EAGER: A novel, non- invasive approach to reliably alter cortical excitability using high frequency (kHz) transcranial magnetic perturbation.

EAGER：一种新颖的非侵入性方法，利用高频 (kHz) 经颅磁扰动可靠地改变皮质兴奋性。

• 批准号: 1946316
• 负责人: Richard Ivry
• 金额: $ 30万
• 依托单位: University of California-Berkeley
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-01 至 2021-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1946316&HistoricalAwards=false
• 关键词: EAGER; novel; non; invasive; approach

The past two decades have witnessed an exponential increase in the use of non-invasive brain stimulation (NIBS) methods. The two most commonly used methods, transcranial electrical stimulation (tES) and transcranial magnetic stimulation (TMS), provide tools to manipulate activity in targeted brain regions, and this give cognitive neuroscientists a method to test functional hypotheses. Despite this potential, there are substantial concerns about the reliability and robustness of the physiological and behavioral changes resulting from these NIBS methods, especially when used to induce modulatory perturbations in the state of neural excitability. The purpose of this project is to create a new and more robust method for modulatory NIBS in human participants. The method, referred to as kilohertz transcranial magnetic perturbation (kTMP), will open a new experimental electromagnetic subspace for perturbing brain function. This method will open several new opportunities for cortical stimulation: larger electrical fields, more precise timing, better spatial control, and both a greater range and a more precise delivery of stimulation frequency. This novel magnetic stimulation holds promise to produce meaningful focal physiological changes, for several reasons. First, subthreshold kilohertz (kHz) electrical stimulation has been shown to alter motor-evoked responses with an effect size similar to that of direct current electric fields. Second, suprathreshold kHz frequency electric fields robustly block nerve conduction in a reversible manner. Third, suprathreshold experiments have shown that kHz tES can mimic low frequency electric fields in the motor cortex of the mouse, presumably due to frequency intermodulation. This project will employ subthreshold electric fields, albeit at much higher amplitude than those presently available with tES and with the frequency specificity not possible with extant TMS methods. kTMP offers a hybrid subthreshold approach that will exploit strong midrange electric field amplitudes with frequency specificity, including frequency intermodulation effects, offering a new approach to perturb brain function. The initial empirical evaluation of kTMP will focus on modulating human motor cortex excitability, the "gold standard" approach for evaluating NIBS methods. Importantly, by substantially expanding the range of electric field induction, it should be possible to obtain dose-dependent functions, something that has proven elusive with other subthreshold NIBS methods. Once these benchmark tests are met, kTMP should be readily adopted for basic cognitive neuroscience research, providing a robust tool to perturb and modulate targeted cortical regions as a means to test functional hypotheses in physiological and behavioral studies. In the long term, kTMP has promise to be employed in the treatment of psychiatric and neurological disorders.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

过去二十年来，使用非侵入性脑刺激（NIB）方法的指数增加。两种最常用的方法是经颅电刺激（TES）和经颅磁刺激（TMS），提供了操纵目标脑区域活动的工具，这为认知神经科学家提供了一种检验功能性假设的方法。尽管存在这种潜力，但仍关注这些NIBS方法引起的生理和行为变化的可靠性和鲁棒性，尤其是在用于诱导神经兴奋性状态的调节性扰动时。该项目的目的是为人类参与者的调节方法创建一种新的，更健壮的方法。该方法称为Kilohertz跨颅磁扰动（KTMP），将打开一个新的实验电磁子空间，以驱动脑功能。 该方法将为皮质刺激打开几个新的机会：较大的电场，更精确的时机，更好的空间控制以及更大的范围和更精确的刺激频率传递。 这种新型的磁刺激有望产生有意义的局灶性生理变化，原因有几个。首先，已证明亚阈值kilohertz（kHz）电刺激会改变运动诱发的响应，其效应大小与直流电场的效应大小相似。其次，上方kHz频率电场以可逆的方式牢固地阻止神经传导。第三，远景实验表明，KHz TE可以模仿小鼠运动皮层中的低频电场，这大概是由于频率间调节。该项目将采用亚阈值电场，尽管幅度要比目前使用TE的幅度要高得多，并且使用现存的TMS方法无法使用频率特异性。 KTMP提供了一种混合子阈值方法，该方法将利用具有频率特异性的强中部电场振幅（包括频率间调节效应），为您提供新的方法来扰动大脑功能。 KTMP的最初经验评估将集中于调节人类运动皮层兴奋性，即评估NIBS方法的“金标准”方法。重要的是，通过实质上扩展电场诱导的范围，应该可以获得依赖剂量的功能，这在其他亚阈值NIBS方法中证明是难以捉摸的。一旦满足这些基准测试，KTMP就应该容易地用于基本的认知神经科学研究，从而为扰动和调节靶向皮质区域的稳健工具作为测试生理和行为研究中功能假设的手段。从长远来看，KTMP承诺将用于治疗精神病和神经系统疾病。该奖项反映了NSF的法定任务，并使用基金会的知识分子优点和更广泛的影响评估标准，认为值得通过评估来获得支持。