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Updated: Oct 3, 2025
Brain State-dependent Brain Stimulation with Real-time Electroencephalography-Triggered Transcranial Magnetic Stimulation
Published on: August 20, 2019
Prefrontal theta phase-dependent rTMS-induced plasticity of cortical and behavioral responses in human cortex
Pedro Caldana Gordon1, Paolo Belardinelli2, Matti Stenroos3
1Department of Neurology & Stroke, University of Tübingen, Germany; Hertie Institute for Clinical Brain Research, University of Tübingen, Germany.
Background:
Prefrontal theta oscillations are involved in neuronal information transfer and retention. Phases along the theta cycle represent varied excitability states, whereby high-excitability states correspond to high-frequency neuronal activity and heightened capacity for plasticity induction, as demonstrated in animal studies. Human studies corroborate this model and suggest a core role of prefrontal theta activity in working memory (WM).
Objective/Hypothesis:
We aimed at modulating prefrontal neuronal excitability and WM performance in healthy humans, using real-time EEG analysis for triggering repetitive transcranial magnetic stimulation (rTMS) theta-phase synchronized to the left dorsomedial prefrontal cortex.
Methods:
16 subjects underwent 3 different rTMS interventions on separate days, with pulses triggered according to the individual's real-time EEG activity: 400 rTMS gamma-frequency (100 Hz) triplet bursts applied during either the negative peak of the prefrontal theta oscillation, the positive peak, or at random phase. Changes in cortical excitability were assessed with EEG responses following single-pulse TMS, and behavioral effects by using a WM task.
Results:
Negative-peak rTMS increased single-pulse TMS-induced prefrontal theta power and theta-gamma phase-amplitude coupling, and decreased WM response time. In contrast, positive-peak rTMS decreased prefrontal theta power, while no changes were observed after random-phase rTMS.
Conclusion:
Findings point to the feasibility of EEG-TMS technology in a theta-gamma phase-amplitude coupling mode for effectively modifying WM networks in human prefrontal cortex, with potential for therapeutic applications.
