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

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%