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多巴胺替代疗法在帕金森病决策、工作记忆及奖赏方面的作用:治疗剂量重要吗?

On the role of dopamine replacement therapy in decision-making, working memory, and reward in Parkinson's disease: does the therapy-dose matter?

作者信息

Torta Diana Maria Elena, Castelli Lorys, Zibetti Maurizio, Lopiano Leonardo, Geminiani Giuliano

机构信息

Department of Psychology, University of Turin, Via Po 14, Turin, Italy.

出版信息

Brain Cogn. 2009 Nov;71(2):84-91. doi: 10.1016/j.bandc.2009.04.003. Epub 2009 May 12.

Abstract

BACKGROUND

Dopaminergic therapy proved to ameliorate motor deficits in Parkinson's disease but its effects on behavior and cognition vary according to factors that include, among others, the evolution of the disease and the nature of the task that is tested. This study addressed the question of whether, in moderate to advanced Parkinson's disease (PD) with motor fluctuations, changes in decision-making and sensitivity to reward occur and to what extent dopaminergic therapy plays a role.

METHODS

Fifteen PD patients (On and Off medication) and thirteen healthy controls were compared on two different tasks which analyzed decision-making processes (the Cambridge Gamble Task, CGT) and working memory abilities with and without the prospect of reward (modified N-back task).

RESULTS

We found that the PD patients were unable to choose an optimal betting strategy and were impulsive in their choices relative to the control group. Further, a detrimental dose-dependent effect of dopaminergic therapy was detected, meaning that those patients who were taking higher doses of therapy were more impulsive in selecting bets and more impaired in making probabilistic choices. Such a dose-dependent effect was not found on the N-back task. However, the results of the PD group in this task supported indirect evidence of the amelioration of performance in rewarded conditions.

CONCLUSION

Our results suggest that the detrimental effects of dopaminergic therapy may be dose-related and that the interaction between monetary reward and dopaminergic therapy can affect and improve some cognitive abilities, such as working memory.

摘要

背景

多巴胺能疗法已被证明可改善帕金森病的运动功能障碍,但其对行为和认知的影响因多种因素而异,其中包括疾病的进展情况以及所测试任务的性质等。本研究探讨了在伴有运动波动的中度至重度帕金森病(PD)患者中,决策和对奖励的敏感度是否发生变化,以及多巴胺能疗法在其中发挥何种作用。

方法

对15名PD患者(服药和未服药状态)和13名健康对照者进行了两项不同任务的测试,这两项任务分别分析决策过程(剑桥赌博任务,CGT)以及有无奖励预期时的工作记忆能力(改良N-回溯任务)。

结果

我们发现,与对照组相比,PD患者无法选择最优的投注策略,且在选择上较为冲动。此外,检测到多巴胺能疗法存在有害的剂量依赖性效应,即服用较高剂量疗法的患者在选择投注时更冲动,在进行概率选择时受损更严重。在N-回溯任务中未发现这种剂量依赖性效应。然而,PD组在该任务中的结果支持了在有奖励条件下表现改善的间接证据。

结论

我们的结果表明,多巴胺能疗法的有害作用可能与剂量相关,并且金钱奖励与多巴胺能疗法之间的相互作用会影响并改善一些认知能力,如工作记忆。

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