School of Behavioral and Brain Sciences, University of Texas at Dallas, 2200 West Mockingbird Lane, Dallas, TX 75235, USA; Wellcome Trust Centre for Neuroimaging, University College London, 12 Queen Square, London WC1N 3BG, UK.
Wellcome Trust Centre for Neuroimaging, University College London, 12 Queen Square, London WC1N 3BG, UK.
Neuroimage. 2018 Jun;173:249-257. doi: 10.1016/j.neuroimage.2018.02.048. Epub 2018 Feb 24.
The external part of the globus pallidus (GPe) is a core nucleus of the basal ganglia (BG) whose activity is disrupted under conditions of low dopamine release, as in Parkinson's disease. Current models assume decreased dopamine release in the dorsal striatum results in deactivation of dorsal GPe, which in turn affects motor expression via a regulatory effect on other nuclei of the BG. However, recent studies in healthy and pathological animal models have reported neural dynamics that do not match with this view of the GPe as a relay in the BG circuit. Thus, the computational role of the GPe in the BG is still to be determined. We previously proposed a neural model that revisits the functions of the nuclei of the BG, and this model predicts that GPe encodes values which are amplified under a condition of low striatal dopaminergic drive. To test this prediction, we used an fMRI paradigm involving a within-subject placebo-controlled design, using the dopamine antagonist risperidone, wherein healthy volunteers performed a motor selection and maintenance task under low and high reward conditions. ROI-based fMRI analysis revealed an interaction between reward and dopamine drive manipulations, with increased BOLD activity in GPe in a high compared to low reward condition, and under risperidone compared to placebo. These results confirm the core prediction of our computational model, and provide a new perspective on neural dynamics in the BG and their effects on motor selection and cognitive disorders.
苍白球外部（GPe）是基底神经节（BG）的核心核团之一，在多巴胺释放水平低的情况下（如帕金森病），其活动会受到干扰。目前的模型假设背侧纹状体中的多巴胺释放减少会导致背侧 GPe 失活，进而通过对 BG 其他核团的调节作用影响运动表达。然而，最近在健康和病理性动物模型中的研究报告了与这种 GPe 作为 BG 回路中继的观点不一致的神经动力学。因此，GPe 在 BG 中的计算作用仍有待确定。我们之前提出了一个重新审视 BG 核团功能的神经模型，该模型预测 GPe 编码的值在纹状体多巴胺驱动水平低的情况下会被放大。为了验证这一预测，我们使用了一种 fMRI 范式，涉及一项基于个体的安慰剂对照设计，使用多巴胺拮抗剂利培酮，其中健康志愿者在低和高奖励条件下执行一项运动选择和维持任务。基于 ROI 的 fMRI 分析揭示了奖励和多巴胺驱动操纵之间的相互作用，与低奖励条件相比，高奖励条件下 GPe 的 BOLD 活动增加，与安慰剂相比，利培酮组的 BOLD 活动增加。这些结果证实了我们计算模型的核心预测，并为 BG 中的神经动力学及其对运动选择和认知障碍的影响提供了新的视角。
