S146. ASSOCIATION OF IMPAIRED MODEL-FREE DECISION-MAKING WITH ABERRANT STRIATAL DOPAMINE, BRAIN ACTIVATION, AND COGNITIVE DIFFICULTIES IN PATIENTS WITH SCHIZOPHRENIA DURING PSYCHOTIC REMISSION

BACKGROUND: Human decision-making ranges between the extremes of automatic and fast model-free behavior (i.e., relying only on previous outcomes) and more flexible, but computationally demanding model-based behavior (i.e., implementing cognitive models). Model-based/model-free decision-making can be investigated using sequential decision tasks and has been shown to be associated with presynaptic striatal dopamine synthesis. During phases of psychotic remission in schizophrenia, dopamine synthesis in the dorsal striatum is reduced. We hypothesized that particularly model-free decision-making is impaired in schizophrenia during psychotic remission and is associated with (i) abnormal dopamine synthesis in dorsal striatum, (ii) aberrant task-activation in dorsal striatum, and (iii) cognitive difficulties in patients (e.g., reduced speed). METHODS: 26 patients with chronic schizophrenia, currently in psychotic remission, and 22 healthy controls (matched by age and gender) were enrolled in the study. Model-based/model-free decision-making was evaluated with a two-stage Markov decision task, followed by computational modeling of subjects’ learning behavior. Presynaptic dopamine synthesis was assessed by 18F-DOPA positron emission tomography and subsequent graphical Patlak analysis. Task-activation was measured by functional magnetic resonance imaging. Cognitive impairments were quantified by Trail-Making-Test A (among others). Associations between decision-making parameters, dopamine synthesis, task-activation, and cognitive impairments were tested by correlation analyses. RESULTS: Patients with schizophrenia showed selectively impaired model-free decision-making. 18F-DOPA uptake (i.e., presynaptic dopamine synthesis capacity) in the dorsal striatum was decreased in patients. Impaired model-free decision-making in patients correlated with (i) decreased dopamine synthesis in dorsal striatum, (ii) abnormal task-activation in dorsal striatum, and (iii) lower speed in Trail-Making-Test A. DISCUSSION: Results demonstrate an association of reduced dorsal striatal dopamine synthesis and brain activity with impaired model-free decision-making in schizophrenia, which potentially contributes to cognitive difficulties.