Abstract
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.
Highlights
Non-invasive brain stimulation (NiBS) is an effective method for research, as well as a promising tool for therapy in cognitive and clinical neuroscience (Paulus, 2003; Hallett, 2007; Liew et al, 2014)
This study adheres to the principles of good scientific practice of the Charité – Universitätsmedizin Berlin (“Grundsätze der Charité zur Sicherung guter wissenschaftlicher Praxis”)
The primary findings are that Retinofugal alternating current stimulation (rACS) is safe based on the following observations: (1) stimulation parameters are within theoretical safety limits, (2) finite element modeling data shows the same for electric fields (EF) estimates and current densities at eye, retina and cortex, and (3) adverse events are comparable to photic stimulation (PS) in direct experimental comparison and rate as well as severity of adverse events did not exceed that of other established brain stimulation methods
Summary
Non-invasive brain stimulation (NiBS) is an effective method for research, as well as a promising tool for therapy in cognitive and clinical neuroscience (Paulus, 2003; Hallett, 2007; Liew et al, 2014). Transcranial alternating current stimulation (tACS), characterized by oscillatory low-voltage stimulation, showed promising effects on the motor system (Feurra et al, 2011, 2013), motor performance (Pogosyan et al, 2009; Joundi et al, 2012), memory (Marshall et al, 2006; Polania et al, 2012), higher order cognition (Santarnecchi et al, 2013, 2016) and tremor (Brittain et al, 2013) Despite these encouraging results, tACS’ mechanisms of action remain unclear (Zaghi et al, 2010) and a retinal contribution to its effects on neural synchrony is still being discussed (Schutter, 2016). To further compare these two methods and investigate retinal effects of ACS, we first aim to establish the safety and tolerability of rACS
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