Parkinson's disease (PD) is a systemic brain disorder where the cortical cholinergic network begins to degenerate early in the disease process. Readily accessible, quantitative, and specific behavioral markers of the cortical cholinergic network are lacking. Although degeneration of the dopaminergic network may be responsible for deficits in cardinal motor signs, the control of gait is a complex process and control of higher-order aspects of gait, such as gait variability, may be influenced by cognitive processes attributed to cholinergic networks. We investigated whether swing time variability, a metric of gait variability that is independent from gait speed, was a quantitative behavioral marker of cortical cholinergic network integrity in PD. Twenty-two individuals with PD and twenty-nine age-matched controls performed a validated stepping-in-place (SIP) task to assess swing time variability off all therapy. The PD cohort also underwent structural MRI scans to measure gray matter volume of the Nucleus Basalis of Meynert (NBM), the key node in the cortical cholinergic network. Swing time variability was also measured ON subthalamic nucleus (STN) deep brain stimulation (DBS) in PD individuals. A subset of eleven individuals with PD completed the SIP task again off all therapy after three years of continuous DBS. Clinical motor assessments were performed for each condition. Swing time variability was significantly greater (i.e., worse) in PD compared to controls and greater swing time variability was related to greater atrophy of the NBM. STN DBS significantly improved cardinal motor signs but did not improve swing time variability. Swing time variability worsened in PD, off therapy, after three years of continuous STN DBS, and NBM atrophy predicted the degree of increase. In contrast, cardinal motor signs did not progress. These results demonstrate that swing time variability is a reliable marker of cortical cholinergic health, and support a framework in which higher-order aspects of gait control in PD are reliant on the cortical cholinergic system, in contrast to other motor aspects of PD that rely on the dopaminergic network.

中文翻译：

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Meynert基底核的萎缩预示着帕金森氏病步态变异的进展

帕金森氏病（PD）是一种系统性脑部疾病，其中皮质胆碱能网络在疾病过程的早期开始退化。缺乏皮质胆碱能网络的容易获得，定量和特定的行为标记。尽管多巴胺能网络的退化可能是主要运动征象缺陷的原因，但步态的控制是一个复杂的过程，而步态高阶方面的控制（例如步态变异性）可能会受到胆碱能网络的认知过程的影响。我们调查了摆动时间可变性（一种独立于步态速度的步态可变性指标）是否是PD中皮层胆碱能网络完整性的定量行为标志。22名患有PD的患者和29名年龄匹配的对照者执行了一项经过验证的就地踏步（SIP）任务，以评估所有疗法的摆动时间变异性。PD队列还进行了结构MRI扫描，以测量皮质胆碱能网络关键节点Meynert基底核（NBM）的灰质体积。还对PD个体的丘脑下核（STN）深度脑刺激（DBS）进行了摆动时间变化的测量。经过连续DBS的三年治疗后，由11名PD患者组成的子集再次通过所有疗法完成了SIP任务。针对每种情况进行了临床运动评估。与对照组相比，PD的摆动时间可变性显着更大（即更差），并且较大的摆动时间可变性与NBM的萎缩程度有关。STN DBS显着改善了主要运动征象，但没有改善摆动时间的可变性。在连续STN DBS连续治疗三年后，PD，停药治疗的摆动时间变异性恶化，而NBM萎缩可预测其增加程度。相反，主要运动征象没有进展。这些结果表明，摆动时间的可变性是皮质胆碱能健康的可靠标志，并且支持一个框架，其中PD的步态控制的高阶方面依赖于皮质胆碱能系统，而PD依赖于其他运动方面多巴胺能网络。