Sleep physiology

1. Sleep Physiology

2. Sleep
• Lucretius postulated that sleep is an absence of wakefulness.
• Macnish, in 1830, proposed a variation of Lucretius’s concept,
defining sleep as “suspension of sensorial power in which the
voluntary functions are absent but the involuntary functions, such as
circulation, respiration, and other functions controlled by the
autonomic nervous system, remain intact.
• Three basic physiological processes of life consist of wakefulness,
nonrapid eye movement (NREM) sleep, and rapid eye movement
(REM) sleep, with independent functions and controls

3. • Awake: State of readiness/alertness & ability to react consciously
to various stimuli.
• Coma: State of unconsciousness from which a person cannot be
aroused by any external stimuli.

4. DEFINITION OF SLEEP
• Behavioral criteria- lack of mobility or slight mobility, closed eyes, a
characteristic species-specific sleeping posture, reduced response to external
stimulation, quiescence, increased reaction time, elevated arousal threshold,
impaired cognitive function, and a reversible unconscious state
• Physiological criteria - based on EEG, electro-oculography (EOG), and
electromyography (EMG) findings as well as other physiological changes in
ventilation and circulation
• The onset of sleep occurs even prior to entrance of stage 1 of NREM N1 sleep
and is defined as subjective heaviness and ptosis of eyelids, clouding of
sensorium, and a decrement in logical or rational perception of visual and
auditory stimuli and reduced capacity to respond with logic. Predormitum
term was originally coined by Critchley (1955) to describe this moment of sleep
onset

6. Sleep Architecture
• Sleep is divided into two independent states: NREM and REM sleep based on
physiological correlates.
• NREM sleep is further divided into three stages, primarily on the basis of EEG
criteria.
• NREM and REM sleep alternate, with each cycle lasting for approximately
90–100 minutes. Four to six such cycles are noted during a normal sleep
period.
• The first two cycles are dominated by slow-wave sleep (stage N3), but in later
cycles, these stages are noted only briefly and sometimes not at all.

7. • Conversely, the duration of the REM sleep cycle increases from the first to the
last cycle, and toward the end of the night, the longest REM cycle may last
as long as 1 hour.
• Thus, the first third of a normal sleep episode is dominated by slow- wave
sleep, and REM sleep dominates the last third

9. • In their 1968 criteria, Rechtschaffen and Kales (RK) divided NREM sleep
into stages 1, 2, 3, and 4.
• In the modified staging criteria adopted by the AASM (Iber et al., 2007), the
traditional RK stage 1 NREM sleep was labeled N1, RK stage 2 was labeled
N2, and RK stages 3 and 4 were combined into one stage, N3
• Sleep scoring and staging is a procedure whereby the sleep recording is broken
up into 30-second segments, “epochs,” of a polysomnographic (PSG) tracing
with a paper or monitor speed of 10 mm/sec

10. NREMand REM sleepstates

12. Awake

13. N1 Stage
• when eyes closed and relaxing and disappear when
eyes are opened
• Decrease of alpha activity to less than 50% and low-
amplitude beta and theta activities.
• Alpha rhythm is best visualized in the posterior
regions of the head (O2-M1),
• Alpha rhythm is attenuated or replaced by low-
amplitude, mixed-frequency activity (4–7 Hz) for
more than half of the epoch.
• EMG - less activity than in wake,
• Breathing becomes shallow,
• Heart rate becomes regular,

14. N1 Stage

15. N2 Stage
• Unique features of stage N2 sleep include 12- to 14-Hz sleep
spindles and biphasic K complexes intermixed with delta waves
(0.5–2 Hz) and up to 75 μV in amplitude occupying less than 20%
of the epoch.
• Stage N2 scored if one or more K complexes or sleep spindles
are noted during the first half of the epoc or last half of the
previous epoch.
• Sleep spindles are generated in the midline thalamic nuclei, are
characterized by 12-to 14-Hz sinusoidal EEG activity in the
central vertex region and must persist for at least 0.5 seconds.
• Relative diminution of physiological bodily functions with
attenuation of blood pressure, brain metabolism, gastrointestinal
secretions, and cardiac activity

16. N2 Stage

17. N3 Stage
• Defined by the presence of a minimum of 20
percent delta waves ranging from 0.5–to-2 Hz
and having a peak-to-peak amplitude>75 μV.
• most restorative form of sleep,
• where one is most likely to observe disorders of
arousal (none-REM parasomnias) such as
somnambulism and sleep terrors

18. N3

19. REM
• paradoxical sleep, or active sleep,
• REM are conjugate, irregular, sharply peaked eye
movements.
• EEG -fast rhythms and theta activity, some of which
may have a sawtooth
• appearance.
• EMG tone should be at the lowest level of any sleep
stage.
• Physiological activity higher-
• 1.BP and PR increase dramatically or may show
intermittent fluctuations.
• 2.Breathing becomes irregular and brain oxygen
consumption increases.

