ELECTROMECHANICAL NONINVASIVE NEURAL STIMULATION: SAFETY AND EFFICACY

机电无创神经刺激：安全性和有效性

• 批准号: 7686133
• 负责人: Timothy Andrew Wagner
• 金额: $ 20.15万
• 依托单位: HIGHLAND INSTRUMENTS, INC.
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-15 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7686133
• 关键词: Adult; Animals; Area; Authorization documentation; Biological Assay; Brain; Brain region; Cells; Cellular Structures; Confidential Information; Data; Deep Brain Stimulation; Deoxyglucose; Development; Devices; Distant; Electroencephalogram; Family Felidae; Felis catus; Foundations; Future; Gliosis; Glucose; Goals; Histology; Hour; Image; Implant; Maps; Marketing; Measurable; Measurement; Mechanical Stimulation; Mental disorders; Metabolic; Methods; Modality; Modification; Movement Disorders; Neurologic; Patients; Pattern; Penetration; Phase; Procedures; Property; Relative (related person); Reporting; Research; Resolution; Rights; Safety; Signal Transduction; Small Business Innovation Research Grant; Source; Staining method; Statistical Models; Structure; Surface; System; Techniques; Technology; Temperature; Thermodynamics; Time; Tissues; Transcranial magnetic stimulation; United States National Institutes of Health; Visual Cortex; Visual evoked cortical potential; Work; area striata; brain tissue; extrastriate visual cortex; improved; innovation; instrument; myelin degeneration; neural stimulation; neuropathology; public health relevance; relating to nervous system; research study; response; simulation; tool; white matter damage

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 and other neuropathologies. Present noninvasive technologies suffer from fundamental limitations and have yet to reach the level of efficacy of invasive methods, such as deep brain stimulation. Electromechanical Stimulation (EMS) is an improved noninvasive modality, which offers the potential of noninvasive deep brain stimulation. Preliminary experiments with this technique have revealed improved focality and penetration compared to other forms of noninvasive stimulation. The work proposed in this study will explore fundamental efficacy and safety criteria related to the technique. The first study component will evaluate the efficacy of EMS, where recordings will be made of the combined local visual evoked potential (VEP)/ electroencephalogram (EEG) from area 17 of anaesthetized adult cats immediately following electromechanical stimulation and compared with baseline, SHAM stimulation, transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), and mechanical stimulation (MS). A statistical analysis will be performed to characterize the signal properties of the VEP/EEG data and determine the effect of electromechanical stimulation on neural response (as a function of magnitude, depth, and duration of effect). It is hypothesized that electromechanical stimulation will result in a significantly larger amplification of the VEP response and power in the EEG signal relative to the other methods of stimulation, a measurable effect in deep brain regions for which other stimulation methods are ineffective, and a significantly longer response duration in comparison to these other techniques. The second component of the study, focused on the safety of the technique, will assess tissue temperature and histology changes to electromechanical stimulation. Animal cortices will be exposed to extended durations of EMS stimulation and evaluated for thermodynamic changes, via implanted micro-thermocouple measurements, and histological changes, via an array of histological staining methods to look for patterns of cell loss or gliosis, and white matter damage and degeneration (myelin). We hypothesize that electromechanical stimulated tissue will be indistinguishable from the non-stimulated tissue and that tissue temperature changes from stimulation will be physiologically insignificant. The final component of this study will assess EMS's efficacy in modifying functional patterns of brain activity by means of high resolution 14[C]2-deoxyglucose imaging (2DG). We will compare these results to 2-DG data previously developed for other stimulation modalities (such as TMS and tDCS) to assess the metabolic and functional effects of EMS (in terms of magnitude, focality, and time). We hypothesize that EMS will demonstrate greater focality, depth of penetration, and magnitude of effect compared to other simulation modalities. Future developments with this technology could provide a platform for innovative and improved neurological treatments while simultaneously providing a tremendous market opportunity. PUBLIC HEALTH RELEVANCE Brain stimulation devices are used to treat a variety of neurologic and psychiatric disorders. Highland Instruments' Electromechanical Stimulation (EMS) is a noninvasive neurostimulation method which improves upon current noninvasive technologies with superior focality, targeting control, and penetration, and for the first time offers the possibility of noninvasive deep brain stimulation (i.e., stimulating deep brain structures without maximally stimulating the surface). The technology could benefit patients with movement disorders and other neuropathologies who are currently not served by present noninvasive options.

描述（由申请人提供）：过去十年来，大脑刺激装置的应用快速增加，以治疗各种运动障碍和其他神经病理学。当前的非侵入性技术受到基本局限性的影响，并且尚未达到侵入性方法的功效水平，例如深脑刺激。机电刺激（EMS）是一种改进的非侵入性形态，它提供了无创深脑刺激的潜力。与其他形式的非侵入性刺激相比，该技术的初步实验显示了焦点和穿透性的改善。本研究提出的工作将探讨与该技术相关的基本功效和安全标准。第一个研究组成部分将评估EMS的功效，其中将记录来自局部视觉诱发电位（VEP）/电脑电图（EEG）（EEG），来自机电刺激和基线后的成年成年猫的17区和基线，与假刺激，刺激性磁刺激（TMS），转移刺激（MS），MS刺激（MS），MS）和TDC（TC），TDC和TDC相比。将进行统计分析以表征VEP/EEG数据的信号特性，并确定机电刺激对神经反应的影响（作为幅度，深度和效果持续时间的函数）。假设机电刺激将导致EEG信号中VEP响应和功率相对于其他刺激方法的显着扩增，与其他技术相比，其他刺激方法无效的深脑区域的可测量效应以及其他刺激方法无效的效果。该研究的第二个组成部分着重于技术的安全性，将评估组织温度和组织学变化机电刺激。动物皮质将通过植入的微甲环比率测量值和组织学变化对EMS刺激的延长持续时间进行，并通过一系列组织学染色方法来寻找细胞损失或胶状病的模式，以及白质损伤和变性（merelin）。我们假设机电刺激的组织将与未刺激的组织没有区别，并且组织温度因刺激而变化在生理上无关紧要。这项研究的最终组成部分将通过高分辨率14 [c] 2-脱氧葡萄糖成像（2DG）来评估EMS在修饰大脑活动的功能模式中的功效。我们将将这些结果与先前用于其他刺激方式（例如TMS和TDC）开发的2-DG数据进行比较，以评估EMS的代谢和功能效应（就大小，焦点和时间而言）。我们假设与其他模拟方式相比，EMS将表现出更大的焦点，穿透深度和效果幅度。这项技术的未来发展可以为创新和改进的神经治疗提供平台，同时提供巨大的市场机会。公共卫生相关性大脑刺激装置用于治疗各种神经系统疾病。高地仪器的机电刺激（EMS）是一种非侵入性神经刺激方法，可以改善具有优越的焦点，靶向控制和穿透性的当前无创技术，并且首次提供了非侵入性深脑刺激的可能性（即，刺激深脑结构而不会刺激表面刺激）。该技术可以使运动障碍患者和其他神经病理学患者受益，这些患者目前尚未以目前的无创选择性服务。