Large-Scale Desynchronization During Interictal Epileptic Discharges Recorded With Intracranial EEG

Abstract

It is increasingly recognized that deep understanding of epileptic seizures requires both localizing and characterizing the functional network of the region where they are initiated, i. e., the epileptic focus. Previous investigations of the epileptogenic focus' functional connectivity have yielded contrasting results, reporting both pathological increases and decreases during resting periods and seizures. In this study, we shifted paradigm to investigate the time course of connectivity in relation to interictal epileptiform discharges. We recruited 35 epileptic patients undergoing intracranial EEG (iEEG) investigation as part of their presurgical evaluation. For each patient, 50 interictal epileptic discharges (IEDs) were marked and iEEG signals were epoched around those markers. Signals were narrow-band filtered and time resolved phase-locking values were computed to track the dynamics of functional connectivity during IEDs. Results show that IEDs are associated with a transient decrease in global functional connectivity, time-locked to the peak of the discharge and specific to the high range of the gamma frequency band. Disruption of the long-range connectivity between the epileptic focus and other brain areas might be an important process for the generation of epileptic activity. Transient desynchronization could be a potential biomarker of the epileptogenic focus since 1) the functional connectivity involving the focus decreases significantly more than the connectivity outside the focus and 2) patients with good surgical outcome appear to have a significantly more disconnected focus than patients with bad outcomes.

Keywords: epilepsy surgery; epileptic focus; epileptiform discharges; functional connectivity; intracranial electroencephalography; surgical outcome.

Figure 1

Illustrative examples of intracranial EEG ictal signals recorded by electrodes within the focus area (red), propagation area (yellow) and silent area (blue). The x-axis displays time (in seconds). Green vertical lines are spaced one second each. The red dashed vertical line displays electrical seizure onset.

Figure 2

Illustrative examples of IEDs as recorded in the focus area (red), propagation area (yellow), and silent area (blue). The x axis displays time (in seconds). Green vertical lines are spaced one second each.

Figure 3

Average time course of the iEEG functional connectivity. The average PLV across pairs of iEEG contacts for each patient is represented with a light solid line and the average across patients is displayed in thick colored lines. Confidence intervals for the average across patients are displayed as a dark shaded area. The time axis is centered on the peak of IEDs (time 0). In general, the average functional connectivity, as measured with the phase-locking value (PLV), increases at IED peak for lower frequency bands (<30 Hz) and decreases for higher frequency bands (>30 Hz). The y-axis displays absolute variation in terms of z-score.

Figure 4

Average time course of the shuffled iEEG functional connectivity; results were only flat noise and no change in connectivity was observed for all frequency bands.

Figure 5

Comparison of PLV variations among the (good outcome—G vs. bad outcome—B) patients groups for each frequency band using a 2-way ANOVA. Connectivity involving the epileptic focus (F-F, F-P, and F-S connections, A) increases in lower frequency bands and decrease in higher frequency bands. Differences between patients groups reach significance at the 5% level for gamma1 and gamma2 bands. Connectivity not involving the focus (P-P, P-S, and S-S, B) shows similar trends but differences were not significant. Outliers are represented with a “+” symbol. Significant differences are represented with a “*” symbol.

Figure 6

Variation of functional connectivity in the high gamma band (60–120 Hz) as measured with PLV index at the IED peak with respect to baseline (-1 to−0.5 s) for two illustrative patients. The variation index was computed for each electrode contact then interpolated over the underlying cortical surface using an in-house algorithm. The resection site targeted by a later surgery is overlaid as a thick contour. The first patient (upper row) had 2 surgeries; the first one targeted mainly the anterior insula (white contour line) while the maximal decrease of PLV was found in the lateral inferior frontal gyrus. The second surgery (orange contour line) targeted left orbitofrontal and frontal lateral regions, which was concordant with the sites of maximal PLV variation. For the second patient, the resected site (orange contour line) overlaps with the two sites with maximal PLV variation. The PLV projection onto the modeled cortex was threshold; only points on the projection of the cortex which account for 95% of the variance were kept.