Effects of time lag and frequency matching on phase-based connectivity

The time- and frequency-varying dynamics of how brain regions interact is one of the fundamental mysteries of neuroscience. In electrophysiological data, functional connectivity is often measured through the consistency of oscillatory phase angles between two electrodes placed in or over different brain regions. However, due to volume conduction, the results of such analyses can be difficult to interpret, because mathematical estimates of connectivity can be driven both by true inter-regional connectivity, and by volume conduction from the same neural source. Generally, there are two approaches to attenuate artifacts due to volume conduction: spatial filtering in combination with standard connectivity methods, or connectivity methods such as the weighted phase lag index that are blind to instantaneous connectivity that may reflect volume conduction artifacts. The purpose of this paper is to compare these two approaches directly in the presence of different connectivity time lags (5 or 25 ms) and physiologically realistic frequency non-stationarities. The results show that standard connectivity methods in combination with Laplacian spatial filtering correctly identified simulated connectivity regardless of time lag or changes in frequency, although residual volume conduction artifacts were seen in the vicinity of the "seed" electrode. Weighted phase lag index under-estimated connectivity strength at small time lags and failed to identify connectivity in the presence of frequency mismatches or non-stationarities, but did not misidentify volume conduction as "connectivity." Both approaches have strengths and limitations, and this paper concludes with practical advice for when to use which approach in context of hypothesis testing and exploratory data analyses.