Noninvasive deep brain stimulation using theta-burst transcranial magnetic-acoustic coupling to modulate cortical rhythms in Parkinsonian mice.

Modulating the subthalamic nucleus (STN) through neural circuits can suppress abnormal discharge rhythms in the primary motor cortex (M1) in Parkinson's disease (PD), thereby enhancing motor function. However, a clinically viable noninvasive deep brain stimulation method for PD has yet to be realized. We developed a noninvasive transcranial magnetic-acoustic coupling stimulation (TMAS) system, employing a theta burst stimulation (TBS) mode, to examine its effects of simulated electrical parameters on cortical rhythms in PD. The theta burst-TMAS (TBTMAS) system was established, and its physical performance parameters were evaluated. The STN of MPTP-induced Parkinsonian mice was targeted using both continuous TBTMAS (cTBTMAS) and intermittent TBTMAS (iTBTMAS) modes. Local field potentials (LFPs) in the M1 were recorded before and after stimulation to assess pathological biomarkers associated with PD. Results showed that both TBTMAS protocols significantly suppressed abnormal beta oscillations and reduced beta power spectral density (PSD) in the M1 of PD mice. In addition, both modes decreased the beta-ripple phase-amplitude coupling (PAC) index and disrupted PAC locking. Notably, the iTBTMAS mode exhibited a more substantial inhibitory effect on beta PSD and enhanced the downmodulation and decoupling of beta-high gamma PAC phase-locking. These findings suggest that TBTMAS can effectively regulate pathological oscillatory activity in the M1 of PD models, offering a promising non-invasive approach for deep brain stimulation therapy.