The Rhythm of Normality: A Comprehensive Normative Database for TMS-EEG Metrics with Reliability Characterization

Couto, B. A. N.; De Martino, E.; Mazhari-Jensen, D.; Jakobsen, A.; Bach, M. M.; Gianotta, A.; Ingemann-Molden, S.; Graven-Nielsen, T.; Casali, A. G.; de Andrade, D. C.

doi:10.64898/2026.04.23.720403

bioRxiv · 10.64898/2026.04.23.720403

The Rhythm of Normality: A Comprehensive Normative Database for TMS-EEG Metrics with Reliability Characterization

Couto, B. A. N.·De Martino, E.·Mazhari-Jensen, D.·Jakobsen, A.·Bach, M. M.·Gianotta, A.·Ingemann-Molden, S.·Graven-Nielsen, T.·Casali, A. G.·de Andrade, D. C.

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Abstract

BackgroundTranscranial Magnetic Stimulation combined with electroencephalography (TMS-EEG) offers unique insights into cortical excitability and connectivity, yet current analyses are primarily limited to group-level inferences with little validation of individual reliability and feature redundancy. ObjectiveTo construct a comprehensive, open-access, and reliable normative dataset of TMS-EEG features that enables individual-level comparison MethodsWe aggregated TMS-EEG data recorded over the primary motor cortex (M1) from 164 healthy adults (30.8 {+/-} 9.8 years; 88 female) across nine studies using harmonized acquisition and preprocessing pipelines. Reliability analysis was conducted on a test-retest subset (N=57) for 968 extracted features, evaluating systematic bias, absolute error, and relative reliability (Intraclass Correlation Coefficient categorized by the lower bound of the 95% confidence interval). Additionally, feature clustering was performed to quantify redundancy and correlations across the high-dimensional feature space. We then established normative distributions and developed an online benchmarking platform. ResultsReliability analyses (N=57) of the high-dimensional feature set revealed that 525 out of 968 features (54.3%) met at least moderate reliability standards (ICC lower bound > 0.5). Cluster analysis indicated substantial redundancy among metrics, with three distinct clusters having a moderate-to-high internal correlation (|r| = 0.64, 0.48, 0.39, respectively). Finally, normative data from the database identified abnormal results in a test patient, supporting the feasibility of individual-level classification in an open-science framework. ConclusionsHarmonization of data acquisition and analysis pipelines led to the development of a reliable normative M1 TMS-EEG reference. This publicly available resource provides a validated tool for future individual-level classifications and an open platform for ongoing community contributions.

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Couto, B. A. N., De Martino, E., Mazhari-Jensen, D., Jakobsen, A., Bach, M. M., Gianotta, A., Ingemann-Molden, S., Graven-Nielsen, T., Casali, A. G., de Andrade, D. C.. 2026-04-27. The Rhythm of Normality: A Comprehensive Normative Database for TMS-EEG Metrics with Reliability Characterization. https://doi.org/10.64898/2026.04.23.720403

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