In a PD mouse model, transcranial magneto-acoustical stimulation (TMAS) targeted to M1 restored cortical–subthalamic balance, improved motor behavior, increased cortical activity and c-Fos, and elevated TH immunoreactivity in SNc without histological damage.

Presents a non‑invasive neuromodulation approach that modulates cortico‑subthalamic circuits and shows potential symptomatic benefit and dopaminergic marker enhancement, making it a promising translational lead for PD therapy pending mechanistic clarification and long‑term validation.

Parkinson's disease (PD) is marked by progressive dopaminergic neurodegeneration and motor circuit dysfunction. Transcranial magneto-acoustical stimulation (TMAS) is a novel non-invasive neuromodulation technique that combines a static magnetic field with low-intensity focused ultrasound. In this study, we investigated the therapeutic potential of TMAS in a PD mouse model by targeting the primary motor cortex (M1). Using dual-channel fiber photometry and behavioral assessments, we found that TMAS significantly enhanced calcium activity in M1 and suppressed abnormal hyperactivity in the subthalamic nucleus (STh), thereby restoring cortical-subcortical functional balance. TMAS also improved interregional neural synchrony and motor performance in pole, wire hang, and open field tests. Anterograde viral tracing confirmed direct anatomical projections from M1 to STh, supporting circuit-level modulation. Histological analysis showed no structural damage after TMAS, and c-Fos expression increased in M1, indicating cortical activation. Furthermore, TMAS increased TH-positive cell counts, mean optical density, and stained area in the substantia nigra pars compacta (SNc), suggesting an enhancement of TH expression in surviving dopaminergic neurons. These findings suggest that TMAS may represent a safe and effective strategy for restoring motor function in PD, offering promising prospects for non-invasive neuromodulation therapy.