SUBJECT: PHYSIOLOGY

TOPIC: SLEEP AND WAKEFULNESS

LECTURER: DR. SIMBULAN

DATE: MARCH 2011

I. RETICULAR FORMATION & thalamic nuclei, and from there

projects diffusely to the whole
RAS cortex.
RETICULAR FORMATION
II. THE THALAMUS & CEREBRAL
• Occupies the midventral portion of the CORTEX
medulla and midbrain
• Made up of various neural clusters and THALAMOCORTICAL OSCILLATIONS
fibers with distinct functions. Some of
these are: • Reciprocal oscillating activity between
o Cell bodies which are the midline thalamic nuclei and
serotonergic, noradrenergic, cerebral cortex.
adrenergic • Refers to the Electrical activity of
o Areas concerned with the neurons with axonal projections to the
regulation of heart rate, blood cortex.
pressure, respiration • Influence the behaviour of the 6-
o Some descending fibers which layered cortical neurons.
inhibit transmission in sensory
• What we see in the EEG is basically a
pathways in the spinal cord
summed up integrated synaptic
o Areas concerned with spasticity
activity of the cortical neurons in the
and adjustment of stretch 6-layered neocortex.
reflexes
• Influenced by signals coming from:
o Concerned with consciousness
o Specific thalamic relay nuclei
and sleep
o Midline and intralaminar
thalamic nuclei.
RETICULAR ACTIVATING SYSTEM

AKA “Ascending Arousal System” (Kandel)/ 2 types of activities of thalamocortical

“Ascending Reticular Activating System” neurons which play a role in arousal
(Guyton and sleep:

• A part of the reticular formation which • Phasic (Burst mode)

is concerned with consciousness and o 0.5 to 4 Hz
sleep o Happens during slow-wave
• A polysynaptic pathway sleep (stage 3 & 4 in REM
• Afferents may come from long phase)
ascending sensory tracts, trigeminal, o Within the Delta frequency
auditory, visual systems, olfactory sleep
system. • Transmission (Tonic mode)
• Destroys the principle on “modality o 30 to 80 Hz (typically 40 Hz)
specificity” o Happens during wakefulness
o It is “Non-specific” in such a and also in REM sleep
way that it can be activated
with various sensory stimulation During Slow- During aware
• Produces conscious, alert state that Wave Sleep state
makes perception possible. Thalamic Thalamic
• Pathway: neurons are neurons are
o Some fibers project directly to hyperpolarize partially
the cortex, bypassing the d, discharge in depolarized;
thalamus. sleep spindle- tonic firing by
o Some fibers end in the like phasic sensory
intralaminar and related bursts stimulation that

PHYSIOLOGY: SLEEP AND WAKEFULNESS Page 1

 produce arousal  Any part of pial surface of
So therefore, the brain
activity in the o An electrode which is directly
thalamocortical over the primary receiving area
oscillations for a particular sense yields a
prevents cortical surface positive (+) wave
neurons from o The surface positive wave is
receiving or followed by a small negative
processing wave
specific inputs. o After a negative wave, the cycle
shall repeat.
• Primary evoked potential
o 1st positive-negative wave
sequence
o Highly specific in its location
o Can be observed only where the
pathways from a particular
sense organ end
o From any of the primary
sensory areas depending on
specific pathway activated;
specific ascending pathway to
thalamic relay nuclei  specific
cortical receiving area (specific
area of parietal or occipital
cortex)

• Diffuse secondary response

o 2nd positive-negative wave
sequence
o Picked up from any part of the
Figure 2. This is a slide from Doc pial surface of the cerebrum;
Simbulan’s lecture which shows the sleeping even on top of the sensory
cycle of a normal patient. In the 1st stage, the cortex itself
alert wakefulness stage, there is a tonic o From most of cortical Surface;
mode of activity in the thalamus as well as it activation of non-specific
exhibits Beta waves in the EEG of Cortical Ascending pathway; nonspecific
areas. It is followed by the relaxed ascending pathway (enters
wakefulness stage which also exhibits a tonic brainstem reticular formation)
mode of activity in the thalamus, but enters intralaminar thalamic n.
manifests alpha waves when viewed in the and diffusely projects to the
EEG of cortical areas. When the patient whole of neocortex.
approaches the NREM sleep, there is a burst
mode of activity, with slow waves in the EEG
of cortical areas. As it enters the REM sleep,
it goes back again to the tonic mode, also
with Beta-like waves.

