Noninvasive Neural Stimulation Technology

无创神经刺激技术

• 批准号: 8734490
• 负责人: Timothy Andrew Wagner
• 金额: $ 87.44万
• 依托单位: HIGHLAND INSTRUMENTS, INC.
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-01 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8734490
• 关键词: Activities of Daily Living; Adverse effects; Adverse event; Aftercare; Authorization documentation; Back; Behavioral; Bradykinesia; Brain; California; Characteristics; Clinical; Clinical Research; Cognitive; Computer Simulation; Confidential Information; Coupling; Data; Deep Brain Stimulation; Development; Devices; Disease; Dopaminergic Agents; Dose; Double-Blind Method; Effectiveness; Electroencephalography; Electromagnetics; Electrophysiology (science); Equipment; Future; Gait; Implant; Intervention; Magnetic Resonance Imaging; Measures; Metabolic; Methods; Modality; Modeling; Motor; Motor Cortex; Motor Evoked Potentials; Movement Disorders; Multicenter Studies; Neurologic; Operative Surgical Procedures; Outcome; Output; Parkinson Disease; Patients; Penetration; Phase; Physiologic pulse; Quality of life; Questionnaires; Randomized; Research; Rights; Risk; Safety; Short-Term Memory; Site; Small Business Innovation Research Grant; Source; Structure; Surface; Symptoms; Tardive Dyskinesia; Techniques; Technology; Testing; Therapeutic; Therapeutic Effect; Time; Tissues; Transcranial magnetic stimulation; Transducers; Translating; Ultrasonics; Ultrasonography; United States National Institutes of Health; Visit; Walking; Work; base; clinical effect; commercialization; comparative efficacy; computer studies; computerized; efficacy testing; follow-up; functional outcomes; human subject; improved; innovation; instrument; motor disorder; neural stimulation; neuropathology; phase 1 study; phase 2 study; randomized placebo controlled trial; relating to nervous system; research study; technology development

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.

描述（由申请人提供）：过去十年，脑刺激装置在治疗各种运动障碍（例如帕金森病（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根本性的局限性，尚未达到深部脑刺激（DBS）等有创方法的功效水平。电声刺激 (ESStim) 是一种改进的无创模式，具有产生更多焦点和更深层次效果​​的潜力。初步研究已证实，与其他形式的无创刺激（例如经颅直流刺激（tDCS））相比，该技术的焦点和穿透力有所提高，与其他技术相比，这已转化为更大程度和更持续时间的刺激效果。该应用的重点是评估 ESStim 对 PD 患者的治疗影响。首先在第一阶段，我们将跟踪 24 名 PD 患者（12 名 SHAM，12 名主动 ESStim 刺激），他们在两周内给予恒定固定剂量的 ESStim 刺激，持续 10 天，每天 20 分钟。我们将评估患者的一系列电生理学、认知和神经安全标志物，包括 64 通道脑电图、加州计算机化评估包、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系统检查。此外，我们将评估帕金森病统一评定量表 (UPDRS)、运动迟缓测试和帕金森病患者的步行能力/步态，在两周内以及最后一次刺激后至少六周内进行评估。接下来在第二阶段，我们将在两周内给予 10 天、每天 20 分钟的恒定固定剂量刺激后，对 48 名 PD 患者（12 名 SHAM、12 名主动 ESStim 刺激、12 名 tDCS 和 12 名 TUS）进行跟踪。我们将通过一系列运动、安全、机械和生活质量 (QOL) 测试来评估这些患者，比较所测试干预措施的效果。在进行 PD 治疗的同时，将使用每位患者基于 MRI 的计算模型开发大脑中产生的电磁场和声场的场模型，并将其与治疗过程中和治疗后记录的疗效测量相关联，以根据个体化患者数据开发剂量模型。总的来说，我们假设所提出的实验、计算研究和技术开发将使我们能够测试 ESStim 与其他非侵入性技术在 PD 患者中的有效性。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以为创新和改进的神经治疗提供一个平台。