title: Starting and stopping mechanisms of absence epileptic seizures are revealed by hazard functions.
abstract: We show that the hazard function provides useful information about the starting and the stopping mechanisms of absence epileptic seizures. The hazard function quantifies changes in the probability that an event (respectively, the starting and the stopping of a seizure) occurs in some small time interval given that it has not occurred yet. It informs us about changes in the concentration of endogenous substances that modulate the neuronal signalling properties of (parts of) the brain. In a pharmacological experiment, we used the hazard function to study the effect of a GABA-transaminase inhibitor (vigabatrin) on the starting and the stopping mechanisms of absence epileptic seizures in a genetic rat model of absence epilepsy (the WAG/Rij rat). This experiment showed that a high GABA level changed the stopping mechanism of the absence epileptic seizures, creating much better conditions for very long seizures to develop. With respect to the starting mechanism, it was found that both with a high and a low GABA level, there was evidence for a recovery mechanism that decreases the probability that a new seizure starts. Initially, this probability is larger with a high GABA level, but gradually it converges to the same constant baseline probability as in the condition with a low GABA level.
authors.affiliation: Nijmegen Institute of Cognition and Information (NICI), Radboud University Nijmegen, P.O. Box 9104, 6500 HE Nijmegen, The Netherlands. maris@nici.ru.nl
authors.forename: Eric
authors.initials: E
authors.lastname: Maris
authors.forename: Brigitte M
authors.initials: BM
authors.lastname: Bouwman
authors.forename: Piotr
authors.initials: P
authors.lastname: Suffczynski
authors.forename: Clementina M
authors.initials: CM
authors.lastname: van Rijn
mesh_terms: D000465:Algorithms; D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use; D003627:Data Interpretation, Statistical; D004569:Electroencephalography / Q000706:statistics & numerical data; D004832:Epilepsy, Absence / Q000503:physiopathology*; D008959:Models, Neurological; D015233:Models, Statistical; D016571:Neural Networks, Computer; D016016:Proportional Hazards Models; D051381:Rats; D020888:Vigabatrin / Q000627:therapeutic use; D005680:gamma-Aminobutyric Acid / Q000378:metabolism / Q000502:physiology
chemical_list: D000927:Anticonvulsants; D005680:gamma-Aminobutyric Acid; D020888:Vigabatrin