Department of Kinesiology, The Pennsylvania State University, Rec. Hall-268N, University Park, PA 16802, USA.
Department of Neurology, Pennsylvania State University-Milton S. Hershey Medical Center, Hershey, PA 17033, USA; Department of Pharmacology, Pennsylvania State University-Milton S. Hershey Medical Center, Hershey, PA 17033, USA.
Parkinsonism Relat Disord. 2014 Jan;20(1):64-8. doi: 10.1016/j.parkreldis.2013.09.019. Epub 2013 Sep 22.
We applied the idea of synergies and the framework of the uncontrolled manifold hypothesis to explore the effects of dopamine replacement therapy on finger interaction and coordination in patients with early-stage Parkinson's disease (PD).
Eight patients performed single-finger and multi-finger force production tasks with both the dominant and non-dominant hand before (off-drug) and after (on-drug) taking their dopaminergic medications. Synergy indices were defined as co-varied adjustments of commands to fingers that stabilized the total force produced by the hand.
PD patients showed significantly lower maximal finger forces off-drug compared to the on-drug condition, while indices of finger individuation (enslaving) were unchanged. The synergy indices were weaker during steady-state force production off-drug compared to on-drug. Anticipatory adjustments of synergies prior to the quick force pulse initiation were delayed and reduced off-drug as compared to the on-drug condition. These drug effects were observed in both the symptomatic and asymptomatic hands of the patients whose symptoms were limited to one side of the body.
The study demonstrates dopaminergic modulation of motor coordination in PD and supports that the analysis of different components of multi-finger synergies offers a set of indices sensitive to the effects of dopamine replacement therapy in early-stage PD. The results suggest an important role of the basal ganglia in synergy formation and in feed-forward synergy adjustments. Future studies using these methods may yield more objective, quantitative biomarker(s) of motor coordination impairments in PD, and better understanding of subcortical involvement in the neural control of natural actions.
我们应用协同作用的思想和非控制流假设的框架，探索多巴胺替代疗法对早期帕金森病（PD）患者手指交互和协调的影响。
8 名患者在服用多巴胺药物之前（停药期）和之后（用药期），分别使用优势手和非优势手进行单指和多指力量产生任务。协同指数被定义为稳定手部产生的总力的手指指令的共同变化调整。
PD 患者停药时手指最大力量明显低于用药时，而手指个体化（奴役）指数不变。与用药时相比，停药时稳态力量产生期间的协同指数较弱。与用药时相比，快速力脉冲启动前的协同性预期调整延迟且减少。这些药物效应在患者的症状手和无症状手均观察到，其症状局限于身体的一侧。
该研究表明多巴胺能调节 PD 中的运动协调，并且支持对多指协同作用的不同成分进行分析提供了一组对早期 PD 中多巴胺替代疗法的效果敏感的指数。结果表明基底神经节在协同形成和前馈协同调整中起着重要作用。未来使用这些方法的研究可能会产生更客观、定量的 PD 运动协调障碍生物标志物，并更好地理解皮质下在自然动作神经控制中的参与。
