Andra Geana1, Deanna M Barch2, James M Gold3, Cameron S Carter4, Angus W MacDonald5, J Daniel Ragland4, Steven M Silverstein6, Michael J Frank7. 1. Department of Department of Cognitive, Linguistic, and Psychological Sciences, Brown University, Providence, Rhode Island. Electronic address: andra_geana@brown.edu. 2. Department of Psychological & Brain Sciences, Washington University in St. Louis, St. Louis, Missouri; Department of Radiology, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, Missouri; Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri. 3. Department of Psychiatry, Maryland Psychiatric Research Center, Baltimore, Maryland. 4. Department of Psychiatry, University of California, Davis, California. 5. Department of Psychology, University of Minnesota, Minneapolis, Minnesota. 6. Department of Psychiatry, University of Rochester, Rochester, New York. 7. Department of Department of Cognitive, Linguistic, and Psychological Sciences, Brown University, Providence, Rhode Island.
Abstract
BACKGROUND: Psychiatric diagnosis and treatment have historically taken a symptom-based approach, with less attention on identifying underlying symptom-producing mechanisms. Recent efforts have illuminated the extent to which different underlying circuitry can produce phenotypically similar symptomatology (e.g., psychosis in bipolar disorder vs. schizophrenia). Computational modeling makes it possible to identify and mathematically differentiate behaviorally unobservable, specific reinforcement learning differences in patients with schizophrenia versus other disorders, likely owing to a higher reliance on prediction error-driven learning associated with basal ganglia and underreliance on explicit value representations associated with orbitofrontal cortex. METHODS: We used a well-established probabilistic reinforcement learning task to replicate those findings in individuals with schizophrenia both on (n = 120) and off (n = 44) antipsychotic medications and included a patient comparison group of bipolar patients with psychosis (n = 60) and healthy control subjects (n = 72). RESULTS: Using accuracy, there was a main effect of group (F3,279 = 7.87, p < .001), such that all patient groups were less accurate than control subjects. Using computationally derived parameters, both medicated and unmediated individuals with schizophrenia, but not patients with bipolar disorder, demonstrated a reduced mixing parameter (F3,295 = 13.91, p < .001), indicating less dependence on learning explicit value representations as well as greater learning decay between training and test (F1,289 = 12.81, p < .001). Unmedicated patients with schizophrenia also showed greater decision noise (F3,295 = 2.67, p = .04). CONCLUSIONS: Both medicated and unmedicated patients showed overreliance on prediction error-driven learning as well as significantly higher noise and value-related memory decay, compared with the healthy control subjects and the patients with bipolar disorder. Additionally, the computational model parameters capturing these processes can significantly improve patient/control classification, potentially providing useful diagnosis insight.
BACKGROUND: Psychiatric diagnosis and treatment have historically taken a symptom-based approach, with less attention on identifying underlying symptom-producing mechanisms. Recent efforts have illuminated the extent to which different underlying circuitry can produce phenotypically similar symptomatology (e.g., psychosis in bipolar disorder vs. schizophrenia). Computational modeling makes it possible to identify and mathematically differentiate behaviorally unobservable, specific reinforcement learning differences in patients with schizophrenia versus other disorders, likely owing to a higher reliance on prediction error-driven learning associated with basal ganglia and underreliance on explicit value representations associated with orbitofrontal cortex. METHODS: We used a well-established probabilistic reinforcement learning task to replicate those findings in individuals with schizophrenia both on (n = 120) and off (n = 44) antipsychotic medications and included a patient comparison group of bipolar patients with psychosis (n = 60) and healthy control subjects (n = 72). RESULTS: Using accuracy, there was a main effect of group (F3,279 = 7.87, p < .001), such that all patient groups were less accurate than control subjects. Using computationally derived parameters, both medicated and unmediated individuals with schizophrenia, but not patients with bipolar disorder, demonstrated a reduced mixing parameter (F3,295 = 13.91, p < .001), indicating less dependence on learning explicit value representations as well as greater learning decay between training and test (F1,289 = 12.81, p < .001). Unmedicated patients with schizophrenia also showed greater decision noise (F3,295 = 2.67, p = .04). CONCLUSIONS: Both medicated and unmedicated patients showed overreliance on prediction error-driven learning as well as significantly higher noise and value-related memory decay, compared with the healthy control subjects and the patients with bipolar disorder. Additionally, the computational model parameters capturing these processes can significantly improve patient/control classification, potentially providing useful diagnosis insight.
Authors: Oliver D Howes; Joseph Kambeitz; Euitae Kim; Daniel Stahl; Mark Slifstein; Anissa Abi-Dargham; Shitij Kapur Journal: Arch Gen Psychiatry Date: 2012-08