Spatiotemporal structure of intracranial electric fields induced by transcranial electric stimulation in humans and nonhuman primates

Abstract

Transcranial electric stimulation (TES) is an emerging technique, developed to non-invasively modulate brain function. However, the spatiotemporal distribution of the intracranial electric fields induced by TES remains poorly understood. In particular, it is unclear how much current actually reaches the brain, and how it distributes across the brain. Lack of this basic information precludes a firm mechanistic understanding of TES effects. In this study we directly measure the spatial and temporal characteristics of the electric field generated by TES using stereotactic EEG (s-EEG) electrode arrays implanted in cebus monkeys and surgical epilepsy patients. We found a small frequency dependent decrease (10%) in magnitudes of TES induced potentials and negligible phase shifts over space. Electric field strengths were strongest in superficial brain regions with maximum values of about 0.5 mV/mm. Our results provide crucial information of the underlying biophysics in TES applications in humans and the optimization and design of TES stimulation protocols. In addition, our findings have broad implications concerning electric field propagation in non-invasive recording techniques such as EEG/MEG.

Conflict of interest statement

A.O. is an inventor on patents and patent applications describing methods and devices for noninvasive brain stimulation.

Figures

Figure 1

Bode plot illustrating the frequency dependency of the magnitude of TES induced electric potentials measured in Monkey 1 (A) and Monkey 2 (B). All shown results are corrected for the dampening of the stimulation and recording system. Normalized mean magnitude over all contacts in dependence of stimulation frequency (log10 units) from 1 Hz–150 Hz for two repeated measurements. A slight decrease in magnitude of up to 10% is visible for higher stimulation strengths.

Figure 2

Bode plot illustrating the frequency dependency of phase differences of TES induced electric potentials measured in Monkey 1 (A) and Monkey 2 (B). Mean phase differences (degree) between all combinations of electrode contacts are shown in dependence of stimulation frequency (log10 units) from 1 Hz–150 Hz for two repeated measurements. Weak phase differences around 1–2 degrees were observed for both monkeys.

Figure 3

Intracranial potential distribution for monkey 1 (A) and monkey 2 (B). Shown is the measured electric potential (in mV scaled for a stimulation intensity of 1 mA, measured at 1 Hz) at different electrode contacts implanted in the left hemisphere. Stimulation electrodes were attached over the left occipital cortex and middle forehead and their locations are indicated with red and blue arrows for both monkeys. A continuously changing posterior - anterior gradient in the electric potential is visible. (C) Stimulation electrodes displayed over the cortical surface for Monkey 1 (left) and Monkey 2 (right).

Figure 4

Intracranial potential distribution for Participant 1 (A) and Participant 2 (B). Measured electric potential (in mV scaled for a stimulation intensity of 1 mA) at different bi-hemispheric stereotactic EEG electrode contacts (Participant 1) or surface ECoG grid on the left hemisphere (Participant 2). Stimulation electrodes were attached bilaterally over the left and right temple in both Participants and indicated with red and blue arrows. A continuously changing left - right gradient in the electric potential is visible for Participant 1. For Participant 2 a sharp change in potential is found close to the left stimulation electrode. Continuously increasing potentials are found with increasing distance to the stimulation electrode. Note the large potentials found in the occipital region are due to the lack of electrode coverage on the right hemisphere which would exhibit even higher values. (C) Stimulation electrodes shown over the cortical surface for Participant 1 (left) and Participant 2 (right, other cross hemispheric electrode not visible).

Figure 5

Intracranial electric field distribution for monkey 1 (A) and monkey 2 (B). The position of the stimulation electrodes on the scalp are indicated with red and blue arrows. The electric field projection along the electrodes (in mV/mm scaled for a stimulation intensity of 1 mA) shows an intricate pattern with high electric fields close to the occipital stimulation electrode (monkey 1). Note that the strongest electric field strength was found not at the most superficial recording electrode but at an electrode a bit deeper in the cortex. The weak electric field strengths near the frontal stimulation electrode are likely due to the larger distance to the frontal electrode. For the second monkey strongly enhanced electric field strength occurred at one electrode. Possible reasons are smaller head size and reduction in muscle tissue that can lead to larger field strengths. Also the contact with highest electric field strength was outside the brain, possibly explaining the large field strength.

Figure 6

Intracranial electric field distribution for Participant 1 (A) and Participant 2 (B) at different bihemispheric stereotactic EEG electrode contacts (Participant 1) or surface ECoG grid on the left hemisphere (Participant 2). The position of the stimulation electrodes on the scalp are indicated with red and blue arrows. Shown is the electric field projection in mV/mm scaled for a stimulation intensity of 1 mA. Highest electric field strength was found at contacts close to the stimulation electrodes (bilaterally) with decreasing strength for increasing depth in the brain for Participant 1. In Participant 2 highest electric field strength was found near the contacts close to the stimulation electrode (left hemisphere) and decreasing values at more remote electrodes.