Gamma oscillations precede interictal epileptiform spikes in the seizure onset zone

Abstract

Objective: To investigate the generation, spectral characteristics, and potential clinical significance of brain activity preceding interictal epileptiform spike discharges (IEDs) recorded with intracranial EEG.Methods: Seventeen adult patients with drug-resistant temporal lobe epilepsy were implanted with intracranial electrodes as part of their evaluation for epilepsy surgery. IEDs detected on clinical macro-and research microelectrodes were analyzed using time-frequency spectral analysis.Results: Gamma frequency oscillations (30-100 Hz) often preceded IEDs in spatially confined brain areas. The gamma-IEDs were consistently observed 35 to 190 milliseconds before the epileptiform spike waveforms on individual macro-and microelectrodes. The gamma oscillations associated with IEDs had longer duration (p , 0.001) and slightly higher frequency (p 5 0.045) when recorded on microelectrodes compared with clinical macroelectrodes. Although gammaIEDs comprised only a subset of IEDs, they were strongly associated with electrodes in the seizure onset zone (SOZ) compared with the surrounding brain regions (p 5 0.004), in sharp contrast to IEDs without preceding gamma oscillations that were often also detected outside of the SOZ. Similar to prior studies, isolated pathologic high-frequency oscillations in the gamma (30-100 Hz) and higher (100-600 Hz) frequency range, not associated with an IED, were also found to be associated with SOZ. Conclusions:The occurrence of locally generated gamma oscillations preceding IEDs suggests a mechanistic role for gamma in pathologic network activity generating IEDs. The results show a strong association between SOZ and gamma-IEDs. The potential clinical application of gammaIEDs for mapping pathologic brain regions is intriguing, but will require future prospective studies. Neurology ® 2015;84:602-608 GLOSSARY HFO 5 high-frequency oscillation; IED 5 interictal epileptiform discharge; iEEG 5 intracranial EEG; SOZ 5 seizure onset zone.Interictal epileptiform spike discharges (IEDs) manifest as sharp-wave deflections in the local field potential recorded within the "irritative zone" of epileptic brain.1 The irritative zone is distinct from the seizure onset zone (SOZ), where the ictal discharge is first observed. The relationship between the 2 zones or between IEDs and seizures remains unclear (for review, see de Curtis and Avanzini 2 ). In particular, the processes underlying IED generation are not well understood, and on a cellular level, recordings show a heterogeneous profile of increased, decreased, or unchanged neuronal firing during IEDs.3,4 Furthermore, the spatial extent of IEDs and their association with SOZ has long been recognized to be highly variable. 2Network local field potential oscillations that can be detected with intracranial EEG (iEEG) provide a powerful window into synchronized activity of neuronal populations. Oscillations in the gamma frequency range (30-100 Hz) were recently implicated in the neuronal network generation of ictal-like discharges in an in vitro...

Ripples on spikes show increased phase‐amplitude coupling in mesial temporal lobe epilepsy seizure‐onset zones

“…The onset of ripple 28 and gamma 29 oscillations can precede inter-ictal epileptiform discharges, while gamma can occur after inter-ictal discharges as well as fast ripples, i.e. fast ripple tail gamma 7 .…”

Advances of Intracranial Electroencephalography in Localizing the Epileptogenic Zone

“…In addition, fast oscillations in the gamma and low ripple range (30-100 Hz) have been found to precede interictal epileptiform spike discharges (IEDs), and these so called gamma-IEDs are strongly associated with the SOZ in TLE [31]. Although HFOs and spikes are closely related, their dynamics differ.…”

Progress and remaining challenges in the application of high frequency oscillations as biomarkers of epileptic brain

“…The association between pHFOs and interictal epileptiform discharges (IEDs) was investigated by various studies [21,22,46,56]. Wang et al, [21] classified neocortical ripples into two subtypes: type I ripples superimposed on an IED, and type II ripples independent of any epileptiform discharges.…”

“…Ren et al, [22] studied the gamma HFOs that precede IEDs and found a strong association between seizure generating brain and gamma HFOs that preceded IEDs, in contrast to IEDs alone. They proposed the gamma HFOs proceeding IEDs may be useful for mapping pathological brain regions.…”

“…Interestingly, analysis of putative pHFOs and nHFOs show that pHFOs have higher voltages and longer duration compared to physiological nHFOs [15]. Since the task-induced HFOs in the epileptic brain can have spectral properties similar to pHFOs [3,15,22], the rigid dichotomy between pHFOs in epileptic brain and physiological ‘event related’ nHFO in non-epileptic brain requires further study to determine if it is always true.…”