Neurostimulation by Ultrasound: Physical, Biophysical and Neural Mechanisms

超声神经刺激：物理、生物物理和神经机制

• 批准号: 8765479
• 负责人: STEPHEN A BACCUS
• 金额: $ 71.84万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-01 至 2018-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8765479
• 关键词: Acoustics; Action Potentials; Affect; Alzheimer' s Disease; Animals; Anxiety; Behavior; Behavioral; Biophysical Process; Brain; Brain region; Cell membrane; Cells; Chemicals; Clinical; Complex; Dependence; Development; Devices; Dystonia; Electroencephalography; Epilepsy; Exocytosis; Foundations; Frequencies; Goals; Heating; Image; Implanted Electrodes; In Vitro; Individual; Interdisciplinary Study; Investigation; Ion Channel; Knowledge; Link; Measurement; Measures; Mediating; Mental disorders; Modeling; Motor Cortex; Nervous system structure; Neurons; Neurosciences; Neurotransmitters; Optics; Outcome; Output; PC12 Cells; Parkinson Disease; Pathway interactions; Pattern; Penetration; Process; Prosthesis; Protocols documentation; Public Health; Radiation; Rattus; Research; Research Project Grants; Resolution; Retina; Retinal; Salamander; Schizophrenia; Signal Transduction; Staging; Stimulus; Stroke; System; Techniques; Technology; Temperature; Testing; Therapeutic; Tissues; Transcranial magnetic stimulation; Transducers; Ultrasonic Transducer; Ultrasonics; Ultrasonography; Vesicle; Vision; Visual; Work; base; design; flexibility; functional restoration; improved; in vivo; insight; nervous system disorder; neural circuit; neuromechanism; neuroregulation; new technology; photoreceptor degeneration; pressure; public health relevance; radiation effect; relating to nervous system; research study; response; spatiotemporal; technology development; tool; visual stimulus

DESCRIPTION (provided by applicant): The goal of this project is to understand the effects of ultrasound (US) on neural activity. US can modify action potential activity in neurons in vitro and in vivo without damaging neural tissue. This phenomenon can be applied in powerful new tools for basic and clinical neuroscience, with broad impact on public health issues related to mental and neurological disorders. To guide and hasten the development of these new tools, our research will provide insight into the physical, biophysical and neural mechanisms underlying US neurostimulation. Our approach is unique in combining technology development with mechanistic studies of US neurostimulation at levels of complexity ranging from the single cell to the whole animal. Our prior and preliminary results suggest that US radiation force causes tissue displacement, resulting in cell membrane strain and thereby affecting neural activity through changes in ion channel activity or neurotransmitter exocytosis. We will investigate this hypothesis by combining US neurostimulation with EEG recording and radiation force imaging in rats, optical displacement measurements and multielectrode recording in the salamander and rat retina in vitro and in vivo, and electrophysiological measurements of ion channel activity and exocytosis in single HEK and PC12 cells. We will also test alternative hypotheses related to two other physical effects of US, cavitation and heating. To distinguish these mechanisms from radiation force we will examine the dependence of US neurostimulation on frequency and intensity. To facilitate these experiments, we will develop and implement new US devices, allowing US to be applied with multifocal and micron-scale resolution. US neurostimulation is likely to have significant impact on public health. Brain stimulation therapies are used to treat Parkinson's disease, dystonia, and epilepsy and hold promise for many others. Compared to current brain stimulation techniques that rely on invasive implanted electrodes or have limited spatial resolution and depth penetration (e.g., transcranial magnetic stimulation), US offers an ideal combination of spatial resolution, depth penetration, and non-invasiveness. US neurostimlation can also be implemented in prosthetic devices; for example, to stimulate retinal circuitry to restore vision. In addition, US neurostimulation promises to become an enormously useful research tool in basic neuroscience, and is therefore relevant to all mental and neurological disorders of public health concern. However, all of these outcomes depend on the ability to apply US neurostimulation safely and with well-controlled, predictable results. Achieving this goal requires a detailed mechanistic understanding of US neurostimulation that our multidisciplinary research project will provide.

描述（由申请人提供）：该项目的目标是了解超声波（US）对神经活动的影响。 US 可以在体外改变神经元的动作电位活动 在体内不损伤神经组织。这种现象可以应用于基础和临床神经科学的强大新工具，对与精神和神经疾病相关的公共卫生问题产生广泛影响。为了指导和加速这些新工具的开发，我们的研究将深入了解美国神经刺激背后的物理、生物物理和神经机制。 我们的方法是独特的，它将技术开发与美国神经刺激的机制研究相结合，其复杂程度从单细胞到整个动物。我们之前和初步的结果表明，美国辐射力会导致组织移位，导致细胞膜应变，从而通过离子通道活性或神经递质胞吐作用的变化影响神经活动。我们将通过将US神经刺激与大鼠脑电图记录和辐射力成像相结合、蝾螈和大鼠视网膜的体外和体内光学位移测量和多电极记录以及单个HEK和胞吐作用的离子通道活性和胞吐作用的电生理学测量来研究这一假设。 PC12细胞。我们还将测试与超声波的另外两种物理效应（空化和加热）相关的替代假设。为了区分这些机制和辐射力，我们将检查美国神经刺激对频率和强度的依赖性。为了促进这些实验，我们将开发和实施新的超声设备，使超声能够以多焦点和微米级分辨率应用。 美国的神经刺激可能会对公众健康产生重大影响。脑刺激疗法用于治疗帕金森病、肌张力障碍和癫痫，并为许多其他疾病带来希望。与目前依赖侵入性植入电极或空间分辨率和深度穿透有限（例如经颅磁刺激）的脑刺激技术相比，US 提供了空间分辨率、深度穿透和非侵入性的理想组合。美国神经刺激也可以在假肢装置中实施；例如，刺激视网膜电路以恢复视力。此外，美国神经刺激有望成为基础神经科学中非常有用的研究工具，因此与公共健康问题的所有精神和神经疾病相关。然而，所有这些结果都取决于安全应用美国神经刺激并获得良好控制、可预测结果的能力。实现这一目标需要我们的多学科研究项目将提供对美国神经刺激的详细机制了解。