Characterization of Second-Order Mixing Effects in Reconstructed Cross-Spectra of Random Neural Fields.

Functional connectivity in electroencephalography (EEG) and magnetoencephalography (MEG) data is commonly assessed by using measures that are insensitive to instantaneously interacting sources and as such would not give rise to false positive interactions caused by instantaneous mixing of true source signals (first-order mixing). Recent studies, however, have drawn attention to the fact that such measures are still susceptible to instantaneous mixing from lagged sources (i.e. second-order mixing) and that this can lead to a large number of false positive interactions. In this study we relate first- and second-order mixing effects on the cross-spectra of reconstructed source activity to the properties of the resolution operators that are used for the reconstruction. We derive two identities that relate first- and second-order mixing effects to the transformation properties of measurement and source configurations and exploit them to establish several basic properties of signal mixing. First, we provide a characterization of the configurations that are maximally and minimally sensitive to second-order mixing. It turns out that second-order mixing effects are maximal when the measurement locations are far apart and the sources coincide with the measurement locations. Second, we provide a description of second-order mixing effects in the vicinity of the measurement locations in terms of the local geometry of the point-spread functions of the resolution operator. Third, we derive a version of Lagrange's identity for cross-talk functions that establishes the existence of a trade-off between the magnitude of first- and second-order mixing effects. It also shows that, whereas the magnitude of first-order mixing is determined by the inner product of cross-talk functions, the magnitude of second-order mixing is determined by a generalized cross-product of cross-talk functions (the wedge product) which leads to an intuitive geometric understanding of the trade-off. All results are derived within the general framework of random neural fields on cortical manifolds.