Abstract
Animal studies show that transcranial alternating current stimulation (tACS) can bias spike timing towards a particular phase of an ongoing oscillation. Also, there is indirect evidence for neural entrainment in humans. However, to date it is unclear whether tACS can bias neural activation towards a particular oscillation phase in humans. In this real-time tACS-transcranial magnetic stimulation (TMS) study we investigated corticospinal excitability at different tACS phases. In a double-blind cross-over study, 20 healthy volunteers received 2 mA (peak-to-peak) tACS targeting the primary motor cortex at their individual alpha (9.81 ± 0.22 Hz) or beta (20.24 ± 0.89 Hz) frequency. During four tACS blocks (∼6.5 min each), 600 single TMS pulses were applied to the hotspot of the first dorsei interosseus muscle at 120% of resting motor threshold. Using our real-time estimated temporal prediction algorithm, TMS was applied at the peak, trough, rising, and falling phase of the tACS oscillation. Outcome measure was motor-evoked potential (MEP) per phase. Results showed an overall main effect of phase (F = 8.62, p < 0.001), which was similar across tACS frequencies (interaction p = 0.765). Specifically, MEPs were larger at the trough/falling phase, compared to peak/rising phase. Averaging MEPs using a sliding window showed that maximal MEP amplitude changed phase throughout a block. For alpha tACS, phase maximal MEPs started at the falling phase and drifted to the trough at the end of block. Similarly, for beta tACS, the preferred phase transitioned from falling/trough to trough/rising. These results are in line with single-unit data in non-human primates, which show that subsets of neurons shift in preferred phase when tACS is applied. Overall, the results provide evidence that tACS can bias preferred phase of neural output. As such, tACS may be a valuable clinical tool for disorders associated with abnormal neural oscillation patterns.