The neurobiology of prefrontal transcranial direct current stimulation (tDCS) in promoting brain plasticity: A systematic review and meta-analyses of human and rodent studies.

The neurobiological mechanisms underlying prefrontal transcranial direct current stimulation (tDCS) remain elusive. Randomized, sham-controlled trials in humans and rodents applying in vivo prefrontal tDCS were included to explore whether prefrontal tDCS modulates resting-state and event-related functional connectivity, neural oscillation and synaptic plasticity. Fifty studies were included in the systematic review and 32 in the meta-analyses. Neuroimaging meta-analysis indicated anodal prefrontal tDCS significantly enhanced bilateral median cingulate activity [familywise error (FWE)-corrected p < .005]; meta-regression revealed a positive relationship between changes in median cingulate activity after tDCS and current density (FWE-corrected p < .005) as well as electric current strength (FWE-corrected p < .05). Meta-analyses of electroencephalography and magnetoencephalography data revealed nonsignificant changes (ps > .1) in both resting-state and event-related oscillatory power across all frequency bands. Applying anodal tDCS over the rodent hippocampus/prefrontal cortex enhanced long-term potentiation and brain-derived neurotrophic factor expression in the stimulated brain regions (ps <.005). Evidence supporting prefrontal tDCS administration is preliminary; more methodologically consistent studies evaluating its effects on cognitive function that include brain activity measurements are needed.