Automatic control of Hypothalamus-Pituitary-Adrenal axis dynamics

In this study, a presentation is made for the automatic control of the hypothalamus-pituitary-adrenal axis which plays an important role in the immune stress responses and the circadian rhythms of mammalian organisms.

Control approaches are implemented on a novel second order nonlinear system which accepts adrenocorticotropin hormone as an input and models the variation of plasma concentrations of adrenocorticotropin and cortisol respectively. The control methods are based on back-stepping and input-output feedback linearization techniques. The controllers adjust the adrenocorticotropin injection to maintain the daily rhythm of the cortisol concentration. In accordance with the periodicity of biological clock mechanism, we provide a sinusoidally varying cortisol reference to the controllers.

Numerical simulations are performed (on MATLAB) to demonstrate the closed loop performance of the controllers. Major concerns in the selection of the control gains are chattering and negative concentration in responses. The simulation results showed that one can successfully find gain levels which do not lead to those issues. However, the gains lie in different ranges for back-stepping and feedback linearization based controllers.

The results showed that, both back-stepping and feedback linearization based controllers fulfilled their duty of synchronization of the cortisol concentration to a reference daily periodic rhythm. In addition to that, the risk of negative valued adrenocorticotropin injection can be eliminated by properly choosing the controller gains.