Murray G K, Corlett P R, Clark L, Pessiglione M, Blackwell A D, Honey G, Jones P B, Bullmore E T, Robbins T W, Fletcher P C
Brain Mapping Unit, Department of Psychiatry, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK.
Mol Psychiatry. 2008 Mar;13(3):239, 267-76. doi: 10.1038/sj.mp.4002058. Epub 2007 Aug 7.
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.
尽管多巴胺系统多年来一直被认为与精神分裂症和精神病的病理生理学有关，但多巴胺功能障碍如何产生精神病症状仍不清楚。最近的理论兴趣集中在将中脑多巴胺神经元在强化学习、动机显著性和预测误差方面的已知作用联系起来，以解释精神病的异常心理体验。然而，这一理论模型尚未得到实证研究。为了研究精神病体验、奖励学习与多巴胺能中脑及相关靶区功能障碍之间的联系，我们让一组患有活跃阳性症状的首发精神病患者和一组健康对照参与者进行了一项工具性奖励条件实验。我们使用功能磁共振成像来表征神经反应。我们观察到，精神病患者在多巴胺能中脑、纹状体和边缘系统中表现出与奖励预测误差相关的异常生理反应，并且我们证明了精神病患者在区分动机显著刺激和中性刺激的能力上存在细微异常。这项研究提供了首个将中脑边缘系统活动异常、奖励学习和精神病联系起来的证据。
