The Effect of Zolpidem on Memory Consolidation Over a Night of Sleep


Non-rapid 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 thalamo-cortical sleep spindles (12-15Hz). 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. 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 (0-1Hz), delta (1-4Hz), theta (4-8Hz), sigma (12-15Hz), as well as spindle-SO coupling. 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. These results are consistent with the hypothesis that sleep, specifically the timing and amount of sleep spindles, plays a causal role in long-term formation of episodic memories. Furthermore, our results emphasize the role of NREM theta activity in human memory consolidation.