SLEEP

■ Sleep is a sedentary state of mind and body, characterized by altered consciousness,

relatively inhibited sensory activity, reduced muscle activity and reduced interactions
with surroundings.
■ It is distinguished from wakefulness by a decreased ability to react to stimuli , but
more reactive than a coma or disorders of consciousness , with sleep displaying
different, active brain patterns.
NEUROTRANSMITT
ERS
SLEEP-PROMOTING
NEUROTRANSMITTERS
■ GABA
– It is the primary inhibitory neurotransmitter of the central nervous system
– It has been well established that activation of GABA-a receptors favors sleep.
– Sleep-promoting neurons in the anterior hypothalamus release GABA, which
inhibits wake-promoting regions in the hypothalamus and brainstem.
■ ADENOSINE
– It also promotes sleep by inhibiting wakefulness-promoting neurons localized to
the basal forebrain, lateral hypothalamus, and tuberomammillary nucleus
WAKEFULNESS-PROMOTING
NEUROTRANSMITTERS
■ Neurochemicals that maintain the waking state are
– acetylcholine (ACh)
– dopamine (DA)
– norepinephrine (NE)
– serotonin (5-HT)
– histamine (HA),
– the peptide hypocretin
■ ACETYL CHOLINE
– Cortical ACh release is greatest during waking and REM sleep and lowest during NREM sleep.
■ SEROTONIN
– 5-HT is released from serotonin-containing neurons of the dorsal raphe nucleus
■ NOREPINEPHRINE
– NE is released from norepinephrine-containing neurons of the locus coeruleus (LC).
– The noradrenergic cells of the LC inhibit REM sleep, promote wakefulness, and project to
various other arousal-regulating brain regions, including the thalamus, hypothalamus, basal
forebrain, and cortex.
■ HISTAMINE
– HA is released from histamine-containing neurons of the tuberomammillary nucleus of the
posterior thalamus.
– The cell bodies of hypocretin-producing neurons are localized to the dorsolateral hypothalamus
and send projections to all the major brain regions that regulate arousal
■ The sleep cycle is regulated by the circadian rhythm, which is driven by the
suprachiasmatic nucleus (SCN) of the hypothalamus.
■ The circadian rhythm also controls the nocturnal release of adrenocorticotropic
hormone (ACTH), prolactin, melatonin, and norepinephrine (NE).
■ GABAergic sleep-promoting nuclei are found in the brainstem, lateral hypothalamus,
and preoptic area
■ Transitions between sleep and wake states are orchestrated by multiple brain structures,
which include:
– Hypothalamus: controls onset of sleep
– Hippocampus: memory region active during dreaming
– Amygdala: emotion center active during dreaming
– Thalamus: prevents sensory signals from reaching the cortex
– Reticular formation: regulates the transition between sleep and wakefulness
– Pons: helps initiate REM sleep. The extraocular movements that occur during
REM are due to the activity of PPRF (paramedian pontine reticular
formation/conjugate gaze center).
FUNCTION
■ Neural maturation
■ Facilitation of learning or memory
■ Targeted erasure of synapses to "forget" unimportant information that might clutter the
synaptic network
■ Cognition
■ Clearance of metabolic waste products generated by neural activity in the awake brain
■ Conservation of metabolic energy
STAGES OF SLEEP
■ Sleep occurs in the following stages:
– Wake
– NREM
■ N1
■ N2
■ N3
■ N4
– REM
■ Approximately 75% of sleep is spent in the
NREM stages, with the majority spent in the
N2 stage.
■ A typical night's sleep consists of 4 to 5
sleep cycles
■ A complete sleep cycle takes roughly 90 to
110 minutes.
■ The first REM period is short, and, as the
night progresses, longer periods of REM and
decreased time in deep sleep (NREM) occur.
WAKE/ALERT

■ EEG recording:
– beta waves - highest frequency,
lowest amplitude
– alpha waves
■ Beta waves are commonly seen
during active mental concentration
■ Alpha waves are seen when a person
closes their eyes and relaxes
N1 (STAGE 1) - LIGHT SLEEP (5%)

■ EEG recording: theta waves - low

voltage
■ This is the lightest stage of sleep
■ Characterized by a sense of calmness,
slow pulse, slow respiration and
decrease in blood pressure
■ This stage lasts around 1 to 5 minutes
■ It consists of 5% of total sleep time
N2 (STAGE 2) - DEEPER SLEEP
(45%)
■ EEG recording: sleep spindles and K
complexes
■ Stage 2 sleep lasts around 25 minutes
in the first cycle and lengthens with
each successive cycle
■ Constitutes about 45% of sleep cycle
making the largest portion of sleep
time
N3/N4 (STAGE 3 and 4) - DEEPEST
NON-REM SLEEP (25%)