III. EVOKED CORTICAL

POTENTIALS
• Assesses the integrity of ascending
pathways.
• Monitors the electrical events
happening in the cortex upon
stimulation of a sense organ
Figure 3. Primary evoked potential (A) and
• Procedure:
Diffuse secondary potential (B).
o Signals are picked up by
implanting 2 electrodes
• They wanted to cut horizontal slices of
different parts of the brain:
neurons in the neocortex to see if they
 A specific sensory cortex
will also be able to cut the horizontal

PHYSIOLOGY: SLEEP AND WAKEFULNESS Page 2

 projections along with it. They found • Very minute voltages (microvolt)
out that despite the transection, which are amplified. Various filters cut
there are still signals which can down certain high frequency and low
be picked up. frequency signal to see the different
o CONCLUSION: activities which are going on in the
 Signals do not come surface of the brain.
from horizontal • Record of the variations in brain
connections from the potential
different layer of the • Can be recorded with scalp electrodes
neocortex, but from through the unopened skill or with
subcortical structures electrode on or in the brain.
 It is a manifestation of • Electrocorticogram (EGoG) is used for
activity of neocortical the record obtained with electrodes on
neurons in response to the pial surface of the cortex
the signals coming from • EEG records may be bipolar or
non-specific ascending unipolar
pathway from the brain o Bipolar:
arousal system  Shows fluctuations in
 Flash of light potential between 2
• Lateral geniculate cortical electrodes
nuclei funnels o Unipolar:
signals from the  Show potential
brainstem differences between a
(reticular cortical electrode and a
formation), which theoretically indifferent
projects to the electrode on some part of
different parts of the body distant from the
the neocortex and cortex
to the intralaminar • “BAT-D-B” sleeping sequence for
midline nuclei. adults
• So the source of o Beta waves of wakefulness 
signals which
Alpha waves  Theta waves 
activate diffuse
Delta waves in REM
secondary
response are
diffused
projections from
brainstem arousal
system

Clinical Significance of Evoked Cortical Potential

To test the integrity of specific sensory pathway of infants, psychiatric patients, and uncooperative or
(1)before
unconscious patients. (Useful especially ALERTtheWAKEFULNESS:
advent of MRI)

IV. ELECTROENCEPHALOGRAM
(EEG); SLEEP WAVES DURING
STAGES OF SLEEP • 14 to 30 Hz
• Lower amplitude
CHARACTERISTICS OF SLEEP: • Frontal region and over other region
during intense mental activity
• Humans sleep in a recumbent posture • Alpha block
• We have a raised threshold to sensory o Transition state from alpha
stimulation rhythm to beta rhythm
• There is a low level of motor output o “Arousal or alerting
during sleeping response”
• Entails a unique behaviour which we o “Prehabituation”
cal “dreaming”  A bored cat was
walking and suddenly
it sees a mouse. It
ELECTROENCEPHALOGRAM (EEG) suddenly ran to catch
it.

