Fig. 1: Successful neural entrainment from tACS is dependent on the Arnold Tongue.

tACS entrains neural oscillations (represented as vertical lines symbolizing action potentials) by a mechanism referred to as the Arnold tongue, which references the inverted triangle shape of the parameter combinations (amplitude, frequency) that allow successful entrainment, i.e. synchronization of neural activity to the rhythmic stimulation waveform.The higher the stimulation amplitude, the more detuning (i.e., mismatch) of the stimulation frequency relative to the endogenous oscillation frequency is allowed to still achieve entrainment. Given the low amplitude of the perturbation to the neuronal membrane voltage by tACS, tuning of the stimulation waveform appears to be an important aspect of rational design of the stimulation waveform. Future tACS clinical trials should apply sine-wave stimulation waveforms that are matched to the endogenous frequency of the targeted oscillation determined by EEG. To what extent this principle predicts outlasting effects of tACS remains unclear given that there is no published preclinical model of these effects and that an attempt to investigate the role of entrainment in the outlasting effects was negative³⁹.