Different coupling modes mediate cortical cross-frequency interactions

Cross-frequency coupling (CFC) has been suggested to constitute a highly flexible mechanism for cortical information gating and processing, giving rise to conscious perception and various higher cognitive functions in humans. In particular, it might provide an elegant tool for information integration across several spatiotemporal scales within nested or coupled neuronal networks. However, it is currently unknown whether low-frequency (theta/alpha) or high-frequency gamma oscillations orchestrate cross-frequency interactions, raising the question of who is master and who is slave. While correlative evidence suggested that at least two distinct CFC modes exist, namely, phase-amplitude-coupling (PAC) and amplitude-envelope correlations (AEC), it is currently unknown whether they subserve distinct cortical functions. Novel non-invasive brain stimulation tools, such as transcranial alternating current stimulation (tACS), now provide the unique opportunity to selectively entrain the low- or high-frequency component and study subsequent effects on CFC. Here, we demonstrate the differential modulation of CFC during selective entrainment of alpha or gamma oscillations. Our results reveal that entrainment of the low-frequency component increased PAC, where gamma power became preferentially locked to the trough of the alpha oscillation, while gamma-band entrainment enhanced AECs and reduced alpha power. These results provide causal evidence for the functional role of coupled alpha and gamma oscillations for visual processing.