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Randomized Controlled Trial
. 2013 Mar 6;33(10):4494-504.
doi: 10.1523/JNEUROSCI.3127-12.2013.

The critical role of sleep spindles in hippocampal-dependent memory: a pharmacology study

Sara C Mednick  1 , Elizabeth A McDevitt, James K Walsh, Erin Wamsley, Martin Paulus, Jennifer C Kanady, Sean P A Drummond
Affiliations
Randomized Controlled Trial

The critical role of sleep spindles in hippocampal-dependent memory: a pharmacology study

Sara C Mednick et al. J Neurosci. .

Abstract

An important function of sleep is the consolidation of memories, and features of sleep, such as rapid eye movement (REM) or sleep spindles, have been shown to correlate with improvements in discrete memory domains. Because of the methodological difficulties in modulating sleep, however, a causal link between specific sleep features and human memory consolidation is lacking. Here, we experimentally manipulated specific sleep features during a daytime nap via direct pharmacological intervention. Using zolpidem (Ambien), a short-acting GABAA agonist hypnotic, we show increased sleep spindle density and decreased REM sleep compared with placebo and sodium oxybate (Xyrem). Naps with increased spindles produced significantly better verbal memory and significantly worse perceptual learning but did not affect motor learning. The experimental spindles were similar to control spindles in amplitude and frequency, suggesting that the experimental intervention enhanced normal sleep processes. Furthermore, using statistical methods, we demonstrate for the first time a critical role of spindles in human hippocampal memory performance. The gains in memory consolidation exceed sleep-alone or control conditions and demonstrate the potential for targeted, exceptional memory enhancement in healthy adults with pharmacologically modified sleep.

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Figures

Figure 1.
Figure 1.
Study time line. The experimental time line for each session for Study 1 (a) and Study 2 (b). On the eve of the experimental day, subjects slept in the laboratory with a bedtime of 11:00 P.M. and a wake time of 5:00 A.M. In study 2, participants took cognitive tests between 6:00 and 8:00 A.M. At 8:30 A.M., subjects were reattached to the PSG monitor, given their medication, and allowed to nap until 90 min of total sleep time was obtained. At 3:00 P.M., subjects were retested on the cognitive tasks.
Figure 2.
Figure 2.
Drug effects on minutes in each sleep stage and spindle density. a, Study 1 compares 5 and 10 mg of ZOL (black bars), 2.5 and 3 g of SO (gray bars), and placebo (white bars). b, Study 2 compares 10 mg of ZOL (black bars), 2.5 g of SO (gray bars), and placebo (white bars). Statistical comparisons are between drug conditions and placebo. ***p < 0.001; **p < 0.01; *p < 0.05.
Figure 3.
Figure 3.
Cognitive performance by drug condition. Difference scores for the verbal paired associate task, the visual texture discrimination task, and the motor sequence task for the three drug conditions: 10 mg of ZOL, 2.5 g of SO, and placebo. Statistical comparisons are between drug conditions and placebo. **p < 0.005; *p < 0.05.
Figure 4.
Figure 4.
Sleep features and memory performance. a, Spindle density in each drug condition (ZOL, black circle; SO, gray circle; placebo, white circle) is shown relative to change scores in verbal memory. b, REM minutes in each drug are shown relative to change scores in perceptual learning. c, Spindle density in each drug condition is shown relative to change scores in motor learning.
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