Data from: On cross-frequency phase-phase coupling between theta and gamma oscillations in the hippocampus

Phase-amplitude coupling between theta and multiple gamma sub-bands is a hallmark of hippocampal activity and believed to take part in information routing. More recently, theta and gamma oscillations were also reported to exhibit phase-phase coupling, or n:m phase-locking, suggesting an important mechanism of neuronal coding that has long received theoretical support. However, by analyzing simulated and actual LFPs, here we question the existence of theta-gamma phase-phase coupling in the rat hippocampus. We show that the quasi-linear phase shifts introduced by filtering lead to spurious coupling levels in both white noise and hippocampal LFPs, which highly depend on epoch length, and that significant coupling may be falsely detected when employing improper surrogate methods. We also show that waveform asymmetry and frequency harmonics may generate artifactual n:m phase-locking. Studies investigating phase-phase coupling should rely on appropriate statistical controls and be aware of confounding factors; otherwise, they could easily fall into analysis pitfalls.

θ波与多个γ亚频段之间的相位-振幅耦合（phase-amplitude coupling）是海马体活动的标志性特征，被认为参与信息路由过程。近期另有研究报道，θ波与γ振荡亦可表现出相位-相位耦合（phase-phase coupling），即n:m锁相（n:m phase-locking），这提示了一种长期以来获得理论支持的重要神经元编码机制。然而，通过分析模拟与真实的局部场电位（local field potentials, LFPs），本研究对大鼠海马体内θ-γ相位-相位耦合的存在性提出了质疑。本研究证实，滤波操作引入的准线性相移会在白噪声与海马体局部场电位中产生虚假耦合强度，且该虚假耦合高度依赖于分析时程的长度；同时，当使用不当的替代检验方法时，可能会错误检测到显著的耦合信号。本研究同时发现，波形不对称性与频率谐波也可能生成人为伪迹性的n:m锁相信号。开展相位-相位耦合相关研究时，应采用恰当的统计控制手段，并警惕混淆变量的干扰；否则极易陷入分析陷阱。