N-methyl-d-aspartate receptor hypofunction causes recurrent and transient failures of perceptual inference.
Veith Weilnhammer, Marcus Rothkirch, Deniz Yilmaz, Merve Fritsch, Lena Esther Ptasczynski, Katrin Reichenbach, Lukas Roediger, Philip R. Corlett, Philipp Sterzer
Brain : a journal of neurology May 13, 2025 DOI: 10.1093/brain/awaf011 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Double-blind, placebo-controlled, cross-over experiment; case-control study Peer reviewed |
|---|---|
| Population | Healthy human participants; individuals with paranoid schizophrenia |
| Intervention | S-ketamine |
| Topics | Ketamine |
| Keywords | Bistable perception Predictive processing Psychosis Schizophrenia Visual perception Psychopharmacology Perception disorders Mental health research Cognitive science |
| Citations | 11 |
| Key findings | S-ketamine shifts perception toward the external mode, and individuals with paranoid schizophrenia also spend more time in the external mode, suggesting schizophrenia symptoms may stem from perception dissociating from prior knowledge. |
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.