2nd sem

4th Module

Physiology of sleep and Arousal

Sleep
Sleep can be defined as “an active state of unconsciousness produced by the body where the
brain is in a relative state of rest and is reactive primarily to internal stimulus.. Sleep is
characterised by:

● low physical activity levels

● reduced sensory awareness

Sleep is also regulated by the circadian rhythm and homeostatic mechanisms.

It is an active state of unconsciousness produced by the body where the brain is in a relative
state of rest and is reactive primarily to internal stimulus.
Sleep…….(.Contd)

● The initial cycle lasts 70 to 100 minutes to complete fully.

● However, the remaining cycles last 90 to 120 minutes each.
● The amount of REM in each cycle progresses throughout the night from being
minimal on the initiation of sleep but eventually is up to 30% of the cycle later
in the night.
● A total of 4 to 5 cycles through this progression is typical in a night.
● Rapid eye movement (REM) sleep is characterized by darting movements of
the eyes under closed eyelids.
 Stages of sleep.
During sleep, the brain cycles through four stages of sleep.
Stages 1 to 3 are what's considered non-rapid eye
movement (NREM) sleep, also as quiet sleep.
Stage 4 is rapid eye movement (REM) sleep, also known as
active sleep or paradoxical sleep.
Each sleep stage has a unique function and role in
maintaining your brain's overall cognitive performance, and
also physical repair..
The entire sleep cycle repeats itself several times a night, with
every successive REM stage increasing in duration and depth
of sleep.
Falling into sleep

Beginning with a fully awake , vigilant individual

● The person is aware about his surroundings ,

● Is able to process information cognitively
● Heart rate , breathing rate is normal. The muscles are normally tensed
● The EEG records a mixture of many fast frequency – low amplitude waves
● This is referred to as beta activity
● Towards the end as the person relaxes , the beta waves slowly change to alpha waves
 NREM Stage 1

The first stage of the sleep cycle is a transition period between wakefulness and sleep.
● The brain slows down
● The heartbeat, eye movements, and breathing also slows with it
● The body relaxes, and your muscles may twitch- hypnagogic hallucinations and Myoclonic
Jerks.
● This brief period of sleep lasts for around five to 10 minutes.
● The early portion of stage 1 sleep produces alpha waves, which are relatively low frequency
(8–13Hz), high amplitude patterns of electrical activity (waves) that become synchronized.
This pattern of brain wave activity resembles that of someone who is very relaxed, yet awake.
As an individual continues through stage 1 sleep, there is an increase in theta wave activity.
Theta waves are even lower frequency (4–7 Hz), higher amplitude brain waves than alpha
waves.
 NREM Stage 2
People spend approximately 50% of their total sleep time during NREM stage 2,

● Lasts for about 20 minutes per cycle.g:

● Person becomes less aware of surroundings
● Body temperature drops
● Eye movements stop
● Breathing and heart rate become more regular
● The brain also begins to produce bursts of rapid, rhythmic brain(theta) wave activity, which are known as
sleep spindles
● A sleep spindle is a rapid burst of higher frequency brain waves that may be important for
learning and memor
● K complex I.e. a sharp negative potential in EEG marked by the downward wave is called a K
Complex.
● Theta waves dominate during this stage.( 12-15 hz) comparatively higher amplitude ans lower
frequency.
● Brain gathers, processes, and filters new memories acquired the previous day.
● ,During this sleep stage, body starts its physical repairs. your body slows down in preparation for
NREM stage 3 sleep and REM sleep—the deep sleep stages when the brain and body repair,
restore, and reset for the coming day.
NREM Stage 3

● Deep,very slow brain waves with large amplitude known as delta waves (0-4
hz) begin to emerge during NREM stage 3 sleep—a stage that is also
referred to as delta sleep.
● This is a period of deep sleep where any noises or activity in the environment
may fail to wake the sleeping person.
● Getting enough NREM stage 3 sleep allows you to feel refreshed the next day.
● Muscles are completely relaxe, blood pressure drops, and breathing slows
● Person progress into moderately deep sleep
● Meanwhile, brain consolidates declarative memories—for example, general
knowledge, facts or statistics, personal experiences, and other things you have
learned.

NREM stage 3 lasts about 20 to 40 minutes, initially. EEG is characterized by

high-voltage, slow-wave frequency.
Stage 3 NReM …..contd

● Body highly relaxed

● Heart beat and breathing is the slowest
● No eye movement
● Tissue repair and growth , cell regeneration active
● Immune system strengthens

Even more Delta waves are produced.

Stage4 : REM sleep / Paradoxical Sleep

● REM is the phase of sleep responsible for dreaming.