PHYSIOLOGY: SLEEP AND WAKEFULNESS Page 3

 o Alerting a relaxed subject
results in the
desynchronization of the EEG,
with reduction in the alpha
activity and increase in beta
activity
(2) RELAXED WAKEFULNESS:
• 8 to 13 Hz
• Drowsy, with eyes closed
• Parietal and occipital sites
(3) NREM SLEEP (STAGE 1 &2):
PHYSIOLOGY: SLEEP AND WAKEFULNESS
• 4 to 7 Hz
• K complexes and Sleep spindles also
appear in stage 2 NREM sleep.
(4) NREM SLEEP/ SLOW WAVE SLEEP
(STAGE 3&4):
• 0.5 Hz to 4 Hz
• Dominant during late slow wave sleep
(5) REM SLEEP (PARADOXIACAL SLEEP):
• Wave similar to wakefulness
Page 4
THE SCIENCE OF SLEEP  Not so restful – associated
with vivid dreaming
• Unconsciousness from which the  Paradox that a person can
person can be aroused by sensory or still be asleep despite
other stimuli. marked brain activity
• Sleep vs. Coma
o Unconscious patient cannot
respond or get aroused to
different stimuli Non-REM Sleep REM sleep
• 2 stages of sleep that alternate with
each other “Dreamless Sleep”/ “Paradoxical
o Slow-wave sleep “Slow-wave Sleep” Sleep”/“Desynchronize
(“Dreamless Sleep”) d Sleep”
 Strong, low frequency of
brainwaves Occurs at the first 1 Appears after end of
 Deep, restful sleep (1st ½ hour of sleep Non-REM Sleep
hour of sleep after being (Appears every 90
awake for the whole day) minutes)
 Stage where most sleep
is.
 Characterized when a
person who was awake Will only last for 5 to
for more than 24 hours 30 minutes
falls into deep sleep
during the 1st hour after Decrease in Muscle tone in the
going to sleep peripheral and body is exceedingly
 Progressive slowing of vascular tone (10 to depressed (Strong
brainwaves arising from 30% decrease in inhibition of spinal
well-described BP, RR, BMR) muscle control areas)
thalamocortical events.
 Has 4 stages Increased Irregular heart rate
• Stage 1 neuroendocrine and respiratory rate
• Stage 2 activity (GH and (Characteristic of
• Stage 3 sexual maturation dream state)
• Stage 4 hormones from
pituitary is maximal Irregular muscle
during sleep contractions occur
o Rapid eye-movement sleep
(“Paradoxical Sleep/ Rapid eyeball
Desynchronized Sleep”) movement
 Fast, low-voltage activity
 Eyes undergo rapid Highly active brain
movements despite the
fact the person is still Penile erection and
asleep highly engorged
 25% of sleep time in clitoris
young adults
 Recurs every 90 minutes Dreams are Dreams are
 forgotten remembered V. FURTHER DESCRIPTION OF
Stage were a Stage where a person SLEEP PHASES; DISTRIBUTION
person will be hard will easily be woken OF SLEEP STAGES
to be woken up up
During the night (Early adulthood)
More difficult in The NREM and REM Phases alternate
arousing people throughout sleep 4- 6 times, at intervals of 90
minutes.
with sensory
stimulus 1) NREM period –
A young adult enters NREM sleep, passes
Return to sleep through stages 1 and 2, and spends 70-100
rapidly minutes in stages 3 and 4.

2) REM period follows –

The time period of REM ranges from 2 – 10
minutes, shorter at first, but becomes longer
in the latter part of the sleep cycle. (There are
about 4-6 REM periods per night).

From Infants to Adults

• AS A CHILD DEVELOPS, SLEEP

GRADUALLY BECOMES RESTRICTED
TO THE NIGHT.

The dark portion connotes the number of

Gamma oscillations at 30–80 Hz are
often seen when an individual is aroused
and focuses attention on something. This
is often replaced by irregular fast activity
as the individual initiates motor activity in
response to the stimulus.
sleeping hours while the while the number of
portion is for the number of waking hours.
Polyphasic (multiphase) sleep following birth
changes first to biphasic (two-phase) sleep
among preschool children and later to
monophasic (single-phase) sleep. Among the
elderly, periods of sleep during the day
becomes more frequent again. o EMG
- Kaya may siesta tayo dati  Electro-myography
nung preschool.   For muscle tone
- So parang habang  The record is the
tumatanda tayo, electromyogram
bumabalik tayo sa pagka- • Body temperature and other autonomic
“infant” uli. parameters are also measured if the
person is awake, and in the different
• REM sleep occupies 80% of total sleep stages of sleep such as heart rate,
per night in premature infants(no respiration and penile erection.
figure), and 50 % in a full-term • Comparing NREM & REM THROUGH
newborn infant Thereafter the POLYSOMNOGRAPHY:
proportion of REM sleep falls rapidly
and plateaus at about 20 – 25% Parame NREM REM
ter
• Children have more total sleep time EEG Progressive Fast, low voltage
and stage 4 sleep than adults slowing of activity
brain waves
EOG Rapid eye
movements
EMG Muscle atonia with
intermittent
muscle twitches
Fluctuating HR
BP shoots up

Many stroke cases

occur in this stage
of sleep
Fluctuating RR

• REM sleep plateaus from 3 y/o.

