**1. Introduction**

154 Neuroimaging – Cognitive and Clinical Neuroscience

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Sleep is a universal biological feature in almost all, if not in all species, and represents a global state of immobility with greatly reduced responsiveness to environmental stimuli, which can be distinguished from coma or anaesthesia by its rapid reversibility (Cirelli & Tononi, 2008). It is by no means a dormant state. When it is prevented, the body tries to recover the lost amount. The existence of sleep rebound after deprivation reveals that sleep is not simply a period of reduced activity or alertness regulated by circadian or ultradian rhythms (Dinges et al., 2005). Notably, in most vertebrates and all mammal species, including man, sleep displays a specific architecture roughly described as a cyclic occurrence of rapid eye movement (REM) sleep and non-REM sleep. Further, dramatic changes in brain electrophysiology, neurochemistry and functional anatomy biologically distinguish the different sleep stages from one another (Hobson & Pace-Schott, 2002; Pace-Schott & Hobson, 2002). Also, human and animal neurophysiologic studies have shown that the magnitude of changes in brain metabolism and neuronal activity in many discrete brain structures during certain sleep stages exceeds that during most of the waking periods (Gottesmenn, 1999; Maquet et al., 1996; Nofzinger et al., 1997; Steriade & Timofeev, 2003). Although the precise functions of sleep are still beyond comprehensive understanding

(Cirelli & Tononi, 2008), many studies point to the critical role of sleep for physiological functioning and adaptation. Its vital importance is well documented by the fact that its deprivation in rodents and flies can cause death more quickly relative to food deprivation (Rechtschaffen, 1998). Thus, sleep is shown to serve many energetic and metabolic, immune, thermoregulatory, cardiovascular, and respiratory functions, all responsible for normal brain and body homeostasis (Siegel, 2009; Tononi & Cirelli, 2006). Notably, along with these functions, sleep is shown to play a key role for important cognitive and psychological processes, among which learning and memory have been most intensively studied (Diekelmann & Born, 2010; Rasch & Born, 2007; Stickgold, 2005; Walker, 2008; Walker & Stickgold, 2006; 2010). Accordingly, an extensive body of research has revealed a cruicial

The Memory, Cognitive and Psychological Functions of Sleep:

**2.2 Electrophysiological signatures of sleep stages** 

stages are shown in Figure 1.

Update from Electroencephalographic and Neuroimaging Studies 157

The distinct sleep stages of either human overnight sleep or human daily naps can be determined by their specific "macroscopic" electrophysiological signatures, which are described by Rechschaffen & Kales (1968) and are commonly used for human sleep stages scoring. Unlike the desynchronized mode of EEG activity during wakefulness, the electrophysiological signatures of different sleep stages are more complex, which reflects a more heterogeneous nature of sleep than that of wake (Hobson & Pace-Schott, 2002). Basically, wakefulness is divided into active wake, characterized by desynchronized lowvoltage fast EEG activity including beta (~ 15-30 Hz) and gamma (> 30 Hz) rhythms as well as by theta (~ 5 Hz) EEG activity with frontal-midline location, and quiet wake, characterized by posterior alpha (~ 10 Hz) and central sigma (~ 12-14 Hz) EEG rhythms that replace the desynchronized EEG mode of the active wake (Niedermeyer, 1993). The

Sleep initiation is described as a replacement of waking EEG by theta or slower rhythms paralleled by an appearance of very slow circular eye movements, and both electrophysiological features form stage 1 of non-REM sleep (Broughton, 1987; Sinton & McCarley, 2000). Stage 2 of non-REM sleep is defined by presence of the classical EEG sleep spindles oscillating at ~ 12-15 Hz with central-parietal location, slower sleep spindles oscillating at ~ 9-13 Hz with frontal location and sporadic biphasic slow waves known as Kcomplexes (Anderer et al., 2001; De Gennaro & Ferrara, 2003). Sleep spindles are present also in the deeper SWS stages, but in less pronounced and discrete forms, among which spindle activity in the frequency range of ~ 8-12 Hz with frontal location is recognized to dominate SWS (Cantero et al., 2002; Salih et al., 2009). K-complexes are regarded as precursors of EEG components of the SWS (Amzica & Steriade, 1997; De Gennaro & Ferrara, 2003). These "macroscopic" human electrophysiological signatures of distinct sleep-wake

