Safety Aspects, Tolerability and Modeling of Retinofugal Alternating Current Stimulation

Abstract

Background While alternating current stimulation (ACS) is gaining relevance as a tool in research and approaching clinical applications, its mechanisms of action remain unclear. A review by Schutter and colleagues argues for a retinal origin of transcranial ACS’ neuromodulatory effects. Interestingly, there is an alternative application form of ACS specifically targeting α-oscillations in the visual cortex via periorbital electrodes (retinofugal alternating current stimulation, rACS). To further compare these two methods and investigate retinal effects of ACS, we first aim to establish the safety and tolerability of rACS. Objective The goal of our research was to evaluate the safety of rACS via finite-element modeling, theoretical safety limits and subjective report. Methods 20 healthy subjects were stimulated with rACS as well as photic stimulation and reported adverse events following stimulation. We analyzed stimulation parameters at electrode level as well as distributed metric estimates from an ultra-high spatial resolution magnetic resonance imaging (MRI)-derived finite element human head model and compared them to existing safety limits. Results Topographical modeling revealed the highest current densities in the anterior visual pathway, particularly retina and optic nerve. Stimulation parameters and finite element modeling estimates of rACS were found to be well below existing safety limits. No serious adverse events occurred. Conclusion Our findings are in line with existing safety guidelines for retinal and neural damage and establish the tolerability and feasibility of rACS. In comparison to tACS, retinofugal stimulation of the visual cortex provides an anatomically circumscribed model to systematically study the mechanisms of action of ACS.

Optimized Electrode Placements for Non-invasive Electrical Stimulation of the Olfactory Bulb and Olfactory Mucosa

“…Furthermore, the proximity of the optimal montages to the eye regions increases the likelihood of visual phosphenes. While the safety and tolerability of any novel approach have to be carefully evaluated, it is to be noted that certain transcranial approaches, given the application, have actually exploited these high-conductivity pathways to intentionally target these sensitive regions ( Haberbosch et al, 2019 ). Fortunately, not only stimulation parameters (current density, charge density, etc.)…”

“…The nifti (.nii) color masks from the MIDA model were first processed in MATLAB to re-create segmentation masks based on intensity values. These masks were then imported into Simpleware (Synopsys Ltd., CA, United States), and any errors in continuity and anatomical details were manually corrected for Bikson and Datta (2012) , Datta et al (2012) , Haberbosch et al (2019) . Masks with similar electrical conductivities were then merged to a single compartment excluding the regions of interest (OB and OE) in order to perform detailed individual current flow analysis through them.…”

Multi-channel transorbital electrical stimulation for effective stimulation of posterior retina

“…As the larger sized electrodes with a diameter of 1 cm were assumed in this study, we strongly believe that it would be safe to inject current much smaller than 3 mA in the proposed montage. In addition, a previous study reported that the maximal electric field amplitude that does not cause any tissue damage is 42 V/m 18 . As much smaller electric field is delivered to the retinal tissues in the suggested montage, the use of the suggested montage will not cause any damage to the retinal tissue.…”

“…The calculated electric field was scaled such that the 1 mA of current was flowing into the reference electrode. We assumed that all tissue compartments were homogeneous, and their electrical conductivity values were set according to a previous study 18 . This process was repeated until the electric field distributions for each of the active electrodes were calculated.…”

“…Generally, the conventional electrode configuration used for tES comprises two active electrodes attached to the skin near the orbital cavity and a single reference electrode placed on the occipital pole or extra-cephalic regions like the wrist and neck 10 , 12 , 18 . According to a numerical simulation study with the conventional electrode montage, most electric fields were delivered to the anterior part of the eye 15 .…”