Electrophysiology-Compatible Wearable Transcranial Focused Ultrasound Neuromodulation Array Probes

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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.