Cognitive states influence dopamine-driven aberrant learning in Parkinson's disease.
Cognitive states influence dopamine-driven aberrant learning in Parkinson's disease.
复制标题
DOI：
10.1016/j.cortex.2017.02.021
复制
发表时间：
2017-05
期刊：
影响因子：
--
通讯作者：
Richardson SP
中科院分区：
文献类型：
--
作者：
Cavanagh JF;Mueller AA;Brown DR;Janowich JR;Story-Remer JH;Wegele A;Richardson SP
多巴胺能紧张度的个体差异是从奖励与惩罚中学习的倾向的基础。这些作用在帕金森患者中有很好的记录，他们在低和高紧张性多巴胺能状态之间摇摆不定，作为药物的功能。然而，很少有研究调查已知影响帕金森病患者下游多巴胺能学习的高级认知状态的影响。多巴胺依赖性认知对学习的影响将为帕金森病患者认知完整性和动机下降提供一个候选机制。在这份报告中，我们测试了两个高层次的认知状态（冲突的成本和意志的价值）的影响，最近已被证明会导致可预测的学习偏差在健康的年轻人作为多巴胺受体亚型和多巴胺能挑战的功能。据推测，帕金森氏症患者关闭药物治疗将有一个冲突的成本增加和意志价值下降，这些影响将得到补救或逆转的药物。参与者包括N=28名帕金森病患者，他们分别接受了开和关多巴胺能药物的测试，以及28名年龄和性别匹配的对照组。在帕金森病患者中观察到了预期的冲突效应成本，但仅限于最近诊断的患者（<5年）。我们发现了一个意想不到的效果，意志任务的价值：药物损害的能力，从困难的a-volitional（指示）的选择。这一新发现在最近诊断的患者中也得到了加强。这两项任务之间的学习偏差ON与OFF药物之间的差异具有强烈的相关性，支持了他们利用多巴胺能张力的常见潜在不平衡的想法，这在早期帕金森症中特别可变。这些决策偏差是特定于早期而不是晚期疾病的发现可能为未来的研究提供了一个机会，以量化特异质疾病进展的表型表达。
Individual differences in dopaminergic tone underlie tendencies to learn from reward versus punishment. These effects are well documented in Parkinson’s patients, who vacillate between low and high tonic dopaminergic states as a function of medication. Yet very few studies have investigated the influence of higher-level cognitive states known to affect downstream dopaminergic learning in Parkinson’s patients. A dopamine-dependent cognitive influence over learning would provide a candidate mechanism for declining cognitive integrity and motivation in Parkinson’s patients. In this report we tested the influence of two high-level cognitive states (cost of conflict and value of volition) that have recently been shown to cause predictable learning biases in healthy young adults as a function of dopamine receptor subtype and dopaminergic challenge. It was hypothesized that Parkinson’s patients OFF medication would have an enhanced cost of conflict and a decreased value of volition, and that these effects would be remediated or reversed ON medication. Participants included N=28 Parkinson’s disease patients who were each tested ON and OFF dopaminergic medication and 28 age- and sex-matched controls. The expected cost of conflict effect was observed in Parkinson’s patients OFF versus ON medication, but only in those that were more recently diagnosed (<5 years). We found an unexpected effect in the value of volition task: medication compromised the ability to learn from difficult a-volitional (instructed) choices. This novel finding was also enhanced in recently diagnosed patients. The difference in learning biases ON vs. OFF medication between these two tasks was strongly correlated, bolstering the idea that they tapped into a common underlying imbalance in dopaminergic tone that is particularly variable in earlier stage Parkinsonism. The finding that these decision biases are specific to earlier but not later stage disease may offer a chance for future studies to quantify phenotypic expressions of idiosyncratic disease progression.