Computational–Experimental Characterization of Transcranial Magneto-Acoustic Stimulation for Dose-Efficient Neural Activation

Background/Objectives: Transcranial magneto-acoustic stimulation (TMAS) is an emerging multiphysics neuromodulation modality that introduces magneto-acoustically induced currents into ultrasound-based neural stimulation. However, how this coupled physical input is converted into neuronal recruitment and measurable biological responses remains insufficiently understood. This study aimed to establish a computational–experimental framework for quantifying TMAS-induced neural activation across stimulation dose, spike timing, and calcium-related response domains. Methods: The model combined ultrasound-induced membrane mechanics, charge-based neuronal electrophysiology, pressure-dependent calcium-current modulation, and a Lorentz-force-mediated current source for TMAS. Regular-spiking excitatory neurons and low-threshold-spiking inhibitory interneurons were simulated to estimate excitation thresholds, firing latency, and spike-pattern transitions. Two model-informed stimulation conditions were examined using in vitro calcium imaging, in vivo hippocampal fiber photometry, and c-Fos/microtubule-associated protein 2 (MAP2) immunofluorescence. Results: TMAS reduced the half-maximal effective dose relative to transcranial ultrasound stimulation by 71.4–76.3% in regular spiking neurons and 51.5–58.2% in low-threshold spiking interneurons, while shortening firing latency and expanding burst-response domains. Experimentally, near-threshold TMAS produced larger peak calcium responses and greater c-Fos/MAP2 immunoreactivity than TUS. Conclusions: TMAS enhances neuronal responsiveness more efficiently than TUS by reducing excitation thresholds, improving spike-timing responses, and reshaping firing-pattern transitions. Consistent with the overall computational comparison, experimental measurements showed greater neuronal activation under TMAS than under TUS at matched ultrasound parameters.