title: Comparison of amplitude recovery dynamics of two limit cycle oscillator models of the human circadian pacemaker.
abstract: At an organism level, the mammalian circadian pacemaker is a two-dimensional system. For these two dimensions, phase (relative timing) and amplitude of the circadian pacemaker are commonly used. Both the phase and the amplitude (A) of the human circadian pacemaker can be observed within multiple physiological measures--including plasma cortisol, plasma melatonin, and core body temperature (CBT)--all of which are also used as markers of the circadian system. Although most previous work has concentrated on changes in phase of the circadian system, critically timed light exposure can significantly reduce the amplitude of the pacemaker. The rate at which the amplitude recovers to its equilibrium level after reduction can have physiological significance. Two mathematical models that describe the phase and amplitude dynamics of the pacemaker have been reported. These models are essentially equivalent in predictions of phase and in predictions of amplitude recovery for small changes from an equilibrium value (A = 1), but are markedly different in the prediction of recovery rates when A < 0.6. To determine which dynamic model best describes the amplitude recovery observed in experimental data; both models were fit to CBT data using a maximum likelihood procedure and compared using Akaike's Information Criterion (AIC). For all subjects, the model with the lower recovery rate provided a better fit to data in terms of AIC, supporting evidence that the amplitude recovery of the endogenous pacemaker is slow at low amplitudes. Experiments derived from model predictions are proposed to test the influence of low amplitude recovery on the physiological and neurobehavioral functions.
authors.affiliation: Biomathematical Modeling Unit, Division of Sleep Medicine, Brigham and Women's Hospital/Harvard Medical School, Boston, MA, USA. premananda.indic@umassmed.edu
authors.forename: Premananda
authors.initials: P
authors.lastname: Indic
authors.forename: Daniel B
authors.initials: DB
authors.lastname: Forger
authors.forename: Melissa A
authors.initials: MA
authors.lastname: St Hilaire
authors.forename: Dennis A
authors.initials: DA
authors.lastname: Dean
authors.forename: Emery N
authors.initials: EN
authors.lastname: Brown
authors.forename: Richard E
authors.initials: RE
authors.lastname: Kronauer
authors.forename: Elizabeth B
authors.initials: EB
authors.lastname: Klerman
authors.forename: Megan E
authors.initials: ME
authors.lastname: Jewett
mesh_terms: D001683:Biological Clocks; D001831:Body Temperature / Q000502:physiology; D002940:Circadian Rhythm / Q000502:physiology*; D006801:Humans; D008027:Light; D008954:Models, Biological