TMS orientation and pulse waveform manipulation activates different neural populations: direct evidence from TMS-EEG

Monophasic and biphasic TMS pulses and coil orientations produce different responses in terms of motor output and sensory perception. Those differences have been attributed to the activation of specific neural populations. However, up to date, direct evidence supporting this hypothesis is still missing since studies were mostly based on indirect measures of cortical activation, i.e., motor evoked potentials or phosphenes. Here, we investigated for the first time the impact of different coil orientations and waveforms on a non-primary cortical area, namely the premotor cortex, by measuring TMS evoked EEG potentials (TEPs). We aimed at determining whether TEPs produced by differently oriented biphasic and monophasic TMS pulses diverge and whether these differences are underpinned by the activation of specific neural populations. To do so, we applied TMS over the right premotor cortex with monophasic or biphasic waveforms oriented perpendicularly (in the anterior-posterior direction and vice-versa) or parallel (latero-medial or medio-laterally) to the target gyrus. EEG was concurrently recorded from 60 electrodes. We analyzed TEPs at the level of EEG sensors and cortical sources both in time and time-frequency domain. Biphasic pulses evoked larger early TEP components, which reflect cortical excitability properties of the underlying cortex, in both parallel directions when compared to the perpendicular conditions. Conversely, monophasic pulses, when oriented perpendicularly to the stimulated gyrus, elicited a greater N100, which is a reliable TEP component linked to GABAb-mediated inhibitory processes, than when parallel to the gyrus. Our results provide direct evidence supporting the hypothesis that TMS pulse waveform and TMS coil orientations affect which neural population is engaged.