Neuromechanical Modeling of Postural Responses:Mechanisms of Balance Impairments in Parkinson's Disease

我们的长期目标是推进我们的科学知识和计算方法，以确定 平衡障碍导致的福尔斯在帕金森病（PD），以指导更合理的发展 有效的治疗和康复，以改善平衡。我们的神经机械研究团队最近的见解 模拟研究与我们正在进行的工作相结合，表征无功平衡控制的变化， 帕金森病患者的康复涉及我们的总体假设，即帕金森病的主要症状是 僵硬是平衡障碍的原因。僵硬通常不被认为是跌倒风险，但我们正在进行的 研究证实了先前未报道的腿僵硬和先前的福尔斯之间的关联。我们认为 确定这种关联的原因将有助于改善平衡障碍的诊断和治疗 在警局我们的目标是确定腿部僵硬对姿势鲁棒性的影响，姿势鲁棒性定义为以下能力： 保持双脚的反应平衡。基于我们的神经力学模拟，我们假设 帕金森氏症的僵硬增加了姿势性肌肉活动的两个不同方面， 姿势稳健性：强直性肌肉活动，定义为静态姿势下肌肉活动的幅度，以及 动态肌肉活动被定义为感觉运动产生的肌肉活动的幅度和时间 反馈反应平衡。我们将使用实验和计算相结合的方法， 系统地分离僵硬，肌肉活动和姿势之间的因果联系和相互作用 PD中的鲁棒性。除了肌电图（EMG）记录外，我们还将建立 使用频域近红外光谱（FDNIRS）测量站立期间的紧张性肌肉活动 结合扩散相关光谱（DCS）。在目标1中，我们将测试特征良好的PD参与者 用已证实的多巴胺反应性强直来鉴定腿部强直对强直性肌肉活动的影响， 动态肌肉活动和姿势的鲁棒性;我们将使用多巴胺药物来操纵刚度， 一个激活操作在目标2中，我们将测试神经典型的参与者，以确定调节的因果作用。 紧张性和动态肌肉活动对姿势鲁棒性的影响;我们将使用EMG调节肌肉活动 生物反馈和适应。在目标3中，我们将开发神经力学模拟， 证明紧张性肌肉活动，动态肌肉活动和姿势之间的机械关系， 鲁棒性我们将用激动剂-拮抗剂肌肉模型来增强我们的神经力学平衡模型。 如果成功的话，我们将1）确定帕金森病中僵硬对平衡受损的因果作用，2）验证一种新的 和临床可行的方法（NIRS）来测量功能相关任务中的刚性，以及3）建立一个 广泛扩展的平衡生成神经力学模型，以模拟多种机制如何 相互作用导致平衡障碍。这些结果将使我们能够确定最佳的治疗目标， 合理开发康复和其他治疗方法，以治疗多种疾病中的平衡障碍。

Our long-term goal is to advance our scientific knowledge and computational approaches to identify causes of balance impairments leading to falls in Parkinson’s disease (PD) to guide the rational development more effective treatments and rehabilitation for improving balance. Recent insights from our neuromechanical simulation studies in tandem with our ongoing work characterizing changes reactive balance control after rehabilitation in people with PD have implicated our overall hypothesis that the cardinal parkinsonian sign of rigidity is a cause of balance impairments. Rigidity is not typically considered in fall risk, yet our ongoing studies demonstrate a previously-unreported association between leg rigidity and prior falls. We believe that identifying the causes of this association will lead to improved diagnosis and treatment of balance impairments in PD. Our objective is to identify the effects of leg rigidity on postural robustness, defined as the ability to maintain the feet in place in reactive balance. Based on our neuromechanical simulations, we hypothesize that parkinsonian rigidity increases two distinct aspects of postural muscle activity that can each reduce postural robustness: tonic muscle activity, defined as the magnitude of muscle activity in static postures, and dynamic muscle activity is defined as the magnitude and timing of muscle activity generated by sensorimotor feedback in reactive balance. We will use combined experimental and computational approaches to systematically isolate the causal linkages and interactions between rigidity, muscle activity, and postural robustness in PD. In addition to electromyographic (EMG) recordings, we will also establish the reliability of measuring tonic muscle activity during standing using frequency domain near-infrared spectroscopy (FDNIRS) combined with diffuse correlation spectroscopy (DCS). In Aim 1 we will test well-characterized PD participants with confirmed dopamine-responsive rigidity to identify the effects of leg rigidity on tonic muscle activity, dynamic muscle activity, and postural robustness; we will manipulate rigidity using dopamine medication and an activation maneuver. In Aim 2 we will test neurotypical participants to identify causal role of modulating tonic and dynamic muscle activity on postural robustness; we will modulate muscle activity using EMG biofeedback and adaptation. In Aim 3 we will develop neuromechanical simulations to quantitatively demonstrate mechanistic relationships between tonic muscle activity, dynamic muscle activity, and postural robustness. We will augment our neuromechanical models of balance with agonist-antagonist muscle models. If successful, we will 1) identify the causal role of rigidity on impaired balance in PD, 2) validate a novel and clinically-feasible method (NIRS) to measure rigidity in functionally-relevant tasks, and 3) establish a broadly extendable generative neuromechanical model of balance to simulate how multiple mechanisms interact to cause balance impairments. These outcomes will enable us to identify optimal treatment targets for the rational development of rehabilitation and other therapies for balance impairments across many disorders.