Department of Psychiatry and Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, MD 21228, USA.
Biol Psychiatry. 2011 Mar 1;69(5):424-31. doi: 10.1016/j.biopsych.2010.10.015. Epub 2010 Dec 17.
Negative symptoms are core features of schizophrenia (SZ); however, the cognitive and neural basis for individual negative symptom domains remains unclear. Converging evidence suggests a role for striatal and prefrontal dopamine in reward learning and the exploration of actions that might produce outcomes that are better than the status quo. The current study examines whether deficits in reinforcement learning and uncertainty-driven exploration predict specific negative symptom domains.
We administered a temporal decision-making task, which required trial-by-trial adjustment of reaction time to maximize reward receipt, to 51 patients with SZ and 39 age-matched healthy control subjects. Task conditions were designed such that expected value (probability × magnitude) increased, decreased, or remained constant with increasing response times. Computational analyses were applied to estimate the degree to which trial-by-trial responses are influenced by reinforcement history.
Individuals with SZ showed impaired Go learning but intact NoGo learning relative to control subjects. These effects were most pronounced in patients with higher levels of negative symptoms. Uncertainty-based exploration was substantially reduced in individuals with SZ and selectively correlated with clinical ratings of anhedonia.
Schizophrenia patients, particularly those with high negative symptoms, failed to speed reaction times to increase positive outcomes and showed reduced tendency to explore when alternative actions could lead to better outcomes than the status quo. Results are interpreted in the context of current computational, genetic, and pharmacological data supporting the roles of striatal and prefrontal dopamine in these processes.
阴性症状是精神分裂症(SZ)的核心特征;然而,个体阴性症状领域的认知和神经基础仍不清楚。越来越多的证据表明纹状体和前额叶多巴胺在奖励学习和探索可能产生比现状更好结果的行为中发挥作用。本研究探讨了强化学习和不确定性驱动的探索是否能预测特定的阴性症状领域。
我们对 51 名 SZ 患者和 39 名年龄匹配的健康对照受试者进行了一项时间决策任务,该任务要求他们逐次调整反应时间以最大化奖励的获得。任务条件的设计使得随着反应时间的增加,预期价值(概率×幅度)增加、减少或保持不变。应用计算分析来估计逐次反应受强化历史影响的程度。
与对照组相比,SZ 患者的 Go 学习受损,但 NoGo 学习正常。这些影响在具有较高阴性症状水平的患者中最为明显。SZ 患者的不确定性驱动探索明显减少,且与快感缺失的临床评分呈选择性相关。
精神分裂症患者,尤其是那些有较高阴性症状的患者,未能加快反应时间以增加积极结果,并且在替代行为可能导致比现状更好的结果时,表现出减少探索的倾向。结果在支持纹状体和前额叶多巴胺在这些过程中作用的当前计算、遗传和药理学数据的背景下进行解释。