• Boxed numbers/values highlighted
shows the percentage of REM Sleep
• 20% of sleep is REM!!

POLYSOMNOGRAPHY
• Measures the sleep state through:
o EEG
 Electroencephalography
 For cortical activity
 The record is the
encephalogram
o EOG
 Electro-oculography
 For eye movements
 The record is through the
electro-oculogram
 Tongue (2⁰ +++ ++ +
respiratory
muscle)
Intercostals (1⁰ +++ ++ +
respiratory
muscle)
Diaphragm ( 1⁰ +++ ++ ++
respiratory
muscle)
• Plus sign denotes more muscle tone
• Pababa nang pababa ang muscle tone –
lowest sa REM for tongue and
intercostals.
• Diaphragm muscle stays the same so
as to avoid respiratory arrest
• Lowest ang muscle tone sa REM sleep
especially the tongue. The tongue and
genioglossus muscles can lose muscle
tone and help obstruct airway passage
that could cause restlessness, so when
wake up, we feel tired.

VI. PHYSIOLOGICAL BASIS OF

EEG, CONSCIOUSNESS AND
EFFECTS OF SLEEP ON MUSCLES OF SLEEP
RESPIRATION:
• EEG is brought about by integrated
1. Wakefulness exerts a tonic stimulating
summated activity of synaptic potential
effect on motoneurones
of various neocortical neurons
especially the pyramidal cell
2. This stimulating effect is withdrawn in
• The surface EEG reflects the
non-REM sleep (via disfacilitation), so the
activity of cortical neurons close to
primary effect of non-REM sleep is to
the EEG electrode.
decrease activation of motoneurones and
muscles. • High-frequency stimulation of the
brainstem reticular formation which
3.) Motoneurone activity is generally “desynchronizes” the EEG. It produces
decreased in REM sleep. This takes place the waves we see.
through processes of inhibition and further • Desynchronizing mechanism
dis-facilitation. o Mechanisms which produce the
low-amplitude, fast irregular
4.) Similar processes may occur at Beta-waves of wakefulness
respiratory motoneurones that drive o Neural basis of arousal: RAS
respiratory muscles. activity
• The activity of RAS is the neuronal basis
Awak NRE RE of EEG
e M M • Lesion in midbrain tegmentum
disrupts the reticular activating system,
 RAS. This results in COMA for long
periods.
o COMA has a synchronized wave
pattern, with a characteristic
slow-wave.
o Sort of similar to slow wave
sleep
• Effect of RAS Stimulation on
Figure B. RAS damaged, therefore EEG
arousal does not take place, and comatose
situation develops, characterized by slow-
waves.
• Arousal
Figure A. RAS still intact, thus EEG arousal
intact.
o Large lesions of lower brain
stem isolating the brain from
incoming sensory signals
through the spinal cord in a
preparation called:
ENCEPHALE ISOLE’ does not
result in coma. Animals with
this lesion are awake, respond
to trigeminal sensory (CN V)
as well as visual and
auditory cues, and move their
faces and eyes in a normal
fashion. The EEG of such animals
is typically low voltage and
fast, a desynchronized
pattern typical of waking. In
addition, lesions of the lateral
and superior portions of the
midbrain that interrupt the
medial lemnisci and other
ascending specific sensory
systems (leaving behind the
reticular core intact) fail to
prevent the EEG arousal to
sensory stimulation.
Cortical Neurons: RAS activation
inhibits burst activity of thalamo-
cortical neurons (which occurs during
slow-wave sleep). Detailed discussion
omitted here. These results in the low-
voltage, irregular fast waves of
wakefulness.
Following Cortical
Stimulation: Thoughts and emotions
(intra-cortical signals) also increase
activity of RAS, and EEG arousal,
through corticofugal fibers descending
to the brainstem reticular
formation. This corticofugal pathway
to the brainstem reticular formation can
keep us awake.