● It is characterized by total body voluntary muscle paralysis (except
for the extraocular muscles).
● This paralysis is thought to be a mechanism to prevent neural stimulus
from dreams to manifest in actual muscular impulses during sleep
● Irregular breathing and pulse rate
● EEG in REM is “Sawtooth waveforms,” theta waves, and slow, alpha
waves in a desynchronized pattern set.
● Vivid dreaming in this stage
● Rapid eye movements
● Lasts almost 10 mins
● Marked increase in brain activity
Sleep cycles…

After almost 10 mins of REM sleep, the individual returns to 2nd stage of
NREM sleep and the all other stages follow.

This takes almost 60-90 mins

The initial stage decreses in time while REM sleep may increase upto almost 30
mins
Melatonin and sleep
Melatonin, secreted from the pineal gland, plays an important role in the regulation of sleep–wake cycles and is an
established marker of the phase of the internal circadian clock [40]. Light suppresses the output of melatonin,
producing peaks during the dark period and very low concentrations of melatonin during the light period.

Cortisol: Triggered by the SCN to help you wake up

Insulin: Helps your body use the sugar, or glucose, derived from your food

Testosterone: Levels fluctuate during the day, and they're at their highest during REM sleep
Melatonin levels
CORTISOL AND SLEEP

Cortisol is a stress hormone that plays a role in sleep-wake cycles. Cortisol levels
are normally highest in the morning and lowest around midnight. Cortisol levels
increase at the end of sleep and peak just before waking up.

Cortisol's role in sleep-wake cycles is:

● In the morning: Cortisol stimulates wakefulness.

● During the day: Cortisol helps maintain alertness.
● At night: Cortisol levels decrease to allow other hormones, like melatonin and
adenosine, to rise and help with sleep.
CORTISOL AND SLEEP
PHYSIOLOGICAL /BIOLOGICAL FUNCTIONS OF SLEEP

Restorative theory :- Sleep helps the body repair and replenish cellular
components that become depleted throughout the day.

Brain function :- Sleep is important for brain function, including how nerve cells
communicate with each other. Sleep also helps regenerate brain parts so that it
can continue to function normally.
PHYSIOLOGICAL /BIOLOGICAL FUNCTIONS OF SLEEP

Brain plasticity :- A healthy amount of sleep is vital for the brain's ability to
adapt to input. If you sleep too little, you may not be able to process what
you've learned during the day, and you may have more trouble remembering it
in the future.
Cognitive skills :- Sleep helps maintain cognitive skills, such as attention,
learning, and memory. Poor sleep can make it more difficult to cope with
stressors and can impact your ability to perceive the world accurately.
Brain housekeeping :- Sleep plays a housekeeping role that removes toxins in
your brain that build up while you are awake
 Ventrolateral preoptic nucleus (VLPO),

The ventrolateral preoptic nucleus (VLPO), also known as the intermediate

nucleus of the preoptic area (IPA), is a small cluster of neurons situated in the
anterior hypothalamus, sitting just above and to the side of the optic chiasm in the
brain of humans and other animals

The VLPO is active during sleep, particularly during non-rapid eye movement sleep
(NREM sleep),and releases inhibitory neurotransmitters, mainly GABA and galanin,
which inhibit neurons of the ascending reticular arousal system that are involved
in wakefulness and arousal
Neural mechanism of sleep and wakefulness
The chemicals involved - in sleep and wakefulness
● Melatonin: A neurotransmitter that helps you fall asleep
● Adenosine: A chemical that causes you to feel sleepy
● Caffeine: Promotes wakefulness by blocking the receptors to adenosine
● Norepinephrine and orexin: Keep some parts of the brain active while we are
awake
● Histamine, serotonin, acetylcholine, adrenaline, and cortisol: Other
neurotransmitters that shape sleep and wakefulness
● GABA: The most common inhibitory transmitter in the brain
The chemicals involved - in sleep and wakefulness

Serotonin, histamine, and norepinephrine cells normally turn off during REM sleep
because thare inhibited by GABAergic neurons.

Norepinephrine and orexin (also called hypocretin) keep some parts of the brain
active while we are awake
Brain waves
brainwaves, are rhythmic or repetitive patterns of neural activity in the central
nervous system.
Brain waves are electrical pulses that occur when billions of neurons in the brain are
activated. They can be measured on the head to gain insights into the functioning of
the human brain.

