Phase-Amplitude Coupling Is Elevated in Deep Sleep and in the Onset Zone of Focal Epileptic Seizures

Abstract

The interactions between different EEG frequency bands have been widely investigated in normal and pathologic brain activity. Phase-amplitude coupling (PAC) is one of the important forms of this interaction where the amplitude of higher frequency oscillations is modulated by the phase of lower frequency activity. Here, we studied the dynamic variations of PAC of high (gamma and ripple) and low (delta, theta, alpha, and beta) frequency bands in patients with focal epilepsy in different sleep stages during the interictal period, in an attempt to see if coupling is different in more or less epileptogenic regions. Sharp activities were excluded to avoid their effect on the PAC. The results revealed that the coupling intensity was generally the highest in stage N3 of sleep and the lowest in rapid eye movement sleep. We also compared the coupling strength in different regions [seizure onset zone (SOZ), exclusively irritative zone, and normal zone]. PAC between high and low frequency rhythms was found to be significantly stronger in the SOZ compared to normal regions. Also, the coupling was generally more elevated in spiking channels outside the SOZ than in normal regions. We also examined how the power in the delta band correlates to the PAC, and found a mild but statistically significant correlation between slower background activity in epileptic channels and the elevated coupling in these channels. The results suggest that an elevated PAC may reflect some fundamental abnormality, even after exclusion of sharp activities and even in the interictal period. PAC may therefore contribute to understanding the underlying dynamics of epileptogenic brain regions.

Interictal coupling of HFOs and slow oscillations predicts the seizure‐onset pattern in mesiotemporal lobe epilepsy

“…Ripples usually predominate during LVF, whereas fast ripples (FRs) are more frequent during PS seizures. 17 In our previous study, we demonstrated that in the interictal period, higher values of PAC exist in the SOZ compared to normal channels 13 ; however, how different types of epilepsy or seizures are associated with different coupling patterns has not been investigated yet. 7 Phase-amplitude coupling (the coupling between the amplitude of high-frequency activity and the phase of the lowfrequency band; PAC) has been the subject of many studies, not only in normal brain activity, but also in patients with epilepsy.…”

“…PS is associated with neuronal hypersynchronization, whereas LVF is associated with increased local neuronal firing due to either disinhibition or hyperexcitation. 13,14 The interaction of HFOs and slow waves can also help distinguish physiologic and pathologic HFOs. Ripples usually predominate during LVF, whereas fast ripples (FRs) are more frequent during PS seizures.…”

“…13 Should we obtain sufficient information from the interictal data, we could eventually eliminate the need of long-lasting and hence expensive stays in the epilepsy monitoring unit to record seizures. Moreover, knowing for instance that the SOP is likely to be PS would be in keeping with better prognostication.…”

Persistent aberrant cortical phase–amplitude coupling following seizure treatment in absence epilepsy models

“…One common type of cross-frequency coupling is phase-amplitude coupling (PAC) where the phase of a slower oscillation is correlated with the amplitude of a faster oscillation. The magnitude of PAC represents the putative interactions between underlying circuits which behave abnormally in models of focal epilepsy (Guirgis et al 2015;Amiri et al 2016;Edakawa et al 2016), but has not yet been evaluated in generalized epilepsies. Critically, PAC is a potentially useful metric as the correlation between different oscillatory EEG components may vary without overt changes in the power spectrum, and can therefore uniquely differ for similar power spectra.…”

Epileptogenic Source Imaging Using Cross-Frequency Coupled Signals From Scalp EEG

“…Our group has previously reported low frequency oscillation modulated high frequency oscillation can be used to successfully define ROI using intracranial recordings [26]. More recently, cross frequency coupling between high (gamma and ripple) and low (delta, theta, alpha, and beta) frequency rhythms was reported to be significantly stronger in the SOZ compared to normal regions in intracranial recording of deep sleep [60].…”