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Neuroscience of Sleep
Professor M.A. Danesi
College of Medicine
University of Lagos
WHAT IS SLEEP?
In 1913, Henri Pieron defined three features of sleep:
• It is periodically necessary
• It has a rhythm relatively independent of external condition
• It is characterized by complete interruption of the sensory and
motor functions that link the brain with the environment.
WHAT IS SLEEP?
• Until late 1950 sleep was viewed as a lapse in the waking state
when there is insufficient stimulation to keep the brain awake.
• This concept changed in the late 1950’s when sleep began to be
regarded as an active process characterized by a cyclic
succession of different psycho- physiological phenomena.
• There are two stages of sleep distinguished by
Electroencephalogram: The slow wave sleep (Non REM) and
REM sleep with EEG Dissynchronization
Non REM Sleep
• There are four stages of Non REM sleep – stages 1-4. As a person falls
asleep the EEG progresses through all the 4 stages of slow wave sleep.
• In stage 1, the person drifts in and out of sleep and can be awaken
easily. The eyes move slowly and muscle activity slows. People
awaken from stage I sleep often remember fragmented visual images
like dream. The EEG 50% consists of relatively low voltage mixed theta
and delta (2 – 7 Hz) activity and <50% contains alpha.
• In stage 2 – eye movements stop and EEG becomes slower: Bursts of
rapid waves called sleep spindles and K – complexes (brief high voltage
discharges) occur. The slow waves are mainly theta. Less than 20% of
EEG is delta.
NON REM SLEEP:
• In stage 3, 20 – 50% of the EEG is delta waves and sleep is
deeper.
• In stage 4 greater than 50% of EEG is delta.
• There is no eye movement or muscle activity.
• It is very difficult to wake someone during stage 3 and 4 non
REM sleep. People awaken during deep sleep do not adjust
immediately and often feel groggy and disoriented for several
minutes. Sleep walking arises in children when they awake from
stage 4 NREM
• During slow wave sleep, parasympathetic activity predominates.
REM SLEEP
• This is defined by relatively low voltage, mixed (2-7H2)
frequency EEG with episodic eye movement and absent
EMG activity of all the skeletal muscles .
• EEG resembles but not identical to waking state. When
people awaken from REM sleep they often recall vivid
dreams.
• In REM sleep, the Hippocampal EEG is highly synchronized
at theta waves
REM SLEEP
• During REM sleep, monophasic sharp waves propagate rostrally from
the Pons to the occipital lobes via the lateral geniculate body and are
referred to as ponto-geniculo-occipital spikes. During REM sleep,
threshold for arousal by environmental stimuli is increased. So by
criteria of external arousability, REM sleep is the deepest sleep.
• At the same time a sleeping human is more likely to awake
spontaneously from REM sleep. By criterion of internal arousability
REM sleep is the lightest stage of sleep.
Is REM sleep important?
• Subjects deprived of REM sleep for up to 16 days show no
sign of psychological disturbance.
• However, when allowed to sleep freely, there is earlier
initiation and increase frequency and marked lengthening
of REM sleep: REM rebound.
• The existence of such rebound suggests that REM sleep is
physiologically necessary.
• It also affirms the common belief that dreaming serves
some important need.
DREAMING
• The discovery of a strong correlation between REM sleep and
visual dreaming in humans has reversed many commonly held
notes on about dreams. Every one dreams in regular cycles
several times at night but they are not well remembered.
• The probability of recall in a dream falls to zero within 8
minutes of the ensuing slow wave sleep after REM sleep.
• As a result we usually remember only morning dreams, which
also turn out to be those with most emotional/ psychological
content.
MEANING OF DREAM
• From ancient times dreams have been regarded as important and
often believed to provide insight into the future. Because of this,
dreams were extensively catalogued in antiquity.
• Sigmund Freud proposed that dreams were the “royal road” to the
unconscious; that they revealed in disguised form the deepest
elements of an individual’s inner life.
• Many normal dreams are unpleasant. Calvin Hall catalogued over
10,000 dreams from normal people and found that approximately 64%
were associated with sadness, apprehension, or anger. Only 18% were
happy or exciting. Hostile acts by or against the dreamer out number
friendly acts.
MEANING OF DREAM
• In 1977 Allan Hobson and Robert MacCarley proposed the “activation
– synthesis hypothesis.
• They suggested that dreaming consists of association and memories
elicited from the forebrain (Neocortex and associated structure) in
response to random signals from the brain stem (ponto-geniculooccipital spikes).
• Dreams were merely the “best fit” the forebrain could provide to this
random bombardment from brain stem.
