Diffusion tractography predicts propagated high-frequency activity during epileptic spasms

Abstract

Objective: To determine the structural networks that constrain propagation of ictal oscillations during epileptic spasm events, and compare the observed propagation patterns across patients with successful or unsuccessful surgical outcomes.

Methods: Subdural electrode recordings of 18 young patients (age 1-11 years) were analyzed during epileptic spasm events to determine ictal networks and quantify the amplitude and onset time of ictal oscillations across the cortical surface. Corresponding structural networks were generated with diffusion magnetic resonance imaging (MRI) tractography by seeding the cortical region associated with the earliest average oscillation onset time, and white matter pathways connecting active electrode regions within the ictal network were isolated. Properties of this structural network were used to predict oscillation onset times and amplitudes, and this relationship was compared across patients who did and did not achieve seizure freedom following resective surgery.

Results: Onset propagation patterns were relatively consistent across each patient's spasm events. An electrode's average ictal oscillation onset latency was most significantly associated with the length of direct corticocortical tracts connecting to the area with the earliest average oscillation onset (p < .001, model R² = .54). Moreover, patients demonstrating a faster propagation of ictal oscillation signals within the corticocortical network were more likely to have seizure recurrence following resective surgery (p = .039). In addition, ictal oscillation amplitude was associated with connecting tractography length and weighted fractional anisotropy (FA) measures along these pathways (p = .002/.030, model R² = .31/.25). Characteristics of analogous corticothalamic pathways did not show significant associations with ictal oscillation onset latency or amplitude.

Significance: Spatiotemporal propagation patterns of high-frequency activity in epileptic spasms align with length and FA measures from onset-originating corticocortical pathways. Considering the data in this individualized framework may help inform surgical decision-making and expectations of surgical outcomes.

Keywords: diffusion MRI tractography; high-frequency oscillations; infantile spasms; intracranial electroencephalography; seizure propagation; surgical outcome.

Figure 1:

ECoG data processing pipeline. Example data shown from patient 03 (top) and patient 16 (bottom). A: Patient locations of subdural electrodes during pre-resection monitoring. B: Example of all electrode tracings during a single spasm event. C: Spectral density of spasm activity, averaged across all events and all electrode tracings after centering these data on their individual broadband peaks. Purple area represents the top 2% of values, and shown limits of this area were used to generate patient-specific bandpass filters for ictal fast oscillation analysis. D: Single-spasm, single-electrode examples of spasm signal detection using bandpassed data. Example tracings are shown and colored for a late onset electrode (red, top) and an early onset electrode (green, bottom). E: Same spasm event as in B, shown with signals colored by gradient of their detected onset time, green-to-red for earlier-to-later detected onsets. Extreme outlier onset detections and electrodes with insufficient involvement across all spasm events are removed as described in Section 2.

Figure 2:

Electrode-associated region of interest (ROI) generation and examples. A: Example of electrode locations from Patient 16. B: Example of the smoothed brain surface with inward vectors used to identify electrode-associated grey-matter/white matter boundary areas. C: Resulting electrode-associated ROI map generated for Patient 16, as seen in example coronal and axial slices. The ROI corresponding to the earliest onset electrode is shown in a lighter green shade. D: Spatial distribution of earliest-onset electrode from all patients with left hemisphere sampling. Electrodes have been mapped to their approximate location on the FreeSurfer template brain. Onset locations from patients who achieved postsurgical seizure freedom are shown in shades of green, while patients who did not are shown in shades of red. E: Spatial distribution of earliest-onset electrodes from all patients with right hemisphere sampling, presented identically to D.

Figure 3:

Similar consistency seen in ictal fast oscillation onset patterns regardless of postsurgical outcome. A: Examples of onset latencies (relative to each event’s mean detected onset time) are depicted for Patient 02 (left) and Patient 16 (right) in the two topmost panels. Each grid row represents onset times from a single subdural electrode, and each column represents a single spasm event, with earlier-detected onsets corresponding to darker squares. The broadly horizontal orientation of shading suggests a consistency in an electrode’s onset times across events. Below these panels, correlations between an electrode’s signal onset time in each spasm event and the mean onset time across all events are shown, with each plotted r value corresponding to the spasm event column directly above. B: Example ranges of each electrode’s onset time across spasm events. Electrode median latency values are shown as a dark blue dot, surrounded by a shaded rectangle that spans the electrode’s interquartile range. C: Stability of onset pattern across different patients. Patient median r values are shown as a vertical line, surrounded by a shaded rectangle that spans the patient’s interquartile range. Patients who achieved postsurgical seizure freedom (ILAE classification = 1) are depicted in green, while those who did not (ILAE classification ≥ 2) are depicted in red.

Figure 4:

Corticocortical tractography from onset electrodes predict latencies and amplitudes of propagated ictal fast oscillations. A: Example subset of structural data from Patient 06, showing surface locations of the onset electrode (green), three propagated electrodes (red, pink, purple), and associated tractography. Example single-spasm tracings from these electrodes are shown below in corresponding colors. B: Centroid length of onset-originating corticocortical tractography predicts average latency of signal onset in propagated electrodes. Electrode pairs from each subject are plotted as dots corresponding to the key in the figure’s upper left, patient-specific random-effect model lines are plotted in the same color, and fixed effects of the model are plotted with 95% confidence intervals in blue. This color scheme was also applied to remaining figure sections. C: Length of onset-originating corticocortical tractography pathways predicts the average total amplitude of signal waveform. D: Weighted FA along pathway predicts corresponding modeled speed of spasm signal propagation. E: Weighted FA along pathway predicts the corresponding signal amplitude.