Review of preclinical feasibility for EEG-phase-controlled iTBS stimulation

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medRxiv Published April 28, 2026 Medically reviewed April 28, 2026 Study authors: Maldonado Osorio, F. A.; Elhamiasl, M.; Gacek, M. K.; Shankman, S. A.; Alekseichuk, I. DOI ↗ By Dr. Ji-eun Park, MD · Brain, Mind & Pain

Key Takeaway

Note that future human trials are needed to evaluate practical benefits of EEG-phase-controlled iTBS.

This publication is a preclinical technical feasibility review rather than a clinical trial. The scope focuses on the technical implementation of prefrontal EEG-phase-controlled intermittent theta burst stimulation. The authors propose a seed-and-sustain hypothesis regarding the stimulation mechanism. No specific patient populations or clinical outcomes are described because the study is preclinical.

The review highlights significant technical challenges. Within-train stimulation pulses corrupt real-time EEG signals. Additionally, there is a general difficulty in predicting EEG theta phase even to initiate an iTBS train. These factors complicate the precise delivery of the intended stimulation protocol.

The authors emphasize that future human trials will be needed to evaluate the practical benefits of this approach. Safety data, adverse events, and tolerability were not reported in this preclinical context. The review concludes that clinical efficacy cannot be claimed at this stage.

Practice relevance is limited to the need for further investigation. Clinicians should not infer specific patient populations or outcomes from this preclinical work. The review serves to outline technical hurdles before human application.

Study Details

EvidenceLevel 5

PublishedApr 2026

View Original Abstract ↓

Brain-state-controlled transcranial magnetic stimulation (TMS) studies with real-time electroencephalography (EEG) show that the phase of ongoing oscillations modulates cortical susceptibility to TMS pulses. Translating this principle to repetitive clinical protocols, such as intermittent theta burst stimulation (iTBS), is an open challenge because within-train stimulation pulses corrupt real-time EEG. Moreover, the general difficulty of predicting EEG theta phase even to initiate an iTBS train applies. We present our solution for prefrontal EEG-phase-controlled iTBS, a personalized stimulation framework. We demonstrate the technical feasibility of aligning each train's initial bursts to the individual prefrontal theta phase and propose a "seed-and-sustain" hypothesis, whereby intra-train stimulation-induced entrainment at the individual theta rhythm carries the later bursts. Future human trials will be needed to evaluate the practical benefits of this approach.