Hyperresponsivity and impaired prefrontal control of the mesolimbic reward system in schizophrenia

Abstract

Using functional magnetic resonance imaging (fMRI), sixteen medicated schizophrenic patients and sixteen healthy controls performed the ‘desire-reason dilemma’ (DRD) paradigm. This paradigm allowed us to directly investigate reward-related brain activations depending on the interaction of bottom-up and top-down mechanisms, when a previously conditioned reward stimulus had to be rejected to achieve a superordinate long-term goal. Patients with schizophrenia and healthy controls showed significant activations in the dopaminergic reward system. In schizophrenic patients, however, we found a significant hyperactivation of the ventral striatum (vStr) when they were allowed to accept the conditioned reward stimuli, and a reduced top-down regulation of activation in the ventral striatum (vStr) and ventral tegmental area (VTA) while having to reject the immediate reward to pursue the superordinate task-goal. Moreover, while healthy subjects exhibited a negative functional coupling of the vStr with both the anteroventral prefrontal cortex (avPFC) and the ventromedial prefrontal cortex (VMPFC) in the dilemma situation, this functional coupling was significantly impaired in the patient group. These findings provide further evidence for a hyperresponsivity of the dopaminergic reward system to reward stimuli and an impaired top-down control of reward signals by prefrontal brain regions in schizophrenia.