Abstracts

Rationale: In children with drug-resistant epilepsy (DRE), identifying the epileptogenic zone (EZ) can be arduous, even when using intracranial EEG (iEEG). Thus, finding new biomarkers of the EZ that add to the traditional iEEG interpretation is important. As epileptogenicity is a complex brain property dependent on the interplay between excitability and connectivity, the ideal biomarker should account for both aspects. Recent studies show that: (1) high excitability reflects on high phase-amplitude coupling (PAC) between slow and fast frequencies of an iEEG contact; and (2) highly synchronous (interconnected) networks underlie seizure generation. 

This suggests that both PAC and functional connectivity (FC) analysis inform us on epileptogenicity, but how to use them in a synergetic way is unexplored._x000D_ _x000D_ We hypothesize that the iEEG contacts in the EZ not only present high excitability (strong PAC) but are also connected to other excitable contacts, creating an interconnected-excitable network. Thus, we developed a new approach to estimate the interconnected-excitability (IC-Ex) of each iEEG contact by combining PAC and network analysis. Our goal is to present a new interictal biomarker to estimate the EZ and predict surgical outcome of children with DRE by locating strong IC-Ex on iEEG, without having to identify clear epileptic activity on the iEEG signals._x000D_
Methods: We studied iEEG data (5-min) from 41 children (13±5 years old) who had epilepsy surgery with known Engel outcome. As Figure 1 shows, we computed PAC of each iEEG contact, FC between all contacts and combined these two to estimate the IC-Ex index. Four frequency bands were studied (Slow: delta, spike; Fast: ripple, fast-ripples) generating frequency-specific IC-Ex indices. iEEG epochs without epileptic discharges were analyzed._x000D_ _x000D_ We compared IC-Ex (Wilcoxon sign-rank) inside and outside seizure-onset-zone (SOZ) contacts, and inside and outside resection (defined by postop MRI) separated by outcome._x000D_ _x000D_ Finally, we tested whether locating and removing the regions with the strongest IC-Ex predicts seizure freedom in our cohort via Receiver-Operating-Characteristic (ROC) curve analysis and Fisher’s test._x000D_
Results: We found that iEEG contacts inside the SOZ present much higher IC-Ex than outside (p< 10^-5 Figure 2A) in various frequencies. Besides, IC-Ex is stronger inside than outside the resection in good outcome patients (where the EZ is indeed resected) but not in poor outcomes (Figure 2B). _x000D_ _x000D_ Finally, removing the regions identified as having the strongest IC-Ex was predictive of seizure-freedom in our pediatric cohort with 75% accuracy and a positive and negative predictive value of 86% and 61% (p=0.002, Figure 2C, AUC=0.79)_x000D_
Conclusions: We present a new interictal iEEG biomarker that quantifies Interconnected-Excitability, can estimate SOZ and predicts postsurgical outcome in children with DRE using short data free of epileptic discharges. Having such an interictal biomarker can provide the surgical team with an additional tool to assess resection strategies and estimate the child’s prognosis for epilepsy surgery, independently from the presence of evident epileptic patterns on the iEEG signals_x000D_
Funding: BCH/Harvard Career Development Fellowship (PI: Tamilia)