Cortical Plasticity Induced by Pairing Primary Motor Cortex Transcranial Magnetic Stimulation With Subthalamic Nucleus Magneto-Acoustic Coupling Stimulation

Paired cortical and deep stimulation has the potential to induce enhanced cortical plasticity. Ideally, such stimulation should be noninvasive and precisely controlled. A novel paired stimulation method, combining transcranial magnetic stimulation (TMS) with transcranial magneto-acoustic coupled stimulation (TMAS), named TMS-TMAS, was proposed to achieve such stimulations. Although the primary motor cortex (M1) is stimulated using TMS, the pulsed magnetic field is coupled with a focused ultrasound field to achieve TMAS-based focused electrical stimulation of the subthalamic nucleus (STN) via the magneto-acoustic coupling effect. Cortical plasticity is induced by precisely controlling the timing of magnetic pulse and ultrasound emissions based on spike timing-dependent plasticity (STDP). The experimental system achieved cortical-focused magnetic stimulation with a transverse resolution of 4.3 mm, a longitudinal resolution of 2.8 mm, and a magnetic field intensity of 1.6 T in the M1 region. Additionally, deep-focused electrical stimulation with a transverse resolution of 1.6 mm, a longitudinal resolution of 9.9 mm, and a coupled electric field intensity of 280 mV/m in the STN region was realized. In vivo animal experiments demonstrated that TMS-TMAS enhanced the amplitude of motor evoked potential (MEP) and reduced response latency. Simulation and experimental results confirmed that TMS-TMAS achieves high spatial resolution, noninvasive paired stimulation of the cortex and deep nuclei, and induces enhanced cortical plasticity when the stimulation sequence satisfies the STDP criteria. This method provides a promising approach for noninvasive paired stimulation and is expected to advance brain science research and the rehabilitation of neuropsychiatric disorders involving deep brain structures.