Overcoming the Barriers to Effective Transcranial Temporal Interference Stimulation in Humans

项目总结/摘要 三分之一的神经和精神疾病患者对治疗有抵抗力。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显著的风险，而非侵入性方法 这些方法具有低空间分辨率并且不能刺激深部脑区域。经颅颞叶干扰 刺激（TIS）作为一种新的工具正在出现，其将非侵入性与有利的聚焦、高聚焦灵活性 以及在深度刺激的可能性。成功应用于脑深部目标以及灵活聚焦， 在老鼠身上得到证实。该提案采取了一系列关键的后续步骤，以便TIS能够有效地应用于 人脑 在目标1中，我们将实现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。以受控 实验中，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。在目标2中，我们将把TIS应用于人类的运动皮层，并使用一个既定的 方法来引出和测量运动诱发电位的TIS波形的相位。使用这个度量，我们 将i）验证TIS的影响是由于节拍模式而不是载波，ii）评估TIS载波的影响 频率，和iii）设计用于瞬时和持续神经调节的方案。 总之，我们的工作提供了有效和安全的TIS调制人脑的协议。这种发展 为大量脑血管病患者提供非侵入性和空间特异性治疗选择的潜力 对现有的治疗形式有抵抗力的疾病，我们的反适应症。

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.