NREM sleep stage transitions control ultradian REM sleep rhythm

Abstract

Study objectives: The cyclic sequence of NREM and REM sleep, the so-called ultradian rhythm, is a highly characteristic feature of sleep. However, the mechanisms responsible for the ultradian REM sleep rhythm, particularly in humans, have not to date been fully elucidated. We hypothesize that a stage transition mechanism is involved in the determination of the ultradian REM sleep rhythm.

Participants: Ten healthy young male volunteers (AGE: 22 ± 4 years, range 19-31 years) spent 3 nights in a sleep laboratory. The first was the adaptation night, and the second was the baseline night. On the third night, the subjects received risperidone (1 mg tablet), a central serotonergic and dopaminergic antagonist, 30 min before the polysomnography recording.

Measurements and results: We measured and investigated transition probabilities between waking, REM, and NREM sleep stages (N1, N2, and N3) within the REM-onset intervals, defined as the intervals between the onset of one REM period and the beginning of the next, altered by risperidone. We also calculated the transition intensity (i.e., instantaneous transition rate) and examined the temporal pattern of transitions within the altered REM-onset intervals. We found that when the REM-onset interval was prolonged by risperidone, the probability of transitions from N2 to N3 was significantly increased within the same prolonged interval, with a significant delay and/or recurrences of the peak intensity of transitions from N2 to N3.

Conclusions: These results suggest that the mechanism governing NREM sleep stage transitions (from light to deep sleep) plays an important role in determining ultradian REM sleep rhythms.

Keywords: Ultradian rhythm; serotonin, dopamine; sleep stage dynamics; transition probability.

Figure 1

An example of the pair matching of the REM-onset interval (ROI) for the baseline night (A) and that for the risperidone night (B). Each pair of REM-onset intervals was matched by the same subject and the same sleep cycle. Among these matched pairs, pairs of which the REM-onset intervals for the risperidone night were altered with the same tendency as the whole were extracted in order to analyze the relationship between the REM-onset interval and the sleep stage transition.

Figure 2

An example of the hypnogram within one REM-onset interval (ROI) (A), the point process time series from N2 to N3 derived from panel A (B) and the transition intensity time series from N2 to N3 obtained from panel B (C). The REM-onset interval in panel A corresponds to the ROI-1 in Figure 1B. The point process in panel B consists of 0 and 1, set to 1 at each point where a transition from N2 to N3 occurred, and otherwise to 0. The transition intensity time series from N2 to N3 is calculated by smoothing the point process in panel B by taking a Hanning window-based weighted moving average for data from 10 min before to 10 min after the current window.

Figure 3

Transition probabilities between 5 behavioral states (Waking [W], REM sleep [R], N1, N2, and N3) for the control group (A) and for the experimental group (B). The thickness of the arrows represents the ratio of global transition probabilities for the second night (control group: A) and for the baseline night (experimental group: B). The black arrow indicates that the normalized transition probability is significantly greater for the risperidone night than for the baseline night (**P < 0.01). The gray arrows indicate that the normalized transition probability does not differ significantly between nights for each group.

Figure 4

Mean ± SD of the REM-onset interval for the second night (gray) and the third night (black) for the control group (A) and mean ± SD of the REM-onset interval for the baseline night (gray) and the risperidone night (black) for the experimental group (B). For the control group, there was no significant difference in the mean REM-onset intervals between the second night and the third night. For the experimental group, the mean REM-onset interval was significantly longer for the risperidone night than for the baseline night (**P < 0.01).

Figure 5

Intensities of transitions from N2 to N3 within paired REM-onset intervals for the baseline night (A) and the risperidone night (B), the mean position of peaks of transition intensities from N2 to N3 for the baseline night and the risperidone night (C), and the mean number of peaks of transition intensities from N2 to N3 for the baseline night and the risperidone night (D). The peak of the intensity of transition from N2 to N3 was significantly delayed for the risperidone night compared to the baseline night (*P < 0.05). The number of peaks of the intensity of transition from N2 to N3 was significantly increased for the risperidone night compared to the baseline night (**P < 0.01).