Bayesian-enhanced closed-loop optimization of ultrasound protocols for targeted and precise neuromodulation

Low-intensity focused ultrasound (LIFU) is a promising neuromodulation modality, but challenges related to high response variability and the poorly understood parameter space undermine progress in clinical applications. To facilitate the development of therapeutic LIFU protocols, we developed an approach for Bayesian-enhanced adaptive control of ultrasound neuromodulation (BEACUN). BEACUN enables efficient, data-driven parameter mapping using a limited number of stimulation-response evaluations. We used functional ultrasound imaging (fUSI) to measure the neural responses to LIFU stimulation in real time, and we carried out in vivo experiments in rats to optimize and validate the performance of the BEACUN search. In live optimizations, we show that BEACUN produces more effective inhibitory LIFU neuromodulation protocols than conventional parameter exploration methods and converges to the optimal solution in 23 ± 3.67 stimulation-response evaluations. Our approach realizes a platform for efficient optimization of neuromodulation parameters that could pave the way for personalized LIFU protocol development in patients.