Mechanisms of improvement in neurorehabilitation of Parkinson's disease

描述(申请人提供)：帕金森氏病(PD)运动康复可以改善临床平衡和疾病严重程度措施。然而，临床量表无法识别特定神经通路的变化，因此可能无法区分康复过程中潜在神经机制的补救变化和代偿变化。我们的长期目标是在有效的帕金森病康复过程中区分补救和补偿，这将显著提高我们对帕金森病患者以及潜在的其他神经疾病患者治疗反应的理解。与临床措施相比，我们将研究肌电(EMG)测量的神经肌肉激活，作为了解帕金森病患者在24周适应的探戈康复舞蹈课前后神经运动活动的直接窗口，这是一种低消耗的有效康复干预措施。我们将使用我们的感觉运动反应模型(SRM)来量化康复前后的神经运动缺陷和恢复，该模型是为了量化年轻人和动物模型在站立平衡扰动时诱发的脑干介导的肌电反应。我们将使用一种新的实验范式来确定与康复相关的运动改善是由于基底节-脑干通路的补救性改变，还是由于小脑-脑干通路的代偿性改变。以前对站立平衡时的扰动反应的研究表明，基底节通路用于立即使神经控制参数适应新的背景，而小脑途径用于在重复的试验中缓慢地适应新的背景。因此，我们将研究在新的站姿宽度下，SRM参数在重复扰动试验中的适应时间过程。我们预测，在新的站姿宽度中，SRM参数的即时变化将反映基底节-脑干修复，而缓慢适应的变化将反映小脑代偿。康复后，我们预测即刻变化幅度的增加将反映基底节-脑干修复，而缓慢适应变化的速度增加将反映小脑-脑干代偿。此外，我们预测，SRM参数可以作为生物标志物，在整个康复过程中识别帕金森病患者之间潜在的运动障碍路径的差异。

DESCRIPTION (provided by applicant): Parkinson's Disease (PD) motor rehabilitation can improve clinical balance and disease severity measures. However, clinical scales cannot identify changes in specific neural pathways, and therefore may not be able to discriminate between remediative and compensatory changes to underlying neural mechanisms during rehabilitation. Our long-term goal is to discriminate between remediation and compensation during effective PD rehabilitation, which would significantly improve our understanding of response to treatment in individuals with PD as well as potentially in other neurological conditions. In contrast to clinical measures, we will study neuromuscular activation measured with electromyography (EMG) as a direct window into the neuromotor activity of individuals with PD before and after 24 weeks of adapted tango rehabilitative dance classes, which is an effective rehabilitative intervention with low attrition. We will quantify neuromotor deficits and recovery before and after rehabilitation using our sensorimotor response model (SRM), which was developed to quantify brainstem-mediated EMG responses evoked during perturbations to standing balance in young individuals as well as in animal models. We will use a novel experimental paradigm to determine whether motor improvements associated with rehabilitation are due to remediative changes in basal ganglia-brainstem pathways or due to compensatory changes in cerebellar-brainstem pathways. Previous studies of perturbation responses during standing balance demonstrate that basal ganglia pathways are used to adapt neural control parameters to new contexts immediately, whereas cerebellar pathways are used to adapt to new contexts slowly, over repeated trials. Therefore, we will examine the timecourse of adaptation of SRM parameters over repeated perturbation trials in novel stance widths. We predict that immediate changes in SRM parameters in novel stance widths will reflect basal ganglia-brainstem remediation, whereas slowly adapting changes will reflect cerebellar compensation. After rehabilitation, we predict that increased magnitudes of immediate changes will reflect basal ganglia-brainstem remediation, whereas increased speed of slowly adapting changes will reflect cerebellar-brainstem compensation. Further, we predict that SRM parameters can serve as biomarkers to identify differences in pathways underlying motor deficits across participants with PD throughout rehabilitation.