Insel Catherine, Reinen Jenna, Weber Jochen, Wager Tor D, Jarskog L Fredrik, Shohamy Daphna, Smith Edward E
Department of Psychology, Harvard University, 52 Oxford Street, Cambridge, MA, 02138, USA,
Cogn Affect Behav Neurosci. 2014 Mar;14(1):189-201. doi: 10.3758/s13415-014-0261-3.
Schizophrenia is characterized by an abnormal dopamine system, and dopamine blockade is the primary mechanism of antipsychotic treatment. Consistent with the known role of dopamine in reward processing, prior research has demonstrated that patients with schizophrenia exhibit impairments in reward-based learning. However, it remains unknown how treatment with antipsychotic medication impacts the behavioral and neural signatures of reinforcement learning in schizophrenia. The goal of this study was to examine whether antipsychotic medication modulates behavioral and neural responses to prediction error coding during reinforcement learning. Patients with schizophrenia completed a reinforcement learning task while undergoing functional magnetic resonance imaging. The task consisted of two separate conditions in which participants accumulated monetary gain or avoided monetary loss. Behavioral results indicated that antipsychotic medication dose was associated with altered behavioral approaches to learning, such that patients taking higher doses of medication showed increased sensitivity to negative reinforcement. Higher doses of antipsychotic medication were also associated with higher learning rates (LRs), suggesting that medication enhanced sensitivity to trial-by-trial feedback. Neuroimaging data demonstrated that antipsychotic dose was related to differences in neural signatures of feedback prediction error during the loss condition. Specifically, patients taking higher doses of medication showed attenuated prediction error responses in the striatum and the medial prefrontal cortex. These findings indicate that antipsychotic medication treatment may influence motivational processes in patients with schizophrenia.
精神分裂症的特征是多巴胺系统异常,而多巴胺阻断是抗精神病药物治疗的主要机制。与多巴胺在奖赏处理中的已知作用一致,先前的研究表明,精神分裂症患者在基于奖赏的学习方面存在缺陷。然而,抗精神病药物治疗如何影响精神分裂症患者强化学习的行为和神经特征仍不清楚。本研究的目的是检验抗精神病药物在强化学习过程中是否调节对预测误差编码的行为和神经反应。精神分裂症患者在接受功能磁共振成像时完成了一项强化学习任务。该任务由两个独立的条件组成,参与者在其中积累金钱收益或避免金钱损失。行为结果表明,抗精神病药物剂量与学习的行为方式改变有关,即服用较高剂量药物的患者对负性强化的敏感性增加。较高剂量的抗精神病药物也与较高的学习率相关,表明药物增强了对逐次试验反馈的敏感性。神经影像学数据表明,抗精神病药物剂量与损失条件下反馈预测误差的神经特征差异有关。具体而言,服用较高剂量药物的患者在纹状体和内侧前额叶皮质的预测误差反应减弱。这些发现表明,抗精神病药物治疗可能会影响精神分裂症患者的动机过程。