Volume 130, Issue 1, Pages 17-25 (January 2006) Influence of Sleep Stages on Esophago-Upper Esophageal Sphincter Contractile Reflex and Secondary Esophageal Peristalsis  Jasmohan S. Bajaj, Shailesh Bajaj, Kulwinder S. Dua, Safwan Jaradeh, Tanya Rittmann, Candy Hofmann, Reza Shaker  Gastroenterology  Volume 130, Issue 1, Pages 17-25 (January 2006) DOI: 10.1053/j.gastro.2005.10.003 Copyright © 2006 American Gastroenterological Association Terms and Conditions

Figure 1 An example of EUCR and 2P elicitation during “awake” period. Manometry: As seen following infusion of 2.7 mL/min water into the proximal esophagus, the esophago-UES contractile reflex (EUCR) is triggered without an accompanying secondary peristalsis (2P). Secondary peristalsis is triggered with continuing infusion with concomitant increases in UES pressure. EEG: Central (C3 or C4) and occipital (O1 or O2) derivations, EOG activity from right and left eye (recorded from the outer canthi). “Awake” state with eyes closed is characterized by alpha waves (8–13 Hz) with slow and rapid eye movements and high activity on electromyography (EMG). Gastroenterology 2006 130, 17-25DOI: (10.1053/j.gastro.2005.10.003) Copyright © 2006 American Gastroenterological Association Terms and Conditions

Figure 2 An example of elicitation of EUCR and 2P in stage II sleep. Manometry: As seen following infusion of 3.8 mL water at the rate of 2.7 mL/min into the proximal esophagus, the UES pressure rose from 8 mm Hg to 20 mmHg (esophago-UES contractile reflex; EUCR). This pressure increase continues until the development of secondary peristalsis (2P) 74 seconds later. EEG: Central (C3 or C4) and occipital (O1 or O2) derivations, EOG activity from right and left eye (recorded from the outer canthi). Stage II is characterized by K complexes (an initial negative sharp wave followed by a positive component) and sleep spindles (episodic, rhythmical complexes occurring with frequency of 7 to 14 cycles per second grouped in sequences lasting 1–2 seconds). There are no eye movements, and EMG activity is decreased compared with “awake” state. Gastroenterology 2006 130, 17-25DOI: (10.1053/j.gastro.2005.10.003) Copyright © 2006 American Gastroenterological Association Terms and Conditions

Figure 3 An example of elicitation of EUCR and 2P during REM sleep. Manometry: Following infusion of 2.2 mL water at the rate of 2.7 mL/min into the proximal esophagus, the UES pressure rose from 6 mm Hg to 12 mm Hg (esophago-UES contractile reflex; EUCR). This pressure increase continues until the development of secondary peristalsis (2P) 52 seconds later. Continued water injection eventually resulted in subject arousal 350 seconds later. EEG: Central (C3 or C4) and occipital (O1 or O2) derivations, EOG activity from right and left eye (recorded from the outer canthi). EEG during REM sleep shows mixed frequency fast activity with superimposed saw-tooth theta waves (4–7 Hz, with notched appearance). EOG shows bursts of horizontal and vertical rapid eye movements and muscular atonia. In addition to REMs, other physiologic activities accompany REM sleep, including middle ear muscle activity, periorbital integrated potentials, and sleep-related erections. There are periods within REM sleep when eye movement activity and presumably other phasic event activity are high. At other times, REM-like background EEG activity continues with very little phasic activity. These 2 phases of REM sleep are called “phasic REM sleep” and “tonic REM sleep.” Gastroenterology 2006 130, 17-25DOI: (10.1053/j.gastro.2005.10.003) Copyright © 2006 American Gastroenterological Association Terms and Conditions

Figure 4 An example of elicitation of EUCR and 2P during slow-wave sleep. Manometry: As seen in stage II and REM sleep, water infusion in the proximal esophagus did not induce changes in UES pressure or development of secondary peristalsis after 139 seconds and infusion of 6.3 mL of water. Subject’s sleep state changed abruptly from SW sleep to arousal after coughing, accompanied by changes in UES pressure. EEG: Central (C3 or C4) and occipital (O1 or O2) derivations, EOG activity from right and left eye (recorded from the outer canthi). The tracing shows delta wave, a high-voltage wave pattern with a frequency range of 2 Hz. This EEG tracing is characteristic of slow-wave sleep. Slow-wave sleep includes both stage III (consisting of 20%–50% delta waves) and stage IV (more than 50% delta waves). There are no eye movements, but, unlike REM sleep, there is muscle activity, which is decreased compared with “awake” state. Gastroenterology 2006 130, 17-25DOI: (10.1053/j.gastro.2005.10.003) Copyright © 2006 American Gastroenterological Association Terms and Conditions

Figure 5 Comparison of the time interval between the onset of infusion to that of arousal/change in sleep stage in slow-wave sleep and elicitation of EUCR (A) and secondary peristalsis (B) in stage II, slow-wave, and REM sleep in 6 subjects who underwent testing in all stages of sleep. The interval for each subject is depicted, and the group mean is shown as a horizontal line. Each subject was tested in “awake,” stage II, slow-wave, and REM sleep. As seen, the interval for arousal/change in sleep stage in slow-wave sleep and elicitation of reflexes in stage II sleep, REM, and “awake” states were not significantly different. Although these intervals were similar between slow-wave and other stages of sleep, continued infusion beyond the elicitation of EUCR and secondary peristalsis in stage II and REM did not result in arousal or cough. Gastroenterology 2006 130, 17-25DOI: (10.1053/j.gastro.2005.10.003) Copyright © 2006 American Gastroenterological Association Terms and Conditions