A bell hidden in a thick box can be made to ring without opening the lid. Just send a sound wave through the walls, and the clapper will tremble. That's roughly how transcranial ultrasound works: sound passes through the skull bones and makes neurons deep in the brain 'ring'—generating electrical impulses. But unlike a simple bell, a neuron has several 'clappers' at once, and which one actually fired has remained a mystery.

In the new study, the authors built a digital replica of this process — a computational pipeline that tracks the fate of the ultrasound wave step by step. First, the sound travels through the skull (using micro-CT of a real human sample), then it turns into heat and micro-vibrations in tissues, which in turn stretch the neuron membrane. The final chord is the Hodgkin-Huxley ion channel model, which produces a map of 'fired' cells. Each point in the brain gets its own activity score — about 8 500 cubic millimeters of tissue around the target responded reliably to stimulation.

The most valuable part is that the predicted activation maps can be verified in real experiments by recording neuronal electrical activity with microelectrodes. This is not just a thought experiment but a tool for selecting safe therapy protocols and figuring out which specific cells (excitatory or inhibitory) respond to sound. In the future, such a model could help treat depression or chronic pain without opening the skull, just by precisely aiming an ultrasound beam.