System Identification of Cortisol Secretion: Characterizing Pulsatile Dynamics

April 20, 2015
Speaker: Rose Faghih, Postdoctoral Associate, MIT/Harvard Neuroscience Statistics Research Laboratory


Cortisol controls the body's metabolism and response to inflammation and stress. Cortisol is released in pulses from the adrenal glands in response to pulses of adrenocorticotropic hormone (ACTH) released from the anterior pituitary; in return, cortisol has a negative feedback effect on ACTH release. Modeling cortisol secretion and the interactions between ACTH and cortisol allows for quantifying normal and abnormal physiology and can potentially lay the basis for a more physiologically-based approach for administering cortisol therapeutically. Simultaneous recordings of ACTH and cortisol is not typical, and determining the number, timing, and amplitudes of pulsatile events from simultaneously recorded data is challenging because several factors have to be considered: (I) stimulator ACTH pulse activity, (II) kinematics of ACTH and cortisol, (III) the sampling interval of the measurements, and (IV) the measurement error from the immunoassay. We model ACTH and cortisol secretion simultaneously using a third-order linear differential equations model with Gaussian measurement errors and sparse pulsatile events as inputs to the model. We propose a novel framework for recovering pulses and parameters underlying the interactions between ACTH and cortisol. We recover the timing and amplitudes of pulses using compressed sensing, and employ generalized cross validation for determining the number of pulses. We analyze serum ACTH and cortisol levels sampled at 10-minute intervals over 24 hours from 10 healthy women. We recover physiologically plausible timing and amplitudes for these pulses and model the feedback effect of cortisol. We recover 15 to 18 pulses over 24 hours, which is highly consistent with cortisol serum measurement analysis using a different model and estimation algorithm. Moreover, we present a mathematical characterization of pulsatile cortisol secretion. We hypothesize that there is a controller in the anterior pituitary that leads to pulsatile release of cortisol, and propose a mathematical formulation for such controller. Our proposed controller achieves pulse control, and the obtained pulses and plasma cortisol levels exhibit cortisol circadian and ultradian rhythms that are in agreement with experimental data. The techniques developed in this study can be adapted to analyze other hormones with similar interactions.

Speaker Bio

Rose T. Faghih received a bachelor’s degree (summa cum laude) in electrical engineering (Honors Program) from the University of Maryland, College Park in 2008, and S.M. and Ph.D. degrees in electrical engineering and computer science with a minor in mathematics from the Massachusetts Institute of Technology (MIT) in 2010 and 2014, respectively. Rose is currently a postdoctoral associate with the MIT/Harvard Neuroscience Statistics Research Laboratory. She is also affiliated with the Laboratory for Information and Decision Systems at MIT. Since the beginning of her graduate studies, she has been advised by Professor Emery Brown and Professor Munther Dahleh. Her research interests are in control, estimation, and system identification of biomedical systems, with a focus on neural and endocrine systems in health and disease. During her graduate studies, Rose was a National Science Foundation Graduate Fellow, and the recipient of an MIT Graduate Fellowship. She received various scholarships and awards during her undergraduate studies, including the University of Maryland Presidential Scholarship, and the Department of Electrical and Computer Engineering Chair’s Award. She has also been inducted into various honor societies including Phi Kappa Phi, Tau Beta Pi, and Eta Kappa Nu.

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