Van Wouwe Nelleke C, Claassen Daniel O, Neimat Joseph S, Kanoff Kristen E, Wylie Scott A
Vanderbilt University Medical Center.
J Cogn Neurosci. 2017 May;29(5):816-826. doi: 10.1162/jocn_a_01099. Epub 2017 Jan 27.
Learning the contingencies between stimulus, action, and outcomes is disrupted in disorders associated with altered dopamine (DA) function in the BG, such as Parkinson disease (PD). Although the role of DA in learning to act has been extensively investigated in PD, the role of DA in "learning to withhold" (or inhibit) action to influence outcomes is not as well understood. The current study investigated the role of DA in learning to act or to withhold action to receive rewarding, or avoid punishing outcomes, in patients with PD tested "off" and "on" dopaminergic medication (n = 19) versus healthy controls (n = 30). Participants performed a reward-based learning task that orthogonalized action and outcome valence (action-reward, inaction-reward, action-punishment, inaction-punishment). We tested whether DA would bias learning toward action, toward reward, or to particular action-outcome interactions. All participants demonstrated inherent learning biases preferring action with reward and inaction to avoid punishment, and this was unaffected by medication. Instead, DA produced a complex modulation of learning less natural action-outcome associations. "Off" DA medication, patients demonstrated impairments in learning to withhold action to gain reward, suggesting a difficulty to overcome a bias toward associating inaction with punishment avoidance. On DA medication, these patterns changed, and patients showed a reduced ability to learn to act to avoid punishment, indicating a bias toward action and reward. The current findings suggest that DA in PD has a complex influence on the formation of action-outcome associations, particularly those involving less natural linkages between action and outcome valence.
在与基底神经节中多巴胺（DA）功能改变相关的疾病，如帕金森病（PD）中，学习刺激、行动和结果之间的偶联关系会受到破坏。尽管在帕金森病中，多巴胺在学习行动方面的作用已得到广泛研究，但多巴胺在“学习抑制”（或抑制）行动以影响结果方面的作用却尚未得到充分理解。本研究调查了多巴胺在帕金森病患者（n = 19）“停药”和“服药”状态下与健康对照组（n = 30）中，学习行动或抑制行动以获得奖励或避免惩罚结果时所起的作用。参与者执行了一项基于奖励的学习任务，该任务使行动和结果效价（行动-奖励、不行动-奖励、行动-惩罚、不行动-惩罚）相互正交。我们测试了多巴胺是否会使学习偏向行动、奖励或特定的行动-结果相互作用。所有参与者都表现出固有的学习偏好，更喜欢有奖励的行动和避免惩罚的不行动，且这不受药物影响。相反，多巴胺对学习较不自然的行动-结果关联产生了复杂的调节作用。在“停药”状态下，患者在学习抑制行动以获得奖励方面存在障碍，这表明难以克服将不行动与避免惩罚联系起来的偏向。在服药状态下，这些模式发生了变化，患者学习行动以避免惩罚的能力下降，表明偏向行动和奖励。目前的研究结果表明，帕金森病中的多巴胺对行动-结果关联的形成具有复杂的影响，特别是那些涉及行动和结果效价之间较不自然联系的关联。
