Melatonin Rhythm Observed throughout a Three-Cycle Bright-Light Stimulus Designed to Reset the Human Circadian Pacemaker

Abstract

Exposure to light and darkness can rapidly induce phase shifts of the human circadian pacemaker. A type 0 phase response curve (PRC) to light that has been reported for humans was based on circadian phase data collected from constant routines performed before and after a three-cycle light stimulus, but resetting data observed throughout the entire resetting protocol have not been previously reported. Pineal melatonin secretion is governed by the hypothalamic circadian pacemaker via a well-defined neural pathway and is reportedly less subject to the masking effects of sleep and activity than body temperature. The authors reasoned that observation of the melatonin rhythm throughout the three-cycle light resetting trials could provide daily phase-resetting information, allowing a dynamic view of the resetting response of the circadian pacemaker to light. Subjects (n = 12) living in otherwise dim light (~10-15 lux) were exposed to a noncritical stimulus of three cycles of bright light (~9500 lux for 5 h per day) timed to phase advance or phase delay the human circadian pacemaker; control subjects (n = 11) were scheduled to the same protocols but exposed to three 5-h darkness cycles instead of light. Subjects underwent initial and final constant routine phase assessments; hourly melatonin samples and body temperature data were collected throughout the protocol. Average daily phase shifts of 1 to 3 h were observed in 11 of 12 subjects receiving the bright light, supporting predictions obtained using Kronauer’s phase-amplitude model of the resetting response of the human circadian pacemaker. The melatonin rhythm in the 12th subject progressively attenuated in amplitude throughout the resetting trial, becoming undetectable for > 32 hours preceding an abrupt reappearance of the rhythm at a shifted phase with a recovered amplitude. The data from control subjects who remained in dim lighting and darkness delayed on average – 0.2 h per day, consistent with the daily delay expected due to the longer than 24-h intrinsic period of the human circadian pacemaker. Both temperature and melatonin rhythms shifted by equivalent amounts in both bright light-treated and control subjects (R = 0.968; p < 0.0001; n = 23). Observation of the melatonin rhythm throughout a three-cycle resetting trial has provided a dynamic view of the daily phase-resetting response of the human circadian pacemaker. Taken together with the observation of strong type 0 resetting in humans in response to the same three-cycle stimulus applied at a critical phase, these data confirm the importance of considering both phase and amplitude when describing the resetting of the human circadian pacemaker by light.

An arousing, musically enhanced bird song stimulus mediates circadian rhythm phase advances in dim light

“…The direction and magnitude of DLMO and CBT minimum phase shifts also were positively related, demonstrating a direct effect on the circadian timing system, similar to other studies (8,18,20,23,30,39,58). DLMO occurred a little over 7 h before CBT minimum, at baseline and after exposure, with a positive relationship between the two markers, as has been reported previously (7,9,14,23).…”

“…At baseline, CBT minimum and DLMO were closely related in both sessions and also with each other, indicating internal phase marker stability and a consistent within-subject temporal relationship between markers (3,7,11,39,58,63,66). The direction and magnitude of DLMO and CBT minimum phase shifts also were positively related, demonstrating a direct effect on the circadian timing system, similar to other studies (8,18,20,23,30,39,58).…”

Improved Neurobehavioral Performance during the Wake Maintenance Zone

“…Dim light melatonin onset (DLMO) times were calculated for each participant according to the 25% threshold method; the amplitude (mesor to peak or trough) of the melatonin rhythm during the constant routine was estimated by fitting a 3-harmonic model to the melatonin data, 22 and DLMO was defined as the clock time at which the plasma melatonin rhythm exceeded a 50% threshold of the amplitude (25% of the peakto-trough amplitude). 23 The biological night was defined as the duration from DLMO to dim light melatonin offset (DLMOff), defined as the clock time at which the melatonin level dropped below the 50% threshold.…”

Influence of changes in luminous emittance before bedtime on sleep in companion dogs

“…Alternatively, the duration of the illumination was too short to have an effect. In dogs, the melatonin response to light is affected to the same degree as in humans (Shanahan et al, 1999). However, in that report, dim light was set at 10-15 lux and bright light was set at 9500 lux.…”