Effects of oral temazepam on sleep spindles during non-rapid eye movement sleep: A high-density EEG investigation

Abstract

Benzodiazepines are commonly used medications that alter sleep spindles during non-rapid eye movement (NREM) sleep, however the topographic changes to these functionally significant waveforms have yet to be fully elucidated. This study utilized high-density electroencephalography (hdEEG) to investigate topographic changes in sleep spindles and spindle-range activity caused by temazepam during NREM sleep in 18 healthy adults. After an accommodation night, sleep for all participants was recorded on two separate nights after taking either placebo or oral temazepam 15mg. Sleep was monitored using 256-channel hdEEG. Spectral analysis and spindle waveform detection of sleep EEG data were performed for each participant night. Global and topographic data were subsequently compared between temazepam and placebo conditions. Temazepam was associated with significant increases in spectral power from 10.33–13.83Hz. Within this frequency band, temazepam broadly increased sleep spindle duration, and topographically increased spindle amplitude and density in frontal and central-posterior regions, respectively. Higher frequency sleep spindles demonstrated increased spindle amplitude and a paradoxical decrease in spindle density in frontal and centroparietal regions. Further analysis demonstrated temazepam both slowed the average frequency of spindle waveforms and increased the relative proportion of spindles at peak frequencies in frontal and centroparietal regions. These findings suggest that benzodiazepines have diverse effects on sleep spindles that vary by frequency and cortical topography. Further research that explores the relationships between topographic and frequency-dependent changes in pharmacologically-induced sleep spindles and the functional effects of these waveforms is indicated.

Widespread reduction in sleep spindle activity in socially anxious children and adolescents

“…Recent findings demonstrating that a drop in activity of these inhibitory neurons coincided with the termination of a sleep spindle indicates a role of GABA neurotransmission in the generation of sleep spindles (Bartho et al 2014). Moreover, benzodiazepines which are known to reduce symptoms of anxiety possibly due to their modulating impact on the GABA-A system (Lydiard et al 2003;Nuss, 2015) was found to increase spindle activity (Plante et al 2015;Aeschbach et al 1994;Borbely et al 1985;Dijk et al 1989;Feige et al 1999;Trachsel et al 1990). This effect has been suggested to result from the potentiation of the thalamic reticular neurons (Plante et al 2015).…”

“…Moreover, benzodiazepines which are known to reduce symptoms of anxiety possibly due to their modulating impact on the GABA-A system (Lydiard et al 2003;Nuss, 2015) was found to increase spindle activity (Plante et al 2015;Aeschbach et al 1994;Borbely et al 1985;Dijk et al 1989;Feige et al 1999;Trachsel et al 1990). This effect has been suggested to result from the potentiation of the thalamic reticular neurons (Plante et al 2015). Our findings of increased arousal in SAD patients together with the negative correlation between arousal ratings and fast spindle activity fully support this argumentation.…”

Slow sleep spindle and procedural memory consolidation in patients with major depressive disorder

“… 35 Specifically, benzodiazepines induce a preferential increase in slow-frequency spindle activities, especially prefrontal slow-frequency spindle activity, at the expense of fast-frequency spindle activity. 15 , 36 Regarding the association between pharmacological effects and memory consolidation, Morgan et al 37 demonstrated that the motor memory consolidation observed in humans was worsened by administering triazolam, but not by administering zolpidem, a short-acting GABA A agonist hypnotic. 37 In our study, hypnotics may have had less of an effect on sleep-dependent procedural memory consolidation, although it may cause it to deteriorate over time in patients medicated for major depression.…”

Effects of oral temazepam on slow waves during non-rapid eye movement sleep in healthy young adults: A high-density EEG investigation

“…Participants also did not have clinically relevant sleep-related breathing or movement disorders, verified by clinical history and screening polysomnogram. Changes in sleep spindles induced by temazepam in this group of participants have been previously reported (Plante et al, 2015)…”

“…Fourth, our study design is not able to discern whether there is a causal relationship between observed changes in slow waves and alterations in sleep spindles induced by temazepam. However, given previously reported absence of correlation between these variables in this data set (Plante et al, 2015), it is less likely that alterations in sleep spindles cause changes in slow waves, or vice versa, and more likely that observed changes in these EEG waveforms reflect the impact of temazepam at the GABA-A receptor, which is widespread throughout the brain and responsible for most of the physiologic activity of GABA in the CNS. Finally, specific pharmacokinetic data in our research participants were not available, which may have provided insight into the basis of the observed NREM period effects.…”