High-frequency oscillations in epileptic brain

Abstract

Purpose of review: It has been 10 years since pathological high-frequency oscillations (pHFOs) were described in the brain of epileptic animals and patients. This review summarizes progress in research on mechanisms of their generation and potential clinical applications over that period.

Recent findings: Initially, pHFOs were recorded with microelectrodes in the hippocampus of rodents and patients with mesial temporal lobe epilepsy (MTLE), but recently pHFOs have also been recorded with clinical depth and grid electrodes in multiple brain areas including the hippocampus and neocortex of patients with different types of epilepsy. One hypothesis is that pHFOs reflect fields of hypersynchronized action potentials (bursts of population spikes) within small discrete neuronal clusters responsible for seizure generation. Studies suggest that pHFOs can be used as a reliable biomarker for epileptogenesis, epileptogenicity, and the delineation of the epileptogenic region.

Summary: Recording of pHFOs with clinical electrodes provides a means for further investigation of their functional role in the epileptic brain and as a potential biomarker of epileptogenesis and epileptogenicity and for presurgical mapping.

Figure 1. Functional difference between interictal spikes that do and do not contain pathological high-frequency oscillations

(a) An example of an IIS simultaneously recorded from several electrode contacts in an epileptic rat. Recordings from microelectrodes 5–8 contain IIS with pHFOs, microelectrodes 1 and 2 contain EEG IIS without pHFOs and no IISs or pHFOs are present in microelectrodes 3 and 4. The pHFOs occurred first at microelectrode 6 and approximately 10 ms later at microelectrodes 5, 7, and 8. (b) A schematic of the role of each recoding sites in the propagation of epileptiform activity. After occurrence at recoding site 6, epileptiform activity propagates further through recording sites 5, 7, and 8 but not through recording sites 1 and 2 (see text for further explanation). (c) A hypothetical case of how mapping of IIS containing pHFOs could be used for determining which parts of neocortex participate in the propagation of epileptiform activity. Grid electrodes marked white record IISs containing pHFOs, whereas those marked black record IISs without pHFOs. pHFOs occur first in electrodes marked ‘A’, then progress through groups of electrodes marked ,‘B’, ‘C’, and ‘D’ (see examples of records on the right). In this case, the part of the neocortex outlined by the dashed ellipse actively participates in the generation and propagation of epileptiform activity from left to right, whereas other electrodes do not. IIS, interictal spike; pHFO, pathological high-frequency oscillation.