Mechanisms of Action of Noninvasive Brain Stimulation with Weak Non-Constant Current Stimulation Approaches

Objective: Non-constant current stimulation (NCCS) is a neuromodulatory method in which weak alternating, pulsed or random currents are delivered to the human head via scalp or earlobe electrodes. This approach is widely used in basic and translational studies. However, the underlying mechanisms of NCCS, which lead to biological and behavioral effects in the brain, remain largely unknown. In this review, we characterize NCCS techniques currently being utilized in neuroscience investigations, including transcranial alternating current stimulation (tACS), transcranial pulsed current stimulation (tPCS), transcranial random noise stimulation (tRNS), and cranial electrotherapy stimulation (CES). Method: We unsystematically searched all relevant conference papers, journal articles, chapters, and textbooks on the biological mechanisms of NCCS techniques. Results: The fundamental idea of NCCS is that these low-level currents can interact with neuronal activity, modulate neuroplasticity and entrain cortical networks, thus, modifying cognition and behavior. We elucidate the mechanisms of action for each NCCS technique. These techniques may cause microscopic effects (such as affecting ion channels and neurotransmission systems) and macroscopic effects (such as affecting brain oscillations and functional connectivity) on the brain through different mechanisms of action (such as neural entrainment and stochastic resonance). Conclusion: The appeal of NCCS is its potential to modulate neuroplasticity noninvasively, along with the ease of use and good tolerability. Promising and interesting evidence has been reported for the capacity of NCCS to affect neural circuits and the behaviors under their control. Today, the challenge is to utilize this advancement optimally. Continuing methodological advancements with NCCS approaches will enable researchers to better understand how NCCS can be utilized for the modulation of nervous system activity and subsequent behaviors, with possible applications to non-clinical and clinical practices.