Localizing the seizure onset zone and predicting the surgery outcomes in patients with drug-resistant epilepsy: A new approach based on the causal network

Background and objective: Accurate localization of the seizure onset zone (SOZ) is crucial for surgical treatment in patients with drug-resistant epilepsy (DRE). However, clinical identification of SOZ often relies on physician experience and has a certain subjectivity. Therefore, it is emergent to develop quantitative computational tools to assist clinicians in identifying SOZ.

Methods: We conduct a retrospective study on intracranial electroencephalography (iEEG) data from 46 patients with DRE. The interactions between different brain regions are quantified by using the phase transfer entropy (PTE), based on which the causal influence index (CII) is proposed to quantify the degree of influence of nodes on the network. Subsequently, the features extracted by the CII are used to construct a random forest classification model, which the performance in identifying SOZ and the generalizability are validated in patients with successful surgeries. Then, based on the CII features of the clinically labeled SOZ, a logistic regression prediction model is constructed to predict the probability of surgical success. The statistical analysis between patients with successful and failed surgery is conducted with the Mann-Whitney U test. Finally, the consistency between the predicted SOZ and the clinically labeled SOZ is verified across different Engel classes.

Results: The classification model combining the low-frequency and high-frequency features can achieve an accuracy of 82.18% (sensitivity: 85.01%, specificity: 79.69%) and an area under curve (AUC) of 0.90 in identifying SOZ. Furthermore, the model exhibits strong generalizability in identifying SOZ in patients with MRI lesional and non-lesional, as well as those implanted with electrocorticography (ECOG) and stereotactic EEG (SEEG) electrodes. Moreover, the prediction model could achieve an average accuracy of 79.8% and an AUC of 0.84. Of note, the prediction of surgical success probability is significant between patients with successful and failed surgeries (P<0.001). Correspondingly, the highest consistency between model-predicted SOZ and clinically labeled SOZ can be observed in patients with successful surgeries, but this consistency gradually decreases with increasing Engel classes.

Conclusions: These results demonstrate that the CII may be a potential biomarker for identifying the SOZ in patients with DRE, which may provide a new perspective for the treatment of epilepsy.