Next Generation Temporal Interference Stimulation for Non-Invasive Neuromodulation

用于非侵入性神经调节的下一代时间干扰刺激

• 批准号: 10615485
• 负责人: Andrei G Pakhomov
• 金额: $ 24万
• 依托单位: OLD DOMINION UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-06-01 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10615485
• 关键词: Animal Experiments; Animals; Brain; Brain region; Calibration; Cells; Cephalic; Charge; Clinical; Consumption; Deep Brain Stimulation; Dementia; Disease; Electric Stimulation; Electrodes; Epilepsy; Evaluation; FOS gene; Frequencies; Health; Hemorrhage; High Frequency Oscillation; Human; Implanted Electrodes; In Vitro; Individual; Infection; Inflammation; Ion Channel; Knowledge; Lead; Link; Location; Medical; Membrane; Membrane Potentials; Mental Depression; Methods; Modeling; Movement Disorders; Muscle; Nerve; Nerve Fibers; Neurons; Optics; Parkinson Disease; Penetration; Periodicals; Peripheral Nervous System; Phase; Physiological; Property; Protocols documentation; Ramp; Reporting; Research; Resolution; Risk; Signal Transduction; Site; Speed; Stimulus; Stroke; Surface; Technology; Testing; Tissues; Translating; addiction; attenuation; chronic pain; clinical application; design; disease diagnosis; disease diagnostic; electric field; experimental study; improved; in silico; in vivo; interest; neural; neuronal circuitry; neuroregulation; neurosurgery; neurotransmission; next generation; novel; peripheral pain; predictive modeling; prevent; simulation; tool; Animal Experiments; Animals; Brain; Brain region; Calibration; Cells; Cephalic; Charge; Clinical; Consumption; Deep Brain Stimulation; Dementia; Disease; Electric Stimulation; Electrodes; Epilepsy; Evaluation; FOS gene; Frequencies; Health; Hemorrhage; High Frequency Oscillation; Human; Implanted Electrodes; In Vitro; Individual; Infection; Inflammation; Ion Channel; Knowledge; Lead; Link; Location; Medical; Membrane; Membrane Potentials; Mental Depression; Methods; Modeling; Movement Disorders; Muscle; Nerve; Nerve Fibers; Neurons; Optics; Parkinson Disease; Penetration; Periodicals; Peripheral Nervous System; Phase; Physiological; Property; Protocols documentation; Ramp; Reporting; Research; Resolution; Risk; Signal Transduction; Site; Speed; Stimulus; Stroke; Surface; Technology; Testing; Tissues; Translating; addiction; attenuation; chronic pain; clinical application; design; disease diagnosis; disease diagnostic; electric field; experimental study; improved; in silico; in vivo; interest; neural; neuronal circuitry; neuroregulation; neurosurgery; neurotransmission; next generation; novel; peripheral pain; predictive modeling; prevent; simulation; tool

Electrostimulation (ES) is a versatile and efficient tool for interrogating, altering, and manipulating neural activities in health and disease. Deep brain ES delivered with implanted electrodes requires an elaborate neurosurgery and carries risks of tissue damage, bleeding, stroke, infection, and inflammation. This limits the use of deep brain ES for disease diagnostics and conditions that may not justify the risks. Non-invasive targeted deep brain ES has long been a major quest, with countless potential applications. The challenge is avoiding stimulation near surface electrodes, where the electric field is the strongest, while stimulating at a depth by a (much) weaker electric field. One way to stimulate at a distance is by temporal interference (TI) of two high-frequency sine waves delivered with a small frequency shift. The interference of two such waves creates an amplitude-modulated stimulus at the target. Assumed demodulation of this signal by neurons leads to their excitation at the modulation frequency. Here, we introduce an entirely different concept of the temporal interference, based on (a) complete cancellation of identical frequency carrier signals at the target, and (b) on the introduction of transient distortions in one or both these signals. The distortions, such as a brief frequency or phase shift, will be concealed by the strong periodic signal near the stimulating electrodes and will not lead to excitation at the surface. However, these distortions will add up at the remote target location. They will stand out from the “silent” background and will readily lead to excitation despite the attenuation of the electric field with distance. We will perform mechanistic studies which support this next generation TI (NG-TI) stimulation paradigm. We will continue with the design and experimental evaluation of different NG-TI protocols in vitro, in comparison with the “standard” TI. We will systematically analyze the impact of TI stimulation parameters, to achieve targeted tuning and modulation of individual neurons and neuronal circuitry. We hypothesize that NG-TI can be improved for more focal stimulation, with much better penetration. It will have lower electric charge stimulation threshold and enable better steerability than the standard TI. The most efficient NG-TI protocols will further be validated by in vivo animal experiments. We will qualitatively compare targeting, possible off-site effects, current consumption, and steerability of NG-TI and the standard TI. We will also define the feasibility and model the electric field parameters for NG-TI stimulation at distances useful for medical applications. The effects will be linked to dielectric and physiological properties of neurons and neural tissue, to build predictive models for non-invasive deep brain stimulation in large animal and human trials. This project will lay the ground to translate the NG-TI technology for disease diagnosis and treatment.

静电（ES）是一种用途广泛，有效的工具，用于询问，改变和操纵中性 健康和疾病的活动。用植入电极传递的深脑ES需要精心制作 神经外科手术并承担组织损伤，出血，中风，感染和注射的风险。这限制了 将深脑ES用于可能无法证明风险合理的疾病诊断和疾病。 长期以来，非侵入性的靶向深脑ES一直是一个重大的追求，具有无数的潜在应用。 面临的挑战是避免在电场强的表面电气附近刺激，而 通过（多）较弱的电场在深度刺激深度。在远处刺激的一种方法是临时 两种高频正弦波的干扰（Ti）以较小的频移提供。干扰 两个这样的波在目标上产生了放大器调节的刺激。假定该信号的解调 神经元在调制频率下导致它们的兴奋。 在这里，我们基于（a）的完整介绍了暂时干扰的完全不同的概念 取消目标处相同的频率载体信号，以及（b）引入瞬态 一个或两个信号中的扭曲。扭曲（例如短暂频率或相移）将是 由刺激电子附近的强元素信号隐藏，不会导致兴奋 表面。但是，这些扭曲将在远程目标位置加起来。他们将从 “沉默”背景，并将很容易地导致兴奋的目的地，距离电场的衰减。 我们将进行机械研究，以支持下一代Ti（NG-TI）刺激范式。我们 相比之下，将继续对不同NG-TI方案的设计和实验评估 使用“标准” Ti。我们将系统地分析TI模拟参数的影响，以实现 单个神经元和神经元电路的靶向调节和调节。我们假设Ng-ti可以是 改进了更高的局灶性刺激，并具有更好的穿透力。它将具有较低的电荷刺激 阈值并启用比标准Ti更好的可固定性。最有效的NG-TI协议将进一步 通过体内动物实验验证。我们将定性地比较目标，可能的异地效果， NG-TI和标准Ti的当前消耗以及可引导性。我们还将定义可行性和 在对医疗应用有用的距离上进行NG-TI模拟的电场参数建模。 效果将与神经元和神经元的营养和物理特性有关，以建立预测性 大型动物和人类试验中非侵入性深脑刺激的模型。这个项目将奠定基础 转化用于疾病诊断和治疗的NG-TI技术。