Department of Psychiatry, University of California San Diego, 9500 Gilman Dr, La Jolla, CA, 92093, USA.
Laureate Institute for Brain Research, Tulsa, OK, 74136, USA.
Psychopharmacology (Berl). 2017 Nov;234(22):3353-3360. doi: 10.1007/s00213-017-4723-5. Epub 2017 Sep 1.
Norepinephrine mediates the adjustment of error-driven learning to match the rate of change of the environment, while phasic dopamine signals prediction errors. We tested the hypothesis that pharmacologic manipulation may modulate this process.
We administered a single dose of methylphenidate, a norepinephrine/dopamine reuptake inhibitor, or placebo in double-blind randomized fashion to 20 healthy human males, who then performed a probabilistic learning task. Each subject was tested in two sessions, receiving methylphenidate in one session and placebo in the other, in randomized order. Task performance was quantified by the percentage of trials on which subjects chose the most likely option, while learning rate was measured using a computational model-based parameter as well as with a behavioral analogue of this parameter.
There was a substance-by-session interaction effect on behavioral learning rate and model-based learning rate, such that subjects receiving methylphenidate exhibited higher learning rates than those receiving placebo in session 1, with no difference observed in session 2, suggesting that subjects retained the increased learning rate across sessions. Higher behavioral learning rate was associated with both higher task performance and with the model-based learning rate. Higher learning rates were advantageous given the high rate of change on the task. Subjects receiving methylphenidate and placebo began the task in session 1 with a similar behavioral learning rate, but those receiving methylphenidate rapidly increased learning rate toward the optimal value, suggesting that methylphenidate accelerated the adaptation of learning rate based on the environment.
The results suggest that methylphenidate may improve disrupted probabilistic learning in disorders involving noradrenergic or dopaminergic dysfunction.
去甲肾上腺素介导了错误驱动学习的调整，以匹配环境变化的速度，而相位多巴胺信号则传递预测误差。我们测试了这样一个假设，即药物干预可能会调节这个过程。
我们以双盲随机的方式向 20 名健康男性单次给药哌甲酯（一种去甲肾上腺素/多巴胺再摄取抑制剂）或安慰剂，然后让他们进行概率学习任务。每个被试者在两个会话中接受测试，以随机顺序分别接受哌甲酯和安慰剂。通过计算模型参数和行为模拟参数来量化任务表现，通过选择最有可能选项的试验百分比来量化学习率。
在行为学习率和基于模型的学习率上存在物质与会话的交互效应，这表明与接受安慰剂的会话 2 相比，接受哌甲酯的被试者在会话 1 中的学习率更高，表明被试者在两个会话中都保持了更高的学习率。更高的行为学习率与更高的任务表现和基于模型的学习率都有关联。更高的学习率在任务变化率高的情况下更具优势。在会话 1 中，接受哌甲酯和安慰剂的被试者开始任务时具有相似的行为学习率，但接受哌甲酯的被试者的学习率迅速朝着最优值增加，这表明哌甲酯加速了基于环境的学习率的适应。
结果表明，哌甲酯可能改善涉及去甲肾上腺素或多巴胺能功能障碍的障碍中的概率学习障碍。