NEURAL SUBSTRATES & CREATION OF
SLOW-WAVE SLEEP (NREM SLEEP)
• Slow wave sleep can be produced
experimentally by stimulating 3
subcortical “synchronizing” regions
below:
o Diencephalic sleep zone
o Medullary synchronizing zone
o Basal foreign sleep zone
• The natural development of slow-
wave sleep in a human subject or
experimental mammal can arise from:
o In part, absence
desynchronized activity
transmitted via the ascending
reticular system. Meaning,
absence of arousing sensory
inputs from the environment, or
from the cortex (lack of
worrying or exciting thoughts/
memories) which descend to
excite the brainstem ascending
reticular system in the reticular
formation.
o Actively produced by the three
“synchronizing regions”
mentioned above, and shown in
figure below:
NEURAL SUBSTRATES & CREATION OF
SLOW-WAVE SLEEP (NREM SLEEP)
• Nuclei in Pontine Reticular
Formation – triggers REM sleep
mechanism. (PGO spikes, ponto-
geniculo-occipital spikes, characteristic
of REM sleep, originate in the lateral
pontine tegmentum). Below is a
neuronal mechanism of REM sleep
originating from the pontine reticular
formation.
of
LEGEND:
AHC= anterior horn cell; CT, cortical; FT, reticular
tegmental nuclei; LC, locus ceruleus; P,
peribrachial region; PT cells, pyramidal cells; RN,
raphe nucleus; TC, thalamocortical; III,
oculomotor nucleus; IV, trochlear nucleus; VI,
trigeminal motor nucleus.
The network of neurons responsible for
generating REM sleep is distributed over many
levels of the brain. The network is shown as
three systems of neurons that mediate the
electrographic phenomena of REM sleep (see
Figure above).
• In many places (the thalamus and
cortex), the architecture of the systems
is known to be far more complex than
indicated here. An increase in the firing
of reticular, thalamocorticular, and
cortical neurons DESYNCHRONIZED
 the EEG (fast, irregular waves of REM • State-dependent changes in aminergic
sleep similar to wakefulness). and cholinergic neuronal function.
Schematic representation of
• Tonic disinhibition and phasic progressive decrease of aminergic
excitation of burst cells results in neurotransmitter release in cerebral
pontine-geniculate-occipital (PGO) cortex as an animal passes from
waves. wakefulness through NREM to REM
sleep.
• Phasic firing by reticular and
vestibular cells causes RAPID EYE • Cortical concentrations of
movements; vestibular (vestibular norepinephrine and serotonin are
nuclei) cells directly excite oculomotor highest in waking, lowest in REM sleep,
neurons. and intermediate in NREM sleep. Top
panel illustrates sagittal sections of the
• Tonic postsynaptic inhibition of spinal brain with aminergic neurons of nucleus
anterior horn cells by the locus coeruleus (noradrenergic) and
pontomedullary reticular formation dorsal raphe nucleus (serotonergic).
causes MUSCLE ATONIA.
Bottom panel illustrates cholinergic neurons
• Muscle twitches occur when of Ch 1-4 (in basal forebrain) and of Ch 5 of
excitation by reticular and “pyramidal peribrachial pontine tegmentum. Cholinergic
tract” motor neurons (corticospinal) neurons release levels of acetylcholine as high
occasionally overcomes the inhibition in REM sleep as they are in waking; release in
of the anterior horn cells. NREM sleep is lower.

NEUROCHEMISTRY OF SLEEP AND

WAKEFULNESS (NEUROTRANSMITTERS
& SLEEP FACTORS)
The graph below summarizes the
changes in levels of activity of
serotoninergic, noradrenergic and
cholinergic neurotransmitter systems

