Anatomical and physiological
bases of consciousness and
sleep wake cycle
Consciousness
• Definitions- consciousness is the ability to be
aware of self and the surroundings.
• It is the ability to know our own existence and of
the existence of objects and events inside and
outside our organism.
• consciousness is a momentary creation of
mental knowledge which describes a relation
between the organism, on one hand, and an
object or event, on the other.
• consciousness is an integration of neural activity
similar in mechanism to the binding of different
aspects of sensation that occurs to produce a
unified perception.
Consciousness--
Anatomy of the consciousness system
• Consciousness system– a diffuse & organized neuronal
system in the brainstem, diencephalon & cerebral
hemisphere
• Structures in this system:
1. Portions of the brainstem reticular formation
2. Neurochemically defined nuclear groups of the
brainstem
3. Thalamic nuclei
4. Basal forebrain
5. Ascending projections to the thalamus & cerebral
cortex
6. widespread areas of the cerebral cortex
Fig. Components of the consciousness system
Reticular formation (RF)
• RF- a complex aggregate of neurons whose cell bodies
form neuronal clusters in the tegmental portion of the
brainstem, i.e., from the level of the decussation of the
pyramids in caudal medulla to the basal forebrain and
thalamus.
• The neurons are
-characterized by long radiating dendrites that have few branches
-axons have numerous collaterals & project for long distances
-reticular= network forming== a single neuron receive many
afferents & make synaptic contact with numerous neurons
Reticular formation
Subdivisions of RF
• Functionally subdivided in to
1. midline region ( the raphe )
2. medial region –containing large neurons that project
to the spinal cord and to oculomotor nuclei
3. lateral region that receive axon colaterals from
many ascending sensory pathways
At the level of the medulla the lateral RF-participate in
complex motor patterns such as respiration, swallowing,
and vomiting
Neurons in the ventrolateral medulla control respiration and
circulatory system via projections to the spinal cord
RF at pons & midbrain contain neuro-chemically defined
groups of neurons that project to the cerebral cortex
either directly or via thalamus
Reticular formation
Afferent pathways to the RF
1.
2.
3.
4.
Collateral branches from the primary ascending
tracts of sensory system (spinothalamic and
spinoreticular pathways), which synapse with cells in
the RF
Fibers from the cerebral cortex, consisting of
corticoreticular fibers from widespread cortical areas
as well as collaterals from the corticospinal and
corticobulbar tracts of the motor system.
Fibers from other structures, including the
cerebellum, basal ganglia, hypothalamus, cranial
nerve nuclei, & the colliculi
Visceral afferents from the spinal cord and cranial
nerves
Efferent pathways of RF
• Efferent pathways project
1. rostrally to the forebrain
2. caudally to the spinal cord
3. to motor & internal regulation systems
Output pathways of the brainstem reticular formation
Neurochemical nuclear groups of the brainstem & basal forebrain
• 1. cholinergic nuclear groups- in the basal forebrain & in the
dorsal tegmentum of the upper pons and midbrain
(=mesopontine tegmentum) –project to cerebral cortex &
thalamus
attention, wakefulness, REM sleep
-Cholinergic structures of basal forebrain project to
a. the cerebral cortex –regulation of behavioral
functions, including cortical arousal, wakefulness,
sensory processing, learning and memory
b. Reticular nucleus of thalamus other thalamic
nuclei– modulate activity of thalamus & thalamocortical
projections
-Cholinergic neurons of mesopontine tegmentum project to
the thalamus & basal forebrain
• 2. monoaminergic groups ( NE, 5-HT & histamine)
Cont-• Regulate behavioral state & state-dependent cortical function