• Hobson suggested that the sense or plot of dreams resulted from
order that was imposed on the chaos of neural signals. That order is a
function of our own personal view of the world, our remote memories.
MEANING OF DREAM
• In 1983, Francis Crick and Mitchison proposed the idea of reverse
learning.
• They postulated that a complex associational neural network such as
the Neocortex might become overloaded by vast amount of incoming
information.
• Consequently, the Neocortex could then develop false or “parasitic”
thoughts that would jeopardize the true and orderly storage of
memory.
• REM sleep served to erase these spurious associations on a regular
basis. Random brain stem waves impinged on the Neocortex resulting
in erasure or unlearning of the false information.
• The process therefore allowed the orderly processing of memory. “We
dream to forget” Crick and Mitchison wrote
MEANING OF DREAM
• However, they proposed a revision in 1986. Erasure of parasitic
thoughts accounted only for bizarre dream content. Nothing could be
said about dream narrative.
• There is evidence linking REM sleep with theta rhythm at the
hippocampus. Theta rhythm encodes memories during REM sleep.
Theta rhythm has been linked with encoding of long term memories.
• REM sleep provides a mechanism, allowing memory processing to
occur “off line”. Each species of mammal could process the
information most important for its survival.
MEANING OF DREAM
• In REM sleep, this information may be accessed again and
integrated with past experience to provide an ongoing
strategy for behaviour.
• Recently, Avi Karm et al at Weitzman Institute of Science
Israel were able to show that memory processing occurs in
humans during REM sleep.
• In their experiment, individuals learned to identify
particular patters on a screen. The memory of this
improved after a night with REM sleep.
• When subjects were deprived of REM sleep, memory
consolidation did not occur.
WHY DO WE SLEEP? Non REM sleep
Energy Conservation
• Brain neurons depend on glycogen for energy. NREM sleep uses much less
energy than wakefulness. Some have suggested NREM sleep may provide
time to restore our brain’s glycogen stores, which are depleted by the
demands of wakefulness. Sleeps targets areas of prior neuronal activities.
Brain Plasticity
• Synaptic efficiency and efficacy of the brain depends on keeping the
synaptic connections refined integrating new neuronal firing patterns.
Sleep periodically occurs to allow the brain to do this, thus maintaining
brain plasticity.
IMMUNE FUNCTION
• Recent studies suggest that sleep may strengthen our immune defenses
and insufficient sleep impair them.
WHY WE SLEEP? REM SLEEP
Memory Consolidation And Learning:
• Visual learning is enhanced by sleep and impaired by sleep loss.
In order to learn a new skill, we must first be trained, then
encode and consolidate it in our memory , if we are to retain it.
• Sufficient sleep the night before initial training has been shown
as crucial for encoding memory.
• REM sleep enhances learning but recent research emphasizes
that we also need NREM sleep stage 2 and 3 as well.
Brain growth
• REM sleep dominates sleep time during critical periods of brain
maturation in infants. REM sleep during infancy may help
establish the right balance of synaptic activation and receptor
sensitivity.
SLEEP ARCHITECTURE
• Normal healthy young adults exhibit alternating cycles of NREM and
REM sleep.
• A cycle of NREM followed by REM sleep is called asleep cycle. Sleep
cycles typically last a mean of 90 to 110 minutes.
• Four to five cycles of NREM – REM sleep are typical observed across
the night of sleep? NREM sleep dominates the 1st third of a night of
sleep and REM sleep the last third.
• REM sleep first occurs 70 to 90 minutes after sleep onset. The 1st REM
sleep is usually short. The duration of REM lengthens across the night.
• NREM stage 3 (represented by 3 & 4) is usually confined to the first
two cycles.
• Early morning sleep alternates between REM and NREM stage 2 sleep.
Sleep architecture
AGE AND SLEEP ARCHITECTURE
• Total sleep time and percentage of time spent in different
stages of sleep are age-dependent sleep needs decline with
age.
• Term new born baby typically sleep 16 to 18 hours per 24
hours; pre-terms sleep even more.
• Infants during the first months of life exhibit a polyphasic
pattern of sleep with typically 5 to 6 sleep cycles that last
50 – 300 minutes alternating with 90 – 180 minutes period
of wakefulness. Hunger and safety drives when a new born
sleeps and wakes.
AGE AND SLEEP ARCHITECTURE
• Beginning 1 to 3 months term, sleep periods begin to adapt
to a day – night cycle and other environmental cues.
• Circadian rhythm of wakefulness and sleep are usually
established by 3 months and consolidated by 6 – 7 months.
• By 2-12 month. Children usually sleep 9 to 12 hours per
night and nap 2 -4.5 hours per day, averaging 14.2 hours
per 24 hours.
