Noninvasive Neural Stimulation Technology

描述(申请人提供)：在过去的十年里，脑刺激设备的应用迅速增加，用于治疗各种运动障碍，如帕金森氏病(PD)和其他神经病理。目前的无创脑刺激技术存在根本性的局限性，尚未达到有创方法的效果，如脑深部刺激(DBS)。电声刺激(ESSTim)是一种改进的非侵入性方式，它提供了更多焦点和更深层次的效果。这项技术的初步研究证实，与其他形式的非侵入性刺激(如经颅直流刺激(TDC))相比，该技术具有更好的焦点和穿透性，与其他技术相比，刺激效果的幅度和持续时间更大。这项应用的重点是评估ESSTim对PD患者的治疗效果。首先，在第一阶段，我们将跟踪24名帕金森病患者(12名假刺激，12名主动ESSTim刺激)，在两周内给予固定剂量的ESSTim刺激10天，每天20分钟。我们将评估患者的一系列电生理、认知和神经安全标记物，包括通道脑电、加州计算机化评估程序包、语言流利性测试、n-back工作记忆测试、PD不良反应问卷和神经学检查。此外，我们将评估帕金森氏病统一评定量表(UPDRS)、运动迟缓测试和PD患者的行走能力/步态，评估持续2周，并在最后一次刺激治疗后至少6周进行评估。在第二阶段，我们将跟踪48名PD患者(12名假刺激，12名主动ESSTim刺激，12名TDC和12名TUS)，在两周的时间内给予固定剂量的刺激10天，每天20分钟。我们将通过一系列运动、安全、机械和生活质量(QOL)测试对这些患者进行评估，比较测试干预措施的效果。在PD治疗的同时，大脑中产生的电磁场和声波的场模型将与每个患者的基于MRI的计算模型一起开发，并与治疗过程中和之后记录的疗效测量相关联，以基于个性化的患者数据开发剂量模型。总体而言，我们假设拟议的实验、计算研究和技术开发将使我们能够测试与其他非侵入性技术相比，ESSTim在PD患者中的有效性。拟议工作的结果将作为未来大规模多中心研究的基础，以进一步验证该技术并优化用于PD治疗的设备。这项技术和刺激方法的未来发展可能为创新和改进的神经治疗提供一个平台。

DESCRIPTION (provided by applicant): The past decade has seen a rapid increase in the application of brain stimulation devices to treat a variety of movement disorders, such as Parkinson's disease (PD), and other neuropathologies. Present noninvasive brain stimulation technologies suffer from fundamental limitations and have yet to reach the level of efficacy of invasive methods, such as deep brain stimulation (DBS). Electrosonic Stimulation (ESStim) is an improved noninvasive modality, which offers the potential of more focal and deeper effects. Preliminary studies with this technique have confirmed improved focality and penetration compared to other forms of noninvasive stimulation (e.g., transcranial DC stimulation (tDCS)), which have translated into a greater magnitude and duration of stimulatory effect compared to the other technologies. This application is focused on evaluating the therapeutic impact of ESStim in PD patients. First in Phase I, we will follow 24 PD patients (12 SHAM, 12 active ESStim stimulation) after giving a constant 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 in the patients including 64 channel EEG, California Computerized Assessment Package, verbal fluency test, n-back working memory test, PD Adverse Effects Questionnaire, and neurological exams. Additionally, we will evaluate the Unified Parkinson's Disease Rating Scale (UPDRS), bradykinesia test, and walking abilities/gait in the PD patients, evaluated over the 2-week period and for at least six weeks following the last stimulation session. Next in Phase II, we will follow 48 PD patients (12 SHAM, 12 active ESStim stimulation, 12 tDCS, and 12 TUS) after giving a constant fixed dose of stimulation for 10 days, 20 mins/day, over a two-week period. We will evaluate these patients with a battery of Motor, Safety, Mechanistic, and Quality of Life (QOL) tests, comparing the efficacy of the tested interventions. In parallel with the PD treatments, field models of the electromagnetic and sonic fields generated in the brain will be developed with MRI based computational models of each patient and correlated with the efficacy measures recorded during and after the treatment sessions to develop dosing models based on the individualized patient data. Overall, we hypothesize that the proposed experiments, computational studies, and technology development will allow us to test the effectiveness of ESStim compared to other noninvasive technologies 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 equipment for use in PD therapy. Future developments with this technology and stimulation method could provide a platform for innovative and improved neurological treatments.