Parkinson’s disease produces tremor in a large subset of patients despite generally inhibiting movement. The pathophysiology of parkinsonian tremor is unclear, leading to uncertainty in how and why treatments reduce tremor with varying effectiveness. Models for parkinsonian tremor attempt to explain the underlying principles of tremor generation in the central nervous system, often focusing on neural activity of specific substructures. In contrast, control system approaches to modeling the human motor system provide qualitative results that help inform conclusions from clinical studies. This article uses an optimal control approach to investigate the hypothesis that an increased delay in the central nervous system—unaccounted by delay compensation mechanisms—produces parkinsonian tremor. This hypothesis is motivated by the excessive inhibition projected from the basal ganglia to the thalamus in Parkinson’s disease. The thalamus relays signals from the cerebellum to the primary motor cortex: previous mapping of optimal control components indicates this prospective delay exists between the estimator (cerebellum) and controller (primary motor cortex). Simulations demonstrate realistic tremor in a neuromuscular model of the wrist. In addition, changes to effort sensitivity in the optimal controller may account for some clinical features of parkinsonian tremor, including the characteristics of re-emergent tremor and the time-varying amplitude and frequency of tremor. Contextualization of the optimal control model with physiological models and clinical observations provides insight into the potential role of the basal ganglia and cerebello-thalamo-cortical circuit and how treatments like dopaminergic medications and deep brain stimulation reduce tremor.

中文翻译：

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帕金森氏病的最佳控制观点：状态估计器和控制者之间的延迟增加导致震颤

尽管通常抑制运动，帕金森氏病仍会在大部分患者中产生震颤。帕金森氏震颤的病理生理学尚不清楚，导致不确定如何以及为何疗法以不同的效果减轻震颤。帕金森病性震颤模型试图解释中枢神经系统震颤产生的基本原理，通常侧重于特定亚结构的神经活动。相反，对人体运动系统进行建模的控制系统方法可提供定性结果，有助于从临床研究中得出结论。本文使用最佳控制方法来研究以下假说：中枢神经系统延迟的增加（由延迟补偿机制无法解释）会产生帕金森氏震颤。该假说是由于在帕金森氏病中从基底神经节到丘脑的过度抑制所致。丘脑将信号从小脑中继到初级运动皮层：最佳控制组件的先前映射表明，这种预期的延迟存在于估计器（小脑）和控制器（初级运动皮层）之间。模拟显示了手腕神经肌肉模型中的真实震颤。另外，在最佳控制器中努力敏感性的改变可能解释了帕金森氏震颤的一些临床特征，包括再发震颤的特征以及震颤的时变幅度和频率。