EEG entropy reflects both intrinsic and stimulation-induced corticospinal excitability

Background: Cortical excitability fluctuates throughout the day on multiple timescales, ranging from milliseconds to hours. This is reflected in the large variability of the brain's response to transcranial magnetic stimulation (TMS). However, robust and interpretable biomarkers of the brain's current excitability state are lacking. Objective: We investigated whether entropy derived from singular value decomposition of short electroencephalography (EEG) segments could serve as a biomarker of cortical excitability as probed by TMS. Methods: Entropy was computed from 1-second EEG segments preceding single-pulse TMS applied over the motor cortex. We assessed whether spontaneous fluctuations in pre-pulse entropy predicted trial-by-trial variability in TMS-induced motor-evoked potentials (MEPs). Additionally, we evaluated whether entropy tracked stimulation-induced changes in cortical excitability. Results: Higher pre-pulse entropy, particularly over frontal regions, was associated with larger MEP amplitudes. TMS locally increased entropy over the motor cortex, while entropy decreased in other regions during the intervention. Participants who showed greater local increases in entropy from pre- to post-intervention also demonstrated larger increases in corticospinal excitability. Conclusion: Entropy derived from short EEG segments reflects both intrinsic and stimulation-induced changes in cortical excitability. This marker may help optimize TMS interventions by informing brain state-dependent stimulation strategies and providing an index of intervention efficacy.