Additionally, ‘external’ influences (i.e. circadian rhythms and sensory stimuli on the Reticular Activating System—RAS) can ‘switch’ between sleep and wakefulness.

Wakefulness is maintained through the tonic activity in the RAS from the upper brain stem and the thalamocortical and cortical projections from the posterior hypothalamus and the basal forebrain. The transition to sleep is caused by both a withdrawal of external stimuli from the RAS and an activation of the hypothalamus’ preoptic area [23]. This leads to a widespread increase in GABAergic activity that gives rise to the relative synchronous oscillations of NREM sleep such as sleep spindles, delta activity and the slow cortical oscillations.

At the microstructure level of NREM sleep organization, the cyclic alternating pattern (CAP) alternates with periods of quiescence (non-CAP periods) (Fig. 3.4c); NREM sleep is thus divided into periods showing CAP and periods not showing CAP. During the CAP periods, phases containing arousal phenomena and therefore indicate increased vigilance (phase A of CAP) alternate with phases without arousal phenomena, which correspond to reduced vigilance (phase B of CAP) [24].

Sleep spindles (Figs. 3.1c and 3.4a) generated by the reticular nucleus of the thalamus (RE) and its connections to the dorsal thalamus (Fig. 3.2b), consist of a 10–14 Hz activity lasting 2–3 s occurring especially in stages 2 and 3 of NREM sleep. The spindle oscillation is transferred to the thalamocortical relay cells, traveling to the cortex, generating rhythmic excitatory postsynaptic potentials and a synchronous activity over widespread cortical regions that can be observed at the macroscopic/EEG level [25]. Inhibitory RE to RE neurons collaterals desynchronize spindle activity limiting both the amplitude and the duration of sleep spindles [26].

Modeling of spindles from the EEG and MEG signal was remarkably unsuccessful in illuminating the nature of the generators that appeared to be dispersed in different areas with little consistent regularity within and across events. This was rather surprising given the rather widespread and consistent spindle imprint on the EEG (in terms of signal morphology of the sigma-band-pass filtered signal of central and dorsal EEG sensors. One plausible explanation was that the problem arose because the source localization algorithms did not have sufficient power to disentangle activity from a mixture of superficial and deep generators. In recent years a series of studies focused on the problem of identifying the generators of spindles from EEG, MEG, simultaneous EEG and MEG [27, 28], EEG triggered fMRI and invasive measurements in humans [29, 30] begin to converge to a rather surprising but consistent picture: spindles are sporadic events that at least in the cortex occur asynchronously over wide areas and with high variability from event to event. Our own tomographic analysis confirms the high variability of generator loci from spindle to spindle but provides a unified picture of the evolution of activity from the awake state through core periods of light sleep and the periods before and during spindles and K-complexes (Ioannides et al., in preparation). All of the established features of spindles are recovered by the tomographic analysis, but they appear strongly when the appropriate comparison is made between conditions. An example is demonstrated in Fig. 3.3: comparing the spectral density of individual events during and just before spindles shows the anterior foci of the low sigma activity and the more posterior foci in the high sigma periods. In addition and in a more ventral level increases during the spindles are seen for the entire sigma band in posterior cingulate and in the right caudate [31].

Spindles appear to play at least three roles. (a) shaping the early organization of sensory-motor cortical circuits [32] (b) maintaining sleep by increasing the threshold perceiving sensory stimuli [33] and (c) helping memory consolidation through a cortico-hippocampal interaction [34].

The delta oscillation (1–4 Hz) has both a thalamic [35] and a cortical component [36] and seems to result from the same circuit that generates sleep spindles. However, spindle and delta activity exclude each other within the thalamocortical neuron, with spindle activity arising at relatively depolarized resting membrane potentials and delta activity arising at more hyperpolarized membrane potentials [37].

Slow cortical oscillations at frequencies bellow 1 Hz, observed during slow wave sleep, are generated in the cerebral cortex with different cortical areas synchronizing in a widespread manner through corticocortical connections. K complexes (Fig. 3.1b), a fluctuating arousal occurring at periodic intervals during NREM sleep, can be triggered by both external sensory stimuli as well as internal very slow sleep oscillations [38]. They appear to have a very dynamic relationship to spindles and to theta bursts (Fig. 3.4a, b) [39, 40].

K complexes, sleep spindles and arousals but also epileptiform discharges and seizures (more about this later) seem to occur during the A phase of CAP and seem to be inhibited during the B phase of CAP (Fig. 3.4c) [41].

During REM, the selective reactivation of the RAS cholinergic system with neurons releasing serotonin or norepinephrine on the thalamocortical system remaining inactive, leads to the observed EEG activity which is similar to what it is observed during wakefulness but with muscle atonia. Lastly, the transition to waking, is caused by the activation of the cholinergic as well as monoaminergic nuclei in the brainstem (Fig. 3.2b) and a resultant activation of the thalamocortical cells [42].

Thanks to the tomographic analysis of MEG data the changes during sleep can be studied non-invasively using MEG. The first tomographic analysis of whole night MEG data revealed the complexity of the processes involved [43] but also provided hints of a global organization and a relatively smooth transition from one stage to the next when the quiet rather than active periods of each sleep stage were compared [44]. The most consistent change running through all sleep staged was identified in near-midline areas on the left hemisphere, one in the frontal lobe and the other in the posterior mid-parietal area. In these two areas the gamma band activity was higher during REM sleep than other sleep stages and active wakefulness. A meta-analysis of recent neuroimaging studies showed that these two areas are at the centre of foci of increased activity identified in experiments with increased resting state activity compared to task periods (areas belonging to the “default system”) and areas identified in experiments requiring understanding own and other peoples intention and introspection (areas of the “Theory of Mind” system). It seems significant that the areas identified in the earlier sleep study, the default mode areas and the Theory of mind area were not just randomly placed with respect to each other. The areas of increased gamma band activity were at the centre and not overlapping with the areas of the two other systems, suggesting they play a pivotal role in maintaining the person’s identity through sleep. This makes us dare pushing beyond the suggestion of Domhoff that the default network might be involved in dreaming [45, 46]; we could suggest that the areas identified as super-active in the gamma band during sleep, and especially the dorsal medial prefrontal cortex are acting like a “Dream Box” releasing consciousness while the rest of the brain is largely subdue. Our recent research, focusing on light sleep suggests that an area close to the “Dream Box” areas is also important for spindles (Ioannides et al., in preparation).