Motivational Context Modulates Prediction Error Response in Schizophrenia

Abstract

Background: Recent findings demonstrate that patients with schizophrenia are worse at learning to predict rewards than losses, suggesting that motivational context modulates learning in this disease. However, these findings derive from studies in patients treated with antipsychotic medications, D2 receptor antagonists that may interfere with the neural systems that underlie motivation and learning. Thus, it remains unknown how motivational context affects learning in schizophrenia, separate from the effects of medication.

Methods: To examine the impact of motivational context on learning in schizophrenia, we tested 16 unmedicated patients with schizophrenia and 23 matched controls on a probabilistic learning task while they underwent functional magnetic resonance imaging (fMRI) under 2 conditions: one in which they pursued rewards, and one in which they avoided losses. Computational models were used to derive trial-by-trial prediction error responses to feedback.

Results: Patients performed worse than controls on the learning task overall, but there were no behavioral effects of condition. FMRI revealed an attenuated prediction error response in patients in the medial prefrontal cortex, striatum, and medial temporal lobe when learning to predict rewards, but not when learning to avoid losses.

Conclusions: Patients with schizophrenia showed differences in learning-related brain activity when learning to predict rewards, but not when learning to avoid losses. Together with prior work, these results suggest that motivational deficits related to learning in schizophrenia are characteristic of the disease and not solely a result of antipsychotic treatment.

Keywords: antipsychotic medication; model-based fMRI; neuroimaging; prediction error; reinforcement learning.

Fig. 1.

Probabilistic learning task. Participants learned to predict gains and losses, which were probabilistically associated with cues in an instrumental task. A sample trial from the gain condition is shown for correct and incorrect choices: participants made a choice (triangle/square), received verbal feedback on their choice (“correct”/“incorrect”), and then received a monetary outcome. Trial structure and probabilities were identical across conditions.

Fig. 2.

Behavioral results. For gain and loss conditions, patients demonstrated slower reaction time (A.Gain/B.Loss) and lower optimal choice performance scores (C.Gain/D.Loss) relative to controls.

Fig. 3.

Condition-group interaction. Interaction results (gain>loss, controls>patients) for prediction error (PE)-related BOLD responses to feedback are shown at a corrected threshold (whole-brain family-wise error [FWE] P < .05). Regression weight plots from clusters in (A) left medial temporal lobe and (B) right putamen are shown to demonstrate the direction of the interaction, and not for statistical inference.

Fig. 4.

Corrected condition-specific group differences. A whole-brain corrected (family-wise error [FWE] P < .05) contrast for controls>patients on prediction error (PE)-related BOLD responses to feedback showed a difference in medial prefrontal cortex in the gain condition. No such difference was significant in the loss condition.