Measurements and models of electric fields in the in vivo human brain during transcranial electric stimulation

Abstract

Transcranial electric stimulation aims to stimulate the brain by applying weak electrical currents at the scalp. However, the magnitude and spatial distribution of electric fields in the human brain are unknown. We measured electric potentials intracranially in ten epilepsy patients and estimated electric fields across the entire brain by leveraging calibrated current-flow models. When stimulating at 2 mA, cortical electric fields reach 0.8 V/m, the lower limit of effectiveness in animal studies. When individual whole-head anatomy is considered, the predicted electric field magnitudes correlate with the recorded values in cortical (r = 0.86) and depth (r = 0.88) electrodes. Accurate models require adjustment of tissue conductivity values reported in the literature, but accuracy is not improved when incorporating white matter anisotropy or different skull compartments. This is the first study to validate and calibrate current-flow models with in vivo intracranial recordings in humans, providing a solid foundation to target stimulation and interpret clinical trials.DOI: http://dx.doi.org/10.7554/eLife.18834.001

Are current flow models for transcranial electrical stimulation fit for purpose?

“…Two recent studies [6,8] now provide important assurance that current flow models indeed do a good job in estimating how much and where to tES delivers current in the brain of an individual. Opitz and colleagues measured the spatial and temporal distribution of the electrical fields generated by 3 alternating transcranial current stimulation (tACS), using implanted electrodes in cebus monkeys and patients with epilepsy undergoing intracranial recordings prior to neurosurgical treatment [8].…”

“…The current strengths measured in the brain exhibited substantial inter-individual differences, but these matched well with estimates from previous modelling studies. A more direct comparison of estimated and actual current was conducted by Huang and colleagues [6]. These authors directly measured the magnitude and spatial distribution of electrical fields in human epilepsy patients with implanted electrodes, and compared these with the estimates from current flow models obtained from structural MRIs of the same patients.…”

“…As long as we do not know how much current is effectively delivered in an individual, the debate about the sources of variable responses to tES (including, for example, cortical state dependencies, individual traits, or genetic variables) is like posting a letter without a stamp nor address, and hoping it will arrive at its destination. With the recent validation of current flow models [6,8], the field is now in a position to better control variance arising from dose differences across individuals, and thereby identify the true biological causes of variable tES effects.…”

“…In providing validation that current flow models are doing a good job in predicting where current flows in the brain, and how much of it gets there, the aforementioned studies [6,8] provide the foundation for individualizing dose delivery of tES. With this, the field can now (re)start addressing what may truly cause variable effects of tES, and whether the controversy about its overall utility in basic and translational research is justified or not.…”

Limitations of ex vivo measurements for in vivo neuroscience

“…However, cadavers are still regularly used to examine possible methodological artifacts in brain imaging studies because of the complete absence of neuronal activity with largely preserved anatomical structures (3,4). Numerous studies have relied on cadavers to establish the conductivity of differing tissue types, with notable discrepancies compared with in vivo measurements (5)(6)(7)(8). Similarly, in developing noninvasive transcranial electric stimulation (TES) procedures, some have suggested the use of cadavers for measuring electric fields generated in the brain during stimulation.…”