The effect of zolpidem on memory consolidation over a night of sleep

Jing Zhang, Ben Yetton, Lauren N. Whitehurst, Mohsen Naji, Sara C. Mednick

Research output: Contribution to journalArticlepeer-review

32 Scopus citations


Study Objectives: Nonrapid eye movement sleep boosts hippocampus-dependent, long-term memory formation more so than wake. Studies have pointed to several electrophysiological events that likely play a role in this process, including thalamocortical sleep spindles (12-15 Hz). However, interventional studies that directly probe the causal role of spindles in consolidation are scarce. Previous studies have used zolpidem, a GABA-A agonist, to increase sleep spindles during a daytime nap and promote hippocampal-dependent episodic memory. The current study investigated the effect of zolpidem on nighttime sleep and overnight improvement of episodic memories. Methods: We used a double-blind, placebo-controlled within-subject design to test the a priori hypothesis that zolpidem would lead to increased memory performance on a word-paired associates task by boosting spindle activity. We also explored the impact of zolpidem across a range of other spectral sleep features, including slow oscillations (0-1 Hz), delta (1-4 Hz), theta (4-8 Hz), sigma (12-15 Hz), as well as spindle-SO coupling. Results: We showed greater memory improvement after a night of sleep with zolpidem, compared to placebo, replicating a prior nap study. Additionally, zolpidem increased sigma power, decreased theta and delta power, and altered the phase angle of spindle-SO coupling, compared to placebo. Spindle density, theta power, and spindle-SO coupling were associated with next-day memory performance. Conclusions: These results are consistent with the hypothesis that sleep, specifically the timing and amount of sleep spindles, plays a causal role in the long-term formation of episodic memories. Furthermore, our results emphasize the role of nonrapid eye movement theta activity in human memory consolidation. Statement of Significance Sleep spindles have emerged as one of the key electrophysiological markers for memory consolidation during sleep, yet interventional studies that directly probe the causal relation are scarce. It also remains under-investigated if other oscillations, such as theta, contribute to memory consolidation during nonrapid eye movement sleep. Using a within-subject, double-blind, placebo-controlled paradigm, this study pharmacologically manipulated a range of spectra features over a night of sleep in order to identify the key mechanism of sleep-dependent memory consolidation. Our results suggest a functional role of both sigma and theta in which optimizing sleep spindles while preserving theta activity may be a goal of future sleep interventions to enhance memory consolidation.

Original languageEnglish
Article numberzsaa084
Issue number11
StatePublished - Nov 1 2020

Bibliographical note

Publisher Copyright:
© Sleep Research Society 2020. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved.

ASJC Scopus subject areas

  • Clinical Neurology
  • Physiology (medical)


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