Focused ultrasound for noninvasive brain stimulation

用于无创脑刺激的聚焦超声

基本信息

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
项目类别：
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&apos 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

项目摘要

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.

我们建议开发用于深部脑刺激 (DBS) 的聚焦超声 (FUS)。DBS 是一种经过验证的疗法用于治疗运动障碍，并对精神疾病（例如医学上的疾病）有很大的希望顽固性抑郁症。电 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 TDCS）等方法的局限性具有到达大脑深层结构的穿透力。是一种使用聚焦超声 (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。据推测，FUS 与离子通道耦合相互作用目标大脑区域自然发生的机械感受器。我们最近证明 FUS 可以提高猴子决策任务的表现。在此，我们建议研究一下其机制这种效应的背后是通过训练清醒猴子的 FUS 频率和压力来提供证据和基于奖励的决策，以及接受功能磁共振成像的麻醉猴子。我们还将测试是否FUS 增强神经活性药物的功效。 FUS 可以为建立因果关系提供新的研究工具健康人的大脑行为关系和神经回路图。它还提供了一种新颖的方法引入不穿过完整血脑屏障的神经活性药物，或增强可穿过完整血脑屏障的药物的作用 BBB。声遗传学的发展可以为患有以下疾病的患者提供深部脑刺激：不适合手术入路。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水肿、出血、病变或热引起的所提出的实验对于确定聚焦超声深部脑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，确定 FUS 单独或与其他因素结合的行为影响是必要的，例如微气泡。我们是目前唯一在基底神经节中开发这种方法的小组清醒、行为正常的猴子，以及检查有或没有微泡的 FUS 技术，以便充分利用其范围。