Zénon Alexandre, Duclos Yann, Carron Romain, Witjas Tatiana, Baunez Christelle, Régis Jean, Azulay Jean-Philippe, Brown Peter, Eusebio Alexandre
1 Institute of Neurosciences, Université Catholique de Louvain, 1200 Brussels, Belgium.
2 Institut de Neurosciences de La Timone UMR 7289, Aix Marseille Université, CNRS, 13385, Marseille, France.
Brain. 2016 Jun;139(Pt 6):1830-43. doi: 10.1093/brain/aww075. Epub 2016 Apr 27.
Adaptive behaviour entails the capacity to select actions as a function of their energy cost and expected value and the disruption of this faculty is now viewed as a possible cause of the symptoms of Parkinson's disease. Indirect evidence points to the involvement of the subthalamic nucleus-the most common target for deep brain stimulation in Parkinson's disease-in cost-benefit computation. However, this putative function appears at odds with the current view that the subthalamic nucleus is important for adjusting behaviour to conflict. Here we tested these contrasting hypotheses by recording the neuronal activity of the subthalamic nucleus of patients with Parkinson's disease during an effort-based decision task. Local field potentials were recorded from the subthalamic nucleus of 12 patients with advanced Parkinson's disease (mean age 63.8 years ± 6.8; mean disease duration 9.4 years ± 2.5) both OFF and ON levodopa while they had to decide whether to engage in an effort task based on the level of effort required and the value of the reward promised in return. The data were analysed using generalized linear mixed models and cluster-based permutation methods. Behaviourally, the probability of trial acceptance increased with the reward value and decreased with the required effort level. Dopamine replacement therapy increased the rate of acceptance for efforts associated with low rewards. When recording the subthalamic nucleus activity, we found a clear neural response to both reward and effort cues in the 1-10 Hz range. In addition these responses were informative of the subjective value of reward and level of effort rather than their actual quantities, such that they were predictive of the participant's decisions. OFF levodopa, this link with acceptance was weakened. Finally, we found that these responses did not index conflict, as they did not vary as a function of the distance from indifference in the acceptance decision. These findings show that low-frequency neuronal activity in the subthalamic nucleus may encode the information required to make cost-benefit comparisons, rather than signal conflict. The link between these neural responses and behaviour was stronger under dopamine replacement therapy. Our findings are consistent with the view that Parkinson's disease symptoms may be caused by a disruption of the processes involved in balancing the value of actions with their associated effort cost.
适应性行为需要根据动作的能量消耗和预期价值来选择动作的能力，而这种能力的破坏现在被视为帕金森病症状的一个可能原因。间接证据表明，丘脑底核（帕金森病深部脑刺激最常见的靶点）参与了成本效益计算。然而，这种假定的功能似乎与目前认为丘脑底核对于根据冲突调整行为很重要的观点不一致。在这里，我们通过记录帕金森病患者在基于努力的决策任务期间丘脑底核的神经元活动，来检验这些相互矛盾的假设。从12名晚期帕金森病患者（平均年龄63.8岁±6.8；平均病程9.4年±2.5）的丘脑底核记录局部场电位，这些患者在未服用左旋多巴和服用左旋多巴时，需要根据所需的努力程度和承诺的奖励价值来决定是否参与一项需要付出努力的任务。使用广义线性混合模型和基于聚类的置换方法对数据进行分析。在行为上，试验接受的概率随着奖励价值的增加而增加，随着所需努力程度的增加而降低。多巴胺替代疗法提高了与低奖励相关的努力的接受率。在记录丘脑底核活动时，我们在1 - 10赫兹范围内发现了对奖励和努力线索的明显神经反应。此外，这些反应反映了奖励的主观价值和努力程度，而不是它们的实际数量，因此它们能够预测参与者的决策。在未服用左旋多巴时，这种与接受的联系被削弱。最后，我们发现这些反应并不表示冲突，因为它们不会随着接受决策中与无差异点的距离而变化。这些发现表明，丘脑底核中的低频神经元活动可能编码了进行成本效益比较所需的信息，而不是信号冲突。在多巴胺替代疗法下，这些神经反应与行为之间的联系更强。我们的发现与以下观点一致，即帕金森病症状可能是由于平衡动作价值与其相关努力成本的过程受到破坏所致。
