Investigating the effects of TMS-related somatosensory inputs on TMS-evoked potentials provides evidence against significant interaction

Abstract The combination of transcranial magnetic stimulation (TMS) and electroencephalography (EEG) has emerged as a non-invasive technique to probe cortical responsivity. However, interpreting TMS–EEG data is challenging due to sensory inputs generated by TMS, which cause peripherally evoked potentials (PEPs) that overlap with TMS-evoked potentials (TEPs). These sensory inputs may also modulate the cortical response, potentially distorting TEPs. To address this and evaluate methods for reducing PEP contamination, we compared two sham designs: a “PEP saturation” method, which delivers high-intensity somatosensory stimuli in both sham and real TMS to saturate PEPs in both conditions, and a “PEP individualized matching stimulus intensity calibration” method, which individually adjusts stimulus intensity to match the PEP amplitude of real TMS. In both conditions, the PEPs from sham and real TMS conditions should match, enabling the subtraction of this confounder. If the TEPs after this subtraction were not different between the two conditions this would indicate the absence of a relevant interaction between PEPs and TEPs, justifying the removal of PEPs from TEPs by subtraction. Our results showed no significant difference in TEPs within 110 ms post-stimulation after sham subtraction regardless of the sham protocol, and whether stimulating the primary motor cortex or the supplementary motor area. These findings provide evidence for the absence of a relevant interaction between TMS-related somatosensory input and TEPs, and indicate the appropriateness of the two sham protocols in removing PEPs from the TMS-EEG response.