Midbrain Activation During Pavlovian Conditioning and Delusional Symptoms in Schizophrenia

Context: Recent theories have suggested that the inappropriate activation of limbic motivational systems in response to neutral stimuli may underlie the development of delusions in schizophrenia. Objective: To investigate the activation of the amygdala, midbrain, and ventral striatum during an aversive pavlovian conditioning task in patients with schizophrenia and healthy control participants using functional magnetic resonance imaging. Design: Cross-sectional case-control functional neuroimaging study. Setting: Academic medical center. Participants: Twenty patients with DSM-IV–diagnosed schizophrenia or schizoaffective disorder and 20 healthy control participants. Main Outcome Measures: Regional brain activation as assessed by functional magnetic resonance imaging blood oxygen level–dependent responses, and delusional symptom severity on the Positive and Negative Syndrome Scale. Results: Patients with schizophrenia showed abnormal activation of the amygdala, midbrain, and ventral striatum during conditioning. Activation of the midbrain in response to neutral rather than aversive cues during conditioning was correlated with the severity of delusional symptoms in the patient group (corrected P = .04). Conclusion: Inappropriate activation of the midbrain in response to neutral stimuli during conditioning is associated with the severity of delusional symptoms in patients with schizophrenia.