Department of Neurology and Neuroscience, Nagoya City University Graduate School of Medical Science, Mizuho-ku, Nagoya, Japan.
Department of Rehabilitation Medicine, Nagoya City University Graduate School of Medical Science, Mizuho-ku, Nagoya, Japan.
PLoS One. 2018 May 30;13(5):e0196661. doi: 10.1371/journal.pone.0196661. eCollection 2018.
Striatal dopamine is functionally important for the acquisition of motor skills. However, it remains controversial as to whether intrinsic processing of motor learning is impaired in patients with Parkinson's disease (PD), and if yes, whether the impairment is associated with altered striatal dopamine release. Additionally, most neuro-imaging studies of patients with PD have focused on motor sequence learning. In contrast, skill acquisition, specifically, the reconstruction of muscle control of isolated movements, has barely been studied.
In this study, we used a repetitive skill training task to measure the peak acceleration of left thumb movement during a process to achieve fine tuning of motor skill. Using 11C-raclopride (RAC) positron emission tomography, we investigated changes in striatal dopamine levels in two conditions of a skill acquisition task: initial skill training (Day 1) and acquired condition (Day 2) with eight patients with PD and age-matched healthy subjects (HS).
In HS, the mean acceleration of each session improved through repeated training sessions on Day 1. However, in patients with PD, the training-associated increase was less than that for HS, and this suggests that repetitive skill training does not result in the effective improvement of motor performance. The regions of interest (ROI) analysis revealed that the RAC-binding potential (BP) was significantly reduced in the right putamen on Day 1 compared with Day 2 in HS. In patients with PD, BP within the right putamen was unchanged. Further, we found that patients with PD had increased dopamine levels within the right ventral striatum (VST) and right caudate (CAU) on Day 2, which was greater than that in HS. These results suggest the impaired activation of the putamen during skill acquisition in patients with PD and compensated hyperactivation of the VST and CAU for the reduced dopamine release within the dorsal putamen (DPU).
Our findings suggest that patients with PD had insufficiency in the process to improve motor skills. Different patterns of striatal dopamine release are relevant to the impairment of these motor functions in patients with PD, at the early stage of the disease.
纹状体多巴胺对于运动技能的获得具有重要的功能作用。然而，帕金森病（PD）患者的运动学习的内在处理是否受损仍存在争议，如果是，这种损伤是否与纹状体多巴胺释放的改变有关。此外，大多数针对 PD 患者的神经影像学研究都集中在运动序列学习上。相比之下，技能获取，特别是孤立运动肌肉控制的重构，几乎没有被研究过。
在这项研究中，我们使用重复性技能训练任务来测量左拇指运动在精细调整运动技能过程中的峰值加速度。使用 11C-racopride（RAC）正电子发射断层扫描，我们研究了纹状体多巴胺水平在技能获取任务的两种情况下的变化：初始技能训练（第 1 天）和获得条件（第 2 天），包括 8 名 PD 患者和年龄匹配的健康受试者（HS）。
在 HS 中，每个训练阶段的平均加速度在第 1 天的重复训练中得到了提高。然而，在 PD 患者中，训练相关的增加低于 HS，这表明重复性技能训练不会导致运动表现的有效改善。感兴趣区域（ROI）分析显示，HS 中第 1 天右壳核的 RAC 结合能力（BP）与第 2 天相比显著降低。在 PD 患者中，右壳核内的 BP 没有变化。此外，我们发现 PD 患者在第 2 天右腹侧纹状体（VST）和右尾状核（CAU）内的多巴胺水平升高，高于 HS。这些结果表明，PD 患者在技能获取过程中壳核的激活受损，以及为了弥补背侧壳核（DPU）内多巴胺释放的减少而对 VST 和 CAU 的过度激活。
我们的发现表明，PD 患者在改善运动技能的过程中存在不足。纹状体多巴胺释放的不同模式与 PD 患者运动功能的损伤有关，这发生在疾病的早期阶段。
