High-frequency oscillations during human focal seizures

Abstract

Discrete high-frequency oscillations (HFOs) in the range of 100-500 Hz have previously been recorded in human epileptic brains using depth microelectrodes. We describe for the first time similar oscillations in a cohort of unselected focal epileptic patients implanted with EEG macroelectrodes. Spectral analysis and visual inspection techniques were used to study seizures from 10 consecutive patients undergoing pre-surgical evaluation for medically refractory focal epilepsy. Four of these patients had focal seizure onset in the mesial temporal lobe, and in all 12 of their seizures, well-localized, segmental, very high frequency band (VHF: 250-500 Hz) oscillations were visually identified near the time of seizure onset from contacts in this zone. Increased high-frequency band (HF: 100-200 Hz) activity compared with the background was distinguished both visually and with spectral analysis later in the seizures of 3/4 mesial temporal patients, involving contacts in the generator region and, in one patient, areas of contralateral peri-hippocampal propagation. Three patients with well-defined neocortical seizure-onset areas also demonstrated focal HF or VHF oscillations confined to the seizure-onset channels during their eight seizures. No discrete HF or VHF activity was present in the poorly localized seizures from the remaining three patients. These results show that discrete HFOs can be recorded from human focal epileptic brain using depth macroelectrodes, and that they occur mostly in regions of primary epileptogenesis and rarely in regions of secondary spread. Absent high-frequency activity seems to indicate poor localization, whereas the presence of focal HFOs near the time of seizure onset may signify proximity to the epileptogenic focus in mesial temporal lobe and neocortical seizures. We postulate that focal HFOs recorded with depth macroelectrodes reflect the partial synchronization of very local oscillations such as those previously studied using microelectrodes, and result from interconnected small neuronal ensembles. Our finding that localized HFOs occur in varying anatomical structures and pathological conditions perhaps indicates commonality to diverse epileptogenic aetiologies.

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.…”

GABAergic synchronization in the limbic system and its role in the generation of epileptiform activity

“…Although, the frequency delimitation of ripples and fast ripples remains a matter of debate, it has been proposed that fast ripples, unlike ripples, are seen exclusively in the epileptic tissue (Bragin et al, 1999;Jirsch et al, 2006). Moreover, experiments performed in both in vitro and in vivo preparations indicate that fast ripples do not depend on inhibitory transmission as they are easily observed during GABA A receptor blockade and, indeed, they appear to represent the synchronous firing of principal (glutamatergic) neurons (D'Antuono et al, 2005;Engel et al, 2009;Bragin et al, 2011).…”

Automatic detection of fast oscillations (40–200Hz) in scalp EEG recordings

“…Recent studies suggest that they may play an important role in normal and pathological brain function. In epileptic patients high frequency oscillations were found in intracranial EEG recordings, both with microelectrodes (Bragin et al, 1999a,b;Staba et al, 2002) and macroelectrodes during ictal (Jirsch et al, 2006) and interictal intervals (Urrestarazu et al, 2007;Jacobs et al, 1893;Worrell et al, 2008;Crepon et al, 2010). The high frequency oscillations appear to be a good indicator of the seizure onset zone , and are possibly related to the outcome of epilepsy surgery .…”