Ghost interactions in MEG/EEG source space: A note of caution on inter-areal coupling measures

&NA; When combined with source modeling, magneto‐ (MEG) and electroencephalography (EEG) can be used to study long‐range interactions among cortical processes non‐invasively. Estimation of such inter‐areal connectivity is nevertheless hindered by instantaneous field spread and volume conduction, which artificially introduce linear correlations and impair source separability in cortical current estimates. To overcome the inflating effects of linear source mixing inherent to standard interaction measures, alternative phase‐ and amplitude‐correlation based connectivity measures, such as imaginary coherence and orthogonalized amplitude correlation have been proposed. Being by definition insensitive to zero‐lag correlations, these techniques have become increasingly popular in the identification of correlations that cannot be attributed to field spread or volume conduction. We show here, however, that while these measures are immune to the direct effects of linear mixing, they may still reveal large numbers of spurious false positive connections through field spread in the vicinity of true interactions. This fundamental problem affects both region‐of‐interest‐based analyses and all‐to‐all connectome mappings. Most importantly, beyond defining and illustrating the problem of spurious, or “ghost” interactions, we provide a rigorous quantification of this effect through extensive simulations. Additionally, we further show that signal mixing also significantly limits the separability of neuronal phase and amplitude correlations. We conclude that spurious correlations must be carefully considered in connectivity analyses in MEG/EEG source space even when using measures that are immune to zero‐lag correlations. HighlightsReliable estimation of neuronal coupling with MEG and EEG is challenged by signal mixing.A number of coupling techniques attempt to overcome this limitation by excluding zero‐lag interactions.Our simulations illustrate that such interaction metrics will still yield false positives.Spurious, or “ghost”, interactions are generally detected between sources in the vicinity of true interacting sources.Signal mixing also severely affects the mutual separability of phase and amplitude correlations.