Transcranial magneto-acoustic stimulation ameliorates cortico-subthalamic circuit dysfunction in MPTP-induced...

Parkinson's disease (PD) is characterized by abnormal oscillatory activity and altered interregional coupling within the cortico-subthalamic (M1-STN) circuit. Transcranial magneto-acoustic stimulation (TMAS) combines focused ultrasound with a static magnetic field, but its modeled physical responses and circuit-level effects remain incompletely characterized. We integrated multiphysics simulations with behavioral testing, simultaneous M1-STN local field potential recordings, Golgi-Cox staining, and histological analyses in MPTP-induced parkinsonian mice. Simulations predicted an acoustic field concentrated in M1, magneto-acoustically induced motional source-current hotspots mainly in superficial cortex, and small passive membrane-potential polarization (approximately ± 0.03 mV) during one 400-ms active sonication period. The estimated mechanical index (∼0.71) and temperature rise (≤3 °C) indicated relatively low predicted mechanical and thermal risk; H&E examination showed no overt cortical histopathological abnormalities. In vivo, TMAS partially ameliorated selected behavioral deficits, attenuated abnormal aperiodic-adjusted beta activity in M1 and STN with region-dependent low-gamma effects, reduced beta-gamma phase-amplitude coupling, and reduced pathologically elevated M1-STN coherence after local bipolar re-referencing. TMAS also increased cortical dendritic spine density and partially attenuated MPTP-related reductions in SNc TH-positive neurons and striatal TH-positive fiber immunoreactivity. These results provide a cross-scale characterization of TMAS-associated physical, electrophysiological, behavioral, and structural changes. Because the acute simulations and chronic biological outcomes were not causally linked and component-specific controls were not included, the findings reflect effects associated with the overall TMAS paradigm rather than proof of a single physical mechanism.