There are five widely recognized brain waves, and the main frequencies of human
EEG waves
 BRAIN WAVES………CONTD

Alpha waves :- Alpha waves have a frequency of 8-12 Hz. They can be seen in
states when a subject is awake, relaxed, and resting. They are waves with high
amplitudes (voltage 20-200 µV) and are therefore easy to distinguish in the EEG.
Alpha waves disappear when the subject is asleep

Beta waves:- Beta waves typically occur at a frequency of 14-30 Hz. These
waves are small and faster and can be seen in states of intellectual activity, focus,
and alertness.
BRAIN WAVES…… CONTD

Theta waves : Theta waves have a frequency of 4-7 Hz. They can be seen in
states of daydreaming or light sleep.Functionally, they have been linked to
coordinating the process of memory storage.They are associated with inhibition of
elicited responses.

Delta waves :-Delta waves have a frequency of 0.5-3 Hz. These waves have a
low frequency and relatively high amplitude. They can mainly be seen in states of
deep sleep.Delta waves during sleep are thought to play a role in transferring
learning and long-term memory storage. Delta waves are usually associated with
the deep stage 3 of NREM sleep, also known as slow-wave sleep.
Wakefulness

Wakefulness is a state of consciousness where a person is conscious, aware, and

can respond to the world around them.

It's characterized by high levels of thought, behavior, and sensory awareness.

Wakefulness is the opposite of being asleep, which is a state of inactivity where

the brain is less responsive to external stimuli.

Wakefulness is characterized by low-amplitude, irregular, fast-wave electrical

activity in the raw electroencephalogram.
Arousal and awakefulness

Arousal is the state of being physiologically alert, awake, and attentive.

Arousal is primarily controlled by the reticular activating system (RAS) in the brain.

The RAS is located in the brain stem and projects to many other brain areas,
including the cortex.

. When the system slows down, you might feel lethargic, sleepy, or have difficulty
concentrating on things. When the system speeds up, you might feel highly active,
be alert, and be ready to respond to different things in the environment.
Arousal
Arousal is the degree of alertness during wakefulness. It involves the activation of the brain's
ascending reticular activating system (ARAS), which affects the autonomic nervous system
and endocrine system.
What Influences Arousal?

The RAS and arousal level are influenced by a number of different things, such as
your emotions, the foods you eat, and the neurotransmitters in the brain.
The neurotransmitters

● norepinephrine,
● serotonin,
● dopamine, and
● acetylcholine

all play a role in the functioning of the RAS.

Higher levels of these neurotransmitters leads to higher states of arousal and attention to
different stimuli.
Sleep, wakefulness - neural mechanism
Within the hypothalamus is the suprachiasmatic nucleus (SCN) – clusters of
thousands of cells that receive information about the amount of light exposure
directly from the eyes via preganglion cells in the retina

SCN control your behavioral rhythm/ CIRCADIAN RHYTHM

The brain stem, at the base of the brain, communicates with the hypothalamus
to control the transitions between wake and sleep..
Sleep, wakefulness and brain ….. CONTD

Sleep-promoting cells within the hypothalamus and the brain stem produce a brain
chemical/ NEUROTRANSMITER called GABA, which acts to reduce the activity of
arousal centers in the hypothalamus and the brain stem.
GABA inhibit the firing of impulse in the neural cells involved in wakefulness.
The brain stem (especially the pons and medulla) also plays a special role in REM
sleep;
it sends signal relax muscles essential for body posture and limb movements, so
that we don’t act out our dreams.
Sleep, wakefulness and brain …. … contd

● The basal forebrain, near the front and bottom of the

brain, also promotes sleep and wakefulness, while part
of the midbrain acts as an arousal system.
● Release of adenosine (a chemical by-product of
cellular energy consumption) from cells in the basal
forebrain and probably other regions supports your
sleep drive.
● Caffeine counteracts sleepiness by blocking the
actions of adenosine.
RETICULAR ACTIVATION SYSTEM

The reticular activating system (RAS) is a network of nerves in the brainstem that
controls sleep, wakefulness, and consciousness. It's located between the
brainstem and the cortex

It controls three sleep and arousal states:

● Waking
● Asleep (resting or slow-wave sleep)
● Asleep and dreaming (paradoxical, active, or rapid eye movement sleep
RETICULAR ACTIVATION SYSTEM……..contd

The RAS is a gatekeeper between your conscious and unconscious mind.

The RAS is made up of multiple neuronal circuits that allow the brain to modulate
between fast and slow sleep rhythms. It releases chemicals that regulate emotions,
movement, and wakefulness.

The RAS also plays a role in establishing alertness, arousal, circadian rhythm, and
fight-or-flight responses. It helps the brain prepare for activity in the morning by
responding to triggers like sounds, the sun, and other external stimuli

It's located at the back of our heads, making it vulnerable in accidents. Damage to
this area can lead to severe conditions like comas, sleep disorders, and even chronic
fatigue syndrome.
RETICULAR ACTIVATION SYSTEM……..contd
CIRCADIAN RHYTHM

A circadian rhythm is a natural process that takes place throughout every day.

