Modelling the Effect of Sex Steroid Hormones on the Resolution of Absence Seizures

Maliha Ahmed

Childhood absence epilepsy (CAE) is an idiopathic generalized epilepsy disorder which affects children between the ages of 4-12 years. It is characterized by sudden brief periods of impaired consciousness occurring several times a day. One of the most confounding features of CAE is its ability to spontaneously resolve in adolescence in roughly 80% of cases, while in others it can progress into more severe types of epilepsy. There remains an inadequate understanding of some of the factors involved in remission that can inform early intervention practices and our research will help fill in those gaps. According to some functional connectivity studies, there exist pre-treatment connectivity differences between patients who ultimately experience remission and those who do not, namely increased frontal cortical connections at the time of diagnosis. There is also substantial evidence on the effect of sex steroids on human (and animal) brain rhythmic discharges, particularly the effect of progesterone metabolite allopregnanolone on the action of gamma-Aminobutyric acid (GABA), an inhibitory neurotransmitter. We have developed a computational model of the thalamocortical network to study the role of allopregnanolone on network behaviour in the eventual resolution of CAE. The results from this research can possibly better inform therapeutic decisions relating to early interventions tailored to intrinsic network connectivity arrangements, which can be evaluated prior to the start of treatment and at the time of diagnosis.

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