Methamphetamine-Induced Disruption of Frontostriatal Reward Learning Signals: Relation to Psychotic Symptoms

ObjectiveFrontostriatal circuitry is critical to learning processes, and its disruption may underlie maladaptive decision making and the generation of psychotic symptoms in schizophrenia. However, there is a paucity of evidence directly examining the role of modulatory neurotransmitters on frontostriatal function in humans. In order to probe the effects of modulation on frontostriatal circuitry during learning and to test whether disruptions in learning processes may be related to the pathogenesis of psychosis, the authors explored the brain representations of reward prediction error and incentive value, two key reinforcement learning parameters, before and after methamphetamine challenge.MethodHealthy volunteers (N=18) underwent functional MRI (fMRI) scanning while performing a reward learning task on three occasions: after placebo, after methamphetamine infusion (0.3 mg/kg body weight), and after pretreatment with 400 mg of amisulpride and then methamphetamine infusion. Brain fMRI representations of lea...