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SUMMARYPrevious studies suggest that sleep-specific brain activity patterns such as sleep spindles and electroencephalographic slow-wave activity contribute to the consolidation of novel memories. The generation of both sleep spindles and slow-wave activity relies on synchronized oscillations in a thalamo-cortical network that might be implicated in synaptic strengthening (spindles) and downscaling (slow-wave activity) during sleep. This study further examined the association between electroencephalographic power during non-rapid eye movement sleep in the spindle (sigma, 12-16 Hz) and slow-wave frequency range (0.1-3.5 Hz) and overnight memory consolidation in 20 healthy subjects (10 men, 27.1 ± 4.6 years). We found that both electroencephalographic sigma power and slow-wave activity were positively correlated with the pre-post-sleep consolidation of declarative (word list) and procedural (mirror-tracing) memories. These results, although only correlative in nature, are consistent with the view that processes of synaptic strengthening (sleep spindles) and synaptic downscaling (slow-wave activity) might act in concert to promote synaptic plasticity and the consolidation of both declarative and procedural memories during sleep. IN TROD UCTI ONEvidence from molecular to behavioural studies indicates that sleep fosters learning, memory and underlying neural plasticity (Diekelmann and Born, 2010). However, the contribution of the predominant sleep stages, rapid eye movement (REM) and non-REM (NREM) sleep, and of associated neural processes to the consolidation of newly encoded memories in the major memory systems, declarative and non-declarative memory, remains to be further elucidated.Recent findings suggest that sleep spindles, brief but powerful bursts of synchronous neuronal firing during mammalian stage 2 sleep in the electroencephalogram (EEG) sigma range (12-16 Hz), and EEG slow-wave activity (SWA), highly-synchronized oscillations during NREM sleep (0.1-3.5 Hz), might represent oscillatory activity that promotes sleep-related synaptic plasticity (Rosanova and Ulrich, 2005;Tononi and Cirelli, 2006). Animal studies indicate that sleep spindles might foster intracellular Ca 2+ -dependent mechanisms leading to the consolidation of new memories through synaptic strengthening (Steriade, 2003). In contrast, SWA and underlying Ôdown-statesÕ of extensive hyperpolarization and neuronal silencing and subsequent Ôup-statesÕ of depolarization and intense neuronal firing (Steriade, 2006) might sharpen the information-to-noise ratio and novel memory representations through synaptic downscaling (Tononi and Cirelli, 2006).Earlier work proposed that NREM sleep might preferentially promote declarative memory, whereas REM sleep might predominantly facilitate non-declarative learning (Plihal and Born, 1997). Consistently, NREM sleep-related sleep spindle density has been shown to be enhanced during nocturnal sleep following training on a declarative word-pair association task (Gais et al., 2002). Additionally, the increase in sle...

Arousal and sleep are fundamental physiological processes, and their modulation is of high clinical significance. This study tested the hypothesis that total sleep time (TST) in humans can be modulated by the non-invasive brain stimulation technique transcranial direct current stimulation (tDCS) targeting a 'top-down' cortico-thalamic pathway of sleep-wake regulation. Nineteen healthy participants underwent a within-subject, repeated-measures protocol across five nights in the sleep laboratory with polysomnographic monitoring (adaptation, baseline, three experimental nights). tDCS was delivered via bi-frontal target electrodes and bi-parietal return electrodes before sleep (anodal 'activation', cathodal 'deactivation', and sham stimulation). Bi-frontal anodal stimulation significantly decreased TST, compared with cathodal and sham stimulation. This effect was location specific. Bi-frontal cathodal stimulation did not significantly increase TST, potentially due to ceiling effects in good sleepers. Exploratory resting-state EEG analyses before and after the tDCS protocols were consistent with the notion of increased cortical arousal after anodal stimulation and decreased cortical arousal after cathodal stimulation. The study provides proof-of-concept that TST can be decreased by non-invasive bi-frontal anodal tDCS in healthy humans. Further elucidating the 'top-down' pathway of sleep-wake regulation is expected to increase knowledge on the fundamentals of sleep-wake regulation and to contribute to the development of novel treatments for clinical conditions of disturbed arousal and sleep.

SUMMAR Y It has been suggested that healthy sleep facilitates the consolidation of newly acquired memories and underlying brain plasticity. The authors tested the hypothesis that patients with primary insomnia (PI) would show deficits in sleep-related memory consolidation compared to good sleeper controls (GSC). The study used a four-group parallel design (n = 86) to investigate the effects of 12 h of night-time, including polysomnographically monitored sleep (Ôsleep conditionÕ in PI and GSC), versus 12 h of daytime wakefulness (Ôwake conditionÕ in PI and GSC) on procedural (mirror tracing task) and declarative memory consolidation (visual and verbal learning task). Demographic characteristics and memory encoding did not differ between the groups at baseline. Polysomnography revealed a significantly disturbed sleep profile in PI compared to GSC in the sleep condition. Night-time periods including sleep in GSC were associated with (i) a significantly enhanced procedural and declarative verbal memory consolidation compared to equal periods of daytime wakefulness in GSC and (ii) a significantly enhanced procedural memory consolidation compared to equal periods of daytime wakefulness and night-time sleep in PI. Across retention intervals of daytime wakefulness, no differences between the experimental groups were observed. This pattern of results suggests that healthy sleep fosters the consolidation of new memories, and that this process is impaired for procedural memories in patients with PI. Future work is needed to investigate the impact of treatment on improving sleep and memory.k e y w o r d s human, insomnia, memory, plasticity, polysomnography, sleep

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