Improving the treatment of neurological disorders by understanding the mechanisms of ultrasound neuromodulation

Ultrasound neuromodulation (UNMOD) is the alteration of nerve activity by delivering mechanical pressure waves to a targeted area to treat neurological disorders. Low-intensity focused UNMOD is a rapidly emerging technology due to being a remotely non-invasive technique and having a millimeter-scale precision. Despite numerous experimental settings demonstrating that ultrasonic waves can modulate the neural activity in different brain areas, the interaction between the ultrasonic source and the neuronal tissue is still not fully understood. By understanding the underlying mechanism, ultrasound neuromodulation therapy can be improved by optimizing the stimulation protocol in silico (3R principles: Replacement). This study focuses on the intramembrane cavitation mechanism, which occurs when ultrasonic pressure waves cause gas cavities to form between the phospholipid membrane leaflets. These gas cavities cause capacitive displacement currents, leading to membrane charge accumulation. In this study, we present work in progress towards simulation predictions obtained by morphologically realistic cortical cell models with the intramembrane cavitation (IC) mechanism. This allows us to determine if this mechanism can predict experimentally observed cell-type specificity to the ultrasonic protocol. Examining the activation site, the importance of charge overtones, and comparison of the optimized model with experimental results will help determine how various ultrasonic parameters affect cortical neuromodulation.