James A Waltz1, Ziye Xu2, Elliot C Brown3, Rebecca R Ruiz4, Michael J Frank5, James M Gold4. 1. Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, Maryland. Electronic address: jwaltz@mprc.umaryland.edu. 2. Department of Biomedical Engineering, Duke University, Durham, North Carolina. 3. Department of Psychiatry, University of Calgary, Calgary, Alberta, Canada. 4. Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, Maryland. 5. Department of Psychiatry and Brown Institute for Brain Science, Brown University, Providence, Rhode Island.
Abstract
BACKGROUND: The current study was designed to test the hypothesis that motivational deficits in schizophrenia (SZ) are tied to a reduced ability to differentially signal gains and instances of loss-avoidance in the brain, leading to reduced ability to form adaptive representations of expected value. METHODS: We administered a reinforcement learning paradigm to 27 medicated SZ patients and 27 control subjects in which participants learned three probabilistic discriminations. In regions of interest in reward networks identified a priori, we examined contrasts between trial types with different expected values (e.g., expected gain-nonmonetary) and between outcomes with the same prediction error valence but different experienced values (e.g., gain-loss-avoidance outcome, miss-loss outcome). RESULTS: Both whole-brain and region of interest analyses revealed that SZ patients showed reduced differentiation between gain and loss-avoidance outcomes in the dorsal anterior cingulate cortex and bilateral anterior insula. That is, SZ patients showed reduced contrasts between positive prediction errors of different objective values in these areas. In addition, we observed significant correlations between gain-loss-avoidance outcome contrasts in the ventral striatum and ratings for avolition/anhedonia and between expected gain-nonmonetary contrasts in the ventral striatum and ventromedial prefrontal cortex. CONCLUSIONS: These results provide further evidence for intact prediction error signaling in medicated SZ patients, especially with regard to loss-avoidance. By contrast, components of frontostriatal circuits appear to show reduced sensitivity to the absolute valence of expected and experienced outcomes, suggesting a mechanism by which motivational deficits may emerge.
BACKGROUND: The current study was designed to test the hypothesis that motivational deficits in schizophrenia (SZ) are tied to a reduced ability to differentially signal gains and instances of loss-avoidance in the brain, leading to reduced ability to form adaptive representations of expected value. METHODS: We administered a reinforcement learning paradigm to 27 medicated SZ patients and 27 control subjects in which participants learned three probabilistic discriminations. In regions of interest in reward networks identified a priori, we examined contrasts between trial types with different expected values (e.g., expected gain-nonmonetary) and between outcomes with the same prediction error valence but different experienced values (e.g., gain-loss-avoidance outcome, miss-loss outcome). RESULTS: Both whole-brain and region of interest analyses revealed that SZ patients showed reduced differentiation between gain and loss-avoidance outcomes in the dorsal anterior cingulate cortex and bilateral anterior insula. That is, SZ patients showed reduced contrasts between positive prediction errors of different objective values in these areas. In addition, we observed significant correlations between gain-loss-avoidance outcome contrasts in the ventral striatum and ratings for avolition/anhedonia and between expected gain-nonmonetary contrasts in the ventral striatum and ventromedial prefrontal cortex. CONCLUSIONS: These results provide further evidence for intact prediction error signaling in medicated SZ patients, especially with regard to loss-avoidance. By contrast, components of frontostriatal circuits appear to show reduced sensitivity to the absolute valence of expected and experienced outcomes, suggesting a mechanism by which motivational deficits may emerge.
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