Melatonin onset (DLMO_25%) times. (a) Subjects scheduled to the 23.5-h day. Data are plotted to a relative clock time with lights out assigned a value of 2400 h on baseline day 1. Black bars represent scheduled sleep. During the imposed 23.5-h segment, lights out and lights on are advanced by 30 min each day. Melatonin onset occurred near to, but advanced relative to, lights out for the subjects during baseline days, whereas during T = 23.5-h days, melatonin onset progressively phase delays relative to lights out. These data demonstrate failure to entrain the circadian pacemaker to the scheduled 23.5-h wakefulness–sleep light–dark cycle. (b) Subjects scheduled to the 24.0-h day. During the imposed 24.0-h segment, melatonin onset appears stable and occurs near to, but advanced relative to, lights out for half of the subjects and delayed for the other half. These data demonstrate that most subjects entrained to the 24.0-h day with a new phase angle, as would be expected to occur in response to the weak environmental synchronizer. A greater dispersion of melatonin onsets can be observed during forced desynchrony, reflecting individual differences in intrinsic circadian period. In two of six subjects, circadian period advanced and in the remaining subjects circadian period delayed during forced desynchrony (Table 1). Subject 18G1 failed to entrain to the 24.0-h day. (c) Subjects scheduled to the 24.6-h day. During the imposed 24.6-h segment, lights out and lights on are delayed by 36 min each day. Melatonin onset occurs near to, but advanced relative to, lights out for half of the subjects and delayed for the other half during baseline days, whereas during the 24.6-h segment, melatonin onset is progressively phase advanced relative to lights out. These data demonstrate a failure to entrain the human circadian pacemaker to the scheduled 24.6-h day. Individual differences in intrinsic circadian period result in a large dispersion of melatonin onsets during the T = 24.6- and T = 28.0-h forced desynchrony protocols.

Observed circadian periods during forced desynchrony T = 28.0 h and during (a) T = 24.0 h and (b) T = 24.6 h protocols. Symbols represent individual subjects for whom observed and intrinsic period data were available. The solid black line represents the line of equality, the dashed line represents a linear fit of the data, and the dotted lines represent the target period to entrain to. The average intrinsic circadian period was similar for both groups of subjects during the forced desynchrony [average ± SD (a) 24.07 ± 0.19 h vs. (b) 24.06 ± 0.20 h]. The circadian period lengthened closer to 24.0 h in two subjects and shortened closer to 24.0 h in three subjects during T = 24.0 h compared with their intrinsic circadian period (τ_m), as assessed during T = 28.0 h. The absolute change in period was significantly greater than 0 (one sample t test: P < 0.05). Subjects scheduled to the 24.6-h day showed a significantly longer observed period during T = 24.6 h (24.19 ± 0.23 h) compared with T = 28.0 h (t test: P < 0.01). These data demonstrate coupling between the endogenous circadian pacemaker and the weak environmental time cues, showing that environmental and/or behavioral periodicity can significantly influence the observed period of the pacemaker when the day length is close to the pacemakers intrinsic period regardless of whether the pacemaker entrains to the environmental day length.

Association between phase angle of melatonin onset and scheduled sleep time during the T = 24.0-h segment and intrinsic circadian period during forced desynchrony (T = 28.0 h) for entrained subjects. Symbols represent individual subjects for whom phase angle and intrinsic period data were available (four of five entrained subjects). The change in the phase angle of entrainment between melatonin onset and the scheduled 24.0-h day, as determined on CR1 and CR2, is negatively and robustly related to intrinsic circadian period (τ_m) with a slope of −11.12. Subjects with a circadian period shorter than 24.0 h advanced, and subjects with a period longer than 24.0 h delayed, such that for every 0.1-h change in circadian period, there was a 1.11-h change in the phase angle of entrainment.