Circadian rhythms are the physical, mental, and behavioral changes an organism
experiences over a 24-hour cycle.

Light and dark have the biggest influence on circadian rhythms, but food intake,
stress, physical activity, social environment, and temperature also affect them as
well as Alcohol or use of stimulants
 CIRCADIAN RHYTHM…. contd

● It is a series of endogenous autonomous oscillators that coordinate internal time

with the external environment.
● Circadian rhythms prepare the body for expected changes in the environment,
such as the time for activity, sleep, and eating
● The circadian rhythm is controlled by the suprachiasmatic nucleus (SCN), which is an
endogenous clock located in the brain's hypothalamus. The SCN is considered the
master circadian pacemaker that drives daily rhythms in behavior and physiology.
●
●
●
Suprachiasmatic nucleus

The SCN is considered to regulate peripheral tissue clocks via a combination of

(1) autonomic innervation of peripheral tissues,

(2) endocrine signaling,

(3) temperature, and

(4) behavioral signals (e.g. feeding)

EEG - Electro EncephloGram

An EEG, or electroencephalogram, is a test that records the electrical signals of

the brain by using small metal discs (called electrodes) that are attached to your
scalp.

Our brain cells communicate with each other using electrical impulses. They’re
always working, even if WE’re asleep. That brain activity will show up on an EEG
recording as wavy lines.
 EEG procedure
A technician puts about 20 small sensors on your scalp using a special glue / gel

These sensors, called electrodes, pick up electrical activity from cells inside your brain called neurons and send them to a
machine, where they show up as a series of lines recorded on paper or displayed on a computer screen.

Once the recording begins the person is asked to remain still. And relax with eyes open first, then with closed. The
technician may ask to breathe deeply and rapidly or to stare at a flashing light, because both of these can change your
brainwave patterns.

The machine is only recording the activity of the brain and doesn’t stimulate it. So It's rare to have a seizure during the test.

You can have an EEG at night while you're asleep. If other body functions, such as your breathing and pulse, are also being
recorded, the test is called polysomnography.

N. B. – pls read the additional document for EeG

EEG uses
To identify:
Brain tumors
Brain damage from a head injury
Brain dysfunction from various causes (encephalopathy)
Inflammation of the brain (encephalitis)
Seizure disorders including epilepsy
Sleep disorders
Stroke
An EEG may also be used to determine if seizures caused a coma, if there is no longer brain
activity, or to find the right level of anesthesia for someone in a coma.
SLEEP DISORDERS.

Sleep disorders (or sleep-wake disorders) involve problems with the quality,
timing, and amount of sleep, which result in daytime distress and impairment in
functioning.

Sleep-wake disorders often occur along with medical conditions or other mental
health conditions, such as depression, anxiety, or cognitive disorders.

There are several different types of sleep-wake disorders, of which insomnia is the
most common. Other sleep-wake disorders include obstructive sleep apnea,
parasomnias, narcolepsy, and restless leg syndrome.
SLEEP DISORDERS …CONTD

Insomnia Disorder :- Insomnia, the most common sleep disorder, involves

problems getting to sleep or staying asleep.
The sleep difficulties must occur at least three nights a week for at least three
months and cause significant distress or problems at work, school
 SLEEP DISORDERS …CONTD

Obstructive sleep apnea :-

Obstructive sleep apnea involves breathing interruptions during sleep. A person with
sleep apnea will have repeated episodes of airway obstruction during sleep causing
snoring, snorting/gasping or breathing pauses. This interrupted sleep causes daytime
sleepiness and fatigue.
SLEEP DISORDERS …CONTD

Narcolepsy
People with narcolepsy experience periods of an irrepressible need to sleep or
lapsing into sleep multiple times within the same day.

Sleepiness typically occurs daily but must occur at least three times a week
SLEEP DISORDERS …CONTD
Circadian Rhythm Sleep-Wake Disorders
With circadian rhythm sleep-wake disorders, a person’s sleep-wake rhythms (body
clock) and the external light-darkness cycle become misaligned. This
misalignment causes significant ongoing sleep problems and extreme sleepiness
during the day leading to significant distress or problems with functioning.
SLEEP DISORDERS …CONTD

SOMNAMBULISM

The act of getting up and walking around while asleep.

Sleepwalking is most common in children, who usually outgrow it by their teens.

Sleepwalking usually occurs one to two hours after falling asleep at night. Rarely, it
may involve unusual behaviors, such as climbing out of a window or urinating in a
wardrobe.