Source Causal Connectivity Noninvasively Predicting Surgical Outcomes of Drug-Refractory Epilepsy

Aims: Drug-refractory epilepsy (DRE) refers to the failure of controlling seizures with adequate trials of two tolerated and appropriately chosen anti-seizure medications (ASMs). For patients with DRE, surgical intervention becomes the most effective and viable treatment, but its success rate is unsatisfactory at only approximately 50%. Predicting surgical outcomes in advance can provide additional guidance to clinicians. Despite the high accuracy of invasive methods, they inevitably carry the risk of post-operative infection and complications. Herein, to noninvasively predict surgical outcomes of DRE, we propose the "source causal connectivity" framework.

Methods: In this framework, sLORETA, an EEG source imaging technique, was first used to inversely reconstruct intracranial neuronal electrical activity. Then, full convergent cross mapping (FCCM), a robust causal measure was introduced to calculate the causal connectivity between remodeled neuronal signals within epileptogenic zones (EZs). After that, statistical tests were performed to find out if there was a significant difference between the successful and failed surgical groups. Finally, a model for surgical outcome prediction was developed by combining causal network features with machine learning.

Results: A total of 39 seizures with 205 ictal EEG segments were included in this prospective study. Experimental results exhibit that source causal connectivity in α-frequency band (8~13 Hz) gains the most significant differences between the surgical success and failure groups, with a p-value of 5.00e-05 and Cohen's d effect size of 0.68. All machine learning models can achieve an average accuracy of higher than 85%. Among them, the SVM classifier with Gaussian kernel function and Bayesian optimization demonstrates the highest accuracy of 90.73%, with a PPV of 87.91%, an NPV of 92.98%, a sensitivity of 90.91%, a specificity of 90.60%, and an F1-score of 89.39%.

Conclusion: Our results demonstrate that the source causal network of EZ is a reliable biomarker for predicting DRE surgical outcomes. The findings promote noninvasive precision medicine for DRE.