Human phase response curve to a 1 h pulse of bright white light

Abstract

The phase resetting response of the human circadian pacemaker to light depends on the timing of exposure and is described by a phase response curve (PRC). The current study aimed to construct a PRC for a 1 h exposure to bright white light (∼8000 lux) and to compare this PRC to a <3 lux dim background light PRC. These data were also compared to a previously completed 6.7 h bright white light PRC and a <15 lux dim background light PRC constructed under similar conditions. Participants were randomized for exposure to 1 h of either bright white light (n=18) or <3 lux dim background light (n=18) scheduled at 1 of 18 circadian phases. Participants completed constant routine (CR) procedures in dim light (<3 lux) before and after the light exposure to assess circadian phase. Phase shifts were calculated as the difference in timing of dim light melatonin onset (DLMO) during pre- and post-stimulus CRs. Exposure to 1 h of bright white light induced a Type 1 PRC with a fitted peak-to-trough amplitude of 2.20 h. No discernible PRC was observed in the <3 lux dim background light PRC. The fitted peak-to-trough amplitude of the 1 h bright light PRC was ∼40% of that for the 6.7 h PRC despite representing only 15% of the light exposure duration, consistent with previous studies showing a non-linear duration–response function for the effects of light on circadian resetting.

Figure 1. Study schedule

Sleep–wake and light exposure schedules for 2 of the 18 circadian phases used to construct the 1 h bright white light PRC and corresponding dim background light PRC. Study days are plotted on the ordinate and 24 h of clock time on the abscissa. The left panels show the 10-day schedule for the participants randomized to receive the light onset at ∼5 h after dim light melatonin onset (DLMO), a time expected to result in a phase delay, for the light (A) and control (B) conditions. The right panels show the 9-day schedule for the participants randomized to receive the light onset between 9 to 10 h after DLMO, a time expected to result in a phase advance, for the light (C) and control (D) conditions. Phase shifts were calculated from the difference in timing of DLMO between CR1 (▴) and CR2 (▾) over three circadian cycles. The schedules and DLMO times are expressed relative to each participant's habitual sleep–wake schedule. Black bars indicate scheduled sleep episodes. White bars indicate waking light levels of 90 lux and grey bars indicate light levels in <3 lux. Light exposures are indicated on study day 6 or 7 by a white box (∼8000 lux, A and C; control, B and D).

Figure 2. Individual plasma melatonin profiles before and after bright or dim background light exposure

Individual plasma melatonin profiles are shown for four participants corresponding to Fig. 1 during constant routine (CR) 1 (•) and CR2 (◦) following exposure to a 1 h bright white light pulse (top panels) or the corresponding <3 lux dim background light condition (bottom panels). The timing of the bright white or <3 lux dim background light exposure on the day before CR2 is marked by an open box. In panel A, the 1 h bright white light exposure caused a −1.44 h phase delay shift (Δϕ) of the circadian pacemaker when timed to occur in the late subjective night compared to an advance of +0.17 h in the <3 lux dim background light condition (panel B). In panel C, bright white light exposure in the early subjective morning caused a +0.99 h phase advance compared to +0.61 h in the <3 lux dim background light (panel D). Dim light melatonin onset (DLMO) level is indicated for each participant by a dotted line.

Figure 3. Phase response curve to 1 h of bright white light or <3 lux dim background light

Exposure to a 1 h pulse of bright white light (left panels) or <3 lux dim background light (right panels). Raw phase shifts were computed using either plasma (▪) or salivary (□) melatonin (panels A, B, D and E) and fitted with a two-harmonic function (continuous line, panels B, C, E and F). Significant phase delays and advances were determined by comparing the overlap of 95% confidence intervals (dashed lines, panels C and F) to the zero phase shift line (continuous horizontal line, all panels) and the −0.54 h no net phase shift line based on drift due to intrinsic circadian period (dashed horizontal line, all panels). Initial phase was defined as the DLMO on CR1 relative to the onset of light exposure; negative values on the abscissa indicate onset of light exposure occurring prior to DLMO on CR1 and positive values indicate onset of light exposure occurring after DLMO on CR1.

Figure 4. Phase response curve to 6.7 h of bright white light or <15 lux dim background light

Exposure to a 6.7 h pulse of bright white light (left panels) or <15 lux dim background light (right panels). Raw phase shifts were computed using either plasma (•) or salivary (□) melatonin. All data were plotted using the same conventions as described in Fig. 3.

Figure 5. Comparison of 1 h and 6.7 h bright white light and dim background light PRCs

The raw data (symbols), two-harmonic fits (continuous lines) and 95% confidence intervals (dashed lines) for both the 1 h (black) and 6.7 h PRCs (grey) to bright white light (left panels) and dim background light (right panels) were plotted by circadian phase defined as the DLMO relative to the midpoint of light exposure, with negative values indicating midpoint of light exposure occurring before DLMO and positive values indicating midpoint of light exposure occurring after DLMO.