Is electric field strength deterministic in cortical neurons' response to transcranial electrical stimulation?

Transcranial electrical stimulation (tES), which modulates cortical excitability via electric currents, has attracted increasing attention because of its application in treating neurologic and psychiatric disorders. To obtain a better understanding of the brain areas affected and stimulation's cellular effects, a multi-scale model was proposed that combines multi-compartmental neuronal models and a head model. While one multi-scale model of tES that used straight axons reported that the direction of electric field (EF) is a determining factor in a neuronal response, another model of transcranial magnetic stimulation (TMS) that used arborized axons reported that EF magnitude is more crucial than EF direction because of arborized axons' reduced sensitivity to the latter. Our goal was to investigate whether EF magnitude remains a crucial factor in the neuronal response in a multi-scale model of tES into which an arborized axon is integrated. To achieve this goal, we constructed a multi-scale model that integrated three types of neurons and a realistic head model, and then simulated the neuronal response to realistic EF. We found that EF magnitude was correlated with excitation threshold, and thus, it may be one of the determining factors in cortical neurons' response to tES.Clinical Relevance-This multi-scale model based on biophysical and morphological properties and realistic brain geometry may help elucidate tES's neural mechanisms. Moreover, given its clinical applications, this model may help predict a patient's neuronal response to brain stimulation effectively.