Elsevier

Epilepsy Research

Volume 61, Issues 1–3, September–October 2004, Pages 89-104
Epilepsy Research

Pre-ictal synchronicity in limbic networks of mesial temporal lobe epilepsy

https://doi.org/10.1016/j.eplepsyres.2004.06.006Get rights and content

Abstract

Purpose: We recorded with intracerebral electrodes the onset of limbic seizures in patients with mesial temporal lobe epilepsy (MTLE) to identify the dynamic interactions between the hippocampus (HIP), amygdala (AMY) and entorhinal cortex (EC). Method: Interactions were quantified by analyzing the interdependencies between stereo-electroencephalographic (SEEG) signals using a nonlinear cross-correlation method. Seizures from 12 patients were analyzed by identifying three periods of interest: (i) the rapid discharge that occurs at seizure onset (“during rapid discharge”, DRD period); (ii) the time interval that precedes this rapid discharge (“before rapid discharge”, BRD period); and the time that follows the rapid discharge (“after rapid discharge”, ARD period). The transition from interictal to ictal discharge was classified into: (i) “type 1 transition” in which the emergence of pre-ictal spiking was followed by a rapid discharge; and (ii) “type 2 transition” that was associated with rapid discharge onset without prior spiking. Results: In both types of transition the BRD period was characterized by significant cross-correlation values indicating strong interactions among mesial temporal structures as compared to those seen during background activity. Interactions between HIP and EC were predominant in 10 of 12 patients (83%). Interactions between EC and AMY were observed in 6 of 12 cases (50%) and between AMY and HIP in 7 of 12 cases (58%). Analysis of coupling directionality indicated that most of the couplings were driven either by HIP (six patients) or by the EC (four patients). The DRD period was characterized by a significant decrease of cross-correlation values. In addition, type 1 transition was characterized by interactions that uniformly involved the three structures, while type 2 transition was associated with interactions between EC and HIP. Finally, analysis of coupling direction demonstrated that the HIP was always the leader in type 1 transition whereas in type 2 the EC was most often the leading structure. Conclusions: This study demonstrates that pre-ictal synchronization between mesial structures is the initial event for seizures starting in the mesial temporal region.

Introduction

Seizures in patients with mesial temporal lobe epilepsy (MTLE) are the most common form of partial epileptic seizures (Williamson et al., 1998). Since they are often resistant to antiepileptic drug treatment, detailed study of the functional organization of the epileptogenic zone in MTLE patients may provide important indications for therapeutic approaches such as selective surgery, selective radio surgery or depth stimulations. Depth-EEG recordings performed with intracerebral electrodes during pre-surgical evaluation have shown that seizures in MTLE patients are generated within the mesial part of the temporal lobe (Bancaud, 1981, Engel et al., 1989, Spencer et al., 1992). However, the precise functional organization of the epileptogenic zone is still a matter of debate (Bartolomei et al., 2001, Bertram et al., 1998).

According to the “focal” model, a single pathological region is responsible for seizure generation. Accordingly, in the past, most studies have focussed on the role of hippocampal alterations in MTLE and some of these investigations have established a link between the presence of hippocampal atrophy and the area of seizure onset (King et al., 1997). In contrast, the “network” model holds that limbic seizures may result from a more extensive alteration of limbic networks within the temporal lobe (Bartolomei et al., 2001, Bertram et al., 1998). Recent findings support this second view. Besides hippocampal atrophy, recent studies have demonstrated a reduction in the volume of other limbic regions, such as the entorhinal cortex in MTLE patients (Bernasconi et al., 1999, Bernasconi et al., 2000, Jutila et al., 2001) (Du et al., 1993). Moreover, experimental studies indicate that seizure onset in MTLE models involves several limbic regions (Avoli et al., 2002, Bertram et al., 1998).

