Graef Susanne, Biele Guido, Krugel Lea K, Marzinzik Frank, Wahl Michael, Wotka Johann, Klostermann Fabian, Heekeren Hauke R
Max Planck Institute for Human Development Berlin, Germany.
Front Hum Neurosci. 2010 Oct 14;4:169. doi: 10.3389/fnhum.2010.00169. eCollection 2010.
The mesocorticolimbic dopamine (DA) system linking the dopaminergic midbrain to the prefrontal cortex and subcortical striatum has been shown to be sensitive to reinforcement in animals and humans. Within this system, coexistent segregated striato-frontal circuits have been linked to different functions. In the present study, we tested patients with Parkinson's disease (PD), a neurodegenerative disorder characterized by dopaminergic cell loss, on two reward-based learning tasks assumed to differentially involve dorsal and ventral striato-frontal circuits. 15 non-depressed and non-demented PD patients on levodopa monotherapy were tested both on and off medication. Levodopa had beneficial effects on the performance on an instrumental learning task with constant stimulus-reward associations, hypothesized to rely on dorsal striato-frontal circuits. In contrast, performance on a reversal learning task with changing reward contingencies, relying on ventral striato-frontal structures, was better in the unmedicated state. These results are in line with the "overdose hypothesis" which assumes detrimental effects of dopaminergic medication on functions relying upon less affected regions in PD. This study demonstrates, in a within-subject design, a double dissociation of dopaminergic medication and performance on two reward-based learning tasks differing in regard to whether reward contingencies are constant or dynamic. There was no evidence for a dose effect of levodopa on reward-based behavior with the patients' actual levodopa dose being uncorrelated to their performance on the reward-based learning tasks.
连接多巴胺能中脑与前额叶皮质及皮质下纹状体的中脑皮质边缘多巴胺（DA）系统，已被证明在动物和人类中对强化敏感。在这个系统中，共存的分离纹状体 - 额叶回路与不同功能相关。在本研究中，我们对帕金森病（PD）患者进行了测试，这是一种以多巴胺能细胞丢失为特征的神经退行性疾病，采用了两项基于奖励的学习任务，假定分别涉及背侧和腹侧纹状体 - 额叶回路。15名接受左旋多巴单药治疗的非抑郁且非痴呆的PD患者在服药和停药状态下均接受了测试。左旋多巴对具有恒定刺激 - 奖励关联的工具性学习任务的表现有有益影响，该任务假定依赖于背侧纹状体 - 额叶回路。相比之下，依赖腹侧纹状体 - 额叶结构、奖励条件不断变化的逆向学习任务，在未服药状态下表现更好。这些结果与“过量假设”一致，该假设认为多巴胺能药物对依赖帕金森病中受影响较小区域的功能有不利影响。本研究在受试者内设计中证明，多巴胺能药物与两项基于奖励的学习任务的表现存在双重分离，这两项任务在奖励条件是恒定还是动态方面有所不同。没有证据表明左旋多巴剂量对基于奖励的行为有剂量效应，患者实际的左旋多巴剂量与他们在基于奖励的学习任务中的表现无关。
