What does this research mean for the field?

Pre-stimulus brain states, particularly those capturing signal dynamics, synchronization, functional connectivity, and complexity, explain a substantial fraction of trial-by-trial variability in post-stimulation evoked responses. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

The study aims to identify how pre-stimulus brain activity influences variability in response to brain stimulation.

May 19, 2026Brain stimulation0 citationsOpen Access

Pre-stimulus brain states predict and control variability in stimulation responses

GRGiovanni RabuffoUniversitat Pompeu Fabra MAMarianna AngiolelliInserm TFTomoki FukaiOkinawa Institute of Science and Technology Graduate University

Key Points

The study aims to identify how pre-stimulus brain activity influences variability in response to brain stimulation.
Analyzed high-density EEG and stereotactic EEG data from 36 epilepsy patients across about 320 sessions and over 10,000 electrical stimulations.
Examined trial-by-trial relationships between pre-stimulus activity and post-stimulus responses using 127 candidate metrics, honing in on the 5 most reliable metrics.
Metrics assessed included signal dynamics, synchronization, functional connectivity, and complexity at both local and global brain levels.
Pre-stimulus brain states accounted for a significant portion of variability in responses, with SEEG showing 17.6% and hd-EEG 7.1% of variance explained, peaking at 85.0%.

Abstract

Introduction Brain stimulation outcomes vary across trials even under identical parameters and targets, limiting reproducibility and clinical translation.Previous work suggests that ongoing brain states, including oscillatory and network-level activity, can modulate stimulation effects, yet the most reliable predictive features and their generalizability across modalities remain unclear. Materials and MethodsWe analyzed simultaneous high-density EEG and stereotactic EEG recordings from 36 epilepsy patients across approximately 320 sessions, comprising more than 10,000 single-pulse electrical stimulations.Trial-by-trial relationships between pre-stimulus spontaneous activity and post-stimulus evoked responses were screened across 127 candidate metrics, after which primary analyses were restricted to the 5 most reliable metrics of interest.These metrics captured signal dynamics, synchronization, functional connectivity, and complexity, and were quantified at both local and whole-brain scales Results Pre-stimulus brain states explained a substantial fraction of post-stimulation variance within session, with higher mean 2 in SEEG than hd-EEG (17.6% vs 7.1%; maxima 85.0%

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