Interpreting the human phase response curve to multiple bright-light exposures.

Czeisler and his colleagues have recently reported that bright light can induce strong (Type O) resetting of the human circadian pacemaker. This surprising result shows that the human clock is more responsive to light than has been previously thought. The interpretation of their results is subtle, however, because of an unconventional aspect of their experimental protocol: They measured the phase shift after three cycles of the bright-light stimulus, rather than after the usual single pulse. A natural question is whether the apparent Type O response could reflect the summation of three weaker Type 1 responses to each of the daily light pulses. In this paper I show mathematically that repeated Type 1 resetting cannot account for the observed Type O response. This finding corroborates the strong resetting reported by Czeisler et al., and supports their claim that bright light induces strong resetting by crushing the amplitude of the circadian pacemaker. Furthermore, the results indicate that back-to-back light pulses can have a cooperative effect different from that obtained by simple iteration of a phase response curve (PRC). In this sense the resetting response of humans is similar to that of Drosophila, Kalanchoe, and Culex, and is more complex than that predicted by conventional PRC theory. To describe the way in which light resets the human circadian pacemaker, one needs a theory that includes amplitude resetting, as pioneered by Winfree and developed for humans by Kronauer.