Non-invasive Modulation of Brain Function by Focused Ultrasound

描述（由申请人提供）：拟议研究的主要目的是开发一种聚焦超声（FUS）方法来可逆地调节（引发或抑制）特定大脑区域的神经活动。我们将开发一种磁共振成像（MRI）引导的超声环境，能够使用电生理记录（脑电图和肌电图）和实时功能磁共振成像（rtfMRI）来评估局部脑功能。我们将基于电生理数据（脑电图和肌电图信号幅度）的闭环监测，以及来自目标脑组织的血氧水平依赖（BOLD）功能磁共振成像信号水平的支持，研究超声参数及其相应的调节作用。因此，我们将研究超声参数的范围，这些参数可诱导初级视觉皮层区域皮层活动的可逆抑制，并引起感觉运动皮层活动的兴奋。FUS的剂量（持续时间）依赖性调节效应及其时间动态将通过fMRI和EEG/EMG的交错采集，使用基于试验的范式设计进行探测。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，检查超声在组织或血管损伤方面的生物效应，包括初始超声后的急性、延迟和长期。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FUS在许多神经和精神疾病的新的潜在治疗应用。

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.