Focused ultrasound for noninvasive brain stimulation

用于无创脑刺激的聚焦超声

• 批准号: 9318920
• 负责人: VINCENT P FERRERA
• 金额: $ 40万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-04-01 至 2022-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9318920
• 关键词: Affect; Alcoholism; Aleurites; Alzheimer' s Disease; Animal Behavior; Animals; Basal Ganglia; Behavior; Behavioral; Blood - brain barrier anatomy; Brain; Brain Mapping; Brain region; Clinical; Cognition; Contralateral; Corpus striatum structure; Coupled; Data; Decision Making; Deep Brain Stimulation; Dependence; Development; Dopamine; Dopamine Antagonists; Dorsal; Dose; Drug Delivery Systems; Drug Targeting; Drug abuse; Edema; Effectiveness; Engineering; Focused Ultrasound; Focused Ultrasound Therapy; Frequencies; Functional Magnetic Resonance Imaging; Goals; Haloperidol; Head; Hemorrhage; Hour; Human; Investigation; Ion Channel; Lesion; Magnetism; Maps; Measures; Mechanoreceptors; Medical; Meninges; Mental Depression; Mental disorders; Methods; Microbubbles; Monkeys; Moods; Morbidity - disease rate; Motivation; Motor Cortex; Movement Disorders; Neurons; Operative Surgical Procedures; Patients; Perception; Performance; Pharmaceutical Preparations; Procedures; Reaction Time; Research; Rest; Rewards; Safety; Series; Speed; Structure; System; Techniques; Testing; Training; Ultrasonic wave; Ultrasonography; arm; awake; base; behavior test; blood oxygenation level dependent response; brain behavior; cranium; dosage; efficacy testing; experimental study; functional MRI scan; improved; innovation; nervous system disorder; neural circuit; neuroregulation; novel; novel strategies; optogenetics; pressure; putamen; relating to nervous system; success; tool; visual motor

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.

我们建议开发重点超声（FUS）来进行深脑刺激（DBS。）DBS是一种经过验证的疗法 对于运动障碍，对精神病疾病（例如医学上）抱有很大的希望 顽固的抑郁症。电气DB的主要缺点是它具有高度侵入性。非侵入性 方法，例如经颅磁或直流电流刺激（TMS和TDC）的方法有限 达到深脑结构的渗透性。是一种新颖的方法，使用聚焦超声（FUS）到达 任何大脑结构并直接刺激或抑制靶向区域的神经元。该方法无创， 但是在空间和时间上精确。已经假设FUS与离子通道耦合相互作用 自然发生在靶向大脑区域的机械感受器。我们最近表明FUS可以 提高猴子决策任务的绩效。在这里，我们建议研究机制 通过在经过训练的醒来的猴子中的频率和压力来改变以做出证据和 基于奖励的决策，并在麻醉猴子中经历了fMRI。我们还将测试FUS是否 增强神经活性药物的功效。 FUS可以提供​​一个新的研究工具来建立因果关系 健康人的脑行为关系和映射神经回路。它还提供了一种新颖的方法 引入不穿越完整BBB的神经活性药物，或增强确实交叉的药物的作用 BBB。声遗传学的发展可能使大脑刺激可用于 不是手术方法的候选人。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，病变或热造成的 效果。提出的实验对于确定聚焦超声深脑的功效至关重要 刺激治疗影响认知和动机的精神疾病。为了获得这些好处，这是 确定单独或与其他因素（例如 微泡。目前，我们是目前唯一在基底神经节中开发这种方法的群体 醒着，表现猴子以及使用有或没有微泡的FUS技术检查 利用其完整范围。