Effect of sleep stage on interictal high-frequency oscillations recorded from depth macroelectrodes in patients with focal epilepsy

Abstract

Purpose: To investigate the effect of sleep stage on the properties of high-frequency oscillations (HFOs) recorded from depth macroelectrodes in patients with focal epilepsy.

Methods: Ten-minute epochs of wakefulness (W), stage 1-2 non-REM (N1-N2), stage 3 non-REM (N3) and REM sleep (R) were identified from stereo-electroencephalography (SEEG) data recorded at 2 kHz in nine patients. Rates of spikes, ripples (>80 Hz), and fast ripples (>250 Hz) were calculated, as were HFO durations, degree of spike-HFO overlap, HFO rates inside and outside of spikes, and inside and outside of the seizure-onset zone (SOZ).

Results: Ripples were observed in nine patients and fast ripples in eight. Spike rate was highest in N1-N2 in 5 of 9 patients, and in N3 in 4 of 9 patients, whereas ripple rate was highest in N1-N2 in 4 of 9 patients, in N3 in 4 of 9 patients, and in W in 1 of 9 patients. Fast ripple rate was highest in N1-N2 in 4 of 8 patients, and in N3 in 4 of 8 patients. HFO properties changed significantly with sleep stage, although the absolute effects were small. The difference in HFO rates inside and outside of the SOZ was highly significant (p < 0.000001) in all stages except for R and, for fast ripples, only marginally significant (p = 0.018) in W.

Conclusions: Rates of HFOs recorded from depth macroelectrodes are highest in non-REM sleep. HFO properties were similar in stages N1-N2 and N3, suggesting that accurate sleep staging is not necessary. The spatial specificity of HFO, particularly fast ripples, was affected by sleep stage, suggesting that recordings excluding REM sleep and wakefulness provide a more reliable indicator of the SOZ.

Figure 1

Examples of ripples and fast ripples across patients and sleep stages. In each case the black trace shows the unfiltered data, whereas the lower (red) trace shows the ripple activity (80- Hz high-pass filter) and the upper (blue) trace shows the fast ripple activity (250- Hz high-pass filter). The amplitudes are as recorded, with the ripple and fast ripple activity having been multiplied by a factor of 10 to aid comparison. In addition, a constant offset has been added to separate the traces (the value of the constant was −500 μV for the ripple activity and 500 μV for the fast ripple activity). (A) Ripple and fast ripple from patient 1, contact RH1-RH2, sleep stage N3. (B) As for (A), but showing a ripple in the absence of a fast ripple. (C) Ripple and fast ripple identified in patient 5, contact LH1-LH2, stage N1-N2. (D) Data from patient 8, contact RH2-RH3, stage N3. A ripple was marked. (E) Ripple and fast ripple from patient 9, contact RA1-RA2, stage N1-N2. (F) Ripple in the absence of a fast ripple from patient 9, contact RAN2-RAN3, stage R. Epilepsia © ILAE [Correction added after online publication 9/26/08:In Figure 1 mV is replaced by μV]

Figure 2

Rates of spikes, ripples, and fast ripples in each sleep stage. The top left panel shows the mean rates over all subjects, whereas the other panels show the results for individual patients. In the majority of cases, rates of high-frequency oscillations (HFOs) were highest in either N1-N2 or N3 sleep. Results are plotted as the mean ± SEM. Epilepsia © ILAE

Figure 3

Duration of ripple and fast ripple events as a function of sleep stage. Most of the paired comparisons were significant, although absolute differences in durations across sleep stage were small, with fast ripples in particular having a consistent duration. Results are plotted as the mean ± SEM. Epilepsia © ILAE

Figure 4

Overlap between spikes and high-frequency oscillations (HFOs) as a function of sleep stage. The values observed for different sleep stages were consistent, with a similar proportion of HFOs occurring at the same time as spikes. Results are plotted as the mean ± SEM. Epilepsia © ILAE

Figure 5

The rates of high-frequency oscillations (HFOs) that occurred inside and outside of spike events. A similar pattern was observed for both as a function of sleep stage, with maximal rates in N1-N2 or N3 sleep. Results are plotted as the mean ± SEM. Epilepsia © ILAE

Figure 6

Spatial specificity of high-frequency oscillations (HFOs) as a function of sleep stage. Rates of spikes and HFOs were considerably higher in seizure-onset zone (SOZ) electrodes, and this effect was largely maintained across sleep stages. Results are plotted as the mean ± SEM. Epilepsia © ILAE