Lack of evidence for cross-frequency phase-phase coupling between theta and gamma oscillations in the hippocampus

Phase-amplitude coupling between theta and multiple gamma sub-bands hallmarks hippocampal activity and is believed to take part in information routing. More recently, theta and gamma oscillations were also reported to exhibit reliable phase-phase coupling, or n:m phase-locking. The existence of n:m phase-locking suggests an important mechanism of neuronal coding that has long received theoretical support. However, here we show that n:m phase-locking (1) is much lower than previously reported, (2) highly depends on epoch length, (3) does not statistically differ from chance (when employing proper surrogate methods), and that (4) filtered white noise has similar n:m scores as actual data. Moreover, (5) the diagonal stripes in theta-gamma phase-phase histograms of actual data can be explained by theta harmonics. These results point to lack of theta-gamma phase-phase coupling in the hippocampus, and suggest that studies investigating n:m phase-locking should rely on appropriate statistical controls, otherwise they could easily fall into analysis pitfalls.