Real-time measurement instead of prediction enables high-precision phase-specific stimulation of the human brain
- 1Institute for Neuromodulation and Neurotechnology, University Hospital and University of Tübingen, Tübingen, 72076, Germany
Abstract
BACKGROUND: Phase-specific brain stimulation provides a tool to probe the functional relevance of ongoing neural oscillations. Current closed-loop stimulation approaches often use predictive algorithms to compensate for processing and stimulation delays, but prediction error can limit phase-targeting accuracy, particularly at higher frequencies. A real-time approach that minimizes latency without relying on phase prediction may improve the precision and interpretability of phase-specific stimulation. METHODS: In this technical proof-of-concept study, we developed and validated a prototype real-time closed-loop system for electroencephalography-triggered transcranial magnetic stimulation (EEG-TMS). The system performs signal acquisition, phase estimation, and stimulation triggering within a 1 ms closed-loop update cycle and does not require phase prediction. Empirical testing was performed in human participants receiving EEG-triggered TMS across eight target phases and ten target frequencies ranging from 4 to 40 Hz. RESULTS: Across all target phases and frequencies, the system achieved single-digit phase accuracy without phase prediction. On average, stimulation was 5.6° away from the intended target phase. The typical single-pulse error was 3.7°, and trial-to-trial variability was 7.8° These results indicate stable phase-targeting performance across the tested phase and frequency range. CONCLUSION: This real-time EEG-TMS system demonstrates the technical feasibility of prediction-free phase-specific stimulation across physiologically relevant frequencies. By reducing dependence on predictive phase extrapolation, the approach provides a platform for studying phase-dependent brain physiology and for developing closed-loop neuromodulation protocols with improved temporal precision.
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BibTeX
@article{guggenberger2026realtime,
title = {{Real-time measurement instead of prediction enables high-precision phase-specific stimulation of the human brain}},
author = {Robert Guggenberger and Farzin Negahbani and Julian-Samuel Gebühr and Marius Keute and Alireza Gharabaghi},
journal = {NeuroImage},
year = {2026},
month = sep,
doi = {10.1016/j.neuroimage.2026.122216},
url = {https://doi.org/10.1016/j.neuroimage.2026.122216},
note = {CC BY},
}
RIS
TY - JOUR
TI - Real-time measurement instead of prediction enables high-precision phase-specific stimulation of the human brain
AU - Robert Guggenberger
AU - Farzin Negahbani
AU - Julian-Samuel Gebühr
AU - Marius Keute
AU - Alireza Gharabaghi
PY - 2026
DA - 2026/09/10
JO - NeuroImage
DO - 10.1016/j.neuroimage.2026.122216
UR - https://doi.org/10.1016/j.neuroimage.2026.122216
AB - BACKGROUND: Phase-specific brain stimulation provides a tool to probe the functional relevance of ongoing neural oscillations. Current closed-loop stimulation approaches often use predictive algorithms to compensate for processing and stimulation delays, but prediction error can limit phase-targeting accuracy, particularly at higher frequencies. A real-time approach that minimizes latency without relying on phase prediction may improve the precision and interpretability of phase-specific stimulation. METHODS: In this technical proof-of-concept study, we developed and validated a prototype real-time closed-loop system for electroencephalography-triggered transcranial magnetic stimulation (EEG-TMS). The system performs signal acquisition, phase estimation, and stimulation triggering within a 1 ms closed-loop update cycle and does not require phase prediction. Empirical testing was performed in human participants receiving EEG-triggered TMS across eight target phases and ten target frequencies ranging from 4 to 40 Hz. RESULTS: Across all target phases and frequencies, the system achieved single-digit phase accuracy without phase prediction. On average, stimulation was 5.6° away from the intended target phase. The typical single-pulse error was 3.7°, and trial-to-trial variability was 7.8° These results indicate stable phase-targeting performance across the tested phase and frequency range. CONCLUSION: This real-time EEG-TMS system demonstrates the technical feasibility of prediction-free phase-specific stimulation across physiologically relevant frequencies. By reducing dependence on predictive phase extrapolation, the approach provides a platform for studying phase-dependent brain physiology and for developing closed-loop neuromodulation protocols with improved temporal precision.
SN - 1053-8119
SN - 1095-9572
ER -