Is the cyclic nature of migrating motor complex dependent on the sleep cycle?
D.A. Gorard (London)
Periodic activity within the enteric nervous system - the MMC
The migrating motor complex (MMC) is a cyclical sequence of fasting gastrointestinal motility. In man its periodicity is approximately 90 minutes, but there is great variability [1, 2]. It is most commonly seen, and thus has been most studied, in the proximal small intestine but can be identified more proximally in the lower esophagus and as far distally as the ileum . The contractile pattern of the MMC consists of a period of quiescence, phase I, followed by irregular contractions of phase II. Phase III, the most easily recognized part of the MMC, is a short burst of phasic contractions at the maximum rate for that site: 3/minute in the gastric antrum, 11-12/minute in the proximal small bowel, 8-9/minute in the ileum. Phases I, II and III occupy approximately 10-20%, 70-85% and 5-10% of each MMC cycle by day.
Approximately half of MMC cycles have an esophageal component . During phase III, there is increased contractile activity of the lower esophageal sphincter (LES), and the pressure oscillations at 3/minute fuse to form a plateau of elevated pressure . The esophageal body up to 15-20 cm above the LES may also be involved. Contractile bursts in the esophageal body can be recorded in relation to phase III in the LES and gastroduodenal regions, and represent the esophageal body component of phase III of the MMC .
The initiation and cycling of MMCs are under the control of the enteric nervous system. The enteric nervous system is more complex and more similar to the central nervous system than any other region of the peripheral nervous system. It is an independent integrated system capable of mediating reflex activity in the absence of central nervous system input. However hormonal and higher neural influences have a modulatory role. Therefore, although MMCs can cycle independently of extrinsic neural input, the central nervous system (CNS) via the autonomic nervous system does influence the MMC. Psychological stress increases phase II activity and decreases the incidence (prolongs the periodicity) of duodenojejunal MMCs [6, 7]. Conversely relaxation influences the MMC by reducing phase II motility . The greatest state of relaxation is sleep, and prolonged motility recordings have shown variations in MMC characteristics during sleep (see below).
Periodic activity within the central nervous system - the sleep cycle
During sleep, the CNS also exhibits cyclical activity. Nocturnal polysomnographic recordings demonstrate "light" sleep (sleep stages 1 and 2), deep or "slow wave" sleep (stages 3 and 4), and episodes of rapid eye movement (REM) sleep. REM sleep is a physiological state very distinct from the non-REM sleep stages. REM sleep episodes recur approximately every 90 minutes in man, and are associated with autonomic disturbances and dreaming. Throughout the night, there is a cycle of non-REM and REM sleep.
Independence of the MMC and sleep cycles
There are similarities between MMC cycles and sleep cycles. Both include a phase of distinct increased activity, phase III episodes and REM sleep episodes, respectively. In the brain, the cyclical pattern of sleep is interrupted by wakefulness. In the gut, the cycling of the MMC is interrupted by food. Thus, in each system, sensory stimuli disrupt periodicity. In man, the MMC and sleep cycles have a similar length. This similar periodicity of the human MMC and sleep cycles has prompted investigation into whether they are linked. In other mammals the periodicity of the two biorhythms may be quite different and have been shown to be unrelated . However, when Finch et al. simultaneously recorded fasting human gastroduodenal motility and the electroencephalogram of nine healthy subjects over forty-one nights, they concluded that the two biorhythms were linked . Their findings supported the concept of an oscillator outside the enteric nervous system, possibly centrally located, which influenced MMC cycling. Yet no coherence between sleep stages and MMC cycling was seen when a depressed patient was studied for two nights . Similarly Kumar et al. found no correlation between stages of sleep and MMC cycling in healthy volunteers  or in irritable bowel syndrom patients  and concluded that these two ultradian rhythms are independent and under the influence of separate oscillators. Our own study supports this concept . When we recorded sleep stage and nocturnal motility from six sites in the small intestine, there was no temporal association between incidence of phase III fronts and sleep stages (Figure 1). The number of phase IIIs within each sleep stage was proportional to the percentage of the sleep study occupied by that sleep stage, and a random distribution of MMCs amongst the sleep stages was observed. Moreover, phase III fronts do not occupy a single time point within a sleep stage, but during their slow migration at night  may traverse more than one sleep stage (Figure 1). In considering that a nocturnal phase III may take up to 1-2 hours to travel from the duodenum to the ileum, it is even less surprising that MMCs cycle is independent of sleep stage.
But sleep does influence gut motility
Although sleep cycles and MMC cycles are independent, it is clear that sleep does modulate gastrointestinal motility. At night, MMC periodicity is shorter and less variable compared to day [16, 17], and the distal progression of phase III is slower . Kellow et al. found that nocturnal MMCs were less likely to have an esophageal component compared to daytime MMCs . Small intestinal motility diminishes during sleep  and this is due to decreased phase II activity at night when phase I (quiescence) dominates the MMC cycle [14, 17, 19]. This is in distinction to the dominance of phase II over daytime fasting motility [12, 17, 19, 20]. Diurnal sleep, like nocturnal sleep is also associated with MMC cycles of shorter periodicity which are dominated by phase I [12, 21]. Therefore it is CNS withdrawal during sleep and not an independent circadian variation of motility that leads to the differing features of nocturnal MMC cycles.
Sleep stage quantitatively influences small intestinal motility [14, 22]. We found that deep sleep (sleep stages 3 and 4) was associated with decreased motility compared to light sleep (stages 1 and 2), whereas motility index for REM sleep was similar to non-REM stages 1 and 2 . Differences in phase II contractility accounted for the variations of motility index between the sleep stages. A similar inverse relationship between depth of sleep and motility has been described in the esophagus (both primary swallow-related contractions and secondary contractions) , stomach  and colon . These reports also found that motility during REM sleep was greater than during deep sleep, and quantitatively resembled motility during sleep stages 1 and 2.
In conclusion, although there is no synchrony of the MMC with the sleep cycle, sleep does influence the MMC.
Figure 1. Sleep stage and small intestinal motility summaries in three healthy volunteers. For each subject, the upper half of the summary depicts sleep stage, and the lower half depicts phase III activity fronts.
W: wakefulness; 1/2: sleep stages 1 and 2; 3/4: sleep stages 3 and 4, REM: rapid eye movement sleep.
Site A represents the duodenojejunal flexure, sites B, C, D, E and F represent sensors at 15 cm, 30 cm, 50 cm, 70 cm and 95 cm distal to the duodenojejunal flexure. (Reproduced with permission from .)
8. Kellow JE, Langeluddecke PM, Eckersley GM, Jones MP, Tennant CC. Progressive muscular relaxation and motility of the small intestine: studies in normal subjects and patients with irritable bowel syndrome. J Gastrointest Motil 1992;4:47-52.
22. Tassinari CA, Coccagna G, Mantovani M, Dalla Bernardina D, Spire JP, Mancia D, Vela A, Vallicioni P. Duodenal EMG activity during sleep in man. In: Jovanovic UD, ed. The nature of sleep. Stuttgart:Fischer-Verlag, 1973:55-58.