AGE AND SLEEP ARCHITECTURE
• Most children aged between 18 and 24 months only need one
nap per day (usually in the afternoon) .
• Most children abandon day time hap by 4 years and is unusual
at 6 years.
• ADOLESCENT:
• Adolescents need 8.5. to 9.25 hour of sleep per 24 hours and
their sleep needs no not decrease with puberty.
• By mid puberty, adolescents are sleepier mid morning and more
alert mid afternoon.
• They need more sleep to maintain wakefulness during the day.
Age and sleep needs
CHANGES IN NON-REM WITH AGE:
• Stage 3&4 are maximal in early childhood, 25-40% of their
sleep time is spent in these stages
• Sleep efficiency decrease with increasing age.
• In older adults there is increased nocturnal arousals and
awakening, decreased sleep efficiency, characterized, by
mild increase in stage 1 marked decrease in stage 3 and
relative preservation of REM sleep.
• They require more time in Bed to obtain 7-8 hours of sleep.
CHANGES OF REM WITH AGE:
• The need for REM sleep begins in utero. REM sleep fills approximately
60-65% of total sleep time of infant born 2-4 weeks premature
• Full term infants spend 50% of the total sleep time in active REM sleep.
• This percentage falls to 40% by 3 to 5 months, reaching adult level of
20-25% by 2-5 years and shows little change after 10 years.
• The ontogenic pattern of REM sleep roughly parallels cerebral
myelination suggesting that REM sleep may be important in promoting
brain maturation and development.
• In 1966 Howard Roffwarg suggested that REM sleep plays a role in
developing brain analogous to that of physical exercise in developing
muscle
PHYSIOLOGIC CHANGES DURING Non REM
SLEEP
• AUTONOMIC NERVOUS SYSTEM
• Increased parasympathetic tone and decreased sympathetic activity in
NREM sleep.
• GASTRIC FUNCTION: In NREM, failure of inhibition of gastric secretion in
1st 2 hours of sleep; overall decrease in gastric motility during sleep.
• Swallowing is suppressed in NREM, stage 3 with prolong gastric mucosa
exposure to reflux.
• In NREM there is decrease in core body temperature by due to
vasodilatation, lowest at third sleep cycle.
• ENDOCRINE: In NREM, growth hormone and prolactin secretion is
increased. In REM certicotropi-cortisol rhythm is increased in the
morning.
PHYSIOLOGIC CHANGES DURING SLEEP: REM
SLEEP
SKELETAL MUSCLE ATONIA: Skeletal muscle atonia during REM is regulated by
a separate group of neuron in the pontine reticular formation called the
sub-laterodorsal Nucleus send direct projections to inter neurons in the
spinal cord to inhibit spinal motor neurons by glycinergic and GABA-ergic
mechanisms.
• Loss of appropriate skeletal muscles atonia during REM sleep due to
lesion on this nucleus is seen in individuals with REM sleep behavioral
disorder. They act out their dream.
PENILE ERECTION
• In REM, there is penile erection and clitoral engorgement. They usually
bear little relationship to dream content and do not correlate with sensual
dreaming. The ability to obtain normal erection is used to distinguish
between physical and psychological impotence.
PHYSIOLOGIC CHANGES DURING REM SLEEP
CEREBRAL BLOOD FLOW:
• Cerebral blood and metabolic rate for glucose and brain oxygen
consumption increase during REM sleep by up to 41% above waking
levels.
• A recent study show that cerebral blood flow velocity has its own
circadian rhythm: CBFV continues to decline into early to mid-morning
hours. Low CBFV value in the morning may help explain the increased
risk of strokes between 6 AM to noon.
BRAIN AND BODY TEMPERATURE REGULATION
• In REM, there is increase in brain temperature. Body and brain
temperature increase and sweating ceases during REM sleep. Absent
thermoregulation results in Poikilothernia.
PATHOGENESIS OF SLEEP
Neural circuits governing sleep
• In 1949, Horace Magoun and Giusep Moruzi found that electrically
stumulating a group of cholinergic neurons at the junction of the pons
and midbrain causes a state of wakefulness and arousal. This region
was named reticular activating system.
• The reticular activating neurons project to thalamocortical neurons
and are characterized by high discharge in waking state.
• Noradrenergic neurons of locus coeruleus, serotonergic neurons of
dorsal raphe and histamine containing neurons of tuberomamillary
nucleus of hypothalamus promote wakefulness
PATHOGENESIS OF SLEEP
• Sleep induction
• A master switch in the brain that allows people to go to sleep was
found by Clifford Saper in 1996.
