tACS competes with ongoing oscillations for control of spike-timing in the primate brain.
Transcranial alternating current stimulation (tACS) is a promising but controversial method for modulating neural activity noninvasively. Much of the controversy revolves around the question of whether tACS can generate electric fields that are strong enough to entrain neuronal spiking activity. Here we show that what matters is not the electric field strength per se, but rather the strength of the stimulation relative to ongoing oscillatory entrainment. We recorded from single neurons in the cortex and subcortex of behaving non-human primates, while applying tACS at different frequencies and amplitudes. When neuronal activity was weakly locked to ongoing oscillations, tACS readily entrained single-neuron activity to specific stimulation phases. In contrast, neurons that were strongly locked to ongoing oscillations usually exhibited decreased entrainment during low-amplitude tACS. As this reduced entrainment is a property of many oscillating systems, attempts to impose an external rhythm on spiking activity may often yield precisely the opposite effect.