Background: the use of combined transcranial magnetic stimulation (TMS) and electroencephalography (EEG) for the functional evaluation of the cerebral cortex in health and disease is becoming increasingly common. However, there is still some ambiguity regarding the extent to which brain responses to auditory and somatosensory stimulation contribute to the TMS-evoked potential (TEP). Objective/Hypothesis: to measure separately the contribution of auditory and somatosensory stimulation caused by TMS, and to assess their contribution to the TEP waveform, when stimulating the motor cortex (M1). Methods: 19 healthy volunteers underwent 7 blocks of EEG recording. To assess the impact of auditory stimulation on the TEP waveform, we used a standard figure of eight coil, with or without masking with a continuous noise reproducing the specific time-varying frequencies of the TMS click, stimulating at 90% of resting motor threshold. To further characterise auditory responses due to the TMS click, we used either a standard or a sham figure of eight coil placed on a pasteboard cylinder that rested on the scalp, with or without masking. Lastly, we used electrical stimulation of the scalp to investigate the possible contribution of somatosensory activation. Results: auditory stimulation induced a known pattern of responses in electrodes located around the vertex, which could be suppressed by appropriate noise masking. Electrical stimulation of the scalp alone only induced similar, non-specific scalp responses in the in the central electrodes. TMS, coupled with appropriate masking of sensory input, resulted in specific, lateralized responses at the stimulation site, lasting around 300 ms. Conclusions: if careful control of confounding sources is applied, TMS over M1 can generate genuine, lateralized EEG activity. By contrast, sensory evoked responses, if present, are represented by nonspecific, late (100e200 ms) components, located at the vertex, possibly due to saliency of the stimuli. Notably, the latter can confound the TEP if masking procedures are not properly used.
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