Objective:  The importance of functional brain connectivity to study physiological and pathological brain activity has been widely recognized. Here, we aimed to 1) review a methodological pipeline to investigate directed functional connectivity between brain regions using source signals derived from high-density EEG; 2) elaborate on some methodological challenges; and 3) apply this pipeline to temporal lobe epilepsy (TLE) patients and healthy controls to investigate directed functional connectivity differences in the theta and beta frequency bands during EEG epochs without visible pathological activity.  Methods:  The methodological pipeline includes: EEG acquisition and preprocessing, electrical-source imaging (ESI) using individual head models and distributed inverse solutions, parcellation of the gray matter in regions of interest, fixation of the dipole orientation for each region, computation of the spectral power in the source space, and directed functional connectivity estimation using Granger-causal modeling. We specifically analyzed how the signal-to-noise ratio (SNR) changes using different approaches for the dipole orientation fixation. We applied this pipeline to 20 left TLE patients, 20 right TLE patients, and 20 healthy controls.  Results:  Projecting each dipole to the predominant dipole orientation leads to a threefold SNR increase as compared to the norm of the dipoles. By comparing connectivity in TLE versus controls, we found significant frequency-specific outflow differences in physiologically plausible regions.  Conclusion:  The results suggest that directed functional connectivity derived from ESI can help better understand frequency-specific resting-state network alterations underlying focal epilepsy.   Significance:  EEG-based directed functional connectivity could contribute to the search of new biomarkers of this disorder.
['Ana Coito', 'Christoph M. Michel', 'Pieter van Mierlo', 'Serge Vulliemoz', 'Gijs Plomp']
Directed Functional Brain Connectivity Based on EEG Source Imaging: Methodology and Application to Temporal Lobe Epilepsy