Human circadian rhythms: a multioscillatory system.

After a brief review on temporal order within the human organism and implications for chronopharmacology, the paper discusses evidence indicating that the human circadian system consists of a multiplicity of oscillators. Subjects who live in isolation without time cues show free-running circadian rhythms deviating from 24 hours. Often, the activity rhythm (wakefulness and sleep) and other rhythmic variables (e.g., temperature) have the same circadian period of about 25 hours (referred to as the state of internal synchronization) but on occasions the activity period may become substantially longer (e.g., 33 hours) while the other rhythms continue with a period of about 25 hours. Such a state is termed internal desynchronization. There are also cases where the activity rhythm can reach extreme values of about 50 hours; to such a circa-bi-dian rhythm other variables are again synchronized, but in a 2:1 ratio. Internal desynchronization can occur both by shortening and by lengthening the activity rhythm. In these two cases the periods of other rhythms also change slightly in a direction opposite to that of the activity rhythm, indicating a loss of coupling between two classes of basic oscillators that both influence the two groups of overt rhythms but by different extents.