Ictal high frequency oscillations distinguish two types of seizure territories in humans

Abstract

High frequency oscillations have been proposed as a clinically useful biomarker of seizure generating sites. We used a unique set of human microelectrode array recordings (four patients, 10 seizures), in which propagating seizure wavefronts could be readily identified, to investigate the basis of ictal high frequency activity at the cortical (subdural) surface. Sustained, repetitive transient increases in high gamma (80-150 Hz) amplitude, phase-locked to the low-frequency (1-25 Hz) ictal rhythm, correlated with strong multi-unit firing bursts synchronized across the core territory of the seizure. These repetitive high frequency oscillations were seen in recordings from subdural electrodes adjacent to the microelectrode array several seconds after seizure onset, following ictal wavefront passage. Conversely, microelectrode recordings demonstrating only low-level, heterogeneous neural firing correlated with a lack of high frequency oscillations in adjacent subdural recording sites, despite the presence of a strong low-frequency signature. Previously, we reported that this pattern indicates a failure of the seizure to invade the area, because of a feedforward inhibitory veto mechanism. Because multi-unit firing rate and high gamma amplitude are closely related, high frequency oscillations can be used as a surrogate marker to distinguish the core seizure territory from the surrounding penumbra. We developed an efficient measure to detect delayed-onset, sustained ictal high frequency oscillations based on cross-frequency coupling between high gamma amplitude and the low-frequency (1-25 Hz) ictal rhythm. When applied to the broader subdural recording, this measure consistently predicted the timing or failure of ictal invasion, and revealed a surprisingly small and slowly spreading seizure core surrounded by a far larger penumbral territory. Our findings thus establish an underlying neural mechanism for delayed-onset, sustained ictal high frequency oscillations, and provide a practical, efficient method for using them to identify the small ictal core regions. Our observations suggest that it may be possible to reduce substantially the extent of cortical resections in epilepsy surgery procedures without compromising seizure control.

Advances of Intracranial Electroencephalography in Localizing the Epileptogenic Zone

“…Another study reported regions with strong ictal HFO (80-270 Hz) coherence coincided with regions with high ictal HFO intensity in 4 out of 5 patients with extratemporal lobe epilepsy [87]. Weiss et al [88]. found that phased-locked high gamma activity, defined by ictal high gamma activity (80-150 Hz) phase-locked to the low-frequency phase (1-25 Hz), may mark the ''seizure core territory''.…”

Seizure localization using ictal phase-locked high gamma

“…[4][5][6][7] Penumbral synaptic currents cannot be reliably differentiated from the depolarizations in the core with standard visual EEG interpretation. 8 Previously, we proposed that the core can be identified using a measure based on high gamma (80-150 Hz) activity phase-locked to low-frequency EEG discharges (PLHG). 8 The existing literature on high-frequency oscillations supports this view.…”

“…8 Previously, we proposed that the core can be identified using a measure based on high gamma (80-150 Hz) activity phase-locked to low-frequency EEG discharges (PLHG). 8 The existing literature on high-frequency oscillations supports this view. [9][10][11] Sites demonstrating increased high-frequency power during seizures 12,13 or at seizure onset [14][15][16][17] are often located within the SOZ, and resection of these sites has been associated with improved postoperative seizure control.…”

“…The PLHG measure was implemented as described in our previous study. 8 Briefly, artifact was addressed either by excluding channels with visualized excess 80-to 150-Hz noise, or removing noise using blind source separation with independent component analysis (EEGLAB, University of California San Diego). 20 Instantaneous high gamma (80-150 Hz, 500th order symmetric finite impulse response) amplitude was derived from the Hilbert transform, normalized to a 30-second preictal baseline, and weighted with the simultaneous phase-locking value computed from the low-frequency (4-30 Hz) phase.…”

Chow–Liu trees are sufficient predictive models for reproducing key features of functional networks of periictal EEG time-series

“…Indeed, it is possible that the results presented in this paper hinge at the presence of some particular frequency bands, such that relevant correlations are caused mainly by activity at these frequencies. In (Weiss et al, 2013) for example, crossfrequency coupling between low-frequencies (≤ 25Hz) and the high-gamma range (> 80Hz) is shown for the "ictal core" region -the region that is directly affected by an ictal wavefront and where neurons show characteristic bursts-but not for its periphery, called the "penumbra". In principle, the CL-algorithm may also detect such rather subtle dependencies, thereby transferring predictive modeling even further to the spatio-temporal and frequency domain.…”