Pinging the Brain with Transcranial Magnetic Stimulation Reveals Cortical Reactivity in Time and Space

Abstract

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 may enable the mechanistic investigation of how TMS treatment paradigms engage network targets in the brain. However, there remains a central controversy about whether the TEP is a genuine marker of cortical reactivity to TMS or the TEP is contaminated 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. Here, we delineated the TEPs cortical origins by localizing successive TEP components in time and space and modulating them subsequently with transcranial direct current stimulation (tDCS). We collected both motor evoked potentials (MEPs) and TEPs elicited by suprathreshold single-pulse TMS to the left primary motor cortex (M1). We found that the earliest TEP component (P25) was localized on the TMS target location (left M1) and the following TEP components (N45 and P60) largely were localized on the primary somatosensory cortex, which may reflect afferent input by hand-muscle twitches. The later TEP components (N100, P180, and N280) largely were localized to the auditory cortex. To casually test that these components reflect cortical and corticospinal excitability, we applied tDCS to the left M1. As hypothesized, we found that tDCS modulated cortical and corticospinal excitability selectively by modulating the pre-stimulus mu-rhythm oscillatory power. Together, our findings provide causal evidence that the early TEP components reflect cortical reactivity to TMS.