Transcranial direct current stimulation (tDCS) is increasingly used as a form of noninvasive brain stimulation to treat psychiatric disorders; however, its mechanism of action remains unclear. Prolonged visual stimulation (PVS) can enhance evoked EEG potentials (visually evoked potentials, VEPs) and has been proposed as a tool to examine long-term potentiation (LTP) in humans. The objective of the current study was to induce and analyze VEP plasticity and examine whether tDCS could either modulate or mimic plasticity changes induced by PVS. Thirty-eight healthy participants received tDCS, PVS, either treatment combined or neither treatment, with stimulation sessions being separated by one week. One session consisted of a baseline VEP measurement, one stimulation block, and six test VEP measurements. For PVS, a checkerboard reversal pattern was presented, and for tDCS, a constant current of 1 mA was applied via each bioccipital anodal target electrode for 10 min (Fig. S1). Both stimulation types decreased amplitudes of C1 compared to no stimulation (F = 10.1; p = 0.002) and led to a significantly smaller increase (PVS) or even decrease (tDCS) in N1 compared to no stimulation (F = 4.7; p = 0.034). While all stimulation types increased P1 amplitudes, the linear mixed effects model did not detect a significant difference between active stimulation and no stimulation. Combined stimulation induced sustained plastic modulation of C1 and N1 but with a smaller effect size than what would be expected for an additive effect. The results demonstrate that tDCS can directly induce LTP-like plasticity in the human cortex and suggest a mechanism of action of tDCS relying on the restoration of dysregulated synaptic plasticity in psychiatric disorders such as depression and schizophrenia.

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