Phase response curve

PRCs are used in various fields; examples of biological oscillations are the heartbeat, circadian rhythms, and the regular, repetitive firing observed in some neurons in the absence of noise.

Specifically, a PRC is a graph showing, by convention, time of the subject's endogenous day along the x-axis and the amount of the phase shift (in hours) along the y-axis.

Normally, the body's various physiological rhythms will be synchronized within an individual organism (human or animal), usually with respect to a master biological clock.

The two common treatments used to shift the timing of sleep are light therapy, directed at the eyes, and administration of the hormone melatonin, usually taken orally.

Note that phase response curves from the experimental setting are usually aggregates of the test population, that there can be mild or significant variation within the test population, that individuals with sleep disorders often respond atypically, and that the formulation of the chronobiotic might be specific to the experimental setting and not generally available in clinical practice (e.g. for melatonin, one sustained-release formulation might differ in its release rate as compared to another); also, while the magnitude is dose-dependent,[2] not all PRC graphs cover a range of doses.

Starting about two hours before an individual's regular bedtime, exposure of the eyes to light will delay the circadian phase, causing later wake-up time and later sleep onset.

Immediately after this peak, light exposure has its greatest phase-advancing effect, causing earlier wake-up and sleep onset.

Because losing sleep to obtain bright light exposure is considered undesirable by most people, and because it is very difficult to estimate exactly when the greatest effect (the PRC peak) will occur in an individual, the treatment is usually applied daily just prior to bedtime (to achieve phase delay), or just after spontaneous awakening (to achieve phase advance).

In a 2006 study Victoria L. Revell et al. showed that a combination of morning bright light and afternoon melatonin, both timed to phase advance according to the respective PRCs, produce a larger phase advance shift than bright light alone, for a total of up to 21⁄2 hours over the course of 3 days.

[13] In a 2019 study Shawn D. Youngstedt et al., showed that in humans "Exercise elicits circadian phase‐shifting effects, but additional information is needed.

The "daily" activity rhythms of her flying squirrels, kept in constant darkness, responded to pulses of light exposure.

When DeCoursey plotted all her data relating the quantity and direction (advance or delay) of phase-shift on a single curve, she created the PRC.

[17] Experimental estimation of PRC in living, regular-spiking neurons involves measuring the changes in inter-spike interval in response to a small perturbation, such as a transient pulse of current.

Phase response curves for light and for melatonin administration
A typical Human Light PRC
The time shown on the x axis is vague: dawn – mid-day – dusk – night – dawn. These times do not refer to actual sun-up etc. nor to specific clock times. Each individual has their own circadian "clock" and chronotype, and dawn in the illustration refers to an individual's time of spontaneous awakening when well-rested and sleeping regularly. The PRC shows when a stimulus, in this case light to the eyes, will effect a change, an advance or a delay. The curve's highest point coincides with the subject's lowest body temperature.