Depth electrode studies in MTLE patients have also revealed that epileptic discharges may be recorded from several limbic regions, including the hippocampus and the entorhinal cortex (Bartolomei et al., 2001, Velasco et al., 2000a). However, in this situation, the relative contribution of the different mesial structures (amygdala, rhinal cortices and hippocampus) remains poorly understood in humans, even though studies in human (Spencer and Spencer, 1994) or animal models (Barbarosie et al., 2000, Lothman et al., 1991) have suggested that the abnormal interaction between entorhinal cortex and hippocampal formations may be responsible for seizures.

In this paper, we analyzed the dynamics of interactions between three limbic areas (i.e., amygdala, entorhinal cortex and hippocampus), which were recorded with depth electrodes, during seizures in MTLE patients. These interactions were quantified by estimating the interdependencies between EEG signals. Specifically, a signal processing method based on nonlinear regression analysis (Meeren et al., 2002, Pijn, 1990, Wendling et al., 2001) was applied to depth-EEG time series in order to characterize the evolution of their cross-correlation. Based on the analysis of interactions between regions at the onset of seizures recorded intracerebrally, our results support the “epileptogenic network” hypothesis, namely that synchronized oscillations among spatially distributed limbic structures represent the substratum of the epileptogenic zone leveling this epileptic disorder .

Section snippets

Patient selection and SEEG recording

Twelve patients undergoing pre-surgical evaluation of drug-resistant MTLE were selected. All patients had a comprehensive evaluation including detailed history and neurological examination, neuropsychological testing, routine magnetic resonance imaging (MRI), surface electroencephalography (EEG) and stereoelectroencephalography (SEEG, depth electrodes). The latter was performed during long-term video-EEG monitoring. SEEG was carried out as part of our patient's normal clinical care, and they

Visual inspection of SEEG signals and analysis of power spectral densities

All selected seizures started from the mesial region of the temporal lobe. Signals recorded by electrodes sampling other temporal lobe regions (i.e., neocortex, temporo-basal cortex, insular cortex) as well as from electrodes positioned in frontal and parietal lobe, did not show EEG modifications, indicating that these regions were not involved at seizure onset. All seizures were characterized by the appearance of a rapid discharge in the three considered mesial structures. The duration of

Discussion

This study demonstrates that SEEG signals recorded from limbic structures of the temporal lobe are characterized by a significantly high correlation during the period preceding the appearance of rapid epileptic discharges. This first period of “synchrony” was also followed by a period of “desynchrony”, that corresponds to the appearance of rapid discharges, marked by a decrease of cross-correlation. To our knowledge this result has not been shown previously and warrants discussion from several

Acknowledgements

The authors wish to thank Professor Massimo Avoli for his constructive suggestions and valuable comments on the present work and Dr Aileen McGonigal for the revision of the English version of this paper and for helpful comments.

References (39)

  • D. Amaral et al.

    Hippocampal formation

  • J. Bancaud

    Epileptic attacks of temporal lobe origin in man

    Jpn. J. EEG EMG

    (1981)
  • M. Barbarosie et al.

    CA3 driven hippocampal entorhinal loop controls raher that sustains in vitro limbic seizures

    J. Neurosci.

    (1997)
  • M. Barbarosie et al.

    CA3-Released entorhinal seizures disclose dentate gyrus epileptogenicity and unmask a temporoammonic pathway

    J. Neurophysiol.

    (2000)
  • J. Bendat et al.

    Random Data: Analysis and Measurement Procedures

    (1971)
  • N. Bernasconi et al.

    Entorhinal cortex in temporal lobe epilepsy: a quantitative MRI study

    Neurology

    (1999)
  • N. Bernasconi et al.

    Morphometric MRI analysis of the parahippocampal region in temporal lobe epilepsy

    Ann. N. Y. Acad. Sci.

    (2000)
  • A. Bragin et al.

    Hippocampal and entorhinal cortex high-frequency oscillations (100--500 Hz) in human epileptic brain and in kainic acid-treated rats with chronic seizures

    Epilepsia

    (1999)
  • I. Cohen et al.

    On the origin of interictal activity in human temporal lobe epilepsy in vitro

    Science

    (2002)
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