EEG Functional Connectivity is a Weak Predictor of Causal Brain Interactions

In recent years there has been an explosion of research evaluating resting-state brain functional connectivity (FC) using different modalities. However, the relationship between such measures of FC and the underlying causal brain interactions has not been well characterized. To further characterize this relationship, we assessed the relationship between electroencephalography (EEG) resting state FC and propagation of transcranial magnetic stimulation (TMS) evoked potentials (TEPs) at the sensor and source level in healthy participants. TMS was applied to six different cortical regions in ten healthy individuals (9 male; 1 female), and effects on brain activity were measured using simultaneous EEG. Pre-stimulus FC was assessed using five different FC measures (Pearson’s correlation, mutual information, weighted phase lag index, coherence and phase locking value). Propagation of the TEPs was quantified as the root mean square (RMS) of the TEP voltage and current source density (CSD) at the sensor and source level, respectively. The relationship between pre-stimulus FC and the spatial distribution of TEP activity was determined using a generalized linear model (GLM) analysis. On the group level, all FC measures correlated significantly with TEP activity over the early (15–75 ms) and full range (15–400 ms) of the TEP at the sensor and source level. However, the predictive value of all FC measures is quite limited, accounting for less than 10% of the variance of TEP activity, and varies substantially across participants and stimulation sites. Taken together, these results suggest that EEG functional connectivity studies in sensor and source space should be interpreted with caution.