13th January 2024

Physiology of Sleep

Sleep is the natural periodic rest state of our mind and body characterised by reduced consciousness, inhibition of sensory activity and drastically reduced muscle activity. Despite spending roughly a third (or ~8 hours/day) of our lives sleeping, sleep is poorly understood, and its exact purpose is not completely certain. There is evidence to suggest that sleep has roles in:

• Restoration and clearance: sleep has been shown to clear waste products from the brain that build up during the day via the ‘glymphatic system’ (clearance system of the brain reliant on glial cells)
• Growth and repair: sleep has been suggested to help in body repair and growth; growth hormone levels peak during sleep
• Memory and learning:  experimental data shows how sleep is critical to brain plasticity, promoting synaptic growth and maintenance while helping consolidate memory.

While the science is not completely clear about the exact functions of sleep, it is readily apparent to any of us who has had a poor night’s sleep that one doesn’t tend to feel clear-headed, energetic, or particularly sharp without a full night of deep restorative sleep!

Sleep is cyclical and goes through various stages with differing physiological activity. Sleep is broadly divided into two categories: Rapid Eye Movement (REM) sleep and Non-Rapid Eye Movement (NREM) sleep. NREM sleep is further subdivided into N1, N2 and N3 substages. Each stage/sub-stage is characterised by changes in muscle tone (as noted on Electromyography or EMG), brain waves (as seen on Electroencephalography or EEG) and changes in response to sensory input.

Stages of Sleep

1) Wakefulness: one is awake, alert, and responsive to outside stimuli. Higher cortical activity (voluntary movement, speech, etc) is readily apparent. As one settles to sleep, one becomes drowsier and response to external stimuli starts to decrease.

EEG tends to show either beta waves (alert) or alpha waves (drowsy).

NREM Sleep:

2) N1 Stage: this is the transition between wakefulness and sleep and where sleep is the lightest. High levels of N1 sleep on sleep studies can suggest that sleep is fragmented and unable to deepen (e.g. due to sleep-related breathing disorders). With a transition to N1 sleep, there is a general decrease in muscle tone and awareness of external stimuli. EEG shows theta waves.

3) N2 Stage: as sleep deepens, there is a transition to N2 sleep. This is where one spends the majority (up to 55%) of total sleep. In N2 sleep, muscle tone further decreases, and there is further loss of awareness (and thus response) to external stimuli. EEG shows sleep spindles and K complexes.

4) N3 Stage (or deep/slow wave sleep): This is the deepest phase of sleep, where the sleeper is least likely to awake in response to external stimuli. It tends to occur more frequently during the first part of the night. EEG characterised by delta waves.

Historically, NREM sleep was divided into four stages. This convention has changed; the previous N4 stage is now classified as part of N3 sleep. In NREM sleep, we can observe release of hormones from the anterior pituitary gland and clinically can observe decreases in temperature, blood pressure, heart rate and respiratory rate.

REM Sleep:

5) Characterised by rapid eye movement, REM sleep is the phase of sleep that is most associated with dreaming. This is the state of sleep where there is complete atonia of the muscles (excluding the extraocular muscles and the diaphragm). This is a result of inhibition of the alpha motor neurones.

REM sleep has been associated with learning, memory consolidation and emotional processing. Observing clinically, we see irregular breathing patterns and periodic rises in blood pressure and heart rate. It has also been seen that there is an increase in O2 consumption from the brain during this stage of sleep. Brain waves on EEG mimic awake states. On average, one spends 20-25% of total sleep in REM sleep. The proportion of time spent in REM sleep decreases as we age.

The Sleep Cycle:

A normal uninterrupted sleep cycle lasts for 70 -110 minutes and progresses in a cyclical fashion. We tend to cycle through 4-5 cycles of sleep during an average night’s sleep. N3 sleep tends to occur predominantly in the first few cycles of sleep (which thus tend to be when sleep is deepest). As the night progresses, one has longer periods of REM sleep, and sleep tends to lighten. There may be very brief arousals (awakenings) that often aren’t remembered or registered by the sleeper on waking.

Image Source: Wikimedia Commons (2013). Hypro zyklus 1 en 103, Licensed under a creative commons licence. Available for free at: https://upload.wikimedia.org/wikipedia/commons/b/bb/Hypro_zyklus_1_en_103.svg (Accessed: 16 August 2022).

Note that by current convention, N4 is part of N3 Sleep

Image Source: Wikimedia Commons (2011). Sleep Hypnogram, Licensed under a creative commons licence. Available for free at: https://commons.wikimedia.org/wiki/File:Sleep_Hypnogram.svg  (Accessed: 16 August 2022).

References

• Douglas K. Stages and architecture of normal sleep [Internet]. Uptodate.com. 2021 [cited 21 July 2022]. Available from: https://www.uptodate.com/contents/stages-and-architecture-of-normal-sleep
• Fuller P, Gooley J, Saper C. Neurobiology of the Sleep-Wake Cycle: Sleep Architecture, Circadian Regulation, and Regulatory Feedback. Journal of Biological Rhythms [Internet]. 2006 [cited 5 August 2022];21(6):482-493. Available from: https://journals.sagepub.com/doi/10.1177/0748730406294627
• Widmaier E, Raff H, Strang K, Vander A. Vander’s Human Physiology: The Mechanisms of Body Function. 12th ed. New York: McGraw-Hill; 2011.