Legend and Explanations: LC – Locus

ceruleus (noradrenergic neurons); DRN –
Dorsal Raphe nuclei (serotoninergic
neurons). LC and DRN neurons are in the
brainstem reticular formation). Ch 1- 4 –
cholinergic neurons in the forebrain; CH 5 –
• Decreasing noradrenergic, cholinergic
cholinergic neurons in the midbrain
pontine and serotoninergic activity
tegmentum.
 tegmentum characterizes drowsiness • Insomnia
and NREM (slow-wave) sleep. - Subjective problem of
insufficient or nonrestorative
• There is almost silent activity of these sleep despite an adequate
serotoninergic and noradrenergic opportunity for sleep
systems in REM sleep, while the
cholinergic system increases its • Problems associated with NREM
activity again (cholinergic neurons in (slow-wave) sleep:
the pontine reticular formation). o Sleepwalking
(somnambulism)
• Wakefulness is characterized by high - Sleepwalkers arise from the
levels of noradrenergic, serotoninergic slow wave sleep stage in a
and cholinergic activity, (Note state of low consciousness
similarity of increased cholinergic and perform activities that are
activity in REM with that of usually performed during a
wakefulness.) state of full consciousness.

[Note that in current sleep literature, o Bed-wetting (nocturnal

serotonin’s role is disputed, as there was enuresis)
this old serotonin hypothesis about sleep. - Involuntary urination while asl
However, sleep researchers have confirmed eep after the age at which
the discussion above with evidence for bladder control usually
serotonin’s role (an increase in occurs.
concentration) in wakefulness, and not
sleep, thus debunking the old serotonin o Night terrors
hypothesis.] - pavor nocturnus,
- Characterized by extreme
terror and a temporary
inability to regain full
consciousness.
- Subject wakes abruptly from
slow wave sleep with waking
OTHER SLEEP-INDUCING FACTORS: usually accompanied by
• Muramyl peptides (related to the gasping, moaning, or
bacterial cell walls) screaming while waking. It is
• Interleukin – 1 ( a cytokine that may often impossible to awaken
mediate effects of muramyl peptides, the person fully because they
and immune responses) are so concentrated on
• Adenosine waking, and after the episode
• Delta-sleep inducing peptide (a the subject normally settles
substance isolated from blood of back to sleep without waking.
sleeping rabbits) A night terror can rarely be
• Prostaglandin D2 – recalled by the subject. They
• Cis-9,10-octadecenoamide typically occur during NREM.
• MELATONIN – mixed results
• Problem associated with REM
• Other sleep peptides – the search
(paradoxical) sleep:
continues
o Narcolepsy
SOME SLEEP DISORDERS - Disease in which there is
episodic sudden loss of
 muscle tone and an  Partial/ local seizures
eventually irresistible urge • Arise from only one
to sleep during daytime hemisphere
activities  General-onset seizures
- Symptoms: • Involves both
o Cataplexy Atonia hemisphere
which occurs when • Further subdivided
one is wide awake. into:
o Unknown cause but
may be due to orexin General-onset seizures are further divided
receptor defect or into:
orexin synthesis (1) Grand mal type
dysfunction. • Loss of consciousness
o Orexins (hypocretins) • Occurs without warning
are hypothalamic
• Followed by a tonic phase (sustained
peptides.
limb muscle contraction; fast EEG
o An auto-immune
activity)Followed by a clonic phase
hypothesis exists, (symmetric jerking of limbs; slow
which results in brain waves)
orexin deficiency.
(2) Petit mal
o Sleep apnea
• Momentary loss of responsiveness
- Caused by obstruction of the
airway during inspiration
- Frequent in obese and
elderly patients
- Cause tiredness and poor
performance due to lack of
sleep
- Lack of muscle tone of
-------------------END OF
genioglossus muscle
TRANSCRIPTION---------------------

YAY! :
o REM behavior disorder
- Newly recognized condition
in which hypotonia fails to
occur during REM sleep
- They “act out their dreams”

)
VII. CLINICAL USES OF EEG
• Helps in localizing pathologic
processes
• Aids in diagnosing and localizing
conditions such as subdural
hematomas.
• Lesions in cortex may cause local GOODLUCK SA EVALS, BATCH 2014!
formation of irregular or slow waves. SUMMER NA! SEE YOU AFTER 2
• Epilepsy MONTHS!
o Syndrome with multiple causes STD WAS GLAD TO SERVE ALL OF YOU
o Seizures are divided into: AND IS NOW SIGNING OFF. >:D<