Ictal propagation of high frequency activity is recapitulated in interictal recordings: effective connectivity of epileptogenic networks recorded with intracranial EEG

Abstract

Seizures are increasingly understood to arise from epileptogenic networks across which ictal activity is propagated and sustained. In patients undergoing invasive monitoring for epilepsy surgery, high frequency oscillations have been observed within the seizure onset zone during both ictal and interictal intervals. We hypothesized that the patterns by which high frequency activity is propagated would help elucidate epileptogenic networks and thereby identify network nodes relevant for surgical planning. Intracranial EEG recordings were analyzed with a multivariate autoregressive modeling technique (short-time direct directed transfer function--SdDTF), based on the concept of Granger causality, to estimate the directionality and intensity of propagation of high frequency activity (70-175 Hz) during ictal and interictal recordings. These analyses revealed prominent divergence and convergence of high frequency activity propagation at sites identified by epileptologists as part of the ictal onset zone. In contrast, relatively little propagation of this activity was observed among the other analyzed sites. This pattern was observed in both subdural and depth electrode recordings of patients with focal ictal onset, but not in patients with a widely distributed ictal onset. In patients with focal ictal onsets, the patterns of propagation recorded during pre-ictal (up to 5 min immediately preceding ictal onset) and interictal (more than 24h before and after seizures) intervals were very similar to those recorded during seizures. The ability to characterize epileptogenic networks from interictal recordings could have important clinical implications for epilepsy surgery planning by reducing the need for prolonged invasive monitoring to record spontaneous seizures.

Keywords: Brain mapping; ECoG; Epilepsy surgery; Epileptic network; High frequency oscillations (HFOs); Seizure onset zone.

Fig. 1

Changes in energy, in the time-frequency domain, for lower (0–40 Hz, left panels), and high frequency (70–120 Hz, right panels) components of ictal activity of several neighboring recording sites in Patient #1. Each plot depicts ECoG signal energy calculated using a matching pursuit (MP) algorithm of signal decomposition for lower frequencies 0–40 Hz (left panel) and for high frequencies (70–120 Hz, right panel), with a red to blue color spectrum where red is the maximum increase in energy and blue is no (zero) increase in energy compared to the pre-ictal baseline interval. The horizontal axis of each plot shows the time scale in seconds (starting from seizure onset at time zero, as identified by epileptologists); vertical axis - frequency scale in Hz.

Fig. 2

Reconstructions of the implanted electrodes in Patient #1, second admission (top left - left posterior oblique view of strip and grid electrodes, top right - left interhemispheric view of strip electrodes, bottom left - axial view of depth electrodes) and an axial T2-weighted MRI depicting a left mesial occipital lesion identified on pre-operative MRI (bottom-right).

Fig. 3

Integrals of SdDTF for lower and high frequency ictal propagations for Patient #2. Red-yellow arrows indicate the directions and intensities of the activity propagation. The width and color of each arrow represent values of SdDTF integrated over frequency and time. Two black arrows indicate electrodes of the epileptogenic zone (RPT2-RPT6) identified by epileptologists. Left panel - integrals of SdDTF for low frequency (0–25 Hz) ictal propagations calculated for consecutive seconds of ictal periods. Right panel - integrals of SdDTF for high frequency (70–115 Hz) ictal propagations calculated for whole ictal period.

Fig. 4

Averages of SdDTF for propagations between the site of ictal onset and all other recording sites, for the two frequency ranges 70–115 Hz and 125–175 Hz, during ictal and preictal periods in Patient #2. Each column shows average of SdDTFs for propagations from the site indicated at the left to all other recording sites (outflowing, green-black, left panel), and to the site indicated at the left from all other recording sites (inflowing, purple-black, right panel). The highest magnitudes indicate the largest outflows (the brightest green), or the largest inflows (brightest purple). Electrodes of the epileptogenic zone (RPT2, RPT6) identified by epileptologists, are marked with red exclamation marks. The color-scale is normalized from minimum to maximum averaged value of SdDTF, which allows for comparisons of different frequency ranges, and inter-, pre-, and ictal periods.

Fig. 5

Averages of SdDTF for propagations between the site of ictal onset and all other recording sites, for two frequency ranges of 70–115 Hz and 125–175 Hz, during ictal and preictal periods for Patient #3. Color conventions and organization of the figure are as in Fig. 4. The right panel shows a right lateral and basal view of the brain with electrode positions depicted.

Fig. 6

Averages of SdDTF for propagations between the site of ictal onset and all other recording sites, for two frequency ranges of 70–115 Hz and 125–175 Hz, during ictal, preictal, and interictal periods for Patient #4. Organization of the figure is as in Fig. 4. The right panel shows placement of depth electrodes by skull X-ray.

Fig. 7

Averages of SdDTF for propagations between the site of ictal onset and all other recording sites, for two frequency ranges of 70–115 Hz and 125–175 Hz, during ictal, preictal, and interictal periods for Patient #5. Organization of the figure is as in Fig. 4. The right panel depicts a superior oblique interhemispheric view of the left hemisphere showing electrode positions.

Fig. 8

Averages of SdDTF for propagations between the site of ictal onset and all other recording sites, for two frequency ranges of 70–115 Hz and 125–175 Hz, during ictal, preictal, and interictal periods for the 1^st admission for Patient #1. Organization of the figure is as in Fig. 4. The bottom panel depicts a left lateral (left) and superior oblique interhemispheric (right) view of the left hemisphere with electrode positions shown.

Fig. 9

Averages of SdDTF for propagations between the site of ictal onset and all other recording sites, for lower frequency 0–40 Hz, during ictal, preictal, and interictal periods for the 1^st admission for Patient #1. Organization of the figure is as in Fig. 4.

Fig. 10

Averages of SdDTF for propagations between the site of ictal onset and all other recording sites, for two frequency ranges of 70–115 Hz and 125–175 Hz, during ictal, preictal, and interictal periods for 2^nd admission of Patient #1. Organization of the figure is as in Fig. 4. Electrode positions are depicted in Figure 2.

Fig. 11

Averages of SdDTF for propagations between the site of ictal onset and all other recording sites, for lower frequency 0–40 Hz, during ictal, preictal, and interictal periods for 2^nd admission of Patient #1. Organization of the figure is as in Fig. 4.

Fig. 12

Averages of SdDTF for propagations between the site of ictal onset and all other recording sites, for two frequency ranges of 70–115 Hz and 125–175 Hz, during ictal, preictal, and interictal periods for Patient #6. Organization of the figure is as in Fig. 4. The center panel (left) shows an inferior left oblique view of the left hemisphere with electrode positions and (right) an axial T2 FLAIR MRI of the infiltrating left temporal lesion. The bottom panel (left) is a coronal view of the depth electrode positions and interhemispheric view with coronal cross sections through the planes traversing the paths of the depth electrodes.

Fig. 13

The mean value of the transformed averaged flows (MTAF) of high frequency activity propagation from and into each recording site, calculated for ictal, preictal, and interictal periods, for both ranges of high frequency, for each patient. Horizontal axis - recording sites, vertical axis - the degree of dominance.

Fig. 14

The mean value of the transformed averaged flows (MTAF) of high frequency activity propagation from and into each recording site, calculated for interictal periods, for both ranges of high frequency, in patients for whom the interictal intervals were available (not all interictal segments were saved for review in all patients). Horizontal axis - recording sites, vertical axis - the degree of dominance.