• Located in the brainstem and hypothalamus
• Send projections to the basal forebrain and cerebral cortex via the
medial forebrain bundle
A. Norepinephrine cells= located in locus ceruleus in the lateral part of
the upper pons
wakefulness & attention
locus ceruleus= melanin pigmented bluish cells & rich
in epinephrine
=sends projections to areas mediating sensory stimulithalamus, hypothalamus, basal forebrain, cerebral cortex, cerebellum,
and spinal cord
B. Raphe nuclei=serotoninergic neurons
wakefulness
-located in the median area of brainstem
-(upper pons & midbrain)=rostral group-project to thalamus,
hypothalamus, basal forebrain, & cerebral hemispheres
- caudal group=( lower pons & medulla) –project to spinal cord &
brainstem
cont
C. Histamine neurons –
arousal & wakefulness
located in the posterior lateral hypothalamus
Cont--
Basal forebrain area---projections ( for attention, motivation & memory)
Thalamus
• Gateway to the cerebral cortex
• Two roles
1. relay station
2. filter & modulate flow of information to cortex
Two main components:
-A. relay nuclei contain
1. relay or projection neurons –containing glutamate –send
excitatory input to the cortex
2. local inerneurons containing GABA- participate in thalamic
local inhibitory circuit
- B. reticular nucleus-containing GABAergic neurons projecting to
other thalamic nuclei- inhibitory function & synchronize for rhythm in
sleep
_cortico-thalamo-cortical loop-coordinate processing of sensory
information
Thalamic nuclei of the consciousness system
Thalamocortical projections of consciousness
Cont--
Basal forebrain
• A group of structures at ventral and medial aspects of
cerebral hemispheres
• Includes:
• 1. nucleus basalis of Meynertcholinergic –projections to widespread areas of cortex
Major source of extrathalamic input to cortex
• 2. septal nucleus
• The medial forebrain bundle – large tract
- extends from midbrain tegmentum through lateral
hypothalamus, into the septum, preoptic area,
hypothalamus, basal olifactory region, & cingulate gyrus
- represents the rostral extent of reticular system=
ascending & descending connections
Basal forebrain area---projections ( for attention, motivation & memory)
Ascending pathways to the cerebral cortex
• Two main types of projection pathways
1. thalamocortical pathways
2. Extrathalamic pathways- involving basal forebrain
& medial forebrain bundle
Ascending pathways of the consciousness system
Thalamocortical pathways
Extrathalamic pathways
Input from
Sensory relay nuclei
spinal cord & brainstem
Chilinergic & monoaminergic
neuron groups in brainstem
& basal forebrain
Projection
pathway
Thalamic radiations
Medial forebrain bundle
Projects to
Specific topographic areas Widespread areas of
of cerebral cortex
cerebral cortex & thalamus
Function
Relay & filter information
to cerebral cortex
Modulate activity of cerebral
cortex & thalamus
Activity
Phasic / excitatory
Tonic- conscious
modulatory
Dependent on
Specific afferent
stimulation
Behavior state (wake-sleep)
Thalamic & extra-thalamic pathways of consciousness system
Cerebral cortex
• All areas of cerebral cortex appear to participate
in consciousness
Physiology of the conscious system
• Single cell- synaptic potential
- action potential
• Neuronal aggregate
-EEG
Functions of the consciousness system
• Maintenance of consciousness, attention and regulation
of wake-sleep cycle
• Consciousness–awareness of environment and self
= two aspects:
1. content of consciousness- representing cognitive
mental functions that reflect the activity of the cerebral
cortex
2. arousal and wakefulness –dependent on the
reticular activating system and its projections which in
turn are activated by sensory stimuli or cortical
influences
Cont--
• Neurons of the RF & basal forebrain diffusely activate
cortex directly & via thalamus.
