Granger Causality Analysis of Interictal iEEG Predicts Seizure Focus and Ultimate Resection

Abstract

BACKGROUNDA critical conceptual step in epilepsy surgery is to locate the causal region of seizures. In practice, the causal region may be inferred from the set of electrodes showing early ictal activity. There would be advantages in deriving information about causal regions from interictal data as well. We applied Granger's statistical approach to baseline interictal data to calculate causal interactions. We hypothesized that maps of the Granger causality network (or GC maps) from interictal data might inform about the seizure network, and set out to see if “causality” in the Granger sense correlated with surgical targets.OBJECTIVETo determine whether interictal baseline data could produce GC maps, and whether the regions of high GC would statistically resemble the topography of the ictally active electrode (IAE) set and resection.METHODSTwenty-minute interictal baselines obtained from 25 consecutive patients were analyzed. The “GC maps” were quantitatively compared to conventionally constructed surgical plans, by using rank order and Cartesian distance statistics.RESULTSIn 16 of 25 cases, the interictal GC rankings of the electrodes in the IAE set were lower than predicted by chance (P < .05). The aggregate probability of such a match by chance alone is very small (P < 10−20) suggesting that interictal GC maps correlated with ictal networks. The distance of the highest GC electrode to the IAE set and to the resection averaged 4 and 6 mm (Wilcoxon P < .001).CONCLUSIONGC analysis has the potential to help localize ictal networks from interictal data.

To resect or not to resect? Unbiased performances of single and combined biomarkers in intra-operative corticography for tailoring during epilepsy surgery

“…We chose our biomarkers with two criteria in mind: 1) to be exhaustive regarding the different types of measures used (i.e. univariate, bivariate and multivariate); 2) biomarkers should have been reported to show an overall significant effect in discriminating between healthy and pathological tissue using inter-ictal intracranial recordings [23][24][25][27][28][29][31][32][33][34][35]60 .…”

“…This can be generalized to a multivariate scenario where the reduction of modelling error of the multivariate model is used instead (see Blinowska 53 for detailed review). Park and colleagues 29 successfully applied time based multivariate Granger causality to inter-ictal ECoG recordings showing that ictal networks can be inferred from inter-ictal recordings. They showed that there was a significant correlation between the epileptogenic location inferred using ictal recordings (i.e.…”

“…Several studies have shown that using certain biomarkers the epileptogenic tissue can be distinguished from the healthy tissue based on inter-ictal intracranial recordings [22][23][24][25][26][27][28][29] , but only statistically on the aggregate group level. A biomarker set is needed that discriminates well between tissue that needs to be surgically removed and tissue that should not at the patient level, which can thus be applied for clinical care.…”

“…We investigated, in our ground-truth scenario, the performances of different biomarkers that were already used in previous studies [23][24][25][27][28][29][30][31][32][33][34][35] . We defined our biomarker pool with the attempt to be exhaustive according to the three different categories univariate, bivariate and multivariate biomarkers.…”

Computational modelling and electrical stimulation for epilepsy surgery

“…Network measures characterizing individual nodes try to describe the importance of a node to the whole network. In different types of networks it has been found that nodes in the SOZ/RA are often more influential compared to non-SOZ/RA nodes in the sense that on average the degree, net outflow, and centrality of SOZ/RA nodes is elevated [38,105,107,[178][179][180][181]. However, it has not been investigated how network analysis can be used to plan the extent of the resection, which might be one of the reasons that it is not used in standard clinical practice [84].…”