Safety parameter considerations of anodal transcranial Direct Current Stimulation in rats

Abstract A commonly referenced transcranial Direct Current Stimulation (tDCS) safety threshold derives from tDCS lesion studies in the rat and relies on electrode current density (and related electrode charge density) to support clinical guidelines. Concerns about the role of polarity (e.g. anodal tDCS), sub-lesion threshold injury (e.g. neuroinflammatory processes), and role of electrode montage across rodent and human studies support further investigation into animal models of tDCS safety. Thirty-two anesthetized rats received anodal tDCS between 0 and 5 mA for 60 min through one of three epicranial electrode montages. Tissue damage was evaluated using hemotoxylin and eosin (HE rather computational modeling suggests average brain current density as a better predictor for anodal tDCS. Nonetheless, under the assumption that rodent epicranial stimulation is a hypersensitive model, an electrode current density of 20.0 A/m 2 represents a conservative threshold for clinical tDCS, which typically uses an electrode current density of 2 A/m 2 when electrodes are placed on the skin (resulting in a lower brain current density).