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

Slow waves are characteristic waveforms that occur during non-rapid eye movement (NREM) sleep that play an integral role in sleep quality and brain plasticity. Benzodiazepines are commonly used medications that alter slow waves, however, their effects may depend on the time of night and measure used to characterize slow waves. Prior investigations have utilized minimal scalp derivations to evaluate the effects of benzodiazepines on slow waves, and thus the topography of changes to slow waves induced by benzodiazepines has yet to be fully elucidated. This study used high-density electroencephalography (hdEEG) to evaluate the effects of oral temazepam on slow wave activity, incidence, and morphology during NREM sleep in 18 healthy adults relative to placebo. Temazepam was associated with significant decreases in slow wave activity and incidence, which were most prominent in the latter portions of the sleep period. However, temazepam was also associated with a decrease in the magnitude of high-amplitude slow waves and their slopes in the first NREM sleep episode, which was most prominent in frontal derivations. These findings suggest that benzodiazepines produce changes in slow waves throughout the night that vary depending on cortical topography and measures used to characterize slow waves. Further research that explores the relationships between benzodiazepine-induced changes to slow waves and the functional effects of these waveforms is indicated.

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

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 15 mg. 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 to 13.83 Hz. 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.

Altered overnight modulation of spontaneous waking EEG reflects altered sleep homeostasis in major depressive disorder: a high-density EEG investigation.

BACKGROUND: Prior investigations have suggested sleep homeostasis is altered in major depressive disorder (MDD). Low frequency activity (LFA) in the electroencephalogram during waking has been correlated with sleep slow wave activity (SWA), suggesting that waking LFA reflects sleep homeostasis in healthy individuals. This study investigated whether the overnight change in waking LFA and its relationship with sleep SWA are altered in MDD. METHODS: 256-channel high-density electroencephalography (hdEEG) recordings during waking (pre- and post-sleep) and during sleep were collected in 14 unmedicated, unipolar MDD subjects (9 women) and age- and sex-matched healthy controls (HC). RESULTS: Waking LFA (3.25-6.25 Hz) declined significantly overnight in the HC group, but not in the group of MDD subjects. Overnight decline of waking LFA correlated with sleep SWA in frontal brain regions in HC, but a comparable relationship was not found in MDD. LIMITATIONS: This study is not able to definitely segregate overnight changes in the waking EEG that may occur due to homeostatic and/or circadian factors. CONCLUSIONS: MDD involves altered overnight modulation of waking low frequency EEG activity that may reflect altered sleep homeostasis in the disorder. Future research is required to determine the functional significance and clinical implications of these findings.

Topographic and sex-related differences in sleep spindles in major depressive disorder: a high-density EEG investigation.

BACKGROUND: Sleep spindles are believed to mediate several sleep-related functions including maintaining disconnection from the external environment during sleep, cortical development, and sleep-dependent memory consolidation. Prior studies that have examined sleep spindles in major depressive disorder (MDD) have not demonstrated consistent differences relative to control subjects, which may be due to sex-related variation and limited spatial resolution of spindle detection. Thus, this study sought to characterize sleep spindles in MDD using high-density electroencephalography (hdEEG) to examine the topography of sleep spindles across the cortex in MDD, as well as sex-related variation in spindle topography in the disorder. METHODS: All-night hdEEG recordings were collected in 30 unipolar MDD participants (19 women) and 30 age and sex-matched controls. Topography of sleep spindle density, amplitude, duration, and integrated spindle activity (ISA) were assessed to determine group differences. Spindle parameters were compared between MDD and controls, including analysis stratified by sex. RESULTS: As a group, MDD subjects demonstrated significant increases in frontal and parietal spindle density and ISA compared to controls. When stratified by sex, MDD women demonstrated increases in frontal and parietal spindle density, amplitude, duration, and ISA; whereas MDD men demonstrated either no differences or decreases in spindle parameters. LIMITATIONS: Given the number of male subjects, this study may be underpowered to detect differences in spindle parameters in male MDD participants. CONCLUSIONS: This study demonstrates topographic and sex-related differences in sleep spindles in MDD. Further research is warranted to investigate the role of sleep spindles and sex in the pathophysiology of MDD.

Electrophysiological traces of visuomotor learning and their renormalization after sleep.

OBJECTIVE: Adapting movements to a visual rotation involves the activation of right posterior parietal areas. Further performance improvement requires an increase of slow wave activity in subsequent sleep in the same areas. Here we ascertained whether a post-learning trace is present in wake EEG and whether such a trace is influenced by sleep slow waves. METHODS: In two separate sessions, we recorded high-density EEG in 17 healthy subjects before and after a visuomotor rotation task, which was performed both before and after sleep. High-density EEG was recorded also during sleep. One session aimed to suppress sleep slow waves, while the other session served as a control. RESULTS: After learning, we found a trace in the eyes-open wake EEG as a local, parietal decrease in alpha power. After the control night, this trace returned to baseline levels, but it failed to do so after slow wave deprivation. The overnight change of the trace correlated with the dissipation of low frequency (<8 Hz) NREM sleep activity only in the control session. CONCLUSIONS: Visuomotor learning leaves a trace in the wake EEG alpha power that appears to be renormalized by sleep slow waves. SIGNIFICANCE: These findings link visuomotor learning to regional changes in wake EEG and sleep homeostasis.

The formation of auditory fear memory requires the synthesis of protein and mRNA in the auditory thalamus.

The medial geniculate nucleus of the thalamus responds to auditory information and is a critical part of the neural circuitry underlying aversive conditioning with auditory signals for shock. Prior work has shown that lesions of this brain area selectively disrupt conditioning with auditory stimuli and that neurons in the medial geniculate demonstrate plastic changes during fear conditioning. However, recent evidence is less clear as to whether or not this area plays a role in the storage of auditory fear memories. In the current set of experiments rats were given infusions of protein or messenger RNA (mRNA) synthesis inhibitors into the medial geniculate nucleus of the thalamus 30 min prior to auditory fear conditioning. The next day animals were tested to the auditory cue and conditioning context. Results showed that rats infused with either inhibitor demonstrated less freezing to the auditory cue 24 h after training, while freezing to the context was normal. Autoradiography confirmed that the doses used were effective in disrupting synthesis. Taken together with prior work, these data suggest that the formation of fear memory requires the synthesis of new protein and mRNA at multiple brain sites across the neural circuit that supports fear conditioning.