Noninvasive Neural Stimulation Technology

描述（由申请人提供）：在过去的十年中，脑刺激装置在治疗各种运动障碍（如帕金森病（PD））和其他神经病理学方面的应用迅速增加。目前的无创脑刺激技术存在着根本性的局限性，其疗效尚未达到深部脑刺激（DBS）等有创方法的水平。电刺激（ESStim）是一种改进的无创治疗方式，它提供了更集中和更深层次的潜在效果。与其他形式的非侵入性刺激（如经颅直流电刺激（tDCS））相比，该技术的初步研究证实了更好的聚焦性和穿透性，与其他技术相比，tDCS已经转化为更大的强度和持续时间的刺激效果。本应用的重点是评估ESStim在PD患者中的治疗效果。在第一阶段，我们将对24名PD患者（12名SHAM， 12名积极的ESStim刺激）进行为期两周的随访，在此之前，我们给予恒定剂量的ESStim 10天的刺激，每天20分钟。我们将评估患者的一系列电生理、认知和神经安全指标，包括64通道脑电图、加利福尼亚计算机评估包、语言流畅性测试、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PD患者的统一帕金森病评定量表（UPDRS）、运动迟缓测试和行走能力/步态，评估时间为2周，最后一次刺激后至少为6周。接下来，在第二阶段，我们将对48例PD患者（12例SHAM， 12例主动estim刺激，12例tDCS和12例TUS）进行为期10天，每天20分钟的恒定固定剂量刺激，为期两周。我们将用一系列的运动、安全、机械和生活质量（QOL）测试来评估这些患者，比较测试干预措施的疗效。在PD治疗的同时，将利用每个患者的基于MRI的计算模型建立大脑中产生的电磁场和声场的场模型，并将其与治疗期间和治疗后记录的疗效测量相关联，以建立基于个性化患者数据的剂量模型。总的来说，我们假设所提出的实验、计算研究和技术发展将使我们能够测试ESStim与其他非侵入性技术在PD患者中的有效性。这项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PD治疗中使用的设备。这项技术和刺激方法的未来发展可以为创新和改进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.