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 = 0.045) when recorded on microelectrodes compared with clinical macroelectrodes. Although gamma-IEDs 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 = 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 gamma-IEDs for mapping pathologic brain regions is intriguing, but will require future prospective studies.

From the Mayo Systems Electrophysiology Laboratory Department of Neurology St Anne's University Hospital Brno Czech Republic

See more in PubMed

Talairach J, Bancaud J. Lesion, “irritative” zone and epileptogenic focus. Confin Neurol 1966;27:91–94. PubMed

de Curtis M, Avanzini G. Interictal spikes in focal epileptogenesis. Prog Neurobiol 2001;63:541–567. PubMed

Keller CJ, Truccolo W, Gale GT, et al. Heterogeneous neuronal firing patterns during interictal epileptiform discharges in the human cortex. Brain 2010;133:1668–1681. PubMed PMC

Alvarado-Rojas C, Lehongre K, Bagdasaryan J, et al. Single-unit activities during epileptic discharges in the human hippocampal formation. Front Comput Neurosci 2013;7:140. PubMed PMC

Quilichini PP, Le Van Quyen M, Ivanov A, et al. Hub GABA neurons mediate gamma frequency oscillations at ictal-like event onset in the immature hippocampus. Neuron 2012;74:57–64. PubMed PMC

Jacobs J, Staba R, Asano E, et al. High frequency oscillations (HFOs) in clinical epilepsy. Prog Neurobiol 2012;98:302–315. PubMed PMC

Worrell GA, Jerbi K, Kobayashi K, Lina JM, Zelmann R, Le Van Quyen M. Recording and analysis techniques for high-frequency oscillations. Prog Neurobiol 2012;98:265–278. PubMed PMC

Stead SM, Bower MR, Brinkmann BH, et al. Microseizures and the spatiotemporal scales of human partial epilepsy. Brain 2010;133:2789–2797. PubMed PMC

Matsumoto JY, Stead SM, Kucewicz MT, et al. Network oscillations modulate interictal epileptiform spike rate during human memory. Brain 2013;136:2444–2456. PubMed PMC

Kucewicz MT, Cimbalnik J, Matsumoto JY, et al. High frequency oscillations are associated with cognitive processing in human recognition memory. Brain 2014;137:2231–2244. PubMed PMC

Andrade-Valenca LP, Dubeau F, Mari F, Zelmann R, Gotman J. Interictal scalp fast oscillations as a marker of the seizure onset zone. Neurology 2011;77:524–531. PubMed PMC

Phase-Amplitude Coupling Localizes Pathologic Brain with Aid of Behavioral Staging in Sleep

Progress and Remaining Challenges in the Application of High Frequency Oscillations as Biomarkers of Epileptic Brain