Ictal and preictal power changes outside of the seizure focus correlate with seizure generalization

Abstract

Objective: The treatment of focal epilepsies is largely predicated on the concept that there is a "focus" from which the seizure emanates. Yet, the physiological context that determines if and how ictal activity starts and propagates remains poorly understood. To delineate these phenomena more completely, we studied activity outside the seizure-onset zone prior to and during seizure initiation.

Methods: Stereotactic depth electrodes were implanted in 17 patients with longstanding pharmacoresistant epilepsy for lateralization and localization of the seizure-onset zone. Only seizures with focal onset in mesial temporal structures were used for analysis. Spectral analyses were used to quantify changes in delta, theta, alpha, beta, gamma, and high gamma frequency power, in regions inside and outside the area of seizure onset during both preictal and seizure initiation periods.

Results: In the 78 seizures examined, an average of 9.26% of the electrode contacts outside of the seizure focus demonstrated changes in power at seizure onset. Of interest, seizures that were secondarily generalized, on average, showed power changes in a greater number of extrafocus electrode contacts at seizure onset (16.7%) compared to seizures that remained focal (3.8%). The majority of these extrafocus changes occupied the delta and theta bands in electrodes placed in the ipsilateral, lateral temporal lobe. Preictally, we observed extrafocal high-frequency power decrements, which also correlated with seizure spread.

Significance: This widespread activity at and prior to the seizure-onset time further extends the notion of the ictogenic focus and its relationship to seizure spread. Further understanding of these extrafocus, periictal changes might help identify the neuronal dynamics underlying the initiation of seizures and how therapies can be devised to control seizure activity.

Keywords: epileptogenesis; epileptogenic zone; intracranial EEG; partial seizure; temporal lobe epilepsy.

Fig. 1. IEEG, time-frequency plots, and spectral power in a seizure that remains focal

(A) Two electrode contact locations superimposed on pre-operative MRI. The left side of the figure represents one contact located inside the seizure focus and the right side of the figure depicts a contact outside the seizure focus. (B) iEEG recording during the onset of a seizure. Both left and right iEEG recording are of the same seizure at the two electrodes indicated in (A). Time scale is same as in (C). The grey line indicates the seizure start interval [0s 1s]. (C) Time-frequency plots during the same time window. (D) Spectral power in the [0s 1s] bin compared to a baseline [−1000s −300s]. The Baseline Confidence here represents a 95% confidence interval. Outside of the seizure focus, there are no clearly visible frequency bands that exhibit changes in power during the seizure initiation interval.

Fig. 2. IEEG, time-frequency plots, and spectral power at seizure start in a seizure that generalizes

(A)–(D) as in Fig. 1, but for a seizure that generalized. Here we observe increases in power outside of the seizure onset area (D).

Fig. 3. Changes in power occur outside the seizure focus at seizure onset

(A) Percentage of electrode contacts showing a significant increase in power at seizure onset time across different regions. The percent of contacts exhibiting changes is greatest in the ipsilateral mesial temporal region (seizure focus). On average, 38.6% of contacts (n = 78 seizures) in the ipsilateral mesial temporal region increased power at the time of onset. (B) Separates the findings by frequency band. Most changes outside of the seizure occur in the delta and theta frequency bands in the ipsilateral lateral temporal and ipsilateral frontal regions. IMT = ipsilateral mesial temporal; ILT = ipsilateral lateral temporal; IF = ipsilateral frontal; CF = contralateral frontal; CLT = contralateral lateral temporal; CMT = contralateral mesial temporal

Fig. 4. Extra-focal changes in power at seizure onset occur at low frequencies in ILT and IF regions

(A) Percent of contacts that show significant power increases at seizure initiation in seizures that remain focal (n = 59) compared with those that secondarily generalize (n = 19). In the ILT and IF regions, the percent of contacts exhibiting changes is significantly higher than in seizures that remain focal. (B) In seizures that remain focal, there are sparse changes outside of the focus. (C) In seizures that generalize, the majority of these changes occur in the delta and theta band. See Figure 3 for definitions of abbreviations.

Fig. 5. Global preictal increases in power occur in the delta, theta, and alpha frequency bands while decreases in power occur in the gamma and high gamma frequency bands

(A) Percent of electrode contacts that show significant power increases in preictal epochs [−35s −5s] of seizures that remain focal compared with those that secondarily generalize in the 6 patients with both types of seizure onset. (B)–(C) Percent of electrodes showing power increase, separated by frequency. This difference is most marked in the delta and theta bands of the ipsilateral regions and the alpha band of the frontal regions of seizures that generalize. (D)–(F) As in Fig. 5 A–C, but for significant power decreases. Most power decreases occur in gamma and high gamma frequency bands of both seizures that remain focal and that generalize.