Mechanisms of physiological and epileptic HFO generation

Abstract

High frequency oscillations (HFO) have a variety of characteristics: band-limited or broad-band, transient burst-like phenomenon or steady-state. HFOs may be encountered under physiological or under pathological conditions (pHFO). Here we review the underlying mechanisms of oscillations, at the level of cells and networks, investigated in a variety of experimental in vitro and in vivo models. Diverse mechanisms are described, from intrinsic membrane oscillations to network processes involving different types of synaptic interactions, gap junctions and ephaptic coupling. HFOs with similar frequency ranges can differ considerably in their physiological mechanisms. The fact that in most cases the combination of intrinsic neuronal membrane oscillations and synaptic circuits are necessary to sustain network oscillations is emphasized. Evidence for pathological HFOs, particularly fast ripples, in experimental models of epilepsy and in human epileptic patients is scrutinized. The underlying mechanisms of fast ripples are examined both in the light of animal observations, in vivo and in vitro, and in epileptic patients, with emphasis on single cell dynamics. Experimental observations and computational modeling have led to hypotheses for these mechanisms, several of which are considered here, namely the role of out-ofphase firing in neuronal clusters, the importance of strong excitatory AMPA-synaptic currents and recurrent inhibitory connectivity in combination with the fast time scales of IPSPs, ephaptic coupling and the contribution of interneuronal coupling through gap junctions. The statistical behaviour of fast ripple events can provide useful information on the underlying mechanism and can help to further improve classification of the diverse forms of HFOs.

Initiation, Propagation, and Termination of Partial (Focal) Seizures

“…HFOs are categorized as ripples and fast ripples (250 -500 Hz) (Jefferys et al 2012a), and it has been proposed that ripples represent inhibitory postsynaptic potentials (IPSPs) generated by principal neurons entrained by synchronously active interneuron networks (Ylinen et al 1995), whereas fast ripples reflect synchronous in-phase or out-ofphase firing of abnormally active (Jefferys et al 2012) principal cells, thus being independent of inhibitory neurotransmission (Dzhala and Staley 2004;Foffani et al 2007;Engel et al 2009;Ibarz et al 2010;Bragin et al 2011). According to the findings reported by Avoli and colleagues (Levesque et al 2012), low-voltage fast activity seizures are mainly associated with increased ripple rates, whereas hypersynchronous seizures are mostly accompanied by fast ripples.…”

Neurosteroids modulate epileptiform activity and associated high-frequency oscillations in the piriform cortex

“…High-frequency oscillations (HFOs, Hz, fast ripples: 250-500 Hz) are recorded in the EEG of epileptic patients and in animal models of temporal lobe epilepsy (Engel and da Silva, 2012;Jefferys et al, 2012). HFOs occur in limbic structures such as the hippocampus and entorhinal cortex as well as in the neocortex, they are thought to reflect the activity of dysfunctional neural networks, and they are used to localize seizure onset zones (Bragin et al, 2004;Jacobs et al, 2009Jacobs et al, , 2010Ibarz et al, 2010;Jiruska et al, 2010;Wu et al, 2010;Lévesque et al, 2011Lévesque et al, , 2012.…”

Two different interictal spike patterns anticipate ictal activity in vitro

“…In addition, we established the occurrence of high frequency oscillations (HFOs, 80-500 Hz) during these different patterns of interictal and ictal epileptiform activity. HFOs occur in limbic structures such as the EC and hippocampus, and are thought to reflect the activity of dysfunctional neural networks (Bragin et al, 2004; see for review Jefferys et al, 2012;Engel and Lopes da Silva, 2012).…”