Investigating the molecular, cellular and circuit effects of transcranial magnetic stimulation

研究经颅磁刺激的分子、细胞和电路效应

• 批准号: 10471360
• 负责人: Arnaud Y Falchier
• 金额: $ 76.48万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10471360
• 关键词: Affect; Anatomy; Area; Biophysics; Brain; Brain region; Computer Models; Controlled Environment; Development; Dose; Electrodes; Electrophysiology (science); Elements; Environment; Foundations; Future; Goals; Hippocampus (Brain); Human; Imaging Techniques; In Vitro; Interneurons; Investigation; Location; Measurement; Measures; Mental disorders; Methodology; Methods; Microscopic; Modeling; Molecular; Monkeys; Morphologic artifacts; Motor Cortex; Motor Evoked Potentials; Mus; Neurons; Outcome; Pharmacological Treatment; Physiologic pulse; Physiological; Population; Positioning Attribute; Preparation; Property; Protocols documentation; Rattus; Reproducibility; Research; Resolution; Safety; Scanning; Slice; Spatial Distribution; Standardization; Technology; Therapeutic; Time; Tissues; Transcranial magnetic stimulation; Translating; Variant; base; brain size; brain tissue; computer framework; electric field; experience; experimental study; heuristics; improved; in vitro Model; in vivo; in vivo Model; nervous system disorder; nonhuman primate; noninvasive brain stimulation; optical imaging; relating to nervous system; repetitive transcranial magnetic stimulation; response; sex; tissue culture; tissue preparation; tool; treatment strategy

Abstract Transcranial magnetic stimulation (TMS) is a non-invasive brain stimulation method which can alter brain activity in humans in a safe manner. Due its ease of application and ability to target specific brain regions, the repetitive application of TMS (rTMS) has the potential of augmenting or even replacing classic pharmacologic treatment-strategies. However, due to the enormous parameter space concerning its application (amplitude, coil position and orientation), optimal, i.e., personalized stimulation parameters for rTMS are very difficult to determine. Most importantly, principled efforts for optimizing TMS stimulation parameters are seriously limited by a poor understanding of molecular and cellular mechanisms. In-vitro recordings and functional optical imaging in slice preparations allow a direct assessment of the interaction of TMS electric fields with neurons in a highly controlled environment and allow for a rapid scan of stimulation parameters not achievable in human studies. Non-human primate (NHP) models are ideally suited to study circuit effects of TMS due their similarity to humans and the ability to perform invasive recordings to measure the electrophysiological response to TMS. Computational models can predict the electric field distribution of TMS in neural tissue, allowing to couple the biophysics of TMS with its physiological effects. Here, we propose to study the effects of changing TMS parameters in detail using in-vitro slice preparation, NHP recordings and computational modelling. We plan to study the molecular, cellular and circuit effects of transcranial magnetic stimulation in three specific aims: 1.) Systematic study of TMS stimulation parameters (stimulation intensity, coil orientation) in-vitro using mouse vs. rat hippocampal slices. 2) We will measure the circuit effects of varying TMS parameters in a NHP model. 3) Computational modelling of TMS electric fields across scales. Our findings will form the foundation for a mechanistic understanding between the biophysics of TMS electric fields and their physiological effects. This can form the basis for future efforts to improve noninvasive stimulation technologies.

摘要 经颅磁刺激(TMS)是一种可以改变大脑的非侵入性脑刺激方法 以安全的方式在人体内活动。由于其易于应用，并且能够针对特定的大脑区域， TMS(RTMS)的重复应用具有扩充甚至取代经典药理作用的潜力 治疗策略。然而，由于涉及其应用的参数空间巨大(幅度， 线圈位置和方向)、最优，即用于rTMS的个性化刺激参数很难 确定。最重要的是，用于优化TMS刺激参数的原则性努力严重有限 这是由于对分子和细胞机制的理解不足所致。体外记录和功能光学 切片制备中的成像允许直接评估TMS电场与神经元的相互作用 高度受控的环境，并允许快速扫描人类无法实现的刺激参数 学习。非人灵长类动物(NHP)模型非常适合于研究TMS的回路效应，因为它们具有相似性 以及进行侵入性记录以测量对TMS的电生理反应的能力。 计算模型可以预测TMS在神经组织中的电场分布，从而使耦合 TMS的生物物理学及其生理效应。 在这里，我们建议使用体外切片制备来详细地研究改变TMS参数的影响， NHP记录和计算模型。我们计划研究分子、细胞和电路效应 经颅磁刺激有三个具体目的：1)TMS刺激参数的系统研究 (刺激强度，线圈方向)使用小鼠和大鼠海马片进行体外实验。2)我们将测量 NHP模型中TMS参数变化的电路效应。3)TMS电场计算模型 不同的尺度。 我们的发现将为从机理上理解TMS电子的生物物理学奠定基础 场及其生理效应。这可以为未来改进非侵入性的努力奠定基础 刺激技术。