Department of Neurology, Semmelweis University, Budapest, Hungary.
Neuropsychopharmacology. 2012 Mar;37(4):950-8. doi: 10.1038/npp.2011.278. Epub 2011 Nov 16.
Clinical evidence suggests that after initiation of dopaminergic medications some patients with Parkinson's disease (PD) develop psychotic symptoms, such as hallucinations and delusions. Here, we tested the hypothesis that the neurocognitive basis of this phenomenon can be defined as the formation of arbitrary and illusory associations between conditioned stimuli and reward signals, called aberrant salience. Young, never-medicated PD patients and matched controls were assessed on a speeded reaction time task in which the probe stimulus was preceded by conditioned stimuli that could signal monetary reward by color or shape. The patients and controls were re-evaluated after 12 weeks during which the patients received a dopamine agonist (pramipexole or ropinirole). Results indicated that dopamine agonists increased both adaptive and aberrant salience in PD patients, that is, formation of real and illusory associations between conditioned stimuli and reward, respectively. This effect was present when associations were assessed by means of faster responding after conditioned stimuli signaling reward (implicit salience) and overt rating of stimulus-reward links (explicit salience). However, unusual feelings and experiences, which are subclinical manifestations of psychotic-like symptoms, were specifically related to irrelevant and illusory stimulus-reward associations (aberrant salience) in PD patients receiving dopamine agonists. The learning of relevant and real stimulus-reward associations (adaptive salience) was not related to unusual experiences. These results suggest that dopamine agonists may increase psychotic-like experiences in young patients with PD, possibly by facilitating dopaminergic transmission in the ventral striatum, which results in aberrant associations between conditioned stimuli and reward.
临床证据表明，一些帕金森病（PD）患者在开始使用多巴胺能药物后会出现精神病症状，如幻觉和妄想。在这里，我们检验了这样一个假设，即这种现象的神经认知基础可以被定义为条件刺激与奖励信号之间形成任意和虚幻的关联，称为异常显著。年轻、从未接受过药物治疗的 PD 患者和匹配的对照组在一项快速反应时间任务中进行了评估，在该任务中，探针刺激之前有条件刺激，可以通过颜色或形状来表示货币奖励。在 12 周后，患者接受多巴胺激动剂（普拉克索或罗匹尼罗）治疗，对患者和对照组进行了重新评估。结果表明，多巴胺激动剂增加了 PD 患者的适应性和异常显著，即条件刺激与奖励之间形成真实和虚幻的关联。当通过条件刺激信号奖励后的更快反应（内隐显著）和对刺激-奖励关系的显性评分（外显显著）来评估关联时，这种效应是存在的。然而，异常感觉和体验是精神病样症状的亚临床表现，在接受多巴胺激动剂治疗的 PD 患者中，与条件刺激和奖励之间的无关和虚幻的关联（异常显著）特别相关。相关和真实的刺激-奖励关联的学习（适应性显著）与异常体验无关。这些结果表明，多巴胺激动剂可能会增加年轻 PD 患者的类似精神病的体验，可能是通过促进腹侧纹状体中的多巴胺传递，从而导致条件刺激与奖励之间的异常关联。
