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In the context of focal drug-resistant epilepsies, the surgical resection of the epileptogenic zone (EZ), the cortical region responsible for the onset, early seizures organization, and propagation, may be the only therapeutic option for reducing or suppressing seizures. The rather high rate of failure in epilepsy surgery of extra-temporal epilepsies highlights that the precise identification of the EZ, mandatory objective to achieve seizure freedom, is still an unsolved problem that requires more sophisticated methods of investigation. Despite the wide range of non-invasive investigations, intracranial stereo-EEG (SEEG) recordings still represent, in many patients, the gold standard for the EZ identification. In this contest, the EZ localization is still based on visual analysis of SEEG, inevitably affected by the drawback of subjectivity and strongly time-consuming. Over the last years, considerable efforts have been made to develop advanced signal analysis techniques able to improve the identification of the EZ. Particular attention has been paid to those methods aimed at quantifying and characterizing the interactions and causal relationships between neuronal populations, since is nowadays well assumed that epileptic phenomena are associated with abnormal changes in brain synchronization mechanisms, and initial evidence has shown the suitability of this approach for the EZ localization. The aim of this review is to provide an overview of the different EEG signal processing methods applied to study connectivity between distinct brain cortical regions, namely in focal epilepsies. In addition, with the aim of localizing the EZ, the approach based on graph theory will be described, since the study of the topological properties of the networks has strongly improved the study of brain connectivity mechanisms.

SUMMARYPurpose: Photosensitive epilepsy (PSE) is the most common form of reflex epilepsy presenting with electroencephalography (EEG) paroxysms elicited by intermittent photic stimulation (IPS). To investigate whether the neuronal network undergoes dynamic changes before and during the transition to an EEG epileptic discharge, we estimated EEG connectivity patterns in photosensitive (PS) patients with idiopathic generalized epilepsy. Methods: EEG signals were evaluated under resting conditions and during 14 Hz IPS, a frequency that consistently induces photoparoxysmal responses (PPRs) in PS patients. Partial directed coherence (PDC), a linear measure of effective connectivity based on multivariate autoregressive models, was used in 10 PS patients and 10 controls. Anterior versus posterior (F3, F4, C3, C4, and P3, P4, O1, O2) and interhemispheric connectivity patterns (F4, C4, P4, O2, and F3, C3, P3, O1) were estimated with focus on beta and gamma band activity.Key Findings: PDC analysis revealed an enhanced connectivity pattern in terms of both the number and strength of outflow connections in the PS patient group. Under resting condition, the greater connectivity in the PS patients occurred in the beta band, whereas it mainly involved the gamma band during IPS (i.e., the frequencies ranging from 40-60 Hz that include the higher harmonics of the stimulus frequency). Both at rest and during IPS, the differences between the PS patients and controls were due primarily to clearly increased connectivity involving the anterior cortical regions. Significance: Our findings indicate that PS patients are characterised by abnormal EEG hyperconnectivity, primarily involving the anterior cortical regions under resting conditions and during IPS. This suggests that, even if the occipital cortical regions are the recipient zone of the stimulus and probably hyperexcitable, the anterior cortical areas are prominently involved in generating the hypersynchronization underlying the spike-and wave discharges elicited by IPS.

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