• They receive inputs from restricted areas of the cortex –
orbitofrontal & superior temporal cortex and stimulation
of these areas evokes an arousal response
• Cholinergic & monoaminergic inputs have a dual effect
on the thalamocortical circuits:
•
1. at the level of the thalamus, they inhibit burst
activity and facilitate sensory stimulation
•
2. at the cortex- they increase excitability and
responsiveness of cortical neurons to thalamic & cortical
inputs
Cont-• Cholinergic neurons of basal forebrain & locus
ceruleus increase their activity in response to new
and challenging stimuli and are involved in arousal,
attention & motivation
• Histaminergic neurons in the posterior lateral
hypothalamus are also involved in cortical arousal
and motivated behavior
• Decreased activity of both cholinergic and
monoaminergic inputs results in progressive
decrease in excitability of thalamocortical circuits
Attention
• Thalamus enhance or attenuate responses to
incoming stimuli and direct attention to specific
input while suppressing other incoming stimuli
• Consciousness system influences degree of
overall attentiveness to the environment and
perception of specific sensory modalities
Functional states of cerebral cortex and
thalamocortical circuits
Thalamocorical
activation
Thalamocorical inactivation
Ascending input from Present
mesopontine RF
Reduced
Thalamic activity
Tonic-single
spikes
Rhythmic burst firing
Sensory processing
Present
impaired
EEG
Low-voltage fast
activity
High-voltage, rhythmic slow
activity
Examples
Wakefulness
REM sleep
Non-REM sleep
General anesthesia
Absence seizure
Coma
Sleep -•
•
•
•
•
B. Sleep: Nature & Stages
Older notions: Some thought sleep was the brain's response to lowered
levels of stimulation from the senses.
Others argued that sleep was a necessary stage for the organism to repair
or to rest itself so that it wouldn't break down. Both these notions are
incorrect.
Defining Sleep: a cyclic, temporary and physiologic loss of consciousness
that is readily, promptly and completely reversed by appropriate stimuli
"Sleep is an actively induced, highly organized brain state" marked by these
four qualities -– 1. Reduced motor activity
– 2. Lowered response to sensory stimulation
– 3. Adoption of stereotypic postures such as lying down with the eyes
closed, and
– 4. Easy reversibility (compared to coma, stupor, hibernation, etc.)
Cont---
Cont--
•
•
•
•
•
•
Non-REM Sleep includes Stages 1 to 4
Stage 1: Mostly theta waves
Stage 2: Sleep spindles and K-complex waves
Stage 3: Mostly delta waves
Stage 4: Delta waves; hard to awaken
May involve dreaming
• REM (Rapid Eye Movement) Sleep (= "paradoxical" sleep)
• Brain waves somewhat similar to awake state or Stage 1 sleep (lowvoltage, mixed/fast waves)
• Rapid eye movements
• Almost complete loss of muscle control ("atonia")
• Penile erections (males) & vaginal moistening (females)
• Easy to awaken
• Usually a time of more intensive, vivid dreams
Characteristics of REM &non-REM sleep
Sleep activity
Eye movement
Body movement
Non-REM sleep
Slow (drowsiness)
Muscle relaxation
Vital signs
Muscle tone
REM sleep
Rapid
Muscle
twitches
Fluctuating
decreased
Penile erection
common
Rare
Dreams
EEG
Common
Low
voltage
Rare
Spindles, V-waves, Kcomplexes, slow waves
Stable
Some tone in postural muscle
Percentage-adults 20-25
75-80
Percentage-infants 50
50
Cont--
• Sleep Cycle
• Movement from Stage 1 to Stage 4 and
back to Stage 1
• REM Sleep substitutes for Stage 1 sleep
during cycle
• Between 90-110 minutes to move through
an entire cycle
• Each night = 3 to 5 complete cycles
Sleep--
• Sleep is an active phenomenon in which hypnogenic
areas of the brain and neurochemical substances
actively promote sleep and inhibit arousal system.
