The difference in brain activation related to the directionality of affective reversal association between patients with schizophrenia and healthy controls

Abstract

The dopaminergic mesolimbic pathway, a classical neural system involved in the pathophysiology of schizophrenia, has been implicated as a core neural system for processing motivationally salient information that is either rewarding or aversive. Affective bias in reversal learning, where reattributing appropriate rewarding values is difficult whereas false aversive values is easy, may underlie clinical manifestations of schizophrenia, such as paranoid delusions and avolition. The present study investigated the affective bias in reversal learning and its underlying neural process in the cortico-striato-limbic network in patients with schizophrenia. Fifteen healthy participants and 14 outpatients with schizophrenia underwent an event-related functional magnetic resonance imaging scanning while performing a monetary incentive contingency reversal task. Patients had higher physical and social anhedonia scale score than healthy controls. Both groups showed greater accuracy when reversing from punishment-to-reward contingency than vice versa without group differences. While healthy controls showed unidirectional acceleration in reaction time when reversing from punishment-to-reward contingency, patients showed significantly diminished punishment-to-reward reversal acceleration. In healthy controls, the anterior cingulate cortex was significantly activated and the amygdala, putamen, and the lateral orbitofrontal cortex activations were also identified during reversal response. In patients with schizophrenia only reversal response-related lateral orbitofrontal cortex activations were identified. Unidirectional punishment-to-reward reversal activations were observed in the lateral orbitofrontal cortex in both groups and in the anterior cingulate gyrus in healthy controls only. Physical anhedonia score correlated with reversal response-related anterior cingulate activity changes in healthy controls, whereas physical and social anhednoia scale scores and PANSS negative symptom scores correlated with the lateral orbitofrontal cortex in the patients. These finding suggest that deficiency in anticipation and engagement in reversing instrumental behavior to obtain reward reflected in the blunted anterior cingulate and compensatory lateral orbitofrontal activity may underlie the neural pathophysiology of anhedonia/avolition in schizophrenia.