Overcoming the Barriers to Effective Transcranial Temporal Interference Stimulation in Humans

克服人类有效经颅颞叶干扰刺激的障碍

• 批准号: 10719222
• 负责人: Sumientra Marijke Rampersad
• 金额: $ 62.48万
• 依托单位: UNIVERSITY OF MASSACHUSETTS BOSTON
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-10 至 2028-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10719222
• 关键词: Address; Agreement; Algorithms; Animals; Area; Behavioral; Biomedical Engineering; Brain; Brain Diseases; Cell Nucleus; Cephalic; Choice Behavior; Clinical; Clinical Trials Design; Computer Models; Data; Deep Brain Stimulation; Development; Diagnosis; Discrimination; Effectiveness; Electrodes; Electrophysiology (science); Euthanasia; FDA approved; Frequencies; Future; Hand; Human; Implant; Investigation; Lateral Geniculate Body; Left; Magnetism; Measures; Membrane; Mental Depression; Mental disorders; Methods; Modeling; Modification; Monkeys; Motor Cortex; Motor Evoked Potentials; Mus; Muscle; Neurons; Neurosciences; Outcome; Output; Pathology; Patients; Pattern; Phase; Positioning Attribute; Primates; Protocols documentation; Reporting; Resistance; Resolution; Risk; Rodent; Safety; Scalp structure; Stimulus; System; Temporal Lobe; Testing; Therapeutic; Visual; Work; biophysical model; brain dysfunction; computerized tools; cranium; electric field; experience; experimental study; flexibility; in silico; metallicity; multidisciplinary; nervous system disorder; neural; neural circuit; neuroregulation; nonhuman primate; noninvasive brain stimulation; novel; novel strategies; response; tool

Project Summary/Abstract One in three patients across neurological and psychiatric disorders are treatment resistant. Neuromodulation could provide these patients with treatment options, but current invasive approaches carry significant risk, while noninvasive approaches have low spatial resolution and cannot stimulate deep brain areas. Transcranial temporal interference stimulation (TIS) is emerging as a novel tool that combines noninvasiveness with favorable focus, high focusing flexibility, and the possibility to stimulate at depth. Successful applications to deep brain targets as well as flexible focusing have been demonstrated in mice. This proposal takes the critical set of next steps so that TIS can be effectively applied to the human brain. In Aim 1, we will realize the key strength of TIS, applying it to deep brain nuclei of non-human primates. In a controlled experiment, we will determine the intensity threshold that produces substantial effects on visual choice behavior, and validate the safety of the stimulation. In Aim 2, we will apply TIS to the motor cortex of humans and use an established method to elicit and measure motor evoked potentials in relation to the phase of the TIS waveform. Using this metric, we will i) validate that effects of TIS are due to the beat pattern and not the carrier, ii) evaluate the effect of the TIS carrier frequency, and iii) devise protocols for transient and sustained neuromodulation. Together, our work provides protocols for effective and safe TIS modulation of the human brain. This development has the potential to provide noninvasive and spatially specific treatment options to the large number of patients with brain disorders that are resistant to, our counter-indicated for, existing forms of treatments.

项目摘要/摘要 神经系统和精神疾病的三分之一患者具有抗治疗性。神经调节可能 为这些患者提供治疗选择，但是当前的侵入性方法具有很大的风险，而无创 方法具有低空间分辨率，无法刺激深脑区域。经颅会干扰 刺激（TIS）正在成为一种新型工具，将非侵入性与有利的焦点相结合，焦点高灵活性， 以及深度刺激的可能性。成功地应用了深度大脑目标以及灵活的聚焦 在小鼠中被证明。该提案采取了一系列关键的下一步，以便可以有效地应用于 人脑。 在AIM 1中，我们将实现TI的关键强度，将其应用于非人类灵长类动物的深脑核。在受控中 实验，我们将确定对视觉选择行为产生实质性影响的强度阈值， 验证刺激的安全性。在AIM 2中，我们将把TIS应用于人类的运动皮层并使用已建立的 引起和测量与TIS波形相关的电势的方法。使用这个指标，我们 i）验证tis的影响是由于节拍模式而不是载体引起的，ii）评估tis载体的效果 频率和iii）设计了瞬时和持续神经调节的方案。 我们的工作共同提供了有效且安全的调节人脑的协议。这种发展有 为大量大脑患者提供非侵入性和空间特定治疗选择的潜力 对我们反对现有治疗形式的抗性疾病。