Brief Trains of Closed-loop TMS Induce Controllable Power in FM-theta Oscillations

Abstract

Objective. Frontal-midline theta (FM-theta; 4-8 Hz) oscillations are thought to support cognition. Brief trains of transcranial magnetic stimulation (TMS) can probe these oscillations with high temporal precision but have rarely changed theta power. One possible reason is that prior studies ignored the instantaneous phase of the oscillation, which strongly shapes the cortical response to TMS. We tested whether brief TMS trains triggered at specific FM-theta phases in real time directionally modulate post-train FM-theta power. Approach. Six healthy adults received TMS over dorsomedial prefrontal cortex (Fz) with concurrent electroencephalography during a whole-report working memory task. A beamformer and real-time phase-estimation pipeline triggered four-pulse 6 Hz trains (110% of resting motor threshold) at FM-theta peaks (0 degrees) or troughs (180 degrees), randomized trial by trial. Post-train spectral power was decomposed into total, induced (non-phase-locked) and evoked (phase-locked) components. Main results. Trough-triggered trains transiently increased post-train FM-theta power relative to peak-triggered trains; task performance did not differ. Cluster-based permutation tests showed trough-peak differences in total (4.6-7.1 Hz) and induced (5.0-7.8 Hz) power ~50-440 ms after the train, suggesting amplification of the oscillation . No evoked effect was detected. The total-power effect was robust at the subject level (Cohen's dz = 1.32, p = 0.023). Within-train theta power did not differ between conditions, suggesting a cortical origin. Significance. To our knowledge, this is the first study to lock brief rhythmic TMS trains to the real-time phase of an ongoing oscillation, and to show phase-dependent modulation of FM-theta power after individual trains on timescales relevant to behavior. Open-loop brief-train protocols may have missed such effects by mixing faciliatory and suppressive phases. Phase-locked brief trains offer a precise tool for testing the causal role of oscillations in cognition.