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

• 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
• 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

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.

项目摘要 非侵入性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（从神经元到电路水平）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，使非侵入性高精度的目标和刺激的大脑回路具有高聚焦性和深部脑渗透在小型和大型动物模型在清醒的行为任务，同时神经活动监测能力。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，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。我们将使用现有的啮齿动物和非人类灵长类动物的复杂行为模型，通过行为评估和电生理记录来验证拟议的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神经调节阵列探头。我们将开发新型64元素WUNTA探针，用于体内行为动物测试，具有同步电生理记录能力。我们将开发所提出的新型神经调节探头，控制软件，并根据一系列计算机模拟和体模实验优化tFUS参数。目标二。通过在清醒、行为正常的大鼠的延髓核进行电生理记录，验证可穿戴tFUS探头在小动物中的性能。在清醒的头部固定大鼠的有效参数搜索后，我们将严格评估可穿戴tFUS探头的性能与电生理记录，大鼠通过奖励驱动的歧视性刺激行为的任务，与已知的神经机制，涉及核丘脑腹侧下托和输入。目标3.验证大型动物的可穿戴tFUS探头的性能，并在清醒的行为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头，验证大型动物可穿戴tFUS探头的性能指标，并优化tFUS参数以实现有效的神经调节。总体而言，所提出的可穿戴式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，有望显着提高我们在各种行为动物模型中以高时空分辨率询问神经回路的能力，并具有巨大的转化为临床应用的潜力。