In recent years, the ongoing development of transcranial electrical stimulation (TES) and transcranial magnetic stimulation (TMS) has demonstrated significant potential in the treatment and rehabilitation of various brain diseases. In particular, the combined application of TES and TMS has shown considerable clinical value due to their potential synergistic effects. This paper first systematically reviews the mechanisms underlying TES and TMS, highlighting their respective advantages and limitations. Subsequently, the potential mechanisms of transcranial electromagnetic combined stimulation are explored, with a particular focus on three combined stimulation protocols: Repetitive TMS (rTMS) with transcranial direct current stimulation (tDCS), rTMS with transcranial alternating current stimulation (tACS), and theta burst TMS (TBS) with tACS, as well as their clinical applications in brain diseases. Finally, the paper analyzes the key challenges in transcranial electromagnetic combined stimulation research and outlines its future development directions. The aim of this paper is to provide a reference for the optimization and application of transcranial electromagnetic combined stimulation schemes in the treatment and rehabilitation of brain diseases.
Although transcranial magnetic stimulation (TMS) is widely used in neuromodulation, conventional TMS struggles to achieve both depth and focal specificity. Temporal interference TMS (TI-TMS) offers a promising approach to enhance stimulation depth while reducing the focal area; however, current research remains largely simulation-based, with limited studies on system implementation and experimental validation in rodent deep brain regions. To address this, we developed a TI-TMS system based on a realistic mouse head model using finite element simulation. Electrophysiological recordings of local field potentials (LFPs) in the ventral hippocampal (vHPC) formation were performed to evaluate changes in θ rhythm power spectral density (PSD) and θ-γ phase-amplitude coupling (PAC) following stimulation. The results demonstrated that TI-TMS enhanced θ rhythm power and strengthened θ-γ PAC, indicating effective modulation of deep brain regions. This study establishes a functional TI-TMS system capable of effectively stimulating deep vHPC, providing an experimental basis for its application in precise neuromodulation of subcortical brain areas.
Temporal interference transcranial alternating current stimulation (TI-tACS) does not readily enable synchronous cross-plane modulation of multiple brain regions in three-dimensional space. To address this challenge, this study proposes a three-dimensional (3D) cross-plane multi-target simultaneous stimulation strategy based on electrode spatial topology. Without increasing the number of electrode groups, the proposed strategy enabled cooperative target formation on multiple planes. Predictable multi-target shifts were achieved by adjusting the current-amplitude ratios across channels. Simulations showed that the strategy stably generated multi-target simultaneous stimulation and exhibited good independent controllability, as evaluated by off-target displacement. A multichannel TI-tACS stimulator was developed and was validated in a saline phantom experiment, where the target formation and shift trends agreed with the simulation results. This work provides an engineering reference for electrode configuration and parameter design for 3D cross-plane multi-target neuromodulation.