• Structures for sleep regulation are
•
1. raphe nuclei ( 5-HT)- in the upper medullary &
lower pontine
•
2. locus ceruleus (NE)- in the lateral portion of
upper pons and lower midbrain
•
3. the nucleus of tractus solitarius in the medulla
•
4. dorsolateral pons (Ach)
•
5. the anterior portion of the hypothalamus
•
6. the reticular nucleus of thalamus
•
7. the basal forebrain preoptic area
Biological Mechanisms of Sleep & Wakefulness
Arousal
• pontomesencephalon
(reticular formation)
• connected to thalamus & basal forebrain
• arousal of cortex & increased alertness to new tasks
• Acetylcholine (ACh) & glutamate = excitatory
• dorsal raphe nucleus
• inhibits basal forebrain GABA cells (therefore, prevents
inhibition in cortex)
• Serotonin
• locus coeruleus
(dorsal pons)
• connected to many areas of the cortex
• influential in the storage of recent memories
• Norepinephrine
Arousal--
• basal forebrain
(anterior to hypothalamus)
• connected to thalamus and cortex
• overall arousal, attention to stimuli, increased
learning
• subject to damage in Alzheimer's disease
(impaired attention & memory)
• Acetylcholine (ACh) = excitatory
GABA = inhibitiory
• hypothalamus
• arousal
• antihistamine drugs may cause drowsiness
• Histamine
sleep
• Sleep
• lower temperature
• lowered brain temperature is associated with
sleep; thus,
• cooling body leads to sleep
• inhibition of arousal
• Adenosine
• adenosine (an end-product of metabolic
processes) builds up in brain during activity
• in the basal forebrain, adenosine receptors
inhibit some arousal neurons and this sustains
sleep
Sleep--
• accumulated adenosine due to lack of sleep will
cause sleepiness over later days ("sleep deficit
or debt")
• Caffeine blocks adenosine receptors
• prostaglandins
• (found in most body cells; involved in
inflammation, pain, & fever in response to
infection; role in labor; inhibited by aspirin) build
up during day & stimulate inhibitory neurons in
the hypothalamus
• GABA
• Increased hypothalamic GABA release helps
lead to sleep
Brain Function in REM Sleep
• Activity in the pons triggers REM sleep
which is associated with a distinctive
pattern: PGO waves (see figure )
• The pons also sends instructions to spinal
cord to inhibit motor neurons associated
with large muscles
Cont---
Comparison of wakefulness and sleep
State
wakefulness
Non-REM sleep
REM sleep
Cholinergic
input
Active
Reduced
Active
Monoaminergic Active
input
Reduced
absent
Sensory
processing
Present for outside
information
Absent
Present for stored
information
(dreaming)
Attention
Present
Absent
Absent
EEG
Alpha –eyes closed Spindles, K
Low amplitude-eyes complex, highvoltage, delta
open
rhythm
Low-voltage, fast
activity
Sleep Abnormalities
• Insomnia= not sleeping enough due to
(1) difficulty falling asleep (onset insomnia)
(2) frequent awakening during sleep (maintenance
insomnia), or
(3) waking up too early (termination insomnia)
• Sleep Apnea= intermittent stopping of breathing during
sleep
• Narcolepsy= frequent, unexpected periods of sleep or
sleepiness during the day.
• Includes one or more of these symptoms:
1. Gradual/sudden onset of sleepiness
2. Cataplexy: muscle weakness while remaining awake.
Often triggered by strong emotions
3. Sleep paralysis: inability to move when falling asleep or
waking up
Sleep Abnormalities
• 4. Hypnagogic hallucinations: dreamlike
experiences at the beginning of sleep.
• Equivalent to REM-like sleep intruding into the
awake state Cause is unknown.
• Possibly due to Overactive ACh synapses in the
pons which send messages to spinal cord; or,
• Axons using the neurotransmitter orexin
(hypocretin) in the hypothalamus connect to
areas which increase arousal & wakefulness.
• Humans with narcolepsy do not have these cells
in the hypothalamus (perhaps due to an
autoimmune disorder).
Cont--
• Periodic Limb Movement D/O = during NREM sleep
individual moves legs and sometimes arms every 20-30
seconds for minutes or hours
• REM Behavior D/O= during REM sleep individual
moves vigorously or violently (kick, punch, etc.); dreams
of violent nature; occurs mostly in older men with brain
diseases, esp. PD.
• Night Terrors = an experience intense anxiety from
which one wakes up screaming in terror
• Sleep Talking We all do it.
• Sleepwalking
• usually children 2-5 years old
• harmless; no danger to wake the sleepwalking person up