TY - JOUR
T1 - The Role of Light Sensitivity and Intrinsic Circadian Period in Predicting Individual Circadian Timing
AU - Stone, Julia E.
AU - McGlashan, Elise M.
AU - Quin, Nina
AU - Skinner, Kayan
AU - Stephenson, Jessica J
AU - Cain, Sean W.
AU - Phillips, Andrew J. K.
N1 - Funding Information:
The authors thank Mark Salkeld at the Adelaide Research Assay Facility for conducting the melatonin radioimmu-noassays.
Publisher Copyright:
© 2020 The Author(s).
PY - 2020/12
Y1 - 2020/12
N2 - There is large interindividual variability in circadian timing, which is underestimated by mathematical models of the circadian clock. Interindividual differences in timing have traditionally been modeled by changing the intrinsic circadian period, but recent findings reveal an additional potential source of variability: large interindividual differences in light sensitivity. Using an established model of the human circadian clock with real-world light recordings, we investigated whether changes in light sensitivity parameters or intrinsic circadian period could capture variability in circadian timing between and within individuals. Healthy participants (n = 12, aged 18-26 years) underwent continuous light monitoring for 3 weeks (Actiwatch Spectrum). Salivary dim-light melatonin onset (DLMO) was measured each week. Using the recorded light patterns, a sensitivity analysis for predicted DLMO times was performed, varying 3 model parameters within physiological ranges: (1) a parameter determining the steepness of the dose-response curve to light (p), (2) a parameter determining the shape of the phase-response curve to light (K), and (3) the intrinsic circadian period (tau). These parameters were then fitted to obtain optimal predictions of the three DLMO times for each individual. The sensitivity analysis showed that the range of variation in the average predicted DLMO times across participants was 0.65 h for p, 4.28 h for K, and 3.26 h for tau. The default model predicted the DLMO times with a mean absolute error of 1.02 h, whereas fitting all 3 parameters reduced the mean absolute error to 0.28 h. Fitting the parameters independently, we found mean absolute errors of 0.83 h for p, 0.53 h for K, and 0.42 h for tau. Fitting p and K together reduced the mean absolute error to 0.44 h. Light sensitivity parameters captured similar variability in phase compared with intrinsic circadian period, indicating they are viable targets for individualizing circadian phase predictions. Future prospective work is needed that uses measures of light sensitivity to validate this approach.
AB - There is large interindividual variability in circadian timing, which is underestimated by mathematical models of the circadian clock. Interindividual differences in timing have traditionally been modeled by changing the intrinsic circadian period, but recent findings reveal an additional potential source of variability: large interindividual differences in light sensitivity. Using an established model of the human circadian clock with real-world light recordings, we investigated whether changes in light sensitivity parameters or intrinsic circadian period could capture variability in circadian timing between and within individuals. Healthy participants (n = 12, aged 18-26 years) underwent continuous light monitoring for 3 weeks (Actiwatch Spectrum). Salivary dim-light melatonin onset (DLMO) was measured each week. Using the recorded light patterns, a sensitivity analysis for predicted DLMO times was performed, varying 3 model parameters within physiological ranges: (1) a parameter determining the steepness of the dose-response curve to light (p), (2) a parameter determining the shape of the phase-response curve to light (K), and (3) the intrinsic circadian period (tau). These parameters were then fitted to obtain optimal predictions of the three DLMO times for each individual. The sensitivity analysis showed that the range of variation in the average predicted DLMO times across participants was 0.65 h for p, 4.28 h for K, and 3.26 h for tau. The default model predicted the DLMO times with a mean absolute error of 1.02 h, whereas fitting all 3 parameters reduced the mean absolute error to 0.28 h. Fitting the parameters independently, we found mean absolute errors of 0.83 h for p, 0.53 h for K, and 0.42 h for tau. Fitting p and K together reduced the mean absolute error to 0.44 h. Light sensitivity parameters captured similar variability in phase compared with intrinsic circadian period, indicating they are viable targets for individualizing circadian phase predictions. Future prospective work is needed that uses measures of light sensitivity to validate this approach.
KW - circadian phase
KW - mathematical model
KW - light sensitivity
KW - intrinsic period
KW - human
KW - oscillator
KW - parameter estimation
KW - individual differences
UR - http://www.scopus.com/inward/record.url?scp=85092628708&partnerID=8YFLogxK
U2 - 10.1177/0748730420962598
DO - 10.1177/0748730420962598
M3 - Article
C2 - 33063595
SN - 0748-7304
VL - 35
SP - 628
EP - 640
JO - Journal of Biological Rhythms
JF - Journal of Biological Rhythms
IS - 6
ER -