Which direction should I go? : A quest for understanding the effect of TMS stimulus orientation on evoked responses

Abstract

The orientation of the electric field (E-field) induced by transcranial magnetic stimulation (TMS) plays a significant role in determining the magnitude of motor evoked potentials (MEP) and TMS-evoked potentials (TEP). However, fundamental mechanisms explaining the interaction of the induced E-field and the underlying neuronal populations are still largely unknown. We recently entered a quest to understand and describe neurophysiological and physical factors affecting the effect of the E-field orientation on the MEP and TEP. We developed a dual-coil TMS transducer capable of fast and accurate electronic control of the induced E-field orientation. With this transducer, we could scan the effect of stimulus orientation on TEPs and MEPs in single and paired-pulse protocols with unprecedented precision and accuracy. We further compared the experimental data with simulations of responses in realistic neuronal and brain models. Our results show that the spatial distribution of MEPs on the target muscle strongly depends on the E-field orientation. Furthermore, the simulations with realistic models indicate that multiple factors are needed to match closely the experimental data, such as the extent of the stimulated cortical area, E-field distribution, and neuronal population alignment relative to the cortical surface. Our studies provide relevant insights into how the physical properties of a TMS pulse interact with neuronal mechanisms of motor output generation and can be the basis for improving the targeting and effectiveness of TMS clinical treatments.