REM Sleep Is Causal to Successful Consolidation of Dangerous and Safety Stimuli and Reduces Return of Fear after Extinction

Abstract

Sleep has a profound impact on memory consolidation. In this study, human participants underwent Pavlovian conditioning and extinction before we manipulated nocturnal memory consolidation by a split-night protocol with 80 healthy male participants in four groups. Recall after a second (recovery) night of sleep revealed that sleeping the first half of the night, which is dominated by slow-wave sleep, did not improve recall. Conversely, sleeping the second half of the night, which is dominated by rapid eye movement (REM) sleep, led to better discrimination between fear-relevant and neutral stimuli in behavioral and autonomic measures. Meanwhile, staying awake in the second half of the night led to an increase of discrimination between extinguished and neutral stimuli, which was paralleled by an activation of the ventromedial prefrontal cortex and amygdala. We conclude that sleep, especially REM sleep, is causal to successful consolidation of dangerous and safety stimuli and reduces return of fear after extinction.

Significance statement: We use a split-night protocol to investigate the influence of different sleep phases on successful consolidation of conditioned fear and extinction. Such a protocol uses the fact that in humans the first half of the night is dominated by slow-wave sleep, whereas during the second half, rapid eye movement (REM) sleep is more predominant. Our data show that only REM-rich sleep during the second half of the night promoted good discrimination between fear-relevant and neutral stimuli during recall, while staying awake led to a recovery of discrimination between extinguished and neutral stimuli. This suggests that sleep following extinction contributes independently to successful extinction memory consolidation.

Keywords: REM; anxiety; fMRI; learning; memory; sleep.