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Precision phase targeting of event-related oscillations using real-time closed-loop TMS-EEG

Güth, M. R.; Headley, D. B.; Baker, T. E.

2026-03-30 neuroscience
10.64898/2026.03.26.713979 bioRxiv
Show abstract

Current closed-loop TMS-EEG systems rely on phase prediction algorithms that require highly periodic signals, limiting their ability to target brief, event-related activity. We developed a real-time closed-loop (RT-CL) TMS-EEG system that directly detects oscillatory phase without prediction, enabling phase-locked stimulation within microseconds. We validated the system against a prediction-based approach using simulated sine waves and human EEG data (N=18), without active TMS delivery. Across frequency-modulated sweeps and spontaneous occipital alpha oscillations (eyes-open vs. closed), the RT-CL system achieved higher triggering probability (16-24%) and reduced the phase error variability (2-10{degrees}). Importantly, when targeting event-related theta oscillations during two spatial navigation tasks, RT-CL produced [~]18% higher triggering probabilities and [~]19{degrees} lower phase error variability than phase prediction. These findings validate the RT-CL system for probing phase-dependent mechanisms during active cognition and the development of precision TMS interventions targeting pathological brain states.

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