Multidimensional Electrophysiological Responses to TMS on the Primary Motor Cortex: A TMS-EEG Characterization of Immediate Cortical Responses

Transcranial magnetic stimulation (TMS) combined with electroencephalography (EEG) enables millisecond-scale characterization of cortical responses, but direct multidimensional comparisons across stimulation protocols remain limited. In a randomized within-subject crossover study, 17 healthy adults received 10 Hz repetitive transcranial magnetic stimulation (rTMS), 1 Hz rTMS, and intermittent theta-burst stimulation (iTBS) over the left primary motor cortex in separate sessions. TMS-evoked potentials (TEPs), power spectral density (PSD), and EEG microstate dynamics were assessed before and immediately after stimulation. Following 10 Hz rTMS, group-level P30 amplitude increased from 0.17 to 0.89 μV, while N45 became less negative from −1.73 to −0.82 μV; PSD increased significantly across 15.5–45 Hz. In contrast, 1 Hz rTMS reduced P30 from 0.68 to 0.39 μV and increased P60 from 0.31 to 1.65 μV, with significant PSD reductions at 12.7–31.7 Hz and 32.2–45 Hz. iTBS reduced the magnitude of N45 from −2.76 to −1.93 μV and decreased P60 from 1.41 to 0.47 μV. These findings demonstrate protocol-specific multidimensional electrophysiological profiles across temporal and spectral measures. This framework facilitates systematic comparison across stimulation protocols and provides a basis for further investigation of TMS-induced cortical responses and individualized neuromodulation.