Very high‐frequency oscillations: Novel biomarkers of the epileptogenic zone

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Throughout most of the 20th century, there was little clinical interest in electroencephalographic (EEG) frequencies > 100Hz. In 1999, the potential clinical relevance and association of high‐frequency oscillations (HFOs; 100 and 500Hz) with epileptogenic human brain were reported.1 HFOs have been observed in both micro‐ and macroelectrode recordings, between seizures, at seizure onset, and during seizures (reviewed in Zijlmans et al).4 Interictal ripples (Rs; 80–250Hz) and fast ripples (FRs; 250 and 500Hz) are both increased in the seizure onset zone (SOZ), and removal of tissue generating interictal HFOs correlates with good surgical outcome.5 HFOs have proven to be more specific in indicating the SOZ than interictal epileptiform spikes.10 A fundamental challenge, however, has been that physiological HFOs associated with normal brain function overlap in frequency with pathological HFOs,11 and how they can be separated remains unclear.14 Despite this and other challenges, HFOs remain a promising biomarker of tissue epileptogenicity.15
Recently ictal very high‐frequency oscillations (VHFOs) with frequencies ≥ 1kHz were described in a cohort of patients with focal epilepsy.16 In 7 of 13 investigated subjects, the authors detected VHFOs in 1 to 4 subdural electrode contacts per patient. The comparison of postoperative seizure outcome with the presence or absence of ictal VHFOs and ictal HFOs and completeness of resection of the tissue generating HFOs and VHFOs was performed, and ictal VHFOs were a more specific marker than ictal HFOs for identifying the epileptogenic zone.16 It is notable that for engineering and practical reasons the majority of human intracranial EEG recordings have not explored local field oscillations > 600Hz.
The aim of the present study was to investigate penetrating depth EEG recordings in a large cohort of patients with drug‐resistant epilepsy and to focus on interictal local field potential (LFP) oscillations between 500Hz and 2kHz. Furthermore, we introduce a technique for visualization, localization, and quantitative description of VHFOs. We hypothesized that interictal VHFOs, by analogy to previously reported very high‐frequency ictal activity, are more specific biomarkers for epileptogenic zone compared to Rs or FRs.
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