Immediate TMS-EEG responses reveal motor cortex excitability

The combination of transcranial magnetic stimulation and electroencephalography (TMS-EEG) is typically used to probe cortical excitability at the network level, as local excitability measures were previously not feasible. However, a recent study revealed immediate TMS-evoked potentials (i-TEPs) following primary motor cortex (M1) stimulation, yet their physiological origin remains uncertain. Here, we aimed to test whether this imme- diate activity is replicable, physiological, and related to motor cortex excitability. Analyses were conducted on data from 28 healthy participants who underwent M1 stimulation using two opposite biphasic current directions. We run a minimal preprocessing and then, upon visual inspection, we divided the sample according to the presence/absence of muscle artifacts (Muscle/NoMuscle groups). First, we successfully replicated i-TEPs for both current directions. Second, source localization revealed that the i-TEPs signal originated in the precentral gyrus of the stimulated hemisphere. Third, we computed the immediate TMS- related power (i-TRP) to disentangle the components contributing to the i-TEP signal. Two oscillatory peaks emerged at 100–200 Hz and 600–800 Hz. Finally, we tested the relationship between i-TRP components and motor evoked potentials (MEPs) amplitude in NoMuscle groups (n = 8 for both current directions, n = 14 for anterior-to-posterior and posterior-to-anterior induced current). The analysis showed a robust positive associa- tion between i-TRP in the 600–800 Hz range and MEP amplitude, suggesting that this component reflects M1 excitability. Overall, our findings converge in indicating the physiological nature of immediate TMS-EEG responses, sug- gesting that they reflect the excitability of the stimulated cortex.