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

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.

电刺激是一种询问、改变和操纵神经的通用而有效的工具 健康和疾病方面的活动。植入电极的深部大脑ES需要精心制作 神经外科手术，有组织损伤、出血、中风、感染和炎症的风险。这限制了 使用深部大脑ES进行疾病诊断和可能无法证明风险合理的情况。 非侵入性靶向深脑ES长期以来一直是一项重大的探索，具有无数的潜在应用。 挑战是避免表面电极附近的刺激，那里的电场最强，而 通过(远)较弱的电场在一定深度进行刺激。一种远距离刺激的方法是通过时间刺激 两个高频正弦波的干扰(TI)，频率漂移很小。的干扰 两个这样的波在目标处产生幅度调制的刺激。假定解调该信号 由神经元导致它们在调制频率下兴奋。 在这里，我们引入了一个完全不同的时间干扰概念，基于(A)完全 在目标处消除相同的频率载波信号，以及(B)在引入瞬变时 这些信号中的一个或两个都有失真。失真，如短暂的频率或相移，将是 被刺激电极附近的强周期信号所隐藏，不会在 浮出水面。然而，这些失真将在远程目标位置累积起来。他们将脱颖而出 “无声”背景，即使电场随着距离的增加而衰减，也很容易导致激发。 我们将进行机制研究，以支持这种下一代TI(NG-TI)刺激范式。我们 将继续进行不同NG-TI方案的体外设计和实验评估，进行比较 与“标准”的TI。我们将系统地分析TI刺激参数的影响，以实现 有针对性地调谐和调制单个神经元和神经元电路。我们假设NG-TI可能是 改进为更多的焦点刺激，具有更好的穿透性。它会有更低的电荷刺激 门槛，并实现了比标准的TI更好的操纵性。最有效的NG-TI协议将进一步 经活体动物实验验证。我们将定性地比较目标，可能的场外影响， 电流消耗，以及NG-TI和标准TI的操纵性。我们还将确定可行性和 模拟在医疗应用中有用的距离的NG-TI刺激的电场参数。这个 效应将与神经元和神经组织的介电和生理特性联系起来，以建立预测 在大型动物和人体试验中的非侵入性脑深部刺激模型。这个项目将奠定基础 将NG-TI技术转化为疾病诊断和治疗技术。