High frequency oscillations and infraslow activity in epilepsy

Abstract

In pre-surgical evaluation of epilepsy, there has been an increased interest in the study of electroencephalogram (EEG) activity outside the 1-70 Hz band of conventional frequency activity (CFA). Research over the last couple of decades has shown that EEG activity in the 70-600 Hz range, termed high frequency oscillations (HFOs), can be recorded intracranially from all brain regions both interictally and at seizure onset. In patients with epilepsy, HFOs are now considered as pathologic regardless of their frequency band although it may be difficult to distinguish them from the physiologic HFOs, which occur in a similar frequency range. Interictal HFOs are likely to be confined mostly to the seizure onset zone, thus providing a new measure for localizing it. More importantly, several studies have linked HFOs to underlying epileptogenicity, suggesting that HFOs can serve as potential biomarkers for the illness. Along with HFOs, analysis of ictal baseline shifts (IBS; or direct current shifts) and infraslow activity (ISA) (ISA: <0.1 Hz) has also attracted attention. Studies have shown that: IBSs can be recorded using the routine AC amplifiers with long time constants; IBSs occur at the time of conventional EEG onset, but in a restricted spatial distribution compared with conventional frequencies; and inclusion of IBS contacts in the resection can be associated with favorable seizure outcome. Only a handful of studies have evaluated all the EEG frequencies together in the same patient group. The latter studies suggest that the seizure onset is best localized by the ictal HFOs, the IBSs tend to provide a broader localization and the conventional frequencies could be non-localizing. However, small number of patients included in these studies precludes definitive conclusions regarding post-operative seizure outcome based on selective or combined resection of HFO, IBS and CFA contacts. Large, preferably prospective, studies are needed to further evaluate the implications of different EEG frequencies in epilepsy.

Keywords: Epilepsy; high frequency oscillations; infraslow activity; intracranial electroencephalogram; seizure.

Figure 1

Interictal high frequency oscillations (HFOs). Left panel: at conventional setting of 1.6-70 Hz and 10 s per page window, the highlighted segment shows spikes in the inferomesial temporal region, occurring independently at AT3 and MT2 in a patient with temporal lobe epilepsy. Right panel: at high frequency setting of 53-600 Hz and 1 s per page window, prominent HFOs are seen in the highlighted segment occurring together with and independently of the spike at MT2; no HFOs are seen in association with the spike at AT3. Note that the highlighted segments in the two panels correspond to each other in time

Figure 2

Ictal high frequency oscillations (HFOs). Left panel: at conventional setting of 1.6-70 Hz and 10 s per page window, conventional seizure onset (marker CO) consisting of rhythmic beta activity is seen in the MT channels located in the inferomesial temporal region of the same patient as in Figure 1. At the time of and preceding the conventional seizure onset, the adjacent AT channels show attenuation (highlighted segment). Right panel: at high frequency setting of 53-600 Hz and 1 s per page window, prominent rhythmic ictal HFOs are seen in AT2-3 and AT3-4 channels but not in the adjacent MT channels, demonstrating temporal and spatial differences between seizure onsets defined by conventional frequency activity and HFOs. Note that the highlighted segments in the two panels correspond to each other in time

Figure 3

Ictal baseline shifts (IBSs). Selected subdural contacts over the lateral temporal (LG), anterior inferomesial temporal (AT and MT) and posterior inferomesial temporal (PT) regions in the same patient as in Figure 1 are shown. At the infraslow setting of 0.016-30 Hz and 30 s per page window, seizure onsets defined by high frequency oscillations (HFO onset) and conventional frequency activity (CFA onset) are shown along with the earliest clinical change (clinical onset). HFO onset was defined in the AT channels, whereas CFA onset was defined in the PT and MT channels. Prominent negative and positive IBSs are seen at or after the CFA seizure onset in a widespread distribution. However, careful inspection shows smaller but distinct IBSs at the time of HFO seizure onset in a restricted distribution involving only three contacts (AT3, AT4 and MT4). Note that a referential montage with an average reference is used