Juhan Aru, Jaan Aru, Viola Priesemann, Michael Wibral, Luiz Lana, Gordon Pipa, Wolf Singer, Raul Vicente
Cross-frequency coupling (CFC) has been proposed to coordinate neural dynamics across spatial and temporal scales. Despite its potential relevance for understanding healthy and pathological brain function, critical evaluation of the available methods for CFC analysis has been lacking. Here we aim to unravel several fundamental problems with the current standard analysis for CFC that make it non-specific and difficult to interpret physiologically. We show that apparent CFC can arise because of spectral correlations due to common non-stationarities and non-linear effects that might be unrelated to a true interaction between frequency components. After reviewing common problems in CFC analysis, we discuss how different statistical/modeling approaches to CFC can be conceptually organized according to their biophysical interpretability and statistical inference approach. This classification provides a possible road-map towards mechanistic understanding of cross-frequency coupling. We end with a list of practical recommendations to avoid common errors and enhance the interpretability of the analysis.