In the last decade, ultrasonic neuromodulation (UNMOD) has gained significant attention, because of its capability to modulate cortical or deep neuronal activity non-invasively, selectively, reversibly, and with millimeter resolution. These favourable properties make UNMOD a promising alternative to state-of-the-art electrical neurostimulation technologies, that require surgery to reach deep targets (deep brain stimulation) or are restricted to centimeter resolution for cortical non-invasive stimulation (e.g., transcranial magnetic stimulation or direct current stimulation).

However, the main drawback of UNMOD is that its underlying physical and biological mechanisms are not well understood, precluding application-targeted optimization of the ultrasonic waveform and limiting the interpretability of experimental ultrasonic neuromodulation studies. Several tentative underlying mechanisms have been proposed with varying presence of an accompanying mathematical framework: e.g., intramembrane cavitation, mechanosensitivity, acoustic radiation force, etc. Furthermore, most likely interaction between multiple mechanisms should be accounted for in order to describe ultrasound-evoked neuronal effects. Consequently, the goal of the proposed research project is to design and validate an inclusive and explanatory multi-compartmental computational model, that contains all the putative UNMOD mechanisms.