Reactive slow waves and state-dissociation in sleep underlie several NREM-sleep states and pathological conditions

 
Stimuli disturbing non-rapid eye movement sleep (NREM sleep; slow wave sleep) may increase the level of vigilance “arousing” the sleeper. A conventional arousal typically manifests as a fast and low-voltage EEG pattern (desynchronisation). Contrasting this “normal” expectation, EEG slow waves (sleep-like synchronised activity) may also develop in response to arousing stimulation during NREM sleep. These reactive slow waves carry “anti-arousal” features promoting or preserving sleep.

Thus, sleep-disturbing stimuli can cause EEG desynchronisation and lead to the elevation of vigilance (arousal) or a sleep-like pattern with slow waves (a paradoxical, sleep promoting “anti-arousal”). Those stimuli create “crossroad” situations, awakening or maintaining sleep. Since sleep is essential for learning and memory, it is important to preserve it. On the other hand, one needs a flexible arousability to awaken in need. Therefore, a version of Hamlet’s dilemma “to wake or not to wake“, is an unconscious in-built alternative in the arousal process.

The phase and degree of homeostatic sleep-regulation determine the selection of response-type: arousal or anti-arousal. Low sleep (homeostatic) pressure evokes conventional desynchronised arousals and when sleep pressure is high, paradoxical slow-wave anti-arousals develop, deepening the sleep. This double nature of arousal finds a comprehensive domain in the cyclic alternating pattern (CAP) a micro-cyclicity of NREM sleep. A1 phase of CAP containing slow waves reflects a high sleep-propensity favouring sleep while A2-3 phases carry higher proneness to arousal.

Sleep research has recognised that sleep is not always a global process; certain cortical areas sleep, while others are awake at the same time. Use-dependent homeostatic need for sleep assigns sleepy or vigilant spots (more daytime use of a cortical area creating more want to sleep). Alternating uni-hemispheric sleep is typical in several species. For example, cetaceans sleep with one hemisphere in parallel with the other one awake, ensuring the safety of the animal swimming in the ocean. The same occurs in birds of passage, spending long times in the air. Depending on the use-dependent need to sleep, certain cortical areas go to sleep earlier or remain longer in sleep than other ones creating a normal dissociation of sleep/wake activity.

The recognition of micro-arousals sheds more light on dissociation: certain cortical areas remain in sleep while others are aroused, and the person behaves as though half sleeping half-awake. We see the pathological forms of this scenario in arousal disorders and in frontal lobe epilepsies.

This double nature of micro-arousals from NREM sleep and the dissociation of parallel sleep and wake patterns can explain several electro-clinical phenomena on the edge of normal and pathological.

Those conditions related to the double nature of arousals from NREM sleep as well as the spatial and functional dissociation of sleeping and aroused brain areas are the followings:

Confusional arousals are most frequent in children. In so-called “sleep-drunkenness” episodes, there is an increased sleep-inertia: while the affected person may move around, the EEG lacks the conventional desynchronized arousal pattern in spots responsible for awareness, while the motor system is “awake”.

Night terror/somnambulism (also called arousal disorders) shows a paradoxical (hypersynchronous) sleep-like slow wave activity in parallel with aroused motor system- sleepwalking.

Idiopathic frontal lobe epilepsies are epileptic variants of arousal disorders.

Epileptic/non-epileptic arousal disorders show similar symptoms and share a genetic origin. Due to their link to arousal-related slow waves in NREM sleep, both manifest during arousals of high homeostatic pressure periods. In somnambulism, a fronto-dorsal slow wave and an anterior limbic fast activity coincide with the hyper-synchronization of the fronto-dorsal cognitive network creating a dissociated state and accordingly, a partially awake and partially sleeping behaviour. In sleep-related genetic frontal lobe epilepsy, arousals occur in a hypersensitive ascending arousal system during high homeostatic pressure periods. The epileptic hypersensitivity turns the arousal disorder epileptic, manifesting hypermotor/arousal/alarm behaviours.

Hypnagogic hypersynchronization is also prevalent in childhood. Sensory stimulation can also elicit the seemingly spontaneous EEG pattern consisting of high amplitude bilateral synchronous slow waves.

These conditions share the following features:

• The double nature of arousal in NREM sleep when sensory stimuli create “crossroad” situations has a major impact.
• They prefer transitional sleep periods between wake and NREM sleep or within NREM sleep.
• They are prevalent in childhood when the brain is more prone to produce slow waves.

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