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

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Abstract

Objective

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.

Methods

We validated the system against a prediction-based approach using simulated sine waves and human EEG data (N=18), without active TMS delivery.

Results

Across frequency-modulated sweeps and spontaneous occipital alpha oscillations (eyes-open vs. closed), the RT-CL system achieved higher triggering probability (11-24%) and reduced the phase error variability (2-10°). Importantly, when targeting event-related theta oscillations during two spatial navigation tasks, RT-CL produced ∼20% higher triggering probabilities and ∼17° lower phase error variability than phase prediction.

Conclusion

These findings validate the RT-CL system for probing phase-dependent mechanisms during active cognition and pathological brain states.

Significance

By precisely targeting brief, variable neural signals, RT-CL could be used for the development of personalized TMS interventions for neuropsychiatric disorders during symptom provocation.

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