Evaluating Current Density Modeling of Non-Invasive Eye and Brain Electrical Stimulation Using Phosphene Thresholds.

B A Sabel,J Haueisen,A Hunold,A Kresinsky,M Dannhauer,L Cardenas-Morales,A Antal

doi:10.1109/tnsre.2021.3120148

Abstract

Because current flow cannot be measured directly in the intact retina or brain, current density distribution models were developed to estimate it during magnetic or electrical stimulation. A paradigm is now needed to evaluate if current flow modeling can be related to physiologically meaningful signs of true current distribution in the human brain. We used phosphene threshold measurements (PTs) as surrogate markers of current-flow to determine if PTs, evoked by transcranial alternating current stimulation (tACS), can be matched with current density estimates generated by head model-based computer simulations. Healthy, male subjects (n=15) were subjected to three-staged PT measurements comparing six unilateral and one bilateral stimulation electrode montages according to the 10/20 system: Fp2-Suborbital right (So), Fp2-right shoulder (rS), Fp2-Cz, Fp2- O2, So-rS, Cz-F8 and F7-F8. The stimulation frequency was set at 16 Hz. Subjects were asked to report the appearance and localization of phosphenes in their visual field for every montage. Current density models were built using multi-modal imaging data of a standard brain, meshed with isotropic conductivities of different tissues of the head using the SimBio and SCIRun software packages. We observed that lower PTs were associated with higher simulated current levels in the unilateral montages of the model head, and shorter electrode distances to the eye had lower PTs. The lowest mean PT and the lowest variability were found in the F7-F8 montage (95±33 μA). Our results confirm the hypothesis that phosphenes are primarily of retinal origin, and they provide the first in vivo evidence that computer models of current flow using head models are a valid tool to estimate real current flow in the human eye and brain.

Highlights

T RANSCRANIAL alternating current stimulation is an emerging technique to alter brain functions by modulating brain oscillations [1]–[3]
We considered the Phosphene thresholds (PTs) to be a functional marker of true current flow in the retina or central visual pathway, which can be compared with estimated current flow as determined
We reasoned that if simulation methods of current flow reflect true current flow, an inverse relationship should exist in that higher current densities in the eye correlate with lower PTs

Summary

Introduction

T RANSCRANIAL alternating current stimulation (tACS) is an emerging technique to alter brain functions by modulating brain oscillations [1]–[3]. During delivery of tACS to healthy subjects or patients with visual system damage, the subjects experience the appearance of flickering lights, called phosphenes, a perceptual phenomenon that varies with stimulation frequency, intensity and electrode placement [9]. Because true current flow cannot be directly measured in the intact eye or brain of healthy subjects, computational models were developed to simulate current flow and density distributions [11]–[14]. Such models may contribute to a better understanding of the origin and appearance of ACS induced phosphenes [15]. We aimed to test this relationship by applying ACS with seven different electrode montages and correlating the PTs in a group of normal subjects with the computational modeling of current flow and current density distribution

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Discussion

Conclusion