Transcranial magneto-acoustical stimulation regulates motor cortex-subthalamic nucleus neural activity to improve motor disorders in a Parkinson's disease mouse model.

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.