Transcranial direct-current stimulation (tDCS) is a noninvasive brain stimulation technique that has been successfully applied for modulation of cortical excitability. tDCS is capable of inducing changes in neuronal membrane potentials in a polarity-dependent manner. When tDCS is of sufficient length, synaptically driven aftereffects are induced. The mechanisms underlying these after-effects are largely unknown, and there is a compelling need for animal models to test the immediate effects and after-effects induced by tDCS in different cortical areas and evaluate the implications in complex cerebral processes. Here we show in behaving rabbits that tDCS applied over the somatosensory cortex modulates cortical processes consequent to localized stimulation of the whisker pad or of the corresponding area of the ventroposterior medial (VPM) thalamic nucleus. With longer stimulation periods, poststimulation effects were observed in the somatosensory cortex only after cathodal tDCS. Consistent with the polarity-specific effects, the acquisition of classical eyeblink conditioning was potentiated or depressed by the simultaneous application of anodal or cathodal tDCS, respectively, when stimulation of the whisker pad was used as conditioned stimulus, suggesting that tDCS modulates the sensory perception process necessary for associative learning. We also studied the putative mechanisms underlying immediate effects and after-effects of tDCS observed in the somatosensory cortex. Results when pairs of pulses applied to the thalamic VPM nucleus (mediating sensory input) during anodal and cathodal tDCS suggest that tDCS modifies thalamocortical synapses at presynaptic sites. Finally, we show that blocking the activation of adenosine A1 receptors prevents the long-term depression (LTD) evoked in the somatosensory cortex after cathodal tDCS.T he effects of weak direct-current (DC) stimulation on the excitability of the central nervous system were reported decades ago. Invasive stimulation in acute animals demonstrated that intracortical or epidural application of weak DC induces polarityspecific changes in the neuronal excitability of motor (1, 2), visual (1), and somatosensory (3) cortices. Interestingly, these changes persist for several minutes after the DC stimulus offset (3), sharing some molecular mechanisms with the classical long-term plasticity. In this regard, it has been demonstrated that anodal DC stimulation applied on the rat sensorimotor cortex modifies adenosine-elicited accumulation of cAMP (4), inducing an increase of protein kinase C and calcium levels (5, 6). tDCS has been successfully applied for modulation of cortical excitability in humans (7-11), and interest is growing in the use of this technique as a noninvasive tool for basic and clinical research in various neurologic pathologies, including chronic pain, stroke, and depression (12-15). Little is known about the molecular and/or cellular mechanisms underlying the neuromodulatory after-effects of tDCS, however. For this reason, new experimental models...

Abstract-In this paper, we provide a broad overview of models and technologies pertaining to transcranial current brain stimulation (tCS), a family of related noninvasive techniques including direct current (tDCS), alternating current (tACS), and random noise current stimulation (tRNS). These techniques are based on the delivery of weak currents through the scalp (with electrode current intensity to area ratios of about 0.3-5 A/m ) at low frequencies (typically 1kHz) resulting in weak electric fields in the brain (with amplitudes of about 0.2-2 V/m). Here we review the biophysics and simulation of noninvasive, current-controlled generation of electric fields in the human brain and the models for the interaction of these electric fields with neurons, including a survey of in vitro and in vivo related studies. Finally, we outline directions for future fundamental and technological research.Index Terms-Brain stimulation, electrical stimulation, transcranial alternating current (tACS), transcranial current stimulation (tCS), transcranial direct current (tDCS), transcranial random noise current stimulation (tRNS).