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测神经回路的机制至关重要，并使能够对脑疾病的非药物治疗。以经颅为中心的超声（TFU）神经调节表明，其在调节大脑中的功效和精度，从神经元到电路水平。我们建议开发高新颖的TFU神经调节系统，以实现在与同时具有神经活动监测能力同时行使的任务中，在小动物模型中，在小动物模型中，在小动物模型中，具有高焦点和深脑穿透性的脑回路的无创高精度的靶向和刺激。我们将开发并验证与颅内电生理记录兼容的新型可穿戴超声神经调节式磁阵阵列（WUNTA）探针，以精确调制和记录行为动物模型中脑电动活动的记录。我们将使用现有的啮齿动物和非人类灵长类动物模型的复杂行为模型来通过行为评估和电生理记录来验证拟议的TFU设备的性能。该项目具有三个特定的目标。 AIM 1。开发可穿戴的TFU神经调节阵列探针与电生理记录和行为评估兼容。我们将开发新型的64个元素WUNTA探针，用于具有同时电生理记录能力的体内表现动物测试。我们将根据一系列计算机模拟和幻影实验开发提出的新型神经调节探针，控制软件，并优化TFU参数。 AIM 2。通过在清醒的伏伏核中验证小动物的可穿戴式TFU探针的性能，表现出大鼠。经过有效的参数搜索，我们将通过奖励驱动的歧视性刺激行为任务对可穿戴的TFU探针的性能进行严格评估，并使用涉及核心辅助的神经机制在大鼠身上进行了大鼠的性能。目标3。验证大型动物可穿戴TFU探针的性能，并在清醒中优化刺激参数，表现出非人类灵长类动物模型。我们将在固定的非人类灵长类动物模型中评估所提出的探针，以验证大型动物可穿戴式TFU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，与醒着的动物中的电生理记录相结合的拟议可穿戴超声神经调节式换能器阵列系统的成功开发有望显着提高我们在各种行为行为的动物模型中质疑具有较高空间分辨率的动物模型中神经回路的能力，并且具有较高的空间分辨率和巨大的潜力，可以转换为临床餐具的巨大潜力。