Work

Nonlinear Model Predictive Control For Circadian Entrainment Using Small-Molecule Pharmaceuticals

Year: 2017

Type: article

Abstract: Recent in vitro studies have identified small-molecule pharmaceuticals effecting dose-dependent changes in the mammalian circadian clock, providing a novel avenue for control. Most studies employ light for clock control, however, pharmaceuticals are advantageous for clock manipulation through reduced invasiveness. In this paper, we employ a mechanistic model to predict the phase dynamics of the mammalian circadian oscillator under the effect of the pharmaceutical under investigation. These predictions are used to inform a constrained model predictive controller (MPC) to compute appropriate dosing for clock re-entrainment. Constraints in the formulation of the MPC problem arise from variation in the phase response curves (PRCs) describing drug effects, and are in many cases non-intuitive owing to the nonlinearity of oscillator phase response effects. We demonstrate through in-silico experiments that it is imperative to tune the MPC parameters based on the drug-specific PRC for optimal phase manipulation.

Source: IFAC-PapersOnLine

DOI: 10.1016/j.ifacol.2017.08.1596

Authors: John H. Abel, Ankush Chakrabarty, Francis J. Doyle III

Institution: Harvard University

Language: English

Topic: Circadian rhythm and melatonin

Subfield: Endocrine and Autonomic Systems

Field: Neuroscience

Domain: Life Sciences

Open Access status: diamond

Funders: National Institutes of Health, National Heart, Lung, and Blood Institute, National Institute of General Medical Sciences

Awards: G1726096465, MECHANISMS AND MODELING OF NETWORKED CIRCADIAN PACEMAKER SYNCHRONIZATION, Training in Sleep, Circadian, and Respiratory Neurobiology