High‐frequency oscillations: What is normal and what is not?

Abstract

SUMMARYHigh-frequency oscillations (HFOs) in the 80-200 Hz range can be recorded from normal hippocampus and parahippocampal structures of humans and animals. They are believed to reflect inhibitory field potentials, which facilitate information transfer by synchronizing neuronal activity over long distances. HFOs in the range of 250-600 Hz (fast ripples, FRs) are pathologic and are readily recorded from hippocampus and parahippocampal structures of patients with mesial temporal lobe epilepsy, as well as rodent models of this disorder. These oscillations, and similar HFOs recorded from neocortex of patients, appear to identify brain tissue capable of spontaneous ictogenesis and are believed to reflect the neuronal substrates of epileptogenesis and epileptogenicity. The distinction between normal and pathologic HFOs (pHFOs), however, cannot be made on the basis of frequency alone, as oscillations in the FR frequency range can be recorded from some areas of normal neocortex, whereas oscillations in the ripple frequency range are present in epileptic dentate gyrus where normal ripples never occur and, therefore, appear to be pathologic. The suggestion that FRs may be harmonics of normal ripples is unlikely, because of their spatially distinct generators, and evidence that FRs reflect synchronized firing of abnormally bursting neurons rather than inhibitory field potentials. These synchronous population spikes, however, can fire at ripple frequencies, and their harmonics appear to give rise to FRs. Investigations into the fundamental neuronal processes responsible for pHFOs could provide insights into basic mechanisms of epilepsy. The potential for pHFOs to act as biomarkers for epileptogenesis and epileptogenicity is also discussed.

Ictal and interictal high frequency oscillations in patients with focal epilepsy

“…Immediately preceding the seizure, inhibitory activity is reduced, which results in a reduction in spike activity, while the epileptogenic activity of the tissue increases, which results in an increase in HFOs. Then, at seizure onset, larger circuits get involved, appearing as rhythmic activity over more channels (Bragin et al, 2005(Bragin et al, , 2007Engel et al, 2009). Within these larger circuits the pathological tissue still oscillates at high frequencies, while in an adjacent but broader area spikes are seen.…”

“…Finally, removal of HFO generating tissue is related to good surgical outcome, more than spikes and the SOZ are (Jacobs et al, 2010), which supports their relation to epileptogenic tissue and potential clinical importance. The current hypothesis is that HFOs result from misconnected or disinhibited neuronal networks leading to highly synchronized neuronal activity over an area of brain tissue, which in turn results in seizure genesis after other areas or networks get involved (Bragin et al, 2004a;Engel et al, 2009;Ogren et al, 2009). …”

“…Ripples have been thought to be more physiological in nature and involved in memory, while FRs appear to be pathological, except for FRs in sensory evoked potentials (Axmacher et al, 2008;Buzsaki et al, 1992;Curio et al, 1997;Engel et al, 2009;Worrell et al, 2008). HFOs often co-occur with epileptic spikes, but there are HFOs without spikes and spikes without HFOs (Jacobs et al, 2008;Urrestarazu et al, 2006).…”

Mechanisms of physiological and epileptic HFO generation

“…The close relationship between hippocampal fast ripples and individual cell bursting is now widely accepted in the field (Bikson et al, 2003a;Engel et al, 2009;Köhling and Staley, 2011). A major reason to focus at their mechanisms is linked with their potential diagnostic value: if fast ripples are biomarkers of abnormal and enhanced forms of neuronal synchronization, then their detection can be used to closely delineate the epileptogenic territories and to eventually identify candidate areas for resection in combinations with other clinical variables (Jacobs et al, 2010;Zijlmans et al, 2012).…”

“…Because the interactions between the different cellular clusters should not proceed stereotypically due to the background noise, one should expect that the contribution of individual neurons and hence the appearance of fast ripple cycles varies substantially in a given region. Microelectrode recordings in humans have shown the coexistence of fast ripples with HFO in the physiological ripple band (Bragin et al, 1999b;Staba et al, 2002;Worrell et al, 2008), and the events themselves show spectral fluctuations being difficult to classify based only on frequency criteria (Blanco et al, 2010;Engel et al, 2009;Ibarz et al, 2010).…”