Apnea-induced rapid eye movement sleep disruption impairs human spatial navigational memory

Abstract

Hippocampal electrophysiology and behavioral evidence support a role for sleep in spatial navigational memory, but the role of particular sleep stages is less clear. Although rodent models suggest the importance of rapid eye movement (REM) sleep in spatial navigational memory, a similar role for REM sleep has never been examined in humans. We recruited subjects with severe obstructive sleep apnea (OSA) who were well treated and adherent with continuous positive airway pressure (CPAP). Restricting CPAP withdrawal to REM through real-time monitoring of the polysomnogram provides a novel way of addressing the role of REM sleep in spatial navigational memory with a physiologically relevant stimulus. Individuals spent two different nights in the laboratory, during which subjects performed timed trials before and after sleep on one of two unique 3D spatial mazes. One night of sleep was normally consolidated with use of therapeutic CPAP throughout, whereas on the other night, CPAP was reduced only in REM sleep, allowing REM OSA to recur. REM disruption via this method caused REM sleep reduction and significantly fragmented any remaining REM sleep without affecting total sleep time, sleep efficiency, or slow-wave sleep. We observed improvements in maze performance after a night of normal sleep that were significantly attenuated after a night of REM disruption without changes in psychomotor vigilance. Furthermore, the improvement in maze completion time significantly positively correlated with the mean REM run duration across both sleep conditions. In conclusion, we demonstrate a novel role for REM sleep in human memory formation and highlight a significant cognitive consequence of OSA.

Keywords: REM sleep; continuous positive airway pressure (CPAP); obstructive sleep apnea; randomized controlled trial; sleep fragmentation; spatial navigational memory.

Figure 1.

Withdrawal of CPAP in REM sleep causes significant REM sleep fragmentation. Continuity of sleep for normal sleep and REM-disrupted conditions. Survival curves (cumulative probability distributions) of stage-specific sleep runs in the normal sleep (white) and REM-disrupted (black) conditions. A, The survival curve for the REM-disrupted night showed a significant shift toward shorter runs of REM sleep compared with the normal night (p < 0.001, log-rank test). No significant difference between sleep conditions was observed in the survival curves for NREM 1 (B), NREM 2 (C), or NREM 3 (D).

Figure 2.

Disruption of REM sleep significantly attenuates the gains in virtual maze performance that occur across normal sleep. A, Completion time improved 31.3% after normal sleep but worsened 4.7% after REM disruption. *p = 0.016, paired t test. B, Total distance traveled improved 34.3% after normal sleep but worsened 0.5% after REM disruption. *p = 0.03, Wilcoxon's signed-rank test. C, Distance spent backtracking improved 56.5% after normal sleep but worsened 0.1% after REM disruption. *p = 0.034, Wilcoxon's signed-rank test.

Figure 3.

Overnight change in virtual maze completion time positively correlates with the mean REM run duration. Scatter plots of the relationship between REM continuity (mean duration of REM sleep runs) and percentage change in completion time for normal sleep (white circles) and REM-disrupted night (black circles). r = 0.34, p = 0.043, Pearson's correlation coefficient.

Figure 4.

Disruption of REM sleep does not affect psychomotor vigilance. There is no difference in mean reaction time between sleep conditions (270 ms during normal sleep, 274 ms during REM disruption, p = 0.865, Wilcoxon's signed-rank test) (A) or in a transform of lapses (3.1 ± 0.4 during normal sleep, 3.3 ± 0.6 during REM disruption, p = 0.71, paired t test) (B).