■ EEG recording: delta waves - lowest

frequency, highest amplitude
■ This is considered the deepest stage
of sleep
■ This stage is the most difficult to
awaken from, and, for some people,
even loud noises (> 100 decibels)
will not awaken them.
■ Although this stage has the greatest
arousal threshold, if someone is
awoken during this stage, they will
have a transient phase of mental
fogginess, known as sleep inertia.
■ As people age, they tend to spend
less time in this slow, delta wave
sleep and more time in stage N2
sleep.
■ Sleep disorders such as sleepwalking,
night terrors, and bedwetting occur
during this stage
RAPID EYE MOVEMENT - REM
(25%)
■ EEG recording: beta, alpha and theta
waves.
■ This stage usually starts 90 minutes after
falling asleep.
■ REM cycles get longer throughout the
night. The first period typically lasts 10
minutes, with the final one lasting up to
an hour.
■ Dreaming occurs during this part of the
sleep.
■ A person is more difficult to arouse by
sensory stimuli than during SWS
■ People tend to awaken spontaneously in
the morning during an episode of REM
sleep
■ Associated with irregular muscle
movements as well as rapid
movements of the eyes.
■ Increase in pulse, respiration and
blood pressure, loss of motor tone,
increased brain O2 use.
■ Increased levels of Acetylcholine
■ The brain is highly active throughout
REM sleep, increasing brain
metabolism by up to 20%.
■ Nightmares, and penile/clitoral
tumescence occur during this stage.
SLEEP DISORDERS
 INSOMNIA

HYPERSOMNIA

NARCOLEPSY
DYSOMNIA
S SLEEP APNEA

CIRCADIAN RHYTHM
DISORDER

KLEIN LEVIN SYNDROME

INSOMNIA
■ Condition of unsatisfactory quality
and/or quantity of sleep, with difficulty
falling asleep, remaining asleep, or
waking early and being unable to return
to sleep
■ Causes:
– Transient insomnia occurs at times
of stress or as jet lag
– Usually secondary to other
disorders, notably painful physical
conditions, depressive disorders
and anxiety disorders
– Excessive use of alcohol or
caffeine
– Dementia
– Provoked by prescribed drugs
– Idiopathic in 15% cases
HYPERSOMNIA
■ Excessive day time sleepiness is
common with a reported prevalence
of 3 to 5%.
■ Many cases are secondary to loss of
night time sleep.
■ Principal causes include insufficient
sleep, narcolepsy, depression, use of
sedatives, obstructive sleep apnea,
shift work sleep disorder or other
medical disorders like
hypothyroidism, Prader Willi
syndrome
NARCOLEPSY
■ Narcolepsy is an important cause of
chronic sleepiness.
■ Affects 1 in 2000 people.
■ Age of onset ranges between 10 to 20
years, although diagnosis is delayed
by several years.
■ A useful clue is that, unlike day time,
sleepiness caused by insufficient night
sleep or that which is often observed
in teenagers, people with narcolepsy
feel refreshed after a full night’s sleep.
■ In addition, narcolepsy is
characterized by a disturbance in
REM sleep, which can occur at any
time and lead to unusual states in
between sleep and wakefulness such a
hypnopompic and hypnogogic
hallucinations
■ The most striking of REM-like states is cataplexy: sudden episodes of partial or
compete paralysis of voluntary muscles, sometimes causing person to fall to the ground.
But this does not occur in all patients and is limited to type 1 narcolepsy
■ Additional features include a tendency to obesity (owing to a low metabolic rate) and
depression is common
■ Types of narcolepsy
■ Type 1 narcolepsy: characterized by cataplexy and marked reduction of a peptide called
orexin-A (also called hypocretin-1) in the CSF
■ Type 2 narcolepsy: not associated with cataplexy and CSF orexin levels are normal,
making diagnosis more challenging
■ Etiology
■ Genetic association
– Predominant genetic association is HLA-DQB1*06:02
– More than 98% patients with type 1 narcolepsy and 50% with type 2 narcolepsy
have this genotype, compared to 15-30% of the general population
– This gene increases the risk of narcolepsy by a factor of 200
– Other genes involved in immune system are also implicated in narcolepsy risk
■ Autoimmunity
– There is an increasing evidence that narcolepsy may be an autoimmune disorder,
triggered by infections or other stimuli
– For example its onset is most common in spring and may follow streptococcal
infections
– Strikingly there was a marked increase in cases of narcolepsy in children given a
specific brand of influenza vaccine in 2009-2010
– It is thought that these genetic and environmental triggers lead to an autoimmune
response that damages the orexin-A producing cells
SLEEP APNEA
■ Individuals with sleep apnea experience
airway collapse in deeper sleep states,
causing them to experience reduced
time in stage N3 and REM sleep.
■ This leads to excessive daytime
drowsiness as proper, efficient sleep is
not obtained throughout the night.
■ There are two types of sleep apnea:
■ Central sleep apnea:
– Occurs when the brain fails to
properly signal respiratory
muscles during sleep.
■ Obstructive sleep apnea:
– It is a mechanical problem in
which there is a partial or
complete blockage of the upper
airway.
CIRCADIAN RHYTHM SLEEP
DISORDER

