Non-invasive Modulation of Brain Function by Focused Ultrasound

描述（由申请人提供）：拟议研究的主要目标是开发一种聚焦超声（FUS）方法，以可逆地调节（诱发或抑制）特定脑区的神经活动。 我们将开发一个磁共振成像（MRI）引导的超声环境，能够使用电生理记录（脑电图和肌电图）和真实的实时功能磁共振成像（rtfMRI）评估局部脑功能。 我们将检查声处理参数及其相应的调制效果的基础上闭环监测的电生理数据（EEG和EMG信号幅度），支持的水平的血氧水平依赖（BOLD）的功能磁共振成像信号源自目标脑组织。 因此，我们将研究的范围内的超声波参数，诱导可逆的抑制区域皮质活动的初级视觉皮层，并引起兴奋的感觉运动皮层的活动。 FUS的剂量（持续时间）依赖性调节效应及其时间动态将通过使用基于试验的范式设计交错采集fMRI和EEG/EMG来探索。 为了探索该方法的安全性，将在不同的时间点进行免疫组织学分析，检查超声处理在组织或血管损伤方面的生物学效应，包括初始超声处理后的急性、延迟和长期时间段。 非侵入性调节特定大脑区域的能力将使研究大脑活动和行为之间的因果关系成为可能，包括研究大脑区域之间的功能连接。 这项研究的成功将导致探索新的潜在的治疗应用FUS的许多神经和精神疾病。 公共卫生相关性：本研究将探索使用聚焦超声声波以非侵入性方式暂时调节特定区域脑组织的功能。 所提出的方法的成功将提供一个诊断评估如何以及大脑的不同部分的功能运作和相互连接。 除了其作为诊断工具的潜在效用之外，以受控方式抑制或激发局部脑组织的能力还提供了治疗各种神经和精神疾病的治疗潜力。

DESCRIPTION (provided by applicant): The main objective of the proposed research is to develop a focused ultrasound (FUS) method to reversibly modulate (either elicit or suppress) neural activities of specific brain regions. We will develop a magnetic resonance imaging (MRI)-guided sonication environment, capable of evaluating local brain function using electrophysiological recordings (electroencephalography and electromyography) and real- time functional magnetic resonance imaging (rtfMRI). We will examine sonication parameters and their corresponding modulatory effects based on closed-loop monitoring of the electrophysiological data (EEG and EMG signal magnitude), supported by the level of the blood-oxygenation-level-dependent (BOLD) fMRI signal originating from the targeted brain tissue. Consequently, we will examine the range of sonication parameters which induce reversible suppression of regional cortical activity in the primary visual cortex and elicit excitation of activity in the sensorimotor cortex. The dose (duration)-dependent modulatory effects of FUS and their temporal dynamics will be probed via interleaved acquisition of fMRI and EEG/EMG using a trial-based paradigm design. To probe the safety of the method, immunohistological analysis examining biological effects of the sonication in terms of tissue or vascular damage will be performed at variable time points, covering acute, delayed, and long-term periods after the initial sonication. The ability to non-invasively modulate a specific brain area would enable the study of causal relations between brain activity and behavior, including the investigation of functional connectivity between brain regions. The success of this study will result in the exploration of novel potential therapeutic applications of FUS for numerous neurological and psychiatric disorders. PUBLIC HEALTH RELEVANCE: This study will explore the use of focused ultrasound sound waves to temporarily modulate the function of region-specific brain tissue in a non-invasive manner. The success of the proposed method will offer a diagnostic assessment of how well the different parts of the brain are functionally operated and connected to each other. Apart from its potential utility as a diagnostic tool, the ability to suppress or excite local brain tissue in a controlled manner also offers therapeutic potential in the treatment of various neurological and psychiatric disorders.