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

Abstract Transcranial magnetic stimulation combined with electroencephalography (TMS–EEG) enables millisecond-scale characterization of immediate cortical responses to stimulation. Nevertheless, systematic multidimensional comparisons of these responses across different TMS protocols at the same cortical target remain limited. In this study, we investigated the immediate electrophysiological modulation of the primary motor cortex (M1) induced by three protocols—1 Hz, 10 Hz, and intermittent theta-burst stimulation (iTBS)—using a unified framework integrating TMS-evoked potentials (TEPs), spectral power, global field metrics, and EEG microstate dynamics. Specifically, 10 Hz TMS enhanced the early excitatory component P30, reduced the inhibitory-related component N45, increased frontocentral β/γ-band activity, and promoted anterior-dominant microstate stability. In contrast, 1 Hz TMS attenuated P30, enhanced the later component P60, and primarily modulated β-band activity over parieto–occipital regions alongside posterior-dominant microstate reorganization. iTBS produced a hybrid pattern characterized by reductions in inhibitory-related components and selective microstate modulation. Across protocols, temporal, spectral, and microstate measures showed internally coherent shifts, defining a multidimensional electrophysiological fingerprint of immediate TMS-induced modulation in M1. This framework enables systematic cross-protocol comparison and provides a structured basis for future investigations of TMS-induced excitability changes and individualized neuromodulation strategies.