Sleep is a state of reduced responsiveness to the environment, decreased voluntary muscle activation, and largely inhibited sensory modalities. Hence, it is a state of altered consciousness. It is considered to be a restorative process unless its excess or insufficiency interferes with patients’ quality of life.
In this article, we will explore the concept of consciousness and sleep, followed by discussing two types of sleep: rapid eye movement sleep (REM) and non-rapid eye movement sleep (NREM). Subsequently, we will review a complex sleep regulatory network and discuss the consequences when it is disrupted.
Consciousness defines an individual’s awareness of themselves and their surroundings together with their own mind – including a person’s own thoughts and dreams. The conscious experience relies on the integration of multiple parts of the nervous system.
Neurologically speaking, the consciousness system is a series of cortical and subcortical brain networks that work in synergy to maintain attention, alertness, and awareness.
Sleep is a physiological state of reduced consciousness. However, consciousness can be also impaired or completely lost as a consequence of pathology. A person can have different degrees of consciousness and in turn awareness.
The Sleep-Wake Cycle
The sleep-wake cycle is a cyclical variation in one’s awareness, comprising of phases of wakefulness and sleep. This is largely influenced by changes in behaviour and physical activity as well as light and dark exposure, and is an example of a circadian rhythm. Circadian rhythms are important in regulating many physiological processes including hormone release e.g. cortisol.
REM vs NREM Sleep
Sleep is divided into two states, which we will now explore in more detail.
During REM sleep, the brain appears more active on an electroencephalogram (EEG) compared to alertness. Interestingly, during this sleep phase almost all muscles of the body are paralysed (REM atonia). The exceptions are respiratory muscles and extraocular muscles.
Sympathetic activity predominates during this phase of sleep, which in turn results in an increased respiratory and heart rate. Additionally, during the REM phase, the human brain produces vivid images and events which we know as dreams.
NREM sleep is characterised by slow, low-frequency EEG patterns. This phase of sleep is additionally divided into 4 stages according to the increasing synchronisation of neural activity and lower frequency of generated waves. In contrast to REM sleep, there is usually little or no rapid eye movement and muscles are not paralysed.
Additionally, parasympathetic activity prevails – resulting in lowered heart rate, respiration rate and renal function, and increased digestion.
Stages of Sleep
The table below summarises the different stages of sleep, as well as their associated EEG patterns.
|Type of sleep||Characteristics of stage||Description of wave pattern|
|Awake||The state of being awake and alert with awareness.||Low-voltage high-frequency beta waves (>14 Hz)|
|Drowsy||Reduced alertness and activity||Alpha waves prominent (8-13 Hz)|
|Stage 1||Transitional sleep||Theta rhythms (4-7Hz)|
|Stage 2||Slightly deeper sleep||Spindles (initiated from the thalamus) and K complex and mixed EEG activity|
|Stage 3 and 4 (slow-wave/deep sleep)||Rapid eye movements classically absent with stage 4 (the deepest sleep stage) lasting 20-40 minutes||Delta waves (<4 Hz)|
|REM||REM sleep featuring rapid eye movements.||Sawtooth waves – low voltage high frequency|
Throughout the course of the night, a person will cycle through NREM and REM sleep. The average length of the first NREM-REM cycle is 70-100 minutes, whereas the later cycles are slightly longer-lasting – approximately 90 to 120 minutes.
A sleep episode begins with a period of NREM stage 1 sleep, progressing through stages 2, 3 and 4. Subsequently the person exits the NREM stage, reversing through the stages to enter the REM sleep state as demonstrated in Figure 3. This cycle repeats throughout the night.
As the night progresses, the proportion of REM sleep per cycle increases, whereas stage 2 begins to account for the majority of NREM sleep. Stages 3 and 4 may disappear altogether in later cycles.
Regulation of Sleep and Wakefulness
The sleep-wake cycle is under a series of complex neurological and endocrine influences.
Neurological regulation of sleep and wakefulness is distributed between two major anatomical structures the brainstem, harbouring reticular activating system (RAS), and the hypothalamus, harbouring suprachiasmatic nucleus (SCN).
The Reticular Activating System (RAS)
The reticular activating system (RAS), located in the anterior brainstem, is the central neurological regulatory centre for the sleep-wake cycle. It plays a critical role in regulating cortical alertness, wakefulness, and attention. The RAS is composed of four main components, all of which play key roles in wakefulness and arousal.
The nucleus coeruleus contains noradrenergic neurones, which project to the cortices of the cerebrum and cerebellum. It is activated by hypocretin (orexin) from the lateral hypothalamus. The activity of this nucleus can affect REM sleep. However, it is primarily involved in increasing the brain’s excitability upon wakefulness and arousal.
The raphe nuclei contain serotonin containing cells. It directly communicates with the hypothalamic suprachiasmatic nucleus. Hence, it has a direct role in circadian rhythm regulation together with arousal and attention.
The pedunculopontine and laterodorsal tegmental nuclei are collectively referred to as the pontomesencephalotegmental complex. This complex is located within the pons and the midbrain, and contains cholinergic neurones that project to areas including the thalamus and cortex. Their activation is responsible for the shift from slow waves sleep rhythms to higher frequency awake rhythms.
The tuberomammillary nucleus contains histaminergic neurones and also plays an essential role in wakefulness and arousal but also memory.
The activity of RAS and hence sleep-wake cycle is heavily regulated by nuclei present within the hypothalamus.
The suprachiasmatic nucleus (SCN) is situated directly above the optic chiasm. It receives input from the retina regarding light intensity. This retinal input makes is well-suited for its role as the major circadian clock in the human brain. In response to light changes, it generates circadian rhythms in rest and activity.
The lateral hypothalamus contains neurones secreting a peptide neurotransmitter called hypocretin (orexin).It is believed to innervate and excite the RAS helping to establish wakefulness and inhibit REM sleep.
The ventrolateral preoptic nucleus (VLPO)is located in the anterior hypothalamus and inhibits the main components of the RAS, hence promoting sleep. It is most active during sleep when it will release inhibitory neurotransmitters such as GABA to suppress RAS-induced wakefulness.
Melatonin is a hormone produced by the pineal gland in response to signals from the SCN. Hence, melatonin release is based on the circadian rhythm.
Melatonin release increases at night, a few hours before sleep, and peaks around midnight. Its levels then gradually decline until the morning when wakefulness is restored. The blue light (400 and 525 nm) emitted from screens is responsible for inhibiting melatonin release to a greater degree than other wavelengths. Consequently, a lengthy and late screen time may make it more difficult for people to fall asleep!
Clinical Relevance – Narcolepsy
Spontaneous episodes of sleep at times when sleep would not normally occur e.g. whilst trying to read a book may be a sign of a pathological condition known as narcolepsy. A concurrent condition that may accompany narcolepsy is cataplexy when there is a loss of muscle tone.
Although not fully understood, it is believed that narcolepsy is caused by immune-mediated destruction of cells in the hypothalamus and other brain areas involved in the regulation of the wake-sleep cycle. The affected cells ordinarily produce hypocretin (orexin).
However, in individuals suffering from narcolepsy levels of hypocretin become very low, even potentially undetectable. This autoimmune destruction is thought to be triggered by an inappropriate response of the immune system to an infection.