EEG microstates modulate TMS-evoked responses in genetic generalized epilepsy

Heterogeneity of neural states leads to different responses to neurostimulation. Electroencephalography (EEG) microstate-locked transcranial magnetic stimulation (TMS) was applied to investigate the effect of microstates at the time of stimulation on the TMS responses in patients with genetic generalized epilepsy (GGE).

Resting-state EEG and TMS-EEG data were collected in 24 patients with GGE. Trials were classified based on four typical microstates at the time of stimulation. TMS-evoked potentials (TEPs), topographical distribution and natural frequency were analyzed to explore the differences in TMS-EEG characteristics across four microstates in GGE. Spearman correlation analysis was performed to examine associations between TEP components and clinical features.

The P180 component of microstate D group (-4.794 μV) was significantly higher than of microstate A group (-1.668 μV, p = 0.027) and microstate C group (-2.079 μV, p = 0.027). Significant differences in the correlation values between each TEP component were detected, especially in microstate A, C and D. Compared with TEP amplitude during random stimulation, microstate A and microstate D showed slightly lower N100 and P180 amplitude, microstate C showed slightly higher P180 amplitude induced by stimulation. There was no difference in the TMS-induced natural frequencies among four microstates. No significant correlations were found between the amplitude of the TEPs and clinical variables in GGE.

Microstate-specific TMS-EEG signatures in GGE may help reduce state-related variability and improve patient stratification and outcome assessment in trials and longitudinal monitoring. However, their robustness and clinical relevance require replication and prospective validation in larger, independent cohorts.