Dynamic Changes in Spectral and Spatial Signatures of High Frequency Oscillations in Rat Hippocampi during Epileptogenesis in Acute and Chronic Stages

Abstract

Objective: To analyze spectral and spatial signatures of high frequency oscillations (HFOs), which include ripples and fast ripples (FRs, >200 Hz) by quantitatively assessing average and peak spectral power in a rat model of different stages of epileptogenesis.

Methods: The lithium-pilocarpine model of temporal lobe epilepsy was used. The acute phase of epilepsy was assessed by recording intracranial electroencephalography (EEG) activity for 1 day after status epilepticus (SE). The chronic phase of epilepsy, including spontaneous recurrent seizures (SRSs), was assessed by recording EEG activity for 28 days after SE. Average and peak spectral power of five frequency bands of EEG signals in CA1, CA3, and DG regions of the hippocampus were analyzed with wavelet and digital filter.

Results: FRs occurred in the hippocampus in the animal model. Significant dynamic changes in the spectral power of FRS were identified in CA1 and CA3. The average spectral power of ripples increased at 20 min before SE (p < 0.05), peaked at 10 min before diazepam injection. It decreased at 10 min after diazepam (p < 0.05) and returned to baseline after 1 h. The average spectral power of FRs increased at 30 min before SE (p < 0.05) and peaked at 10 min before diazepam. It decreased at 10 min after diazepam (p < 0.05) and returned to baseline at 2 h after injection. The dynamic changes were similar between average and peak spectral power of FRs. Average and peak spectral power of both ripples and FRs in the chronic phase showed a gradual downward trend compared with normal rats 14 days after SE.

Significance: The spectral power of HFOs may be utilized to distinguish between normal and pathologic HFOs. Ictal average and peak spectral power of FRs were two parameters for predicting acute epileptic seizures, which could be used as a new quantitative biomarker and early warning marker of seizure. Changes in interictal HFOs power in the hippocampus at the chronic stage may be not related to seizure occurrence.

Keywords: epileptogenesis; high frequency oscillations; qualitative analysis; quantitative analysis; spectral power.

Figure 1

Wavelet analysis of 10 min EEG in left DG. The EEG signal in the left DG was decomposed into five layers and five frequency bands were extracted, spanning 16.5–31.25, 31.25–62.5, 62.5–125, 125–250, and 250–500 Hz [(fs/2)/2ⁿ]. (A) 1 day before SE; (B) 10 min before SE; (C) 10 min after SE; (D) 1 h after diazepam injection.

Figure 2

Waveforms and spectrograms showing the spectral and temporal characteristics of HFOs at 80–200 Hz (ripple). The left waveforms are filtered with a band pass filter of 80–200 Hz. The right spectrograms are the accumulated time–frequency representations of the corresponding waveforms. ESA indicates an electrical signal from the CA1, which has epileptic activity; ENM indicates an electrical signal from a normal CA1 area. Both waveforms and spectrograms indicate that epileptic seizures were associated with increases in ripples. Those ripples were characterized by rhythmic bursts, which are significantly different from systematic artifacts such as power line noise and its harmonics. The spectrograms indicates that ripples occurred in two frequency bands around 90 and 110 Hz.

Figure 3

Waveforms and spectrograms showing the spectral and temporal characteristics of HFOs at 200–500 Hz (fast ripple). The left waveforms are filtered with a band pass filter of 200–500 Hz. The right spectrograms are the accumulated time–frequency representations of the corresponding waveforms. ESA indicates an electrical signal from the area that has epileptic activity; ENM indicates an electrical signal from a normal area (control). Both waveforms and spectrograms indicated that epileptic seizures were associated with increases in fast ripples. The fast ripples are characterized by rhythmic bursts, which are significantly different from systematic artifacts, such as power line noise and its harmonics. The spectrograms indicate that the fast ripples occur around 220–260 Hz.

Figure 4

Fast Ripples (FRs) in 30 min EEG at different states in the acute phase of epilepsy. Paper speed: 0.00048 mm/s, sensitivity: 0.005 uv/mm. EEG was subjected to filtering analysis. (A) In the 15 min before and after SC, FRs increased gradually prior to stage 4 of Racine’s criterion. (B) In the 15 min before and after diazepam injection, FRs decreased gradually following diazepam treatment.

Figure 5

Waveforms and spectrograms showing the spectral and temporal characteristics of the initiation of an epileptic seizure. The left waveforms are filtered with a band pass filter of 80–500 Hz. The right spectrograms are time–frequency representations of the corresponding waveforms. ESA indicates an electrical signal from the CA1, which has epileptic activity; while ENM indicates an electrical signal from a normal CA1 area. The green arrows indicate the initiation of the seizure. Both waveforms and spectrograms indicated that the initiation of epileptic seizures were associated with increased high frequency oscillations at 80–500 Hz.

Figure 6

Waveforms and spectrograms showing the spectral and temporal characteristics of the termination of an epileptic seizure. The left waveforms are filtered with a band pass filter of 80–500 Hz. The right spectrograms are time–frequency representations of the corresponding waveforms. ESA indicates an electrical signal from the epileptic area, while ENM indicates an electrical signal from the normal area (control). The green arrows indicate the end of the epileptic seizure. Both waveforms and spectrograms indicated that the termination of epileptic seizures were associated with diminished high frequency oscillations at 80–500 Hz.

Figure 7

Dynamic changes of average and peak spectral power of γ oscillations for six channels in the acute phase in one rat (A,B). (A) Average spectral power of γ oscillations. (B) Peak spectral power of γ oscillations. Average and peak spectral power of γ oscillations showed no systematic changes.

Figure 8

Dynamic changes of average and peak spectral power of γ oscillations for six channels in the acute phase in one rat (A–D). (A) Average spectral power of ripples. (B) Average spectral power of FRs. (C) Peak spectral power of ripples. (D) Peak spectral power of FRs. The frequency bands of ripples and FRs exhibited specific and sharp increases, when SE began and then continuously decreased, finally ending at a lower level after injection of diazepam. EEG signals above 80 Hz appeared to be more stable than γ oscillations.