Enhancing Physical Therapy with Brain Stimulation for Treating Postural Instability

专有：本建议书包括高地仪器的商业秘密和其他专有或机密信息，仅供美国国立卫生研究院(NIH)用于评估本SBIR建议书的目的。不授予任何其他权利。这项建议和 未经高地文书许可，不得在NIH以外的地方披露本文中包含的商业秘密和其他专有或机密信息的全部或部分。这一限制不限制NIH使用数据中包含的信息的权利，如果该信息是从 另一个不受限制的来源。本图例适用于整个提案，包括但不限于本提案的摘要、引言、具体目标、研究计划(所有组成部分)、商业化计划和人类主体部分。 摘要 在帕金森病(PD)患者中，姿势不稳定是导致残疾的主要原因，依赖于 其他的，和死亡。目前帕金森病的治疗方法，包括药物和手术方法，都是有限的 对姿势不稳定的影响。帕金森病的物理治疗(PT)正越来越多地被用作 诱导依赖运动的可塑性，这对患者的平衡有显著的好处。然而，PT是 仍未针对每个患者的需求量身定做，并且尚未优化以与其他疗法协同工作 警察。近年来，人们对非侵入性脑刺激(Nibs)的使用越来越感兴趣。 治疗帕金森病的设备及其与PT方案相结合的能力。但是，最终 传统的NIBS方法对帕金森病症状的影响很小，而且不一致，尤其是 保持耐心平衡。据推测，这些技术在聚焦、穿透和定向方面的局限性 控制转化为他们有限的治疗效果。电声刺激(ESSTim™)是一种改进的NIBS 一种通过结合独立控制的方式克服其他技术限制的方式 电磁场和超声场通过可调谐的机电来聚焦和增强刺激电流 神经组织中的偶联。这项建议的重点是评估ESStime对帕金森病的治疗效果 患者作为PT的辅助治疗。首先，在第一阶段，我们将跟踪18名PD患者(9名假ESSTim，9名活动 ESSTim)在给予固定剂量的ESStim10天的刺激后进行PT，每天20分钟，超过两分钟- 一周的时间。我们将评估一系列电生理学、认知和神经安全标记物； 平衡；生活质量(QOL)测试；统一帕金森病评定量表(UPDRS)；以及传感器- 为期两周的运动迟缓、姿势和行走能力/步态测试中的生物力学指标 并在最后一次治疗后至少六周。接下来在第二阶段，我们将关注40个PD 患者(20例假刺激，20例主动ESSTim刺激)在提供一个多月的治疗(即，增加 治疗2周后)，并按上述方法对患者进行评估，但现在至少在治疗结束后8周。 最后，我们将测试ESSTim增强PT训练对帕金森病患者姿势不稳定的效果是否 以基线疾病状态和有效刺激剂量为指导。为了测试这一点，我们将构建和 评估多变量线性回归模型和广义线性回归模型以预测临床结果。我们会 还建立了每个人的大脑刺激场的MRI导出模型(电场和声场模型) 帕金森病受试者的刺激野特征与治疗结果相关。总体而言，我们 假设拟议的实验、计算研究和技术发展将使我们 目的：探讨ESSTim辅助治疗帕金森病患者PT的疗效。拟议工作的结果 将作为未来大规模多中心研究的基础，以进一步验证技术和优化 ESSTim联合PT在帕金森病治疗中的应用

Proprietary: This proposal includes trade secrets and other proprietary or confidential information of Highland Instruments and is being provided for use by the National Institutes of Health (NIH) for the sole purpose of evaluating this SBIR proposal. No other rights are conferred. This proposal and the trade secrets and other proprietary or confidential information contained herein shall further not be disclosed in whole or in parts, outside of NIH without Highland Instrument's permission. This restriction does not limit the NIH's right to use information contained in the data if it is obtained from another source without restriction. This legend applies to the entire proposal, including, but not limited to the Abstract, Introduction, Specific Aims, Research Plan (all components), Commercialization Plan, and Human Subject's Sections of this proposal. Abstract In patients with Parkinson’s Disease (PD), postural instability is a leading cause of disability, dependence on others, and mortality. Current treatments for PD, including pharmacological and surgical methods, have limited impact on postural instability. Physical therapy (PT) for PD is becoming increasingly used as a means to induce exercise-dependent plasticity that can result in significant benefits for patient balance. However, PT is still untailored to each patient need, and has not been optimized to work synergistically with other therapies in PD. In recent years, there has been an increased interest in the use of noninvasive brain stimulation (NIBS) devices for the treatment of PD and in their ability to couple their effects with PT regimens. But, ultimately conventional NIBS methods have showed minimal and inconsistent effects on PD symptoms, and in particular patient balance. It has been postulated that these techniques’ limitations in focality, penetration, and targeting control translate into their limited therapeutic effects. Electrosonic Stimulation (ESStim™) is an improved NIBS modality that overcomes the limitations of other technologies by combining independently controlled electromagnetic and ultrasonic fields to focus and boost stimulation currents via tuned electromechanical coupling in neural tissue. This proposal is focused on evaluating the therapeutic impact of ESStim in PD patients as adjunct therapy to PT. First in Phase I, we will follow 18 PD patients (9 SHAM ESStim, 9 active ESStim) undergoing PT after giving a fixed dose of ESStim for 10 days of stimulation, 20 mins/day, over a two- week period. We will assess a battery of electrophysiology, cognitive, and neurological safety markers; balance; Quality of Life (QOL) tests; the Unified Parkinson’s Disease Rating Scale (UPDRS); and sensor- based, biomechanical metrics during bradykinesia, posture, and walking abilities/gait tests over the 2-week period and for at least six weeks following the last treatment session. Next in Phase II, we will follow 40 PD patients (20 SHAM, 20 active ESStim stimulation) after providing treatment over a month (i.e., increasing treatment by 2 weeks), and assess the patients as above, but now for at least 8 weeks after treatment ends. Finally, we will test whether the effects of ESStim enhanced PT training for postural instability in PD can be guided by the baseline disease state and the effective dose of stimulation. To test this we will build and evaluate multivariate linear and generalized linear regression models to predict the clinical outcomes. We will also build MRI derived models of the stimulation fields in the brain (electrical and sonic field models) of each of the PD subjects and correlate the stimulatory field characteristics with therapeutic outcomes. Overall, we hypothesize that the proposed experiments, computational studies, and technology development will allow us to test the effectiveness of ESStim as adjunct therapy to PT in PD patients. The results of the proposed work will serve as the basis for a future large-scale multicenter study to further validate the technique and optimize the methodology of ESStim coupled with PT for use in PD therapy.