Focused ultrasound for noninvasive brain stimulation

我们建议开发用于脑深部电刺激（DBS）的聚焦超声（FUS）。DBS是一种经过验证的治疗方法 运动障碍，并持有相当大的承诺，精神疾病，如医学 顽固性抑郁症电DBS的主要缺点是它是高度侵入性的。无创 方法，如经颅磁刺激或直流电刺激（TMS和TDCS）， 穿透力到达大脑深层结构。是一种新的方法，使用聚焦超声（FUS）， 任何大脑结构，并直接刺激或抑制目标区域的神经元。该方法是非侵入性的， 但在空间和时间上都是精确的据推测，FUS与离子通道偶联相互作用， 机械感受器，自然发生在目标大脑区域。我们最近发现，FUS可以 提高猴子在决策任务中的表现。在这里，我们建议研究 通过改变清醒的猴子的FUS频率和压力来解释这种效应，这些猴子被训练来提供证据， 奖励为基础的决定，并在麻醉猴子接受功能磁共振成像。我们还将测试FUS是否 增强神经活性药物的功效。FUS可以为建立因果关系提供一种新的研究工具 脑行为关系和映射健康人的神经回路。它还提供了一种新的方法， 引入不穿过完整BBB的神经活性药物，或增强穿过完整BBB的药物的作用。 的BBB。声遗传学的发展可以使脑深部电刺激术适用于那些 不适合手术入路我们的方法结合了安全控制，以证明神经 FUS或FUS+微泡的行为效应不是由于水肿、出血、病变或热损伤引起的。 所提出的实验对于建立聚焦超声脑深部的功效至关重要。 刺激治疗影响认知和动机的精神疾病。为了获得这些好处， 必须确定FUS单独或与其他因素结合的行为影响， 微泡我们是目前唯一一个在基底神经节中开发这种方法的小组， 唤醒，行为猴子以及检查FUS技术与微泡，以 充分发挥其作用。

We propose to develop focused ultrasound (FUS) for deep brain stimulation (DBS.) DBS is a proven therapy for movement disorders and holds considerable promise for psychiatric conditions such as medically intractable depression. The main drawback of electrical DBS is that it is highly invasive. Non-invasive methods, such as transcranial magnetic or direct current stimulation (TMS and TDCS) have limited penetrability to reach deep brain structures. Is a novel approach that uses focused ultrasound (FUS) to reach any brain structure and directly stimulate or inhibit neurons in the targeted region. The method is non-invasive, but spatially and temporally precise. It has been hypothesized that FUS interacts with ion-channel coupled mechanoreceptors that occur naturally in the targeted brain region. We have recently shown that FUS can improve performance on a decision-making task in monkeys. Here, we propose to study the mechanism underlying this effect by varying FUS frequency and pressure in awake monkeys trained to make evidence and reward based decisions, and in anesthetized monkeys undergoing fMRI. We will also test whether FUS enhances the efficacy of neuroactive drugs. FUS could provide a new research tool for establishing causal brain-behavior relationships and mapping neural circuits in healthy humans. It also provides a novel method for introducing neuroactive drugs that do no cross the intact BBB, or enhancing the effect of drugs that do cross the BBB. The development of sonogenetics could make deep brain stimulation available for patients who are not candidates for surgical approaches. Our approach incorporates safety controls to demonstrate that neural and behavioral effects of FUS or FUS+microbubbles are not due to edema, hemorrhage, lesions or thermal effects.The proposed experiments are essential for establishing the efficacy of focused ultrasound deep brain stimulation to treat psychiatric illnesses that affect cognition and motivation. To reap these benefits, it is necessary to determine the behavioral effects of FUS alone or in combination with other factors such as microbubbles. We are currently the only group currently developing this approach in the basal ganglia of awake, behaving monkeys as well as examining the FUS technique with and without microbubbles in order to exploit its full scope.