Jeremy P Caulfield

Establishing a neurobiological account of delusion formation that links cognitive processes, brain activity, and symptoms is important to furthering our understanding of psychosis. OBJECTIVE: To explore a theoretical model of delusion formation that implicates prediction error-dependent associative learning processes DESIGN: Within-subject, randomized, placebo-controlled study. SETTING: Hospital-based clinical research facility PARTICIPANTS: One , left-handed volunteer with a mean +/- SD age of 29 +/- 2 years. MAIN OUTCOME MEASURES: Brain activation, blood plasma levels of and scores from psychiatric ratings scales (Brief Psychiatric Ratings Scale, Present State Examination, and Clinician-Administered Dissociative States Scale). RESULTS: Low-dose perturbs error-dependent learning activity in the right frontal cortex (P = .03). High-dose produces perceptual aberrations (P = .01) and delusion-like beliefs (P = .007). Critically, subjects showing the highest degree of frontal activation with placebo show the greatest occurrence of perceptual aberrations (P = .03) and ideas or delusions of reference (P = .04). CONCLUSIONS: These findings relate aberrant prediction error-dependent associative learning to referential ideas and delusions via a perturbation of frontal cortical function. They are consistent with a model of delusion formation positing disruptions in error-dependent learning.