American Journal for Young Scientists ยท ISSN 3068-9015
A Minimal HPA Axis Model Linking Cortisol Dynamics, Genetics, and Temporal Lobe Epilepsy
Authors: Mahita Chava
Published: September 5, 2025
Category: Computational Neuroscience
Abstract
Temporal lobe epilepsy (TLE) is the most common type of epilepsy due to the unique location of the hippocampus within the temporal lobe. Previous research has supported the idea that cortisol produced through the Hippocampus-Pituitary Gland-Adrenal Gland (HPA) Axis inhibits activity of the hippocampus. Current anti epileptic drugs target activity in the hippocampus to treat TLE; however, the impacts of such drugs on the HPA Axis are not studied deeply. Our minimal mathematical model of the HPA axis relates the levels of cortisol and hippocampal activity as well as adrenal gland size depending on how long an anti epileptic drug is taken. Through this model, we can understand why anti epileptic drugs need to be taken for several weeks before improvement can be seen in patient health. Moreover, we use model parameter D, a proxy for the maximum hippocampal activation when cortisol levels exceed the threshold. This parameter is determined by genetics. Nonlinear dynamical systems study through phase portraits revealed existence of 1 or 2 stable fixed points, corresponding to the epileptic and healthy states, as well as 0 or 1 unstable point depending on the genetics. The model predicts that higher values of D can be associated with an epileptic state while lower values of D can be associated with a healthy state.