• They found a cluster of cells in the Ventrolateral pre-optic area of the
Hypothalamus (VLPO).
• Activation ofVPLO nucleus of hypothalamus contribute to onset of
sleep.
• These cells appear to have connections to the body’s main arousal
systems.
• When the Cluster is switched on, all brain cells involved in arousal and
wakefulness turn off.
• When the cluster is switch off, brain cells involved in wakefulness turn
on.
PATHOGENESIS OF SLEEP
• When activated the VLPO cells apparently send direct inhibitory messages
to other nerve cells that contain neurotransmitters involved in
wakefulness, such as histamine noradrenaline and serotonin thereby
shuting down of the body’s arousal system.
• Histamine, for example is believed to be the primary chemical agent
stimulating wakefulness, which is why antihistamines cause drowsiness.
• A healthy intact hypothalamus is critical for normal sleep. People who
have trouble falling asleep may have a malfunction in the VLPO region of
the hypothalamus
• Sleep promoting factors. These are Muramyl peptides, prostaglandins,
interleukin 1, interferon alpha, tumor necrosis factors. Function of sleep
state may be to optimized the process that counter infections
PATHOGENESIS OF SLEEP
REM SLEEP
• Most Serotonergic neurons in the dorsal Raphe nucleus fire maximally during
waking, decreases firing during non REM sleep and completely stop firing
during REM sleep.
• Jouvet suggested that these neurons normally inhibit phasic REM events and
that their silence during REM sleep indicates a termination of this inhibition.
• Another population of brain cells that may be involved in the induction or
maintenance of REM sleep secretes acetylcholine.
• Hobson et al found that these cholinoceptive cells in the Gigantocelllular
Tegmental field, fire rapidly in a phasic manner throughout REM sleep.
• The ponto-Geniculo-occipital (PGO) waves provide a useful marker for the
beginning of REM sleep.
Factors affecting sleep
Environmental Temperature:
• Excessive environmental temperature (too hot worse than too cold) can
disrupt sleep quality. We are unable to regulate our body temperature
during REM sleep.
• Hot bath 1 to 2 hour prior to bed time can reduce sleep latency and
increase the amount of stage 3 sleep in the 1st half of the night.
Exercise
• Exercise late in the evening can increase body temperature and reduce
sleep latency and increase stage 3.
• we are unable to regulate body temperature during REM sleep
Factors affecting sleep
Drug Effects:
• Benzodiazepine suppresses stage 3 and 4 sleep and abrupt withdrawal
causes rebound of stage 3-4 sleep.
• Tricyclic antidepressants and SSRI suppress REM sleep. Abrupt
withdrawal of these drugs cause REM sleep rebound
• Alcohol taken just before bed in those not too used to it can cause an
increase in stage 3 and suppression of REM sleep in the first half of the
right followed by a rebound of REM sleep in the second half.
• Abrupt withdrawal of alcohol and antidepressants can cause REM
sleep rebound
CIRCADIAN RHYTHM
• The timing of and need for sleep (and wakefulness) are governed by
the shifting balance of two intrinsic regulatory process: The circadian
rhythm of alertness and sleepiness; and the homeostatic drive for
NREM sleep.
• The longer we are awake the greater our need for NREM Stage 3 sleep.
The homoeostatic drive for NREM 3 sleep is particularly noticeable
after 12 hours of prior wakefulness, typically peaking in the late
evening for those who follow a day night schedule.
• If we entrained in the light/dark cycle, we tend to have decreased
alertness between 2 a.m and 5 a.m with lesser dip in the midafternoon (2-5 pm), whereas in the early evening, we tend to be wide
awake, finding it difficult to sleep.
Hypothalamus and pineal gland
Influence Circadian Rhythm
• Our primary endogenous circadian peacemaker is the Suprachiasmatic
nucleus in the anterior ventral hypothalamus. Circulation allows us to
keep time in the absence of clues.
• Internal clocks allow us to anticipate and synchronize brain and body
functions so they occur at appropriate and optimal times with our
internal and external worlds.
• Melatonin primarily secreted by the pineal gland, helps the
Suprachiasmatic nucleus sense the length of the night: Bright light
suppresses melatonin secretion. Sleep occurs during the peak of
melatonin secretion. Melatonin level rises about 2 hours before sleep
onset and peak at mid-night, with 10 fold levels compared to day.
Melatonin in Circadian Rhythm
CORE BODY TEMPERATURE
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This greatly influence our desire or inability to sleep. It is easier to fall asleep
as our circadian core body temperature is falling.
We are more likely to awake from sleep on the rising limb of our core body
temperature.
