Abstracts

Rationale: Patients with focal epilepsy demonstrate widespread alterations to structural and functional networks. While some alterations may be aberrancies from underlying disease, others may be adaptive responses to combat epileptic foci. In this vein, prior work analyzed epilepsy networks with directed connectivity and single pulse electric stimulation, and found connectivity profiles suggesting the interictal state is maintained by a tonically suppressive network with high net inward connectivity into the seizure onset zones (SOZs). Other groups since described similar network, suppressive motifs. These findings led to the present follow-up investigation on seizure initiation and termination. Specifically, “what causes seizure termination?” Classically, seizure termination has been postulated to follow an exhaustion of metabolic resources. This model posits that seizures end because involved regions can no longer sustain highly synchronized oscillatory activity. In this investigation, we posit that instead suppressive network responses mediate transitions out of the ictal state.

Methods: We investigated 60 patients with drug resistant focal epilepsy admitted to Vanderbilt Medical Center’s epilepsy monitoring unit for stereoelectroencephalography (SEEG). For each patient, epileptologists designated channels as SOZs, PZs, or non-involved zones (NIZs) based on their involvement in seizure onset and propagation. SEEG recordings were preprocessed with a high-pass filter at 1Hz, low pass filter at 150Hz, and butterworth notch filters at 60 & 120Hz. A bipolar montage was applied to all contacts in grey matter. Functional connectivity was computed with partial directed coherence (PDC) between all bipoles, which we refer to as nodes, for all 4 periods for every seizure: interictal, pre-ictal, ictal, and post-ictal. For each period we summarized connectivity matrices, as the net directed connectivity in all nodes within each region of interest. To probe network reorganization, we examined changes in the proportion of directed connections for each region over all 4 periods.


Results: PZs and SOZs demonstrate significantly higher net inward connectivity compared to the NIZ across all 4 periods(Fig. 1, p=1.07x10^-10, one-way ANOVA) showing stably high net inward connectivity with no significant changes to net connections. However, the proportion of inward connectivity to the SOZ from the NIZ significantly increases in the ictal period(Fig. 2, p=4.72x10^-3). Inward connections to SOZs from NIZs seem to diminish at seizure termination.

Conclusions: These connectivity profiles demonstrate stable inward connectivity up until seizure generation. During the ictal period NIZs seem to increase connectivity with SOZs until seizure termination. This change in connectivity towards SOZs may represent network suppression combatting seizure activity. This network reorganization may be evidence of an inhibitory response to seizure activity by the broader network which is responsible for seizure termination. Future neuromodulation studies may utilize this network phenomenon to promote organic seizure termination.

Funding: This work was funded by NIH grants T32EB021937, T32GM007347, F31NS120401, R01NS112252, R01NS134625