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Background It has been suggested that patients with schizophrenia are impaired in the use of prediction error signals resulting in disturbances of motor control. Alterations in fronto-striatal dopamine transmitter systems are regarded to contribute to these deficits. It is unclear whether the use of predictive strategies for motor control may be systematically related to impaired cognitive functions in patients. In healthy subjects, cognitive flexibility has been related to medial prefrontal cortex (PFC) function, while cognitive stability was related to lateral PFC integrity with both brain regions being modulated by striatal activity. Despite these findings, the interplay of cognitive flexibility and stability needed for motor control and its associations to alterations on the brain system level have not been investigated systematically in this patient group. Methods We assessed patients with schizophrenia (N=22) and healthy controls (N=22) on first, detection of relevant unexpected events (cognitive flexibility) and second, distractor resistance to irrelevant prediction errors (cognitive stability) using a serial prediction task including the digits 1-2-3-4. We applied an event-related design in a functional magnetic resonance imaging (fMRI) environment (3T) to explore brain networks underlying cognitive flexibility and stability, respectively. In analyses, the minimum cluster extent was set to k &amp;gt; 20 and corrected using the false discovery rate (FDR) with p &amp;lt; 0.05. Since we were specifically interested in the role of the striatum, we applied small volume correction at p &amp;lt; 0.05 with the minimum cluster extent set to k &amp;gt; 5 in a region of interest analyses. Participants were also assessed on general cognitive function using the Brief Assessment of Cognition in Schizophrenia (BACS) battery and on motor symptoms using the Heidelberg Scale for Neurological Soft Signs (NSS). Results Patients detected less behaviorally relevant events (M(Pat) = 0.57 vs. M(HC) = 0.78, F(41,1) = 16.32, p &amp;lt; 0.001) and ignored less irrelevant events (M(Pat) = 0.87 vs. M(HC) = 0.93, F(41,1) = 11.78, p &amp;lt; 0.001) implying impairments of both cognitive flexibility and stability in patients. Motor symptoms (NSS) and cognitive deficits (BACS) in patients were exclusively related to cognitive flexibility, but not stability. Brain correlates of reduced flexibility in patients were found in a fronto-striato-thalamo network. More specifically, reduced striatal activation in patients was related to weaker event discrimination and reduced detection of unexpected relevant events. Additionally, exploratory follow-up analyses revealed reduced fronto-striato-temporal activation in patients associated with weaker distractor resistance during the stability task. Note, chlorpromazine equivalents as an indicator of antipsychotic dosage as well as positive and negative symptoms were unrelated to measures of cognitive flexibility and stability. Discussion Together, our findings provide evidence for distinctive neurobiological alterations underlying reduced cognitive flexibility and stability in schizophrenia with reduced flexibility being associated with general cognitive and motor impairments. Our main imaging results show reduced activation in a fronto-striato-thalamo network in response to relevant prediction errors in patients, while impaired cognitive stability may be rather related to alterations in a fronto-striato-temporal network. Reduced caudate activation during behavioral relevant events, which was associated with weaker event discrimination and detection of relevant prediction errors in patients, supports a model of striatal gating being essentially impaired in patients.

T136. NEURAL CORRELATES OF ALTERED COGNITIVE FLEXIBILITY AND STABILITY FOR MOTOR CONTROL IN SCHIZOPHRENIA – JUST TWO SIDES OF THE SAME COIN?