In normal individual who awake during the day and sleep of night, the core
body (CBT), typically begins to fall about 2 hours before the usual bed time
and continues to fall, reaching its through at about 4.30am.
Beginning about 6 am-6.30 a.m, the CBT begins to rise, and rise across the day
dealing between noon and 1 p.m.
Trying to fall asleep when the CBT is rising is a challenge.
CORE BODY TEMPERATURE
• Another lesser dip in CBT occurs between 2 p.m to 5 p.m if one
has been up all night and cannot sleep, this is the best time to
try to sleep.
• At about 8 p.m, the CBT again starts to rise peaking around 10.
pm.
• The first appearance of REM sleep in a sleep period is unrelated
to prior wakefulness.
• REM sleep periods occur more often during the trough of core
body temperature curve. If a person sleeps at this period, REM
sleep dominate the sleep and may even have sleep onset REM
periods (SOREMPS).
Sleep needs
• Sleep needs of individuals vary from 4 to 11 hours per day. The
proper amount of sleep is that which permits us to be awake, alert
and energetic throughout the day.
• The number of hours a person needs to sleep depends on the
person’s somnotype.
• More recently, we have begun to understand that genetic and
individual traits significantly influence who among us can better
tolerate insufficient sleep, irregular sleep-wake cycles, and sleep
deprivation.
• Brief sleepers spend proportionately less time than others in state 1
and 2 and more time in stage 3 and 4.
Sleep needs
Impact Of Sleep Deprivation
• Sleep deprivations occur if one spends less time than the sleep needs
• Sleepiness cause accidents, because of attention lapses and delayed
response times at critical moments.
• Sleep deprivation was fund to have been a significant contributing factor
to Chernobyl nuclear reaction melt down, challenges space shuttle
disaster and principal cause of more than 100,000 police reported traffic
accidents in USA.
• A study showed that 20 % of 1.3 million motor accident occurred between
mid-night and 6. a.m, and in two thirds, the diverse fell asleep.
• A study also found that the risk of fatigue- related fatal motor crash
increases 15- fold after a driver has been awake mere than 13 hours
compared to the first hour.
Impact Of Sleep Deprivation
• Young males (16-25 yrs) are 3 to 5 times more likely than females to
experience drowsy- driving crash than females. Those who combine
school work with part-time job extracurricular activities with late night
socializing are particularly at risk.
• Medical Resident who had worked 24 hours or longer were 2-3 times
more likely to have a motor vehicle crash following that shift. Residents
who worked a traditional on-call schedule made 36 % more serious
medical errors and 6 times more serious diagnostic errors compared
with residents working less than 16 hours.
• Surgeons awake at night made 20 % more errors and took 14 % longer
to complete tasks.
Impact Of Sleep Deprivation
• Investigators found that performance on tasks by subjects after 24
hours awake was comparable with those with blood alcohol levels of
0.1%.
• Speed is more affected than accuracy and newly learned skilles are
more affected than more familiar activities .
• Tasks oust affected by sleep loss are long, monotonous, without feed
back, externally paced, newly learned or have a memory component.
• Chronic sleep loss results in cumulative increase in objective sleepiness
and sleep debt. Subjective perception of sleepiness correlates poorly
with objective measures.
Impact Of Sleep Deprivation
• The following are warning signs of sleepiness.
1. falling asleep in conferences, lectures or rounds.
2. feeling restless and inevitable with others
3. Difficulty concentrating or staying on task
4. Slow reaction time.
5. Inconsistent performance
6. Poor decision making.
7. Reduced short term memory
8. Decreased ability to learn.
9. Repeated yawning
10.Reduced head control.
STRATEGIS TO COPE WITH SLEEP DEPRIVATION.
• Sleep needs are genetically determined: one cannot learn
to sleep less. Human do not adapt to getting less sleep.
• Self reports of sleepiness are unreliable.
• Caffeine can help combat sleepiness. Effects occur with 5
to 30 minutes with a half life of 3 to 7 hours.
• Beneficial effects of caffeine during sleep loss are roughly
equivalent to 3-4 hours prophylactic nap.
STRATEGIS TO COPE WITH SLEEP DEPRIVATION.
• The most effective strategy is to get adequate sleep before anticipated
sleep loss and avoid starting out with sleep debts.
• Schedule naps substantially improve alertness and performance. At
least 45 minutes is needed for sustained benefit, preferably taken in a
quiet restful environment and at appropriate times in the circadian
circle (2.a .m -5 am or 2. pm -5.p.m)
• However, avoid prolonged naps (e.g 60-90 minutes ) lest you enter
stage 3 NREM, because when you awake from stage 3 sleep, you may
experience sleep inertia.
Ladies and Gentlemen
• Thank you for listening