Electrophysiology-Compatible Wearable Transcranial Focused Ultrasound Neuromodulation Array Probes

电生理学兼容的可穿戴经颅聚焦超声神经调制阵列探头

基本信息

批准号：
10616201
负责人：
BIN HE
金额：
$ 358.3万
依托单位：
CARNEGIE-MELLON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-09-11 至 2026-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10616201
关键词：
Acoustics Animal Model Animal Testing Animals Area Behavior Behavior assessment Behavior monitoring Behavioral Brain Brain Diseases Central Nervous System Cephalic Clinical Complex Computer Simulation Computer software Development Devices Electrophysiology (science)Elements Engineering Focused Ultrasound Head Hippocampus Human Methods Modeling Monitor Neural Inhibition Neurons Neurosciences Research Nucleus Accumbens Penetration Performance Phase Play Rattus Resolution Rewards Rodent Role Saccades Safety Scanning Series Specificity Stimulus System Techniques Technology Testing Therapeutic Time Tissues Transducers Validation Visual Cortex Work attenuation awake brain electrical activity cell type density electrical microstimulation experimental study flexibility frontal eye fields histological studies in vivo light weight model building multi-electrode arrays neural neural circuit neural stimulation neuromechanism neuroregulation new technology nonhuman primate novel spatiotemporal superior colliculus Corpora quadrigemina translational potential ultrasound

项目摘要

Project Summary Noninvasive high precision neuromodulation technologies are crucial for probing mechanisms of neural circuits and enabling the non-pharmacological treatment of brain disorders. Transcranial-focused ultrasound (tFUS) neuromodulation has demonstrated its efficacy and precision in modulating the brain, from neuron to circuit level. We propose to develop highly novel tFUS neuromodulation systems enabling noninvasive high precision targeting and stimulation of brain circuits with high focality and deep brain penetration in small and large animal models during awake behaving tasks with simultaneous neural activity monitoring capabilities. We will develop and validate novel wearable ultrasound neuromodulation transducer array (WUNTA) probes, compatible with intracranial electrophysiological recordings, for precise modulation and recording of brain electrical activities in behaving animal models. We will use existing rodent and non-human primate models of complex behaviors to validate the performance of the proposed tFUS device through behavioral assessments and electrophysiological recordings. This project has three specific aims. Aim 1. Developing wearable tFUS neuromodulation array probes compatible with electrophysiological recordings and behavior assessments. We will develop novel 64-element WUNTA probes for in vivo behaving animal testing, with simultaneous electrophysiological recording capability. We will develop the proposed novel neuromodulation probes, control software, and optimize the tFUS parameters based on a series of computer simulations and phantom experiments. Aim 2. Validating the performance of wearable tFUS probe for small animals through electrophysiological recordings at the nucleus accumbens in awake, behaving rats. Following an effective parameter search on awake head-fixed rats, we will rigorously evaluate the performance of a wearable tFUS probe with electrophysiological recordings, on rats through a reward-driven discriminative stimulus behavior task, with known neural mechanisms involving the nucleus accumbens and inputs from the ventral subiculum. Aim 3. Validating the performance of wearable tFUS probe for large animals and optimizing stimulation parameters in an awake, behaving non-human primate model. We will assess the proposed probe in a head-fixed, behaving non-human primate model, validating the performance metrics of the wearable tFUS probe for large animals and optimizing tFUS parameters to achieve effective neuromodulation. Overall, the successful development of the proposed wearable ultrasound neuromodulation transducer array system, integrated with electrophysiological recordings in awake behaving animals, promises to significantly advance our ability to interrogate neural circuits in various behaving animal models with a high spatiotemporal resolution and has tremendous potential for translation to clinical utility.

项目概要无创高精度神经调节技术对于探索神经回路机制和实现脑部疾病的非药物治疗至关重要。经颅聚焦超声 (tFUS) 神经调节已证明其在调节大脑（从神经元到回路水平）方面的有效性和精确性。我们建议开发高度新颖的 tFUS 神经调节系统，在小型和大型动物模型中，在清醒行为任务期间，能够以高焦点和深度脑穿透的方式对脑回路进行非侵入性高精度定位和刺激，并具有同步神经活动监测功能。我们将开发和验证新型可穿戴超声神经调节换能器阵列（WUNTA）探头，该探头与颅内电生理记录兼容，用于精确调节和记录行为动物模型的脑电活动。我们将使用现有的复杂行为啮齿动物和非人类灵长类动物模型，通过行为评估和电生理记录来验证所提出的 tFUS 设备的性能。该项目有三个具体目标。目标 1. 开发与电生理记录和行为评估兼容的可穿戴 tFUS 神经调节阵列探针。我们将开发新型 64 元件 WUNTA 探针，用于动物体内行为测试，并具有同步电生理记录功能。我们将开发所提出的新型神经调节探针、控制软件，并基于一系列计算机模拟和模型实验优化 tFUS 参数。目标 2. 通过对清醒、行为正常的大鼠伏核的电生理记录，验证可穿戴 tFUS 探针对小动物的性能。在对清醒的头部固定大鼠进行有效参数搜索后，我们将通过奖励驱动的判别刺激行为任务，严格评估具有电生理记录的可穿戴 tFUS 探针对大鼠的性能，其中已知的神经机制涉及伏核和来自腹下托。目标 3. 验证大型动物的可穿戴 tFUS 探头的性能，并在清醒、行为正常的非人类灵长类动物模型中优化刺激参数。我们将在头部固定的非人类灵长类动物模型中评估所提出的探针，验证大型动物的可穿戴 tFUS 探针的性能指标，并优化 tFUS 参数以实现有效的神经调节。总体而言，所提出的可穿戴超声神经调节换能器阵列系统的成功开发，与清醒行为动物的电生理记录相结合，有望显着提高我们以高时空分辨率询问各种行为动物模型中神经回路的能力，并具有巨大的转化潜力以达到临床实用性。