title: Reduction of Pavlovian Bias in Schizophrenia: Enhanced Effects in Clozapine-Administered Patients.
abstract: The negative symptoms of schizophrenia (SZ) are associated with a pattern of reinforcement learning (RL) deficits likely related to degraded representations of reward values. However, the RL tasks used to date have required active responses to both reward and punishing stimuli. Pavlovian biases have been shown to affect performance on these tasks through invigoration of action to reward and inhibition of action to punishment, and may be partially responsible for the effects found in patients. Forty-five patients with schizophrenia and 30 demographically-matched controls completed a four-stimulus reinforcement learning task that crossed action ("Go" or "NoGo") and the valence of the optimal outcome (reward or punishment-avoidance), such that all combinations of action and outcome valence were tested. Behaviour was modelled using a six-parameter RL model and EEG was simultaneously recorded. Patients demonstrated a reduction in Pavlovian performance bias that was evident in a reduced Go bias across the full group. In a subset of patients administered clozapine, the reduction in Pavlovian bias was enhanced. The reduction in Pavlovian bias in SZ patients was accompanied by feedback processing differences at the time of the P3a component. The reduced Pavlovian bias in patients is suggested to be due to reduced fidelity in the communication between striatal regions and frontal cortex. It may also partially account for previous findings of poorer "Go-learning" in schizophrenia where "Go" responses or Pavlovian consistent responses are required for optimal performance. An attenuated P3a component dynamic in patients is consistent with a view that deficits in operant learning are due to impairments in adaptively using feedback to update representations of stimulus value.
authors.affiliation: Maryland Psychiatric Research Center, Department of Psychiatry, School of Medicine, University of Maryland, Baltimore, Maryland, United States of America.|School of Public Health, Faculty of Health Sciences, Curtin University, Perth, Western Australia, Australia.|Curtin Health Innovation Research Institute-Biosciences, Curtin University, Perth, Western Australia, Australia.
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Albrecht
authors.affiliation: Maryland Psychiatric Research Center, Department of Psychiatry, School of Medicine, University of Maryland, Baltimore, Maryland, United States of America.
authors.forename: James A
authors.initials: JA
authors.lastname: Waltz
authors.affiliation: Department of Psychology, University of New Mexico, Albuquerque, New Mexico, United States of America.
authors.forename: James F
authors.initials: JF
authors.lastname: Cavanagh
authors.affiliation: Department of Cognitive, Linguistic and Psychological Sciences, Brown University, Providence, Rhode Island, United States of America.|Department of Psychiatry and Brown Institute for Brain Science, Brown University, Providence, Rhode Island, United States of America.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Frank
authors.affiliation: Maryland Psychiatric Research Center, Department of Psychiatry, School of Medicine, University of Maryland, Baltimore, Maryland, United States of America.
authors.forename: James M
authors.initials: JM
authors.lastname: Gold
mesh_terms: D000328:Adult; D003024:Clozapine / Q000008:administration & dosage*; D003342:Corpus Striatum / Q000503:physiopathology*; D018913:Event-Related Potentials, P300 / Q000187:drug effects*; D005260:Female; D005625:Frontal Lobe / Q000503:physiopathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012054:Reinforcement, Psychology; D012559:Schizophrenia / Q000188:drug therapy / Q000503:physiopathology
chemical_list: D003024:Clozapine