Abstracts

Rationale: Epilepsy is believed to be a disorder of brain networks with abnormal signaling and connections between brain areas capable of generating seizures. Functional connectivity is one approach to study network interactions. Some studies suggest in the EEG gamma-frequency band, which heavily involves inhibitory neuronal activity, there is reduced gamma coupling associated with the seizure onset zone (SOZ), others found an increase. Here, we measured gamma event coupling based on correlation of individual gamma cycles with respect to the SOZ, brain region, and seizure outcome to help reconcile these differences and better understand networks generating seizures.

Methods: Thirty-seven patients with medication-resistant seizures suspected to begin in the temporal lobe who required depth electrode evaluation were included in this study. Nineteen were seizure free (SF) after surgery and 18 continued to have seizures (not-SF). Postoperative CT scans registered to MRI were used to localize electrode contacts positioned in gray matter, then contacts were grouped in relation to the SOZ and the following brain regions: mesial (M), lateral temporal lobe (L) and extra-temporal lobe areas (E). EEG was processed to detect peaks of each gamma cycle, and High Gamma Event Coupling (HGEC; 65-100Hz) strength was calculated using Shannon entropy from perievent histograms constructed for each pair of contacts. A connectivity matrix of HGEC strength was generated for each patient. In addition, epileptic spikes were detected and the distance between contacts was calculated to be used as covariates in the statistical model.

Results: Overall, HGEC strength was strongest inside the SOZ, intermediate outside the SOZ, and weakest between contacts inside and outside the SOZ (p < 0.001), and stronger in SF patients than non-SF patients, but the differences in strength were small (effect size: η2 < 0.005;see Fig. 1). Analysis in relation to SOZ, brain region, and seizure outcome showed that in extra-temporal areas inside the SOZ, out of it and between contact pairs one being inside and the other outside the SOZ (η2 > 0.15), got high HGEC values that were stronger in SF than in not-SF patients. The same analysis using low gamma- or theta-frequency showed that coupling strength was weaker and effect size smaller than with HGEC. Interictal spikes were weakly corelated with HGEC (r = 0.064) and the effect size was small (η2 = 0.009). Longer inter-contact distances correlated with weaker HGEC, but the decay in strength with longer distances was the same or less for HGEC than it was for low gamma- or theta-frequency event coupling (τ = 0.02 vs. 0.087 and 0.04).

Conclusions: HGEC is a sensitive measure of EEG functional connectivity and independent of interictal spikes or the severity or progression of epilepsy. Results are consistent with the hypothesis that the SOZ is functionally disconnected from remote brain areas. The decreased functionally connectivity, likely from inhibitory networks located in extra-temporal areas, could contribute to seizure recurrence in surgical patients who have incomplete removal or disconnection of the seizure network.

Funding: Please list any funding that was received in support of this abstract.: This study was supported by the NIH grant NS106957 (RS).