Author's Personal Copy Probabilistic Reversal Learning Is Impaired in Parkinson's Disease
Author's Personal Copy Probabilistic Reversal Learning Is Impaired in Parkinson's Disease
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通讯作者：
D. A. Peterson;C. Elliott;D. Song;S. Makeig;H. Poizner
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作者：
D. A. Peterson;C. Elliott;D. Song;S. Makeig;H. Poizner
在许多日常环境中，我们的选择与其潜在回报之间的关系是概率和动态的。此外，选择的难度可能会有很大的不同。虽然大量的理论和经验证据表明，多巴胺介导奖励学习，多巴胺在概率和动态奖励学习的影响仍然不清楚。我们采用了一种概率奖励学习任务，最初用于研究灵长类动物黑质多巴胺细胞的放电率[（2006）中脑多巴胺神经元编码未来行动的决定。Nat Neurosci 9：1057 - 1063]，用作人类的反向学习任务。我们试图研究帕金森病（PD）的多巴胺耗竭如何影响概率奖励学习和适应奖励意外事件的逆转。在256次试验中，受试者学会了从奖励概率差异很小或很大的图像对中选择更有利的图像。在随后的其他相同的逆转阶段，奖励概率意外的刺激被逆转。研究了17名轻度至中度PD患者的多巴胺能药物，并与15名年龄匹配的对照组进行了比较。与对照组相比，PD患者具有明显的逆转前和逆转后缺陷，这取决于他们必须学习的选择的难度。患者还表现出对逆转的适应性受损。一个计算模型的受试者的试验的试验选择表明，适应性是敏感的增益与患者加权前逆转反馈。总的来说，研究结果表明，黑质多巴胺能系统在学习中做出选择的概率和动态的奖励突发事件的环境。近年来已经清楚的是，帕金森病（PD）不仅影响运动的启动和控制，而且影响动机驱动和寻求奖励的行为（Borek等人，2006年），这本身是学习新的反应的基础。PD的经典神经病理学是黑质丘脑部多巴胺细胞的变性（Dauer和Przedborski，2003）。这不仅在传出靶中产生显著降低的多巴胺能活性的紧张水平，而且可能损害阶段性多巴胺能活性。已经积累了大量的理论和经验证据，表明中脑多巴胺系统的阶段性活性对于基于试验反馈的学习至关重要（Abler等人，2006年）。主要的概念是，阶段性多巴胺活动信号实际与预期的奖励值，或奖励“预测错误”（蒙塔格等...
—In many everyday settings, the relationship between our choices and their potentially rewarding outcomes is probabilistic and dynamic. In addition, the difficulty of the choices can vary widely. Although a large body of theoretical and empirical evidence suggests that dopamine mediates rewarded learning, the influence of dopamine in probabilistic and dynamic rewarded learning remains unclear. We adapted a probabilistic rewarded learning task originally used to study firing rates of dopamine cells in primate substantia nigra pars compacta [ (2006) Midbrain dopamine neurons encode decisions for future action. Nat Neurosci 9:1057–1063] for use as a reversal learning task with humans. We sought to investigate how the dopamine depletion in Parkinson's disease (PD) affects probabilistic reward learning and adaptation to a reversal in reward contingencies. Over the course of 256 trials subjects learned to choose the more favorable from among pairs of images with small or large differences in reward probabilities. During a subsequent otherwise identical reversal phase, the reward probability contingencies for the stimuli were reversed. Seventeen PD patients of mild to moderate severity were studied off of their dopaminergic medications and compared to 15 age-matched controls. Compared to controls , PD patients had distinct pre-and post-reversal deficiencies depending upon the difficulty of the choices they had to learn. The patients also exhibited compromised adaptability to the reversal. A computational model of the subjects' trial-by-trial choices demonstrated that the adaptability was sensitive to the gain with which patients weighted pre-reversal feedback. Collectively, the results implicate the nigral dopa-minergic system in learning to make choices in environments with probabilistic and dynamic reward contingencies. It has become clear in recent years that Parkinson's disease (PD) affects not only the initiation and control of movements, but also motivational drive and reward-seeking behavior (Borek et al., 2006), which themselves are fundamental to the learning of new responses. A classic neuropathology of PD is the degeneration of dopamine cells in the substantia nigra pars compacta (Dauer and Przedborski, 2003). This not only produces a substantially reduced tonic level of dopaminergic activity in efferent targets, but also likely impairs phasic dopaminergic activity A broad body of theoretical and empirical evidence has accumulated suggesting that phasic activity of the midbrain dopa-mine system is critical to trial by trial feedback-based learning (Abler et al., 2006). The predominant concept is that the phasic dopamine activity signals actual versus expected reward values, or a reward " prediction error " (Mon-tague et …