  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, the standard CFC
analysis and physiological interpretation come with fundamental problems. For
example, apparent CFC can appear because of spectral correlations due to common
non-stationarities that may arise in the total absence of interactions between
neural frequency components. To provide a road map towards an improved
mechanistic understanding of CFC, we organize the available and potential novel
statistical/modeling approaches according to their biophysical
interpretability. While we do not provide solutions for all the problems
described, we provide a list of practical recommendations to avoid common
errors and to enhance the interpretability of CFC analysis.
