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

Abstract

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.

Competitive dynamics underlie cognitive improvements during sleep

“…We performed power spectral analysis to quantify normalized sigma activity and analyzed HRV profiles. Our intervention was successful, whereby zolpidem enhanced sigma activity during stage 2 sleep (central channels: t = 2.112, p = .0349; parietal channels: t = 2.214, p = .0270, corrected by Tukey's multiple comparisons), consistent with prior literature (Mednick et al, 2013;Zhang et al, 2020).…”

The Treatment of Sleep Dysfunction in Neurodegenerative Disorders

“…Adverse effects of benzodiazepines include tolerance, dependence, and withdrawal, as well as both acute [80,81] and chronic [82] impairment of attention and psychomotor speed. Impairment of memory consolidation is also well supported, although refuted by some studies [83][84][85]. While risks of such adverse effects are lower with Z-drugs, they are not absent [86,87].…”

Slow oscillation-spindle coupling is negatively associated with emotional memory formation following stress

“…In humans, this coordination has been demonstrated in epilepsy patients with intracranial hippocampal recordings (Staresina et al, 2015). Although hippocampal ripples cannot be detected non-invasively, slow oscillation-spindle coupling as detected via scalp EEG has been associated with memory consolidation in healthy humans (Denis et al, 2020;Mikutta et al, 2019;Niknazar et al, 2015;Zhang et al, 2020).…”

“…Although hippocampal ripples cannot be detected non-invasively, slow oscillation-spindle coupling as detected via scalp EEG has been associated with memory consolidation in healthy humans (e.g. Niknazar et al , 2015; Mikutta et al , 2019; Denis, Mylonas, et al , 2020; Zhang et al , 2020).…”