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（ES）是一种多功能和有效的工具，用于询问、改变和操纵神经元， 健康和疾病的活动。用植入电极输送的深部脑ES需要一个精心设计的 神经外科手术，并具有组织损伤、出血、中风、感染和炎症的风险。这限制了 使用脑深部ES进行疾病诊断和可能无法证明风险的条件。 非侵入性靶向深部脑ES长期以来一直是一个主要的探索，具有无数的潜在应用。 挑战在于避免刺激表面电极附近，那里的电场最强， 在一个较深的地方用（弱得多的）电场刺激。一种远距离刺激的方法是通过时间 干扰（TI）的两个高频正弦波提供了一个小的频移。的干扰 两个这样的波在目标处产生调幅刺激。假设此信号的解调 导致它们在调制频率下兴奋。 在这里，我们引入一个完全不同的概念的时间干扰，基于（a）完全 在目标处消除相同频率的载波信号，以及（B）关于瞬态的引入 这些信号中的一个或两个的失真。失真，如短暂的频率或相移，将是 被刺激电极附近的强周期性信号所隐藏，并且不会导致刺激电极处的激励。 面然而，这些失真将在远程目标位置累积。他们将从 在“无声”背景下，尽管电场随距离衰减，但将容易导致激发。 我们将进行支持下一代TI（NG-TI）刺激范例的机制研究。我们 将继续设计和实验评价不同NG-TI协议在体外，比较 “标准”TI。我们将系统地分析TI刺激参数的影响，以实现 对单个神经元和神经元回路进行有针对性的调谐和调制。我们假设NG-TI可以 改进了更多的焦点刺激，具有更好的穿透力。它将具有较低的电荷刺激 阈值，并实现比标准TI更好的可操控性。最有效的NG-TI协议将进一步 通过体内动物实验验证。我们将定性比较目标，可能的场外影响， 电流消耗，以及NG-TI和标准TI的可操纵性。我们还将确定可行性和 在对医疗应用有用的距离处对NG-TI刺激的电场参数进行建模。的 影响将与神经元和神经组织的介电和生理特性联系起来， 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。