Focused ultrasound for noninvasive brain stimulation

我们建议开发聚焦超声(FUS)用于脑深部刺激(DBS)。DBS是一种行之有效的治疗方法 治疗运动障碍，并在治疗精神疾病方面有相当大的希望 顽固性抑郁症。电子DBS的主要缺点是它具有高度侵入性。非侵入性 经颅磁刺激或直流电刺激(TMS和TDC)等方法受到限制 可穿透性达到大脑深层结构。是一种新的方法，使用聚焦超声(FUS)来达到 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。已经假设FUS与离子通道耦合相互作用 机械感受器，自然地出现在目标大脑区域。我们最近已经证明，FUS可以 提高猴子在决策任务中的表现。在这里，我们建议研究这一机制。 通过改变清醒猴子的FUS频率和压力来支持这种效应 以奖励为基础的决策，以及接受功能磁共振成像的麻醉猴子。我们还将测试FUS是否 增强神经活性药物的疗效。FUS可以为确定因果关系提供一种新的研究工具 健康人的脑-行为关系和神经回路图。它还提供了一种新的方法来 引入不会跨越完整的血脑屏障的神经活性药物，或者增强确实跨越的药物的效果 BBB。声遗传学的发展可以为患有以下疾病的患者提供脑深部刺激 不适合做外科手术。我们的方法结合了安全控制来证明神经 FUS或FUS微泡的行为影响不是由于浮肿、出血、损伤或热引起的。 所提出的实验对于确定聚焦超声脑深部的疗效是必不可少的。 刺激治疗影响认知和动机的精神疾病。为了获得这些好处，它是 有必要单独确定FU的行为影响或与其他因素结合使用，如 微泡。我们目前是目前唯一一个在丘脑基底节区开发这种方法的研究小组。 清醒，表现猴子以及检查有和没有微泡的FUS技术，以便 充分利用它的范围。

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.