Abstract

Introduction Non-invasive brain stimulation techniques modulate cortical excitability in healthy subjects and in patients. Electric fields can induce directional cell migration (i.e. electrotaxis) of epithelial cells, endothelial cells, fibroblasts, and neutrophils. Human lymphocytes respond in vitro to electric fields migrating toward the cathode. Whereas repetitive transcranial magnetic stimulation (rTMS) increases peripheral lymphocytes number, no data are available about transcranial direct current stimulation (tDCS).The possible effect of tDCS on lymphocytes has potential implication on its safety. Objective The aim of the present study is to investigate the effect of tDCS on peripheral lymphocytes in humans. Materials and Methods Eight healthy right-handed subjects (six women and two men aged 23–39; mean+SD: 29.6±5,64) participated in the study. Subjects underwent anodal and sham tDCS in a cross over design. Anodal tDCS was performed with the active electrode (anode) placed over the left temporal lobe (T3) and the reference (cathode) over the right arm (current intensity at 2mA, 20min, electrode size of 35cm 2 ). Peripheral blood samples for immunological testing were collected at baseline (T0) and one (T1) and four hours (T2) after tDCS offset and monoclonal antibodies identified the following lymphocyte subsets: T-lymphocytes (CD3+, CD4+3+, CD8+3+ and CD3+DR+), B-lymphocytes (CD20+), IL-2 receptor (CD25+) and natural killer cells (CD56+16+3−). Monocytes were also tested (CD14+, CD14+DR+). Results Baseline values were comparable between sham and active tDCS. While T-lymphocytes and B-lymphocytes significantly increased after stimulation offset (factor time point: total lymphocytes, p : 0.035; CD3+, p : 0.010, CD4+3+, p : 0.012; CD20, p : p : 0.042, total monocytes, p : 0.004; CD14+, p : 0.005; CD14+DR+, p : 0.003) in both stimulation conditions without significant differences. Discussion In the present study the extra-cephalic reference anodal tDCS on dominant hemisphere did not affect the number of circulating lymphocytes and monocytes. Changes in lymphocytes number both in anodal and sham stimulation could depend onlymphocytes circadian rhythm.These results could have important implications for anodal tDCS clinical use and safety especially in immunodepressed and stroke patients. Infact, cerebrovascular lesions in the dominant hemisphere are associated to decreased total blood lymphocytes countand greater morbidity.In conclusion, unlike TMS, anodal tDCS does not influence peripheral lymphocytes thus further supporting the systemic safety of this technique.

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