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