Epileptic seizures in a heterogeneous excitatory network with short-term plasticity.

Epilepsy involves a diverse group of abnormalities, including molecular and cellular disorders. These abnormalities prove to be associated with the changes in local excitability and synaptic dynamics. Correspondingly, the epileptic processes including onset, propagation and generalized seizure may be related with the alterations of excitability and synapse. In this paper, three regions, epileptogenic zone (EZ), propagation area and normal region, were defined and represented by neuronal population model with heterogeneous excitability, respectively. In order to describe the synaptic behavior that the strength was enhanced and maintained at a high level for a short term under a high frequency spike train, a novel activity-dependent short-term plasticity model was proposed. Bifurcation analysis showed that the presence of hyperexcitability could increase the seizure susceptibility of local area, leading to epileptic discharges first seen in the EZ. Meanwhile, recurrent epileptic activities might result in the transition of synaptic strength from weak state to high level, augmenting synaptic depolarizations in non-epileptic neurons as the experimental findings. Numerical simulation based on a full-connected weighted network could qualitatively demonstrate the epileptic process that the propagation area and normal region were successively recruited by the EZ. Furthermore, cross recurrence plot was used to explore the synchronization between neuronal populations, and the global synchronization index was introduced to measure the global synchronization. Results suggested that the synchronization between the EZ and other region was significantly enhanced with the occurrence of seizure. Interestingly, the desynchronization phenomenon was also observed during seizure initiation and propagation as reported before. Therefore, heterogeneous excitability and short-term plasticity are believed to play an important role in the epileptic process. This study may provide novel insights into the mechanism of epileptogenesis.

The extension of epileptogenicity as the driving force of the epileptogenic network evolution and complex symptoms.

The concept of epileptogenic network was proposed with epilepsy increasingly understood as the result of network disorder. These alterations of networks proved to be associated with the increased seizure susceptibility in response to external stimulus or internal noise. However, the driving force behind its evolution is unclear. Substantial epilepsy research suggested that the epileptogenicity could be observed beyond clinically defined epileptogenic zone. Therefore, the mechanism of the epileptogenic network evolution may be related with the extension of epileptogenicity. In this paper, a small-world network with each node represented by a bistable computational model was established. Furthermore, part of the nodes connected with the primary epileptogenic zone would be transformed into secondary epileptogenic nodes during the evolution of networks, which represents the formation of secondary epileptogeniciy due to the kindling-like effect. Escape time was defined to quantify the likelihood of a node to develop into epileptic state. Meanwhile, phase synchronization was introduce to analyze the synchronization patterns in simulated multiunit systems. Results showed that the extension of epileptogenicity could increase the seizure likelihood of almost all nodes. Particularly, the synchronization patterns were significantly changed with the occurrence of the secondary epileptogenicity, which might imply the variation of functional connectivity between areas. Meanwhile, the reversal of nonspontaneous epileptogenicity could lead to running-down phenomenon. The extension of epileptogenicity seemed to provide novel insights into the diagnosis and treatment, indicating the possible minimum resection to reach excellent long-term surgical outcomes.

Distinguishing Dependent-Stage Secondary Epileptogenesis in a Complex Case of Giant Hypothalamic Hamartoma With Assistance of a Computational Method.

Besides gelastic seizures, hypothalamic hamartoma (HH) is also noted for its susceptibility to remote secondary epileptogenesis. Although clinical observations have demonstrated its existence, and a three-stage theory has been proposed, how to determine whether a remote symptom is spontaneous or dependent on epileptic activities of HH is difficult in some cases. Herein, we report a case of new non-gelastic seizures in a 9-year-old female associated with a postoperatively remaining HH. Electrophysiological examinations and stereo-electroencephalography (SEEG) demonstrated seizure onsets with slow-wave and fast activities on the outside of the HH. By using computational methodologies to calculate the network dynamic effective connectivities, the importance of HH in the epileptic network was revealed. After SEEG-guided thermal coagulation of the remaining HH, the patient finally was seizure-free at the 2-year follow-up. This case showed the ability of computational methods to reveal information underlying complex SEEG signals, and further demonstrated the dependent-stage secondary epileptogenesis, which has been rarely reported.

Localization of Epileptogenic Zone With the Correction of Pathological Networks.

Patients with focal drug-resistant epilepsy are potential candidates for surgery. Stereo-electroencephalograph (SEEG) is often considered as the "gold standard" to identify the epileptogenic zone (EZ) that accounts for the onset and propagation of epileptiform discharges. However, visual analysis of SEEG still prevails in clinical practice. In addition, epilepsy is increasingly understood to be the result of network disorder, but the specific organization of the epileptic network is still unclear. Therefore, it is necessary to quantitatively localize the EZ and investigate the nature of epileptogenic networks. In this study, intracranial recordings from 10 patients were analyzed through adaptive directed transfer function, and the out-degree of effective network was selected as the principal indicator to localize the epileptogenic area. Furthermore, a coupled neuronal population model was used to qualitatively simulate electrical activity in the brain. By removing individual populations, virtual surgery adjusting the network organization could be performed. Results suggested that the accuracy and detection rate of the EZ localization were 82.86 and 85.29%, respectively. In addition, the same stage shared a relatively stable connectivity pattern, while the patterns changed with transition to different processes. Meanwhile, eight cases of simulations indicated that networks in the ictal stage were more likely to generate rhythmic spikes. This indicated the existence of epileptogenic networks, which could enhance local excitability and facilitate synchronization. The removal of the EZ could correct these pathological networks and reduce the amount of spikes by at least 75%. This might be one reason why accurate resection could reduce or even suppress seizures. This study provides novel insights into epilepsy and surgical treatments from the network perspective.