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

在过去的二十年中，非侵入性脑刺激（NIBS）方法的使用呈指数级增长。两种最常用的方法，经颅电刺激（tES）和经颅磁刺激（TMS），提供了操纵目标大脑区域活动的工具，这给认知神经科学家提供了一种测试功能假设的方法。尽管有这种潜力，但对于这些NIBS方法引起的生理和行为变化的可靠性和稳健性，特别是当用于诱导神经兴奋性状态的调节性扰动时，仍然存在很大的担忧。该项目的目的是为人类参与者的调节性NIBS创造一种新的、更健壮的方法。这种方法被称为千赫兹经颅磁扰动（kTMP），将为干扰大脑功能开辟一个新的实验电磁子空间。这种方法将为皮质刺激开辟几个新的机会：更大的电场，更精确的时间，更好的空间控制，更大的范围和更精确的刺激频率传递。由于几个原因，这种新颖的磁刺激有望产生有意义的局部生理变化。首先，亚阈值千赫兹（kHz）电刺激已被证明可以改变运动诱发反应，其效应大小与直流电场相似。第二，阈值以上千赫频率电场以可逆的方式强有力地阻断神经传导。第三，超阈值实验表明，kHz tES可以模拟小鼠运动皮层中的低频电场，可能是由于频率互调。该项目将采用亚阈值电场，尽管其振幅远高于目前可用的tES，并且具有现有TMS方法无法实现的频率特异性。kTMP提供了一种混合亚阈值方法，该方法将利用具有频率特异性的强中程电场振幅，包括频率互调效应，提供了一种干扰大脑功能的新方法。kTMP的初步经验评估将侧重于调节人类运动皮质兴奋性，这是评估NIBS方法的“金标准”方法。重要的是，通过大幅扩大电场感应范围，应该有可能获得剂量相关函数，这是其他亚阈值NIBS方法难以实现的。一旦这些基准测试得到满足，kTMP应该很容易被用于基础认知神经科学研究，提供一个强大的工具来干扰和调节目标皮质区域，作为测试生理和行为研究中的功能假设的手段。从长远来看，kTMP有望用于精神和神经疾病的治疗。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

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.