Data_Sheet_1_Safety Aspects, Tolerability and Modeling of Retinofugal Alternating Current Stimulation.PDF

BackgroundWhile 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.
ObjectiveThe goal of our research was to evaluate the safety of rACS via finite-element modeling, theoretical safety limits and subjective report.
Methods20 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.
ResultsTopographical 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.
ConclusionOur 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.

研究背景
交流电刺激（alternating current stimulation, ACS）在科研领域的应用价值日益凸显，且正逐步向临床应用靠拢，但其具体作用机制仍未明确。舒特（Schutter）及其团队的一项综述提出，经颅交流电刺激的神经调控效应起源于视网膜。有趣的是，另有一类交流电刺激的应用形式可通过眶周电极精准靶向视觉皮层的α振荡，即视路交流电刺激（retinofugal alternating current stimulation, rACS）。为进一步对比这两种刺激方式，并探究交流电刺激的视网膜相关效应，本研究首先旨在明确视路交流电刺激的安全性与耐受性。

研究目标
本研究旨在通过有限元建模、理论安全限值分析以及受试者主观报告，评估视路交流电刺激的安全性。

研究方法
招募20名健康受试者，分别接受视路交流电刺激与光刺激，并在刺激结束后报告不良事件。我们从电极层面分析刺激参数，并基于超高空间分辨率磁共振成像（magnetic resonance imaging, MRI）构建的人类头部有限元模型，提取分布式度量估计值，随后将其与现有安全限值进行对比。

研究结果
拓扑建模结果显示，前视觉通路（尤其是视网膜与视神经）的电流密度最高。视路交流电刺激的参数与有限元模型估算结果均远低于现有安全限值，且未发生严重不良事件。

研究结论
本研究结果符合现有的视网膜与神经损伤安全指南，证实了视路交流电刺激的耐受性与可行性。相较于经颅交流电刺激（transcranial alternating current stimulation, tACS），视觉皮层的视路刺激可提供一个解剖学上限定明确的模型，用于系统探究交流电刺激的作用机制。