Electrophysiology-Compatible Wearable Transcranial Focused Ultrasound Neuromodulation Array Probes

项目摘要 非侵入性的高精度神经调节技术对于探测神经回路的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)的神经调节已经证明了它在调节大脑从神经元到电路水平的有效性和精确度。我们建议开发高度新颖的tFUS神经调节系统，在具有同步神经活动监测能力的清醒行为任务中，能够在小动物和大动物模型中以高聚焦和深脑穿透的非侵入性高精度靶向和刺激脑回路。我们将开发和验证与颅内电生理记录兼容的新型可穿戴超声神经调制换能器阵列(WUNTA)探针，用于精确调制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复杂行为模型，通过行为评估和电生理记录来验证所建议的tFUS设备的性能。这个项目有三个具体目标。目的1.研制与电生理记录和行为评估兼容的可穿戴tFUS神经调制阵列探针。我们将开发新型的元件Wunta探针，用于活体动物行为测试，具有同步电生理记录能力。我们将在一系列计算机模拟和体模实验的基础上，开发新型神经调节探针、控制软件，并优化tFUS参数。目的2.通过清醒行为大鼠伏隔核的电生理记录，验证可穿戴式小动物tFUS探头的性能。在对清醒的头部固定的大鼠进行有效的参数搜索后，我们将通过奖励驱动的辨别刺激行为任务，严格评估带有电生理记录的可穿戴tFUS探头在大鼠身上的性能，其中包括伏隔核和腹侧下丘的输入。目的3.在清醒的非人类灵长类动物模型中，验证可穿戴式tFUS探头在大型动物中的性能，并优化刺激参数。我们将在头部固定、行为正常的非人类灵长类动物模型中评估建议的探头，验证用于大型动物的可穿戴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，有望显著提高我们以高时空分辨率询问各种行为动物模型的神经回路的能力，并具有巨大的临床应用潜力。

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.