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）：在过去的十年中，脑刺激装置在治疗各种运动障碍和其他神经病理方面的应用迅速增加。目前的非侵入性技术存在根本性的局限性，尚未达到侵入性方法（如深部脑刺激）的疗效水平。机电刺激（EMS）是一种改进的无创方式，为无创深部脑刺激提供了潜力。该技术的初步实验表明，与其他形式的无创刺激相比，该技术的聚焦性和穿透性得到了改善。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。第一个研究部分将评估EMS的效果，在机电刺激后立即记录麻醉的成年猫的17区局部视觉诱发电位(VEP)/脑电图（EEG），并与基线、假手术刺激、经颅磁刺激（TMS）、经颅直流刺激（tDCS）和机械刺激（MS）进行比较。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（作为影响程度、深度和持续时间的函数）。假设与其他刺激方法相比，机电刺激将导致脑电图信号中VEP响应和功率的显著放大，在其他刺激方法无效的脑深部区域产生可测量的效应，并且与其他技术相比，反应持续时间显着延长。研究的第二个组成部分，重点是该技术的安全性，将评估组织温度和组织学变化的机电刺激。动物皮质将暴露在长时间的EMS刺激下，并通过植入的微热电偶测量和组织学变化来评估热力学变化，通过一系列组织学染色方法来寻找细胞丢失或胶质瘤的模式，以及白质损伤和退化（髓鞘）。我们假设机电刺激的组织将无法与非刺激的组织区分，并且刺激引起的组织温度变化在生理上是微不足道的。本研究的最后一部分将通过高分辨率14[C]2-脱氧葡萄糖成像（2DG）来评估EMS在改变脑活动功能模式方面的功效。我们将把这些结果与之前为其他刺激方式（如TMS和tDCS）开发的2-DG数据进行比较，以评估EMS的代谢和功能影响（在强度、聚焦性和时间方面）。我们假设，与其他模拟模式相比，EMS将表现出更大的聚焦性、穿透深度和影响程度。这项技术的未来发展可以为创新和改进神经治疗提供一个平台，同时提供巨大的市场机会。与公共卫生相关的脑刺激装置被用于治疗各种神经和精神疾病。Highland Instruments的机电刺激（EMS）是一种非侵入性神经刺激方法，它在现有非侵入性技术的基础上，具有优越的聚焦性、靶向控制和穿透性，并首次提供了非侵入性脑深部刺激（即刺激深部脑结构而不最大限度地刺激表面）的可能性。这项技术可以使患有运动障碍和其他神经疾病的患者受益，这些患者目前没有采用目前的非侵入性选择。