Closed-loop EEG-synchronized Transcranial Magnetic Stimulation: Advancing State-dependent Neuromodulation Toward Clinical Translation

Conventional transcranial magnetic stimulation (TMS) is delivered independent of ongoing brain activity, despite strong evidence that cortical excitability fluctuates with endogenous oscillatory dynamics. The objective of this review is to synthesize current evidence on electroencephalography (EEG)-synchronized TMS and evaluate its potential as a clinically translatable, state-dependent neuromodulation strategy. We integrate findings from experimental, technical, and early clinical studies of real-time EEG-triggered TMS, focusing on phase-specific stimulation, system latency, and closed-loop control architectures. EEG-synchronized TMS enables phase-dependent modulation of cortical excitability and plasticity, with improved consistency compared to open-loop protocols. Real-time systems require sub-100 ms latency and precise phase estimation, yet remain constrained by signal-to-noise limitations and TMS-induced artifacts. Emerging adaptive and machine learning–driven systems demonstrate feasibility for individualized neuromodulation. Closed-loop EEG- TMS represents a promising advance toward precision neuromodulation, with potential to enhance therapeutic efficacy in neuropsychiatric disorders. Standardization, artifact mitigation, and scalable system design remain critical barriers to widespread clinical adoption.