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 (F 3,279 = 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 (F 3,295 = 13.91, p < .001), indicating less dependence on learning explicit value representations as well as greater learning decay between training and test (F 1,289 = 12.81, p < .001). Unmedicated patients with schizophrenia also showed greater decision noise (F 3,295 = 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.
Original language | English (US) |
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Pages (from-to) | 1035-1046 |
Number of pages | 12 |
Journal | Biological Psychiatry: Cognitive Neuroscience and Neuroimaging |
Volume | 7 |
Issue number | 10 |
Early online date | Apr 18 2021 |
DOIs | |
State | Published - Oct 2022 |
Bibliographical note
Funding Information:Funding for this study was provided by the National Institute of Mental Health ROI1s (Grant No. MH084840 [to DMB], Grant No. MH084826 [to CSC], Grant No. MH084821 [to JMG], Grant No. MH084861 [to AWM], and Grant No. MH084828 [to SMS]). AG had full access to all study data and takes responsibility for the integrity of the data and accuracy of the data analysis. AG performed the data analysis. All authors developed the study concept and design and aided in interpretation and provided critical revisions. All authors approved the final version of the paper for submission. We wish to thank the participants in this study, who gave generously of their time, and the many staff who helped complete this project. MJF reports consulting fees from Hoffman LaRoche Pharmaceuticals. JMG has consulted with Acadia Pharmaceuticals and reports royalty payments from the Brief Assessment of Cognition in Schizophrenia. All other authors report no biomedical financial interests or potential conflicts of interest.
Funding Information:
Funding for this study was provided by the National Institute of Mental Health ROI1s (Grant No. MH084840 [to DMB], Grant No. MH084826 [to CSC], Grant No. MH084821 [to JMG], Grant No. MH084861 [to AWM], and Grant No. MH084828 [to SMS]).
Publisher Copyright:
© 2021 Society of Biological Psychiatry
Keywords
- Classification
- Computational psychiatry
- Modeling
- Reinforcement learning
- Schizophrenia
PubMed: MeSH publication types
- Journal Article
- Research Support, N.I.H., Extramural