Elsevier

Neuroscience Letters

Volume 566, 30 April 2014, Pages 21-26
Neuroscience Letters

Using ictal high-frequency oscillations (80–500 Hz) to localize seizure onset zones in childhood absence epilepsy: A MEG study

https://doi.org/10.1016/j.neulet.2014.02.038Get rights and content

Highlights

  • Ictal high-frequency oscillations correlate with absence seizures.

  • The rate of fast ripples is associated with absence seizure frequency.

  • Ictal high-frequency oscillations are mainly located to medial prefrontal cortex.

  • Compared with spikes, high-frequency oscillations have more focal distribution.

Abstract

This study aimed to use ictal high-frequency oscillations (HFOs) ranging from 80 Hz to 500 Hz to locate seizure onset zones in childhood absence epilepsy (CAE) using non-invasive magnetoencephalography (MEG). Ten drug-naïve children with CAE were studied using a 275-channel MEG system. MEG data were digitized at a sampling rate of 6000 Hz. HFO spectral power in real-time spectrograms was assessed using Morlet continuous wavelet transform. Magnetic sources were volumetrically localized through dynamic magnetic source imaging with a slide window. HFOs were identified in all patients. The total time of fast ripples (250–500 Hz) was greater than that of ripples (80–250 Hz) during absence seizures. The rate of fast ripples was associated with seizure frequency. HFO duration was significantly longer when co-occurring with spikes than when occurring independently, and the maximum frequency of HFOs co-occurring with spikes was higher than that of HFOs occurring independently. HFOs were predominantly localized in the medial prefrontal cortex (MPFC), whereas spikes were widespread to a variety of regions during the absence seizures. Compared with spikes, HFOs appeared to be more focal. The findings indicate that HFOs in the MPFC have a primary function in initializing epileptic activity in CAE.

Introduction

Childhood absence epilepsy (CAE) is a non-convulsive event characterized by brief (approximately 5–30 s) disruptions in consciousness, as well as 3 Hz bilateral, synchronous spike-and-wave discharges (SWDs) on normal background activity on electroencephalography (EEG) [1]. Although the argument of initialization in CAE has lasted for more than a decade, the exact absence seizure onset zones (SOZ) have not been fully elucidated.

Magnetoencephalography (MEG), a relatively new clinical neuroimaging modality, is well suited for the study of epileptic discharges because MEG can noninvasively detect and localize neuromagnetic signals [2], [3], [4], [5]. Brain activity in a low-frequency range (<80 Hz) has been conventionally studied in epilepsy. Recent advances in brain research have demonstrated that the epileptic brain generates high-frequency oscillations (HFOs, 80–500 HZ); these HFOs can be divided into ripples (80–250 Hz) and fast ripples (FRs) (250–500 Hz) [6], [7], [8]. Reports over the last decade on human epileptic brain with intracranial recording have suggested that HFOs are linked to epileptogenic zones [6], [7], [9], [10]. Studies have demonstrated that good surgical outcome is well correlated with the removal of HFO-generating areas rather than spike-generating areas [10], [11], [12], [13]. Furthermore, the use of HFOs as biomarkers of epileptogenicity in resective procedures improves seizure outcome and represents a novel approach for the treatment of epilepsy.

The objective of the present study was to investigate the spectral and spatial features of HFOs in CAE with MEG, a new clinical neuroimaging modality that can be used to measure very weak magnetic signals from the brain. We hypothesize that the ictal HFOs in CAE will provide novel insight into the initialization of absence seizures in the brain.

Section snippets

Patients

Ten patients (5–11 years old) were recruited from the Department of Neurology of Nanjing Children's Hospital from November 2012 to November 2013 (Table 1).

The inclusion criteria were as follows: (1) clinical diagnosis of typical absence epilepsy consistent with the International League Against Epilepsy Proposal for Revised Classification of Epilepsies and Epileptic Syndromes [1]; (2) clinical EEG recordings with bilateral, synchronous, symmetrical, approximately 3 Hz spike waves, on a normal

Results

None of the 10 children recruited in the study had taken any medicine. Therefore, all subjects were drug naïve and the effect of drugs on MEG data could be eliminated. The clinical details are shown in Table 1. The children are aged 5–11 years, with an average age of 8 years. The seizure frequency ranged from 3 to 15 times per day. We successfully obtained 33 stereotyped ictal MEG recordings from the 10 children.

According to our routine MEG system and environmental noise test, the polarity

Discussion

In this study, HFOs were identified with polarity spectrogram, and the sources for HFOs were localized to the MPFC with dMSI. The results indicate that HFOs in the MPFC may have a primary function in the absence seizures.

Acknowledgements

This study was supported by Key Project of Medical Science and Technology Development Foundation, Nanjing Department of Health (No. ZKX11002, http://www.njh.gov.cn/html/list_83.shtml). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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