Authors :
Haiteng Jiang, Carnegie Mellon University; Zhengxiang Cai, Carnegie Mellon University; Gregory A. Worrell, Mayo Clinic; Bin He, Carnegie Mellon University
Rationale: Drug-resistant focal epilepsy is widely recognized as a network disease in which epileptic seizure propagation is likely coordinated by different neuronal oscillations such as low frequency oscillations (LFOs, <30 Hz), high frequency oscillations (HFOs, >30 Hz) or low-to-high cross-frequency coupling. However, the mechanism by which different oscillatory networks constrain the propagation of focal seizures remains unclear. Here, we hypothesize that a push-pull antagonism between the SOZ and the surrounding regions accounts for differences seen in focal seizure dynamics and that this antagonism is made up of both within-frequency (LFOs or HFOs) and cross-frequency (interactions between LFOs and HFOs) directed information flow (Fig.1). Methods: We investigated invasive electrocorticography (ECoG) data from 24 drug-resistant focal epilepsy patients with 54 focal onset seizures and constructed the time-evolving within-frequency and cross-frequency directional interaction networks across pre-seizure, seizure and post-seizure periods. The within-frequency directional interaction was estimated using the adaptive direct transfer function whereas cross-frequency directional interaction was calculated via cross-frequency directionality. The strengths of the multiple oscillatory 'push-pull' antagonisms were computed and then compared between the focal epileptic network in focal seizures and the distributed epileptic network in focal seizures that spread to the surrounding regions.
Results: In the within-frequency epileptic network, we found that SOZ always sent stronger information flow to surrounding regions and focal seizures spread was accompanied by weaker information flow in the LFOs from the surrounding regions to SOZ during the early ictal period. In the cross-frequency epileptic network, focal seizures spread was associated with either decreased information flow from surrounding regions' HFOs to SOZ's LFOs or increased information flow from SOZ's LFOs to surrounding regions' HFOs during the middle ictal period.
Conclusions: Our results suggest that focal seizures have a natural tendency to spread and that those that remain focal do so, in large part because of numerous within and cross-frequency push-pull dynamics, potentially reflecting impaired excitation-inhibition interactions of the epileptic network.
Funding: This work was supported in part by NIH grants EB021027, NS096761.