■ Disturbance of sleep due to a

mismatch between a person’s
intrinsic circadian rhythm, and
external sleep wake demands
KLEIN LEVIN SYNDROME

■ Rare secondary sleep disorder

■ Characterized by episodes of
somnolence, increased appetite and
hypersexuality, often lasting for days
or week, with long intervals of
normality between them
■ Usually affects adolescent boys
■ Symptoms suggest a hypothalamic
disorder, but its etiology is unknown
 NIGHTMARES

NIGHT TERRORS

SOMNAMBULISM
PARASOMNI
AS REM SLEEP DISORDER

RESTLESS LEG SYNDROME

SLEEP PARALYSIS
NIGHTMARE
■ Awakening from REM sleep to full
consciousness with detailed dream
recall
■ Occurs during REM sleep
■ Peak frequency around the age 5 or 6
years
■ May be stimulated by frightening
experiences during the day
■ Frequent nightmares usually occur
during a period of anxiety
■ Other causes include PTSD, fever,
psychotropic drugs and alcohol
detoxification
NIGHT TERROR
■ Less common than nightmares
■ Sometimes familial
■ Condition begins and usually ends in
the childhood, but occasionally
persists into adult life
■ Occurs in the stage 3 or 4 of NREM
sleep with no recall of the dream
■ After a few hours of going to sleep,
the child sits up and appears terrified.
They may scream and usually appear
confused and there is a marked
increase in heart rate and respiratory
rate
SOMNAMBULISM/SLEEP
WALKING
■ Somnambulism is a common
occurrence in school-aged children,
most common between the ages of 5
and 12 years with 15% of children in
this age group walk in their sleep at
least once
■ Occasionally the disorder persists
into adult life
■ Sleepwalking may be familial
■ These individuals tend to make
purposeful movements, but they are
not acting out their dreams.
■ Dreams occur during the REM phase of the sleep cycle, in which the body is fully
paralyzed. Sleepwalking occurs because the sleep cycle is still in the maturing phase,
and proper sleep/wake cycles are not yet regulated.
■ Sleepwalking is typically associated with common behaviors, such as dressing, eating,
and urinating.
■ Sleepwalking occurs in the non-rapid eye movement phases, usually in N3.
REM SLEEP DISORDER
■ During REM, individuals are typically
atonic, meaning we do not move due to
temporary muscle paralysis.
■ If the temporary atonia of REM sleep is
disturbed, it may be possible to
physically act out (often unpleasant)
dreams with vocalizations and sudden
limb movements. This is called rapid eye
movement (REM) sleep disorder.
■ The cause of this disorder is not entirely
known but may be associated with
degenerative neurological conditions
such as Parkinson disease or Lewy body
dementia.
■ Antidepressant use has also been shown
to cause REM sleep disorder.
RESTLESS LEG SYNDROME

■ Distressing and painful condition that

can result in severe insomnia and
periodic limb movements during
sleep
■ Common with 2.5% of the population
having significant symptoms
■ Risk factors include female gender,
pregnancy, ageing, low iron and
parkinsonism
SLEEP PARALYSIS

■ It is an inability to perform voluntary

movements during the transitions
between sleep and wakefulness
■ Occurs either at sleep onset
(hypnogogic) or during awakening
(hypnopompic)
■ The episodes are often accompanied
by extreme fear
SLEEP HYGIENE
Sleeping and waking up around the same time daily, even on weekends

Increased physical activity in the afternoon and early evening hours

Cool and dark rooms

Light bedtime snacks that have calcium and small amounts of sugar

Evening relaxation routines such as PMR and evening prayers

Avoidance of long naps, especially during the later part of the day

Making and cleaning your bed everyday

Getting into bed only when ready for sleep

Eating at regular times daily and avoiding large meals near bedtime
Avoidance of sensory stimulation at night by substituting TV and cellphone
usage with light reading

Avoidance of caffeine and fizzy drinks in the evening

Avoidance of excessive smoking in the evenings

Avoidance of stimulant drugs such as amphetamines, cocaine and MDMA

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