The Relation between Induced Electric Field and TMS-Evoked Potentials: A Deep TMS-EEG Study

Transcranial magnetic stimulation (TMS) in humans induces electric fields (E-fields, EF) that perturb and modulate the brain's endogenous neuronal activity and result in the generation of TMS-evoked potentials (TEPs). The exact relation of the characteristics of the induced E-field and the intensity of the brains' response, as measured by electroencephalography (EEG), is presently unclear. In this pilot study, conducted on three healthy subjects and two patients with generalized epilepsy (total: 3 males, 2 females, mean age of 26 years; healthy: 2 males, 1 female, mean age of 25.7 years; patients: 1 male, 1 female, mean age of 26.5 years), we investigated the temporal and spatial relations of the E-field, induced by single-pulse stimuli, and the brain's response to TMS. Brain stimulation was performed with a deep TMS device (BrainsWay Ltd., Jerusalem, Israel) and an H7 coil placed over the central area. The induced EF was computed on personalized anatomical models of the subjects through magneto quasi-static simulations. We identified specific time instances and brain regions that exhibit high positive or negative associations of the E-field with brain activity. In addition, we identified significant correlations of the brain's response intensity with the strength of the induced E-field and finally prove that TEPs are better correlated with E-field characteristics than with the stimulator's output. These observations provide further insight in the relation between E-field and the ensuing cortical activation, validate in a clinically relevant manner the results of E-field modeling and reinforce the view that personalized approaches should be adopted in the field of non-invasive brain stimulation.