SWS is hallmarked by synchronous high-voltage (> 75 µV) EEG delta (~ 1-4 Hz) waves and slow (< 1 Hz) oscillations (SO) (Achrermann & Borbely, 1997; Crunelli & Hughes, 2010; Steriade et al., 1993), both recognized as slow wave activity (SWA) (Fig. 1). SO are also shown to occur in stage 2 of non-REM sleep (Crunelli & Hughes, 2010; Nir et al., 2011), and the SO during both stage 2 of non-REM sleep and SWS are shown to group and synchronize sleep spindles and delta waves (Mölle et al., 2002; Mölle et al., 2004; Steriade, 2001). Whereas sleep spindles originate form interactions between thalamo-cortical circuits involving γaminobutyric (GABA)-ergic thalamic neurons and glutamate-ergic cortical neurons (De Gennaro & Ferrara, 2003; Steriade, 2006), SO are shown to have a neocortical origin (Achrermann & Borbely, 1997; Nir et al., 2011; Steriade et al., 1993), although they are also proposed to emerge form the thalamus (Crunelli & Hughes, 2010). Another important EEG signature of SWS seen not only in animals but also in human intracranial EEG recordings, is reflected by hippocampal sharp-wave/ripple (SWR) bursts. Hippocampal sharp waves generated in the hippocampal CA3 region are fast depolarizing events, on which highfrequency oscillations (~ 80-200 Hz) originating from an interaction between inhibitory interneurons and pyramidal cells in CA1 (so-called ripples) are superimposed (Buzsáki, 2006; Csicsvari et al., 1999). Notably, SO have been shown to group also SWR in rodents (Battaglia et al., 2004; Sirota et al., 2003), and a temporal phase-coupling between SO, sleep spindles and SWR has been demonstrated in human depth EEG records during SWS (Clemens et al., 2007; 2011; Nir et al., 2011). The complex relationship between these sleep signatures is regarded as reflecting brain plasticity mechanisms at a system level, which is

electrophysiological signatures of both active and quiet are show in Figure 1.

role for sleep in human cognitive abilities (Mander et al., 2008; Schabus et al., 2006; 2008; Yoo et al., 2007b), heuristic creativity and insightfulness (Cai et al., 2009; Stickgold et al., 1999; 2001; Wagner et al., 2004; Yordanova et al., 2008; 2009; 2010), constructive thinking and decision making (Durrant et al., 2011; Venkatraman et al., 2011), and emotional regulation (Walker, 2009; Walker & van der Helm, 2009). The latter engages consolidation of emotional memory (Nishida et al., 2009; Wagner et al., 2001; 2006; Walker, 2009) and emotional processing (Gujar et al., 2011a; 2011b; Yoo et al., 2007a). Collectively, these various associations suggest that sleep provides unique conditions for off-line memory consolidation, reconsolidation and information reprocessing to take place. However, it is still not precisely known whether these mechanisms are distinctly different from the restoring and energetic functions of sleep, whether the two types of functions are coupled, or whether the latter simply facilitate the cognitive functions of sleep.

Many electroencephalographic (EEG) and neuroimaging studies including functional magnetic resonance imaging (fMRI) have found that the structural and functional organization of the neural substrate undergoes changes during sleep in relation to human cognition. The entity of neural mechanisms underpinning cognitive and psychological functions of the brain is generally recognized as brain plasticity, i.e., as the capability of the neural substrate to reorganize over time as a result of previous experiences. In this chapter, studies demonstrating that sleep affects cognition by neural plasticity mechanisms in humans will be updated and overviewed to provide a converging framework for better understanding the role of sleep for memory, cognitive abilities and psychological functioning. Since mechanisms of brain plasticity are closely related to sleep physiology, architecture and neurobiological regulation, the reader will be first introduced to neurobiology of sleep.
