Transcranial alternating current stimulation (tACS) can modulate human neural activity and behavior. Accordingly, tACS has vast potential for cognitive research and brain disorder therapies. The stimulation generates oscillating electric fields in the brain that can bias neural spike timing, causing changes in local neural oscillatory power and cross-frequency and cross-area coherence. tACS affects cognitive performance by modulating underlying single or nested brain rhythms, local or distal synchronization, and metabolic activity. Clinically, stimulation tailored to abnormal neural oscillations shows promising results in alleviating psychiatric and neurological symptoms. We summarize the findings of tACS mechanisms, its use for cognitive applications, and novel developments for personalized stimulation.

Neural oscillations in the primary motor cortex (M1) shape corticospinal excitability. Power and phase of ongoing mu (8-13 Hz) and beta (14-30 Hz) activity may mediate motor cortical output. However, the functional dynamics of both mu and beta phase and power relationships and their interaction, are largely unknown. Here, we employ recently developed real-time targeting of the mu and beta rhythm, to apply phase-specific brain stimulation and probe motor corticospinal excitability non-invasively. For this, we used instantaneous read-out and analysis of ongoing oscillations, targeting four different phases (0°, 90°, 180°, and 270°) of mu and beta rhythms with suprathreshold single-pulse transcranial magnetic stimulation (TMS) to M1. Ensuing motor evoked potentials (MEPs) in the right first dorsal interossei muscle were recorded. Twenty healthy adults took part in this double-blind randomized crossover study. Mixed model regression analyses showed significant phase-dependent modulation of corticospinal output by both mu and beta rhythm. Strikingly, these modulations exhibit a double dissociation. MEPs are larger at the mu trough and rising phase and smaller at the peak and falling phase. For the beta rhythm we found the opposite behavior. Also, mu power, but not beta power, was positively correlated with corticospinal output. Power and phase effects did not interact for either rhythm, suggesting independence between these aspects of oscillations. Our results provide insights into real-time motor cortical oscillation dynamics, which offers the opportunity to improve the effectiveness of TMS by specifically targeting different frequency bands.

Over the past decade several studies have shown that transcranial alternating current stimulation (tACS) delivered at the beta (15-25 Hz) frequency range can increase corticospinal excitability of the primary motor cortex (M1). The aim of this study was to systematically quantify the effect size of beta-tACS on corticospinal excitability in healthy volunteers, as well as to identify significant outcome predictors. A meta-analysis was performed on the results of 47 experiments reported in 21 studies. Random effects modelling of the effect sizes showed that beta-tACS significantly increases M1 excitability (Ē = 0.287, 95% CI = 0.133-0.440). Further analysis showed that tACS intensities above 1 mA peak-to-peak yield a robust increase in M1 excitability, whereas intensities of 1 mA peak-to-peak and below do not induce a reliable change. Additionally, results showed an impact of tACS montages on these effects. No difference in effect size for online compared to offline application of tACS was found. In conclusion, these findings indicate that beta-tACS can increase cortical excitability if stimulation intensity is above 1 mA, yet more research is needed to titrate the stimulation parameters that yield optimal results.