Non-invasive neuromodulation using low-intensity transcranial focused ultrasound in the human brain

在人脑中使用低强度经颅聚焦超声进行非侵入性神经调节

• 批准号: RGPIN-2020-04176
• 负责人: Chen, Robert
• 金额: $ 4.01万
• 依托单位: University of Toronto
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2021
• 资助国家: 加拿大
• 起止时间: 2021-01-01 至 2022-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=739722
• 关键词: Non; invasive; neuromodulation; using; low

Low-intensity focused ultrasound (LIFUS) is an emerging but powerful method for non-invasive neuromodulation of the human brain. Compared to transcranial magnetic stimulation (TMS) and transcranial direct current stimulation, LIFUS is more focal and can reach greater depths. Only a few studies have tested LIFUS in animals and humans. How LIFUS affects the human brain remains unclear. Importantly, different LIFUS parameters and induction of brain plasticity have not been systematically investigated. We will systematically investigate the neuromodulatory effects of LIFUS in the human brain. Healthy subjects will be recruited. Aim 1 will investigate the effects of different parameters of LIFUS including pulse repetition frequency, intensity, duty cycle, sonication duration on the excitability, intracortical facilitatory and inhibitory circuits in the motor cortex (M1) using single and paired pulse TMS. Aim 2 will assess how LIFUS affects connections to the motor cortex from other brain areas. LIFUS will be applied to the cerebellum to modulate the cerebello-thalamocortical pathway while TMS is applied to the contralateral M1. Similarly, LIFUS to M1 and TMS to the contralateral M1 will test interhemispheric connections. Further studies will test the connections of the posterior parietal cortex and dorsal premotor cortex to M1. Aim 3 will assess the functional consequences of LIFUS. Subjects will perform a cued reaction time task during LIFUS of M1. Inhibitory functions will be tested by applying LIFUS to the right inferior frontal gyrus and the presupplementary motor area while subjects perform a stop signal task. Aim 4 will use induce brain plasticity to assess the after effects of LIFUS. LIFUS in regular trains and in theta burst pattern will be applied the M1. Changes in M1 will be assessed by TMS up to 80 min after LIFUS. Aim 5 will test how LIFUS changes functional brain connectivity. We will apply LIFUS to the M1, cerebellum, premotor cortex or posterior parietal cortex in the MRI and assess changes resting state functional magnetic resonance imaging (fMRI). Aim 6 will examine the neurotransmitters mediating the effects of LIFUS. Normal subjects will be administered a single dose of a drug with known mechanism of action including carbamazepine (Na+ channel blocker), nimodipine (L-type Ca2+ channel blocker), lorazepam (increases GABA transmission), dextromethorphan (NMDA receptor antagonist) or placebo. The effects of each drug will be compared to that of placebo. This will be the first study to comprehensively and systematically examine LIFUS for neuromodulation. The proposed studies will define the optimal parameters, and determine the effects and the underlying mechanisms of LIFUS for neuromodulation in the human brain. It will lead to the development and adoption of LIFUS as a valuable tool in neuroscience research to understand and non-invasively modulate brain functions and connectivity.

低强度聚焦超声（LIFUS）是一种新兴但强大的非侵入性人脑神经调节方法。与经颅磁刺激（TMS）和经颅直流电刺激相比，LIFUS更聚焦，可以达到更深的深度。只有少数研究在动物和人类身上测试了LIFUS。LIFUS如何影响人类大脑仍不清楚。重要的是，不同的LIFUS参数和大脑可塑性的诱导还没有系统地研究。 我们将系统地研究LIFUS在人脑中的神经调节作用。将招募健康受试者。目的1：利用单脉冲和双脉冲经颅磁刺激（TMS）研究LIFUS的不同参数（脉冲重复频率、强度、占空比、声处理持续时间）对运动皮层（M1）兴奋性、皮层内易化和抑制回路的影响。目标2将评估LIFUS如何影响从其他大脑区域到运动皮层的连接。LIFUS将应用于小脑以调节小脑-丘脑皮质通路，而TMS应用于对侧M1。同样，LIFUS到M1和TMS到对侧M1将测试半球间的连接。进一步的研究将测试后顶叶皮层和背侧运动前皮层与M1的联系。目标3将评估LIFUS的功能后果。受试者将在M1的LIFUS期间执行提示反应时间任务。当受试者执行停止信号任务时，将通过对右侧额下回和前补充运动区应用LIFUS来测试抑制功能。目的4用诱导脑可塑性的方法评价LIFUS的后效。LIFUS在常规列车和theta突发模式中将应用于M1。将通过TMS评估M1的变化，直至LIFUS后80分钟。目标5将测试LIFUS如何改变功能性大脑连接。我们将在MRI中将LIFUS应用于M1，小脑，运动前皮质或后顶叶皮质，并评估静息状态功能磁共振成像（fMRI）的变化。目的6将检查介导LIFUS效应的神经递质。正常受试者将接受单剂量的具有已知作用机制的药物给药，包括卡马西平（Na+通道阻滞剂）、尼莫地平（L型Ca 2+通道阻滞剂）、劳拉西泮（增加GABA传递）、二甲双胍（NMDA受体拮抗剂）或安慰剂。将每种药物的作用与安慰剂进行比较。 这将是第一项全面系统地检查LIFUS神经调节的研究。拟议的研究将定义最佳参数，并确定LIFUS对人脑神经调节的影响和潜在机制。它将导致LIFUS作为神经科学研究中的一种有价值的工具的开发和采用，以了解和非侵入性地调节大脑功能和连接。