N-methyl-d-aspartate receptor hypofunction causes recurrent and transient failures of perceptual inference.
Brain : a journal of neurology May 13, 2025 Veith Weilnhammer, Marcus Rothkirch, Deniz Yilmaz et al. 11 citations
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.