Investigating the Origin of TMS-evoked Brain Potentials Using Topographic Analysis

The combination of transcranial magnetic stimulation (TMS) and electroencephalography (EEG) represents an increasingly popular tool to non-invasively probe cortical excitability in humans. TMS-evoked brain potentials (TEPs) are composed of successive components reflecting the propagation of activity from the site of stimulation, thereby providing information on the state of brain networks. However, TMS also generates peripherally evoked sensory activity which contributes to TEP waveforms and hinders their interpretation. In the present study, we examined whether topographic analysis of TEPs elicited by stimulation of two distinct cortical targets can disentangle confounding signals from the genuine TMS-evoked cortical response. In 20 healthy subjects, TEPs were evoked by stimulation of the left primary motor cortex (M1) and the left angular gyrus (AG). Topographic dissimilarity analysis and microstate analysis were used to identify target-specific TEP components. Furthermore, we explored the contribution of cortico-spinal activation by comparing TEPs elicited by stimulation below and above the threshold to evoke motor responses. We observed topographic dissimilarity between M1 and AG TEPs until approximately 80 ms post-stimulus and identified early TEP components that likely reflect specific TMS-evoked activity. Later components peaking at 100 and 180 ms were similar in both datasets and attributed to sensory-evoked activity. Analysis of sub- and supra-threshold M1 TEPs revealed a component at 17 ms that possibly reflects the cortico-spinal output of the stimulated area. Moreover, supra-threshold M1 activation influenced the topography of almost all later components. Together, our results demonstrate the utility of topographic analysis for the evaluation and interpretation of TMS-evoked EEG responses.