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 每三名神经和精神疾病患者中就有一人对治疗有抵抗力。神经调节可以 为这些患者提供治疗选择，但目前的侵入性方法具有很大的风险，而非侵入性方法 这些方法的空间分辨率较低，无法刺激大脑深层区域。经颅时间干扰 刺激(TIS)是一种新的工具，它结合了非侵入性和良好的聚焦，高聚焦灵活性， 以及深度刺激的可能性。深部大脑靶点的成功应用以及灵活的聚焦 已经在小鼠身上得到了证实。这项建议采取了一系列关键的后续步骤，以便TIS可以有效地应用于 人脑。 在目标1中，我们将认识到TIS的关键优势，将其应用于非人类灵长类动物的脑深部核团。在受控的 实验中，我们将确定对视觉选择行为产生重大影响的强度阈值，以及 验证刺激的安全性。在目标2中，我们将TIS应用于人类的运动皮质，并使用已建立的 诱发和测量与TIS波形位相关系的运动诱发电位的方法。使用这一指标，我们 将i)验证TIS的影响是由于节拍模式而不是载体，ii)评估TIS载体的影响 频率，以及iii)为短暂和持续的神经调节设计方案。 我们的工作共同为人类大脑的有效和安全的TIS调制提供了协议。这一发展已经 为大量脑部疾病患者提供非侵入性和空间特异性治疗选择的可能性 对现有治疗形式具有抵抗力的疾病。