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.

To diagnose and lateralise temporal lobe epilepsy (TLE) by building a classification system that uses directed functional connectivity patterns estimated during EEG periods without visible pathological activity. Resting-state high-density EEG recording data from 20 left TLE patients, 20 right TLE patients and 35 healthy controls was used. Epochs without interictal spikes were selected. The cortical source activity was obtained for 82 regions of interest and whole-brain directed functional connectivity was estimated in the theta, alpha and beta frequency bands. These connectivity values were then used to build a classification system based on two two-class Random Forests classifiers: TLE vs healthy controls and left vs right TLE. Feature selection and classifier training were done in a leave-one-out procedure to compute the mean classification accuracy. The diagnosis and lateralization classifiers achieved a high accuracy (90.7% and 90.0% respectively), sensitivity (95.0% and 90.0% respectively) and specificity (85.7% and 90.0% respectively). The most important features for diagnosis were the outflows from left and right medial temporal lobe, and for lateralization the right anterior cingulate cortex. The interaction between features was important to achieve correct classification. This is the first study to automatically diagnose and lateralise TLE based on EEG. The high accuracy achieved demonstrates the potential of directed functional connectivity estimated from EEG periods without visible pathological activity for helping in the diagnosis and lateralization of TLE.

Social impairments are a hallmark of Autism Spectrum Disorders (ASD), but empirical evidence for early brain network alterations in response to social stimuli is scant in ASD. We recorded the gaze patterns and brain activity of toddlers with ASD and their typically developing peers while they explored dynamic social scenes. Directed functional connectivity analyses based on electrical source imaging revealed frequency specific network atypicalities in the theta and alpha frequency bands, manifesting as alterations in both the driving and the connections from key nodes of the social brain associated with autism. Analyses of brain-behavioural relationships within the ASD group suggested that compensatory mechanisms from dorsomedial frontal, inferior temporal and insular cortical regions were associated with less atypical gaze patterns and lower clinical impairment. Our results provide strong evidence that directed functional connectivity alterations of social brain networks is a core component of atypical brain development at early stages of ASD.