1. ¹Brain Mapping Unit, Department of Psychiatry, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK
2. ²CAMEO, Cambridgeshire and Peterborough Mental Health Partnership NHS Trust, Cambridge, UK
3. ³Behavioural and Clinical Neuroscience Institute, Cambridge, UK
4. ⁴Hôpital de la Salpêtrière, Pavillon Claude Bernard, 47 Bd de l'Hôpital, Paris, France

Correspondence: Dr GK Murray, Brain Mapping Unit, Department of Psychiatry, University of Cambridge, Addenbrooke's Hospital, Box 255, Cambridge CB2 2QQ, UK. E-mail: gm285@cam.ac.uk

Received 21 February 2007; Revised 23 May 2007; Accepted 18 June 2007; Published online 7 August 2007.

Abstract

While dopamine systems have been implicated in the pathophysiology of schizophrenia and psychosis for many years, how dopamine dysfunction generates psychotic symptoms remains unknown. Recent theoretical interest has been directed at relating the known role of midbrain dopamine neurons in reinforcement learning, motivational salience and prediction error to explain the abnormal mental experience of psychosis. However, this theoretical model has yet to be explored empirically. To examine a link between psychotic experience, reward learning and dysfunction of the dopaminergic midbrain and associated target regions, we asked a group of first episode psychosis patients suffering from active positive symptoms and a group of healthy control participants to perform an instrumental reward conditioning experiment. We characterized neural responses using functional magnetic resonance imaging. We observed that patients with psychosis exhibit abnormal physiological responses associated with reward prediction error in the dopaminergic midbrain, striatum and limbic system, and we demonstrated subtle abnormalities in the ability of psychosis patients to discriminate between motivationally salient and neutral stimuli. This study provides the first evidence linking abnormal mesolimbic activity, reward learning and psychosis.