SUMMARYObjective: In patients with epilepsy, seizure relapse and behavioral impairments can be observed despite the absence of interictal epileptiform discharges (IEDs). Therefore, the characterization of pathologic networks when IEDs are not present could have an important clinical value. Using Granger-causal modeling, we investigated whether directed functional connectivity was altered in electroencephalography (EEG) epochs free of IED in left and right temporal lobe epilepsy (LTLE and RTLE) compared to healthy controls. Methods: Twenty LTLE, 20 RTLE, and 20 healthy controls underwent a resting-state high-density EEG recording. Source activity was obtained for 82 regions of interest (ROIs) using an individual head model and a distributed linear inverse solution. Grangercausal modeling was applied to the source signals of all ROIs. The directed functional connectivity results were compared between groups and correlated with clinical parameters (duration of the disease, age of onset, age, and learning and mood impairments). Results: We found that: (1) patients had significantly reduced connectivity from regions concordant with the default-mode network; (2) there was a different network pattern in patients versus controls: the strongest connections arose from the ipsilateral hippocampus in patients and from the posterior cingulate cortex in controls; (3) longer disease duration was associated with lower driving from contralateral and ipsilateral mediolimbic regions in RTLE; (4) aging was associated with a lower driving from regions in or close to the piriform cortex only in patients; and (5) outflow from the anterior cingulate cortex was lower in patients with learning deficits or depression compared to patients without impairments and to controls. Significance: Resting-state network reorganization in the absence of IEDs strengthens the view of chronic and progressive network changes in TLE. These resting-state connectivity alterations could constitute an important biomarker of TLE, and hold promise for using EEG recordings without IEDs for diagnosis or prognosis of this disorder.

The different patterns of time-varying connectivity in LTLE and RTLE suggest that they are not symmetrical entities, in line with our neuropsychological results. The highest outflow region was concordant with invasive validation of the epileptogenic zone. This enhanced characterization of dynamic connectivity patterns could better explain cognitive deficits and help the management of epilepsy surgery candidates.

ObjectiveTo 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.MethodsResting-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.ResultsThe 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.SignificanceThis 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.

EEG-based directed functional connectivity could contribute to the search of new biomarkers of this disorder.

Neuroimaging studies have shown that spontaneous brain activity is characterized as changing networks of coherent activity across multiple brain areas. However, the directionality of functional interactions between the most active regions in our brain at rest remains poorly understood. Here, we examined, at the whole‐brain scale, the main drivers and directionality of interactions that underlie spontaneous human brain activity by applying directed functional connectivity analysis to electroencephalography (EEG) source signals. We found that the main drivers of electrophysiological activity were the posterior cingulate cortex (PCC), the medial temporal lobes (MTL), and the anterior cingulate cortex (ACC). Among those regions, the PCC was the strongest driver and had both the highest integration and segregation importance, followed by the MTL regions. The driving role of the PCC and MTL resulted in an effective directed interaction directed from posterior toward anterior brain regions. Our results strongly suggest that the PCC and MTL structures are the main drivers of electrophysiological spontaneous activity throughout the brain and suggest that EEG‐based directed functional connectivity analysis is a promising tool to better understand the dynamics of spontaneous brain activity in healthy subjects and in various brain disorders.