Abstracts

Rationale: The relations between amplitude and phase across different EEG frequency bands have been widely investigated. It has been observed that the amplitude of higher frequency oscillations is often modulated by the phase of lower frequency activities. This modulation is shown to facilitate the communication among specific brain regions during sleep. Few studies have been done on cross frequency coupling (CFC) in high frequency bands (>50 Hz), so in this study we investigate and quantify the variation of CFC between high and low frequency bands during different sleep stages, and also compare CFC in seizure onset zone (SOZ) and normal regions.Methods: We studied polysomnographic data of 5 patients with focal epilepsy. Sleep was scored manually according to AASM 2.0 criteria. There was no generalized seizure at least 6 hours before sleep and 2 hours after sleep. During the first sleep cycle, the first 5 minutes of each stage (stage N1, N2, N3 and REM) was selected for analysis. Selected portions had to be apart from other stages for at least 15 seconds. The data was then split into epochs of 30 seconds. Each epoch of each channel was band-pass filtered into low and high frequency bands: Low frequency: delta (0.1-4), theta (4-8), alpha (8-13) and beta (13-30) High frequency: 50-250 Hz with a step size of 10 Hz Then the envelope amplitude and phase of the filtered signals were obtained using Hilbert transform: h(t)=f(t)+f'(t)=A(t) exp(jϕ(t)) where f'(t) represents the Hilbert transform of the signal f(t), and A(t) and ϕ(t) represent the instantaneous envelope amplitude, and instantaneous phase of the signal, respectively. The Modulation Index was calculated for each epoch, and each pair of low and high frequencies. Higher values of this index represent stronger coupling between two frequency bands. The raw index was then normalized and its statistical significance (z-score) was measured by calculating 200 surrogate modulation index values.Results: CFC in different sleep stages: The average modulation index in delta band is higher in stage N3 compared to REM for all patients (p<0.05). The same result is observed for theta, alpha and beta bands for three of the 5 patients. This index is also significantly lower in stage N1 compared to REM for three patients in all bands. Figure 1 represents the average of modulation index in delta band for all channels for the 5 investigated patients. CFC in SOZ and non-SOZ: The average modulation index in delta band in all stages is significantly higher in SOZ channels compared to non-SOZ channels (p<0.05) in four of the 5 patients. The same result is seen for theta and alpha bands in stages N1, N2 and N3.Conclusions: Cross frequency coupling varies during different sleep stages and therefore, this factor should be carefully considered to avoid confusing physiological and epileptic coupling alterations. Changes of CFC can be observed in interictal periods away from seizures. The differences between CFC inside and outside of SOZ during different vigilance states may serve as a new index for localizing the epileptic brain region.