Pinging the brain with transcranial magnetic stimulation reveals cortical reactivity in time and space

Background: Single-pulse transcranial magnetic stimulation (TMS) elicits an evoked electroencephalography (EEG) potential (TMS-evoked potential, TEP), which is interpreted as direct evidence of cortical reactivity to TMS. Thus, combining TMS with EEG can be used to investigate the mechanism underlying brain network engagement in TMS treatment paradigms. However, controversy remains regarding whether TEP is a genuine marker of TMS-induced cortical reactivity or if it is confounded by responses to peripheral somatosensory and auditory inputs. Resolving this controversy is of great significance for the field and will validate TMS as a tool to probe networks of interest in cognitive and clinical neuroscience. Objective: Here, we delineated the cortical origin of TEP by spatially and temporally localizing successive TEP components, and modulating them with transcranial direct current stimulation (tDCS) to investigate cortical reactivity elicited by single-pulse TMS and its causal relationship with cortical excitability. Methods: We recruited 18 healthy participants in a double-blind, cross-over, sham-controlled design. We collected motor-evoked potentials (MEPs) and TEPs elicited by suprathreshold single-pulse TMS targeting the left primary motor cortex (M1). To causally test cortical and corticospinal excitability, we applied tDCS to the left M1. Results: We found that the earliest TEP component (P25) was localized to the left M1. The following TEP components (N45 and P60) were largely localized to the primary somatosensory cortex, which may reflect afferent input by hand-muscle twitches. The later TEP components (N100, P180, and N280) were largely localized to the auditory cortex. As hypothesized, tDCS selectively modulated cortical and corticospinal excitability by modulating the pre-stimulus mu-rhythm oscillatory power. Conclusion: Together, our findings provide causal evidence that the early TEP components reflect cortical reactivity to TMS.