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.