Circadian clock assessment method in humans

A Circadian Clock Assessment (CCA) method was developed for identifying circadian phase, period (τ), mesor and amplitude using human core temperature (Tc) records showing normal or disrupted circadian Tc rhythms (CTcR). CCA uses an algorithm for identifying daily Tc nadirs and a series of fit polynomial curves for identifying circadian characteristics. CCA fit irregular Tc curve shapes better and produced more accurate estimates of circadian characteristics than Cosinor when applied to artificially generated data. CCA estimates showed less day-to-day variability than Cosinor on normal, entrained CTcR data. When CTcR was obviously disrupted, CCA produced estimates of τ that better agreed with visual estimates. CCA failed to identify τ once, in one data set that included both abnormally long (~30 h) and short (~ 12 h) days. Cosinor failed in this case as well. Cosinor had difficulty fitting abnormally long days, occasionally estimated τ in the hundreds of hours, and frequently produced estimates of τ that disagreed, by several hours, with τ estimated using a series of fit cosine curves. In conclusion, CCA is capable of estimating circadian characteristics when CTcR appears normal, as well as when CTcR is obviously disrupted. Applications include individualization of chronotherapy, therapies aimed at clock resynchronization, and basic research studying day-to-day changes in circadian characteristics.