Shuai Zhang, Penglei Liu, Yihao Xu, Jinrui Mi, Ke Yue, Xiangyu Zhang, Shaocong Zhai, Yi Wang, Guizhi Xu
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.