thereby determining what is consciously experienced. Computational modeling and two fMRI experiments showed that this region detects conflicts caused by ambiguous sensory information. Disrupting inferior frontal cortex activity with transcranial magnetic stimulation slowed the updating of conscious experience in response to such conflicts. These findings indicate that prefrontal cortex is not merely involved in introspection or action but actively contributes to shaping the contents of consciousness.