Brain stimulation competes with ongoing oscillations for control of spike timing in the primate brain

Transcranial alternating current stimulation (tACS) is commonly used to enhance brain rhythms, in the hopes of improving behavioral performance. Unfortunately, these interventions often yield highly variable results. Here, we identify a key source of this variability by recording from single neurons in alert non-human primates. We find that, rather than enhancing rhythmic activity, tACS appears to compete with the brain’s endogenous oscillations for control of spike timing. Specifically, when the strength of stimulation is weak relative to endogenous oscillations, tACS actually decreases the rhythmicity of spiking. However, when stimulation is comparatively stronger, tACS imposes its own rhythm on spiking activity. Thus the effect of tACS depends categorically on the strength of neural entrainment to endogenous oscillations, which varies greatly across behavioral states and brain regions. Without carefully considering these factors, attempts to impose external rhythms on specific brain regions may often yield precisely the opposite of the intended effect.