It is widely known that patients with schizophrenia (SZ) show a reduced tendency to engage in goal- directed behavior that could lead to rewards. It has often been thought that motivational deficits in schizophrenia stem from a reduced ability to experience pleasure, called anhedonia. A number of recent studies challenge this view, however, finding that SZ patients frequently report normal hedonic experience. The reduction in reward-seeking behavior in schizophrenia is thus likely to have a more complicated explanation, possibly related to the physiology of reward processing. Abnormalities in brain regions involved in reward processing are, in fact, evident from neuroimaging studies of schizophrenia. These findings point to an important contradiction in the literature: schizophrenia patients report normal hedonic experience, but often show evidence of abnormal physiological associated with reward processing. In order to investigate the reasons for this apparent contradiction, we propose to adapt a paradigm from the experimental literature, which has been used, in conjunction with functional magnetic resonance imaging (fMRI), to identify the part of the brain (orbitofrontal cortex) whose activity most closely tracks the reported experience of food rewards. In this paradigms, participants receive small squirts of liquid food rewards, like tomato juice and chocolate milk, in the MRI scanner, while periodically rating the experience of pleasure associated with each food on a visual analog scale. This paradigm will allow us to determine, in a more graded fashion, correspondences between brain physiology and reported hedonic experience in schizophrenia, and the extent to which these relationships resemble those observed in healthy volunteers. Our prediction is that the correspondence between self- reports of pleasure and neural responses to food rewards in orbitofrontal cortex will be significantly weaker in schizophrenia patients than in healthy volunteers. Furthermore, we hypothesize that MRI responses to food rewards will relate more systematically to clinical ratings of negative symptoms, such as avolition, in schizophrenia. These results would potentially have important implications for understanding motivational deficits in patients, and for developing better treatments for the negative symptoms of schizophrenia. PUBLIC HEALTH RELEVANCE: Schizophrenia is a complex mental disorder affecting approximately 1% of the population, that results in chronic disability for more than 3 of affected individuals through their adult lives, as well as a tremendous public health burden, in terms of the extremely high rate of unemployment in individuals with schizophrenia and the enormous financial costs to public health care system. Because of the close relationship between functional disability in schizophrenia and negative symptoms of the disorder, such as anhedonia (the inability to experience pleasure) and avolition (reduced motivation), it is critical that progress be made in understanding and developing therapeutic mechanisms for treating this class of symptoms. The goal of the proposed project is to investigate the neural processes associated with the experience of pleasure in schizophrenia, in order to increase our knowledge of the origins of negative symptoms, and to identify potential treatment targets.