High-frequency oscillations and seizure generation in neocortical epilepsy

Abstract

Neocortical seizures are often poorly localized, explosive and widespread at onset, making them poorly amenable to epilepsy surgery in the absence of associated focal brain lesions. We describe, for the first time in an unselected group of patients with neocortical epilepsy, the finding that high-frequency (60-100 Hz) epileptiform oscillations are highly localized in the seizure onset zone, both before and temporally removed from seizure onset. These findings were observed in all six patients with neocortical epilepsy out of 23 consecutive patients implanted with intracranial electrodes for pre-surgical evaluation during the study period. The majority of seizures (62%) in these patients were anticipated by an increase in high-frequency activity in the 20 min prior to neocortical seizure onset. Contrary to observations in normal brain, high-frequency activity was strongly modulated by behavioural state, and was maximal during slow-wave sleep, which may explain the propensity for neocortical onset seizures to begin during sleep. These findings point to an important role for neuromodulatory circuits, probably involving the thalamus, in mechanisms underlying seizure generation in neocortical epilepsy. These findings demonstrate that high-frequency epileptiform oscillations may prove clinically useful in localizing the seizure onset zone in neocortical epilepsy, for identifying periods of increased probability of seizure onset, and in elucidating mechanisms underlying neocortical ictogenesis. Confirmation that prolonged bursts of high-frequency activity may predict focal onset neocortical seizures will require prospective validation on continuous, prolonged recordings in a larger number of patients. Importantly, the results show that the dynamic range utilized in current clinical practice for localization of epileptogenic brain largely ignores fundamental oscillations that are signatures of an epileptogenic brain. It may prove that many currently available clinical EEG systems and EEG analysis methods utilize a dynamic range that discards clinically important information.

Mechanisms of physiological and epileptic HFO generation

“…Initially they were described in hippocampus and entorhinal cortex of patients with TLE (Bragin et al, 1999a(Bragin et al, , 2002bStaba et al, 2002Staba et al, , 2004) using microelectrode recordings. Later they were observed using clinical depth and grid electrodes in patients with temporal lobe epilepsy as well in patients with different types of neocortical epilepsy (Bagshaw et al, 2009;Jacobs et al, 2008;Jirsch et al, 2006;Worrell et al, 2004Worrell et al, , 2008. Whether mechanisms of pathological HFOs observed in the hippocampus of epileptic animals and those observed in the neocortex of epileptic patients are the same or different remains unclear.…”

High-Frequency Network Activity, Global Increase in Neuronal Activity, and Synchrony Expansion Precede Epileptic SeizuresIn Vitro

“…Recent studies have suggested an important role of HFA in epileptogenesis (Bragin et al, 1999(Bragin et al, , 2000(Bragin et al, , 2004 and in seizure initiation (Allen et al, 1992;Fisher et al, 1992;Bikson et al, 2003;Grenier et al, 2003;Bragin et al, 2005). However, studies specifically on the role of HFA in the preictal state are sparse, generally fail to address the cellular and network mechanisms of its buildup, and in some cases consider it an epiphenomenon (Worrell et al, 2004;Khosravani et al, 2005).…”

Cortical abnormalities in epilepsy revealed by local EEG synchrony

“…Extending interictal ICEEG interpretation using quantitative techniques, however, have disclosed critical background features relevant to surgical decisionmaking that are not apparent to visual inspection. For example, very high frequency (> 100 Hz), low amplitude activity (< 5 μV) has been associated with the epileptogenic zone (Worrell, Parish et al 2004;Alarcon, Binnie et al 1995;Allen, Fish et al 1992), as has neuronal synchrony recorded from hippocampal microelectrodes (Colder, Wilson et al 1996) and spectrogram measurements of EEG amplitude (Asano, Muzik et al 2004). Such techniques may be used to detect signatures of cortical abnormality that are not necessarily associated with the well known paroxysmal features, and that may be linked to seizures.…”