Delusions, the persistent bizarre beliefs characteristic of psychosis, may arise from disturbances in prediction error-dependent learning. In a placebo-controlled study with 18 human subjects, ketamine—an NMDA receptor antagonist that induces aberrant prediction error signals—was administered during re-exposure to a conditioned fear stimulus. This led to stronger subsequent fear memory compared to placebo, with the degree of strengthening correlating with individual vulnerability to ketamine's psychotogenic effects and with prediction error brain signals. A partial replication in an independent sample with an appetitive learning procedure (8 subjects) supported these findings. The results suggest a link between altered prediction error, memory strength, and psychosis, potentially explaining both the emergence and persistence of delusional beliefs.
Ketamine, a drug that induces temporary psychosis-like symptoms, increased the sense of agency in healthy adults, mimicking the exaggerated action-effect binding seen in schizophrenia. In a small experiment, 14 participants given low-dose ketamine showed greater compression of time between their actions and outcomes compared to placebo. The size of this effect correlated with unusual bodily experiences caused by the drug. The findings suggest ketamine can reproduce certain agency disturbances characteristic of schizophrenia, and that these changes are linked to broader alterations in body awareness.