Abstracts

RATIONALE: The transient hypersynchrony of neuronal firing of epileptic seizures can be considered as the transitory stabilization of unstable dynamical states. We present an approach to characterize the dynamics of the transition to seizure, using in vitro, in vivo data, and recordings from patients with intractable epilepsies.
METHODS: Recording methods.
EEG recordings were performed with subdural, depth and/or scalp electrodes in 5 patients with localization-related epilepsy, and 3 with generalized epilepsy. The EEG signals were digitized at 200 Hz. For the in vivo experiments, Long Evans rats were treated with the inhibitor of cholesterol synthesis AY9944, which results in atypical absence seizures, and electrocorticography performed as described (1). In vitro field potential recordings were obtained from the CA1 area in rat hippocampal brain slices, during spontaneous interictal and ictal activity induced by superfusion with low-magnesium ACSF. Data were stored using the PCLAMP software.
Analysis methods.
Peaks were detected in all recordings using an algorithm that selects peaks based on amplitude and width criteria. Interpeak interval (IPI) plots were constructed as described (2). IPI scatter plots were approximated by algebraic equations and analyzed by standard nonlinear dynamical methods, using the software packages INSITE and Origin (Microcal Software Inc.).
RESULTS: First and second-return IPI and peak amplitude plots revealed that the transition to seizure had similar dynamical characteristics in all cases. The analysis of the one-dimensional maps obtained by fitting the first-return plots indicated that a subharmonic, or flip, bifurcation is present in the pre-ictal activity in the in vitro experiments and in most of the patient recordings. This bifurcation leads to type III intermittency in most cases.
Bifurcation analysis using the map parameters revealed periodic, quasiperiodic and possibly chaotic regimes. The presence of chaotic dynamics is discussed.
The transition from absence to generalized tonic-clonic seizures in a patient is compared with the dynamics of the seizure activity in the in vivo rat model of atypical absence epilepsy.
CONCLUSIONS: The transition to seizure is marked by a subharmonic, or flip, bifurcation that leads to the transient stabilization of the metastable steady state representing high-frequency hypersynchronous neuronal firing. The similarity in the dynamical regimes in the in vitro experiments,in the patient recordings and in vivo experiments suggest that similar collective dynamics are operating in the generation of seizures.
Support: The Savoy Foundation and the Canadian Institutes of Health Research
(1)Cortez et al. 2001, Neurology 56:341-349
(2)Perez Velazquez et al. 1999, Eur. J. Neurosci. 11:2571-2576