No abstract

No abstract

The US Air Force Office of Scientific Research convened a meeting of researchers in the fields of neuroscience, psychology, engineering, and medicine to discuss most pressing issues facing ongoing research in the field of transcranial direct current stimulation (tDCS) and related techniques. In this study, we present opinions prepared by participants of the meeting, focusing on the most promising areas of research, immediate and future goals for the field, and the potential for hormesis theory to inform tDCS research. Scientific, medical, and ethical considerations support the ongoing testing of tDCS in healthy and clinical populations, provided best protocols are used to maximize safety. Notwithstanding the need for ongoing research, promising applications include enhancing vigilance/attention in healthy volunteers, which can accelerate training and support learning. Commonly, tDCS is used as an adjunct to training/rehabilitation tasks with the goal of leftward shift in the learning/treatment effect curves. Although trials are encouraging, elucidating the basic mechanisms of tDCS will accelerate validation and adoption. To this end, biomarkers (eg, clinical neuroimaging and findings from animal models) can support hypotheses linking neurobiological mechanisms and behavioral effects. Dosage can be optimized using computational models of current flow and understanding dose–response. Both biomarkers and dosimetry should guide individualized interventions with the goal of reducing variability. Insights from other applied energy domains, including ionizing radiation, transcranial magnetic stimulation, and low-level laser (light) therapy, can be prudently leveraged.

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 0–5 mA for 60 minutes through one of three epicranial electrode montages. Tissue damage was evaluated using hemotoxylin and eosin (H&E) staining, Iba-1 immunohistochemistry, and computational brain current density modeling. Brain lesion occurred after anodal tDCS at and above 0.5 mA using a 25.0 mm2 electrode (electrode current density: 20.0 A/m2). Lesion initially occurred using smaller 10.6 mm2 or 5.3 mm2 electrodes at 0.25 mA (23.5 A/m2) and 0.5 mA (94.2 A/m2), respectively. Histological damage was correlated with computational brain current density predictions. Changes in microglial phenotype occurred in higher stimulation groups. Lesions were observed using anodal tDCS at an electrode current density of 20.0 A/m2, which is below the previously reported safety threshold of 142.9 A/m2 using cathodal tDCS. The lesion area is not simply predicted by electrode current density (and so not by charge density as duration was fixed); 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/m2 represents a conservative threshold for clinical tDCS, which typically uses an electrode current density of 2 A/m2 when electrodes are placed on the skin (resulting in a lower brain current density).