20. REM

21. Hypnogram
• Pictorial representation of the sleep stages from sleep
onset to offset
• Helpful in staging and interpretation at baseline and prior
to and following treatment

22. Proportion of Time During the
Night That an Adult Spends in Various Sleep Stages

23. • Sleep microstructure consists of momentary dyanamic phenomenons called
as arousals
• An arousal is a shift in the EEG frequency and an arousal index is defined as
the number of arousals per hour of sleep, upto 10 can be considered normal
arousal index, while a higher index signifies sleep fragmentation

24. Ontogeny of Sleep Patterns with Age
• Newborns have a polyphasic sleep pattern with 16 hours of sleep per day.
• The sleep requirement decreases to approximately 10 hours per day by age 3–
5 years.
• In preschool children, sleep assumes a biphasic pattern.
• Adults exhibit a monophasic sleep pattern, with an average duration of 7.5–8
hours per night.
• The newborn infant spends approximately 50% of the time in REM sleep, but
by age 6 years this time is decreased to the normal adult pattern of 25%

25. • Newborn baby goes immediately into REM sleep, or active sleep,
• In premature babies, it is often difficult to differentiate REM sleep from
wakefulness.
• By age 3 months, the NREM-REM cyclical pattern of adult sleep is established.
However, the duration of the NREM-REM cycle is shorter in infants, lasting for
approximately 45–50 minutes and increasing to 60–70 minutes by age 5–10
years, and to the normal adult cyclical pattern of 90–100 minutes by age 10
years.
• Sleep spindles begin to appear at about 3 months of age; K complexes are seen
by about 6 months

26. Ontogeny of Sleep. Changes in sleep stage in
infants, children, adults, and elder adults,
demonstrating the evolution of sleep by sleep
stage.W
, wake; R, rapid eye movement (REM)
sleep; N1, N2, N3, stages N1, N2, and N3 NREM
sleep, respectively. Compared with early life,
older adults spend more time awakein bed, less
time in R and N3 sleep, and more time in lighter
stages of sleep

29. Functions of Sleep
• Sleep deprivation studies in humans have shown an impairment of
performance, which demonstrates the need for sleep.
• The performance impairment of prolonged sleep deprivation results
from a decreased motivation and frequent “microsleeps.”
• Overall, human sleep deprivation experiments have proven that sleep deprivation
causes sleepiness and impairment of performance, vigilance, attention,
concentration, and memory.
• Sleep deprivation may also cause some metabolic, hormonal, and
immunological effects.

30. chronic sleep deprivation -
Glucose intolerance,
memory impairment
decrement of thyrotropin
concentration,increased evening
cortisol level, sympathetic
hyperactivity, which may serve as
risk factors for obesity,
hypertension,and diabetes mellitus
increase in ghrelin levels
associated with short
sleep reduced leptin-
increased appetite, BMI
Studies from Van
Cauter’s (Spiegel et
al., 1999)-
elevationof cortisol level
following even partialsleep
loss, suggesting an
alterationin hypothalamic-
pituitary-adrenal axis
function

31. • The restorative theory suggests that sleep is needed to restore cerebral
function after periods of waking. The findings of increased secretion of
anabolic hormones (e.g., growth hormone, prolactin, testosterone, and
luteinizing hormone) and decreased levels of catabolic hormones (e.g.,
cortisol) during sleep, as well as the subjective feeling of being refreshed
after sleep.
• In NREM sleep restoring the body is further supported by the presence
of increased slow-wave sleep after sleep deprivation.
• Role of REM sleep- in development of CNS and increased protein
synthesis in the brain

32. • The energy conservation theory- during 8 hours of sleep, only 120 calories
are conserved.
• The adaptation theory- sleep allows creatures to survive under a variety of
environmental conditions.
• The memory consolidation theory- new memories can be strengthened by
sleep (Stickgold and Walker, 2007)
 Memory is stored in 2 stages
 short-term memory - labile
 long-term memory - stable and consolidated
 memory consolidation occurs during both slow-wave and REM sleep

33. • The theory of maintenance of synaptic and neuronal network integrity -
Intermittent stimulation of neural network synapses is necessary to
preserve CNS function (Kavanau, 1997).
• Synaptic homeostasis theory - subserving different functions e.g., energy
metabolism, synaptic excitation, long-term potentiation, and response to
cellular stress during wakefulness and protein synthesis, memory consolidation

34. • The thermoregulatory function theory -The preoptic anterior
hypothalamic neurons participate in thermoregulation and NREM sleep.
• Iliff et al., 2012- sleep state-dependent enhanced brain flushing as depicted by
enhanced CSF flow through a relatively newly discovered drainage system, the
so-called glymphatic system .
CSF-flow in delaying and preventing neurodegenerative disease-
associated metabolites during sleeping, including alpha-
synucleinopathies and tauopathies

35.  80% of the dreams occur in REM sleep
 In REM sleep, there is activation of the basal forebrain which results in highly
emotionally charged complex and bizzare dreams.
 While NREM dreams are realistic and rational.
 Awakening from REM sleep: generally oriented and easier to recall dream
 Awakening from NREM sleep: disoriented and confused.
Dreams

36. References
• Bradley 8th edition.
• Guyton & Hall 18th edition.
• PSG and Neurochemistry Source: Nir, Y., Tononi,
G., 2010. Dreaming and the brain: from
phenomenology to neurophysiology. Trends
Cogn.Sci. 14(2), 88–100.
• Kryger, M.H., Avidan, A., Berry, R., 2013. Atlas of
Clinical Sleep Medicine, second ed.
Saunders/Elsevier, Philadelphia
• Biology of Sleep Kryger MH, Avidan, AY, Berry, R.
Atlas of clinical sleep medicine. Second edition.
ed. Philadelphia, PA.

37. THANK
YOU