Computational modelling reveals contrasting effects on reinforcement learning and cognitive flexibility in stimulant use disorder and obsessive-compulsive disorder: remediating effects of dopaminergic D2/3 receptor agents
Computational modelling reveals contrasting effects on reinforcement learning and cognitive flexibility in stimulant use disorder and obsessive-compulsive disorder: remediating effects of dopaminergic D2/3 receptor agents
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DOI：
10.1007/s00213-019-05325-w
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发表时间：
2019-08-01
影响因子：
3.4
通讯作者：
Cardinal, Rudolf N.
中科院分区：
文献类型：
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作者：
Kanen, Jonathan W.;Ersche, Karen D.;Cardinal, Rudolf N.
强迫性的基本原理障碍，如兴奋剂使用障碍（SUD）和强迫症（OCD），其特征是行为灵活性的缺陷，其中一些已被概率逆转学习（PRL）范式捕获。本研究使用计算模型来描述在SUD和OCD中观察到的PRL行为模式的强化学习过程，并显示多巴胺D-2/3受体激动剂普拉克索和D-2/3拮抗剂氨硫pride如何影响这些反应。方法采用分层贝叶斯方法对三组PRL数据进行分析：SUD患者、强迫症患者和健康对照组。在双盲安慰剂对照随机设计中，参与者完成了三个疗程，分别接受安慰剂、普拉克索和氨硫pride。我们使用桥式抽样估计边际似然来比较七个模型。结果：与对照组（安慰剂组）相比，刺激约束的持久性（衡量参与者对相同刺激的反应程度，无论结果如何）在SUD中显著增加，但在OCD中下降。患有SUD的个体也表现出较少的奖励驱动学习，而SUD和强迫症组都表现出从惩罚（非奖励）中学习的增加。普拉克索和氨硫pride对对照组和强迫症组的效果相似；两者都增加了惩罚驱动的学习。这些d- 2/3调节药物对SUD组的影响不同，在其他影响中，纠正奖励驱动的学习和减少持久性行为的方面。我们提供了一个简明的计算解释，说明持久性倾向和奖惩驱动的学习如何在SUD和OCD中不同地促进PRL。D-2/3药物调节了这些过程，特别是修复了SUD的缺陷，这可能为治疗效果提供了信息。
Rationale Disorders of compulsivity such as stimulant use disorder (SUD) and obsessive-compulsive disorder (OCD) are characterised by deficits in behavioural flexibility, some of which have been captured using probabilistic reversal learning (PRL) paradigms. Objectives This study used computational modelling to characterise the reinforcement learning processes underlying patterns of PRL behaviour observed in SUD and OCD and to show how the dopamine D-2/3 receptor agonist pramipexole and the D-2/3 antagonist amisulpride affected these responses. Methods We applied a hierarchical Bayesian method to PRL data across three groups: individuals with SUD, OCD, and healthy controls. Participants completed three sessions where they received placebo, pramipexole, and amisulpride, in a double-blind placebo-controlled, randomised design. We compared seven models using a bridge sampling estimate of the marginal likelihood. Results Stimulus-bound perseveration, a measure of the degree to which participants responded to the same stimulus as before irrespective of outcome, was significantly increased in SUD, but decreased in OCD, compared to controls (on placebo). Individuals with SUD also exhibited reduced reward-driven learning, whilst both the SUD and OCD groups showed increased learning from punishment (nonreward). Pramipexole and amisulpride had similar effects on the control and OCD groups; both increased punishment-driven learning. These D-2/3-modulating drugs affected the SUD group differently, remediating reward-driven learning and reducing aspects of perseverative behaviour, amongst other effects. Conclusions We provide a parsimonious computational account of how perseverative tendencies and reward- and punishment-driven learning differentially contribute to PRL in SUD and OCD. D-2/3 agents modulated these processes and remediated deficits in SUD in particular, which may inform therapeutic effects.