Mechanism of action of tDCS with transcranial direct current stimulation

tDCS consists of two surface electrodes, an anode and a cathode, and the output of the stimulation type is set by the control software to act on the cerebral cortex with weakly polarized direct current. Unlike other non-invasive brain stimulation techniques such as transcranial electrical stimulation and transcranial magnetic stimulation, tDCS does not elicit neuronal firing through suprathreshold stimulation, but rather works by modulating the activity of neural networks. At the neuronal level, the basic mechanism of cortical excitability modulation by tDCS is to cause hyperpolarization or depolarization of the resting membrane potential depending on the polarity of the stimulus. Anodic stimulation generally increases cortical excitability, and cathodic stimulation decreases cortical excitability. Membrane polarization is the primary mechanism for the immediate effects of tDCS stimulation.

However, in addition to the immediate effect, tDCS also has a post-stimulation effect, and if the stimulation lasts long enough, the change in cortical excitability can persist for up to 1 h after the stimulation is completed; therefore, its mechanism of action cannot be explained by the polarization of the neuronal membrane potential alone. Further studies have confirmed that tDCS, in addition to changing the polarity of the membrane potential, can also modulate the synaptic microenvironment, such as changing the activity of NMDA receptors or GABA, thus playing a role in regulating synaptic plasticity. tDCS's aftereffect mechanism is similar to that of synaptic long-duration facilitation, and animal studies have found that a sustained increase in post-synaptic excitatory potentials can be observed in the motor cortex with anodic stimulation. The modulation of cortical excitability during tDCS stimulation is dependent on the level of membrane polarization, whereas the after-effect effect at the end of stimulation is mainly due to synaptic activity within the cortex.

TDCS similarly modulates excitability in distal septal cortex and subcortical areas. tDCS anodic stimulation of premotor cortical areas affects changes in the excitability of connected distal septal cortical areas. Stimulation of area M1 in the left hemisphere not only affected corticospinal circuits involved in the generation of motor evoked potentials, but also modulated transcallosal inhibition in the contralateral hemisphere via inhibitory interneurons.