CRANIAL NERVES

Cranial Nerves

It gives us a quick way to differentiate whether something is due to an UMN or LMN lesion.

Also lets you know if they have an contraindications to c-spine manipulations

Anything below the skull is innervated by the spinal nerves and anything within the skull is cranial nerves attaching to the brainstem

C-spine manipulation can have an effect on circulation (can be + or -)

o Spinal nerves – spinal cord

o Cranial nerves – brain stem

Functions

Motor and sensory components

Mediates vision, hearing, olfaction, taste (anything around the face)

Carries parasympathetic innervations of autonomic ganglia and act as a control center

Exclusively in the head and neck

Exception: CN X – thorax and abdomen visceral sensation

Supplies CNS with regional information from the external environment so the CNS can then adapt and change

Review

1. CN I: Olfactory (S)

2. CN II: Optic (S)

3. CN III: Oculomotor (M)

4. CN IV: Trochlear (M)

5. CN V: Trigeminal (Both)

6. CN VI: Abducens (M)

7. CN VII: Facial (Both)

8. CN VIII: Vestibulocochlear (S)

9. CN IX: Glossopharyngeal (Both)

10. CN X: Vagus (Both)

11. CN XI: Spinal Accessory Nerve (M)

12. CN XII: Hypoglossal (M)

Nuclei

Nuclei located in brain stem except for oculomotor and optic nerve

Organized into columns/groups (7 longitudinal columns) so that similar functioning cranial nerves are put close to one another.

Similar functions are located together so that neural connections are more efficient (economization of neural connections)

Very focal damage to brain stem will limit the effect on specific functions (so if you have the similar nuclei clustered together then when

you have damage you will most likely only lose one function)

However, it is very rare to have an injury that is so focal, they are typically wide spread because the brainstem is so small

Similar to LMNs, cranial nerves mediate many delicate fine movements (e.g. eye, larynx)

Receives input from higher-order processing structures and can be controlled by them

1. Cerebellum

2. Reticular Formation

3. Cortex

Clinical

Local lesions can cause deficits in many functions so in a cranial nerve test you’ll normally find multiple signs rather than just 1

A positive finding on a cranial nerve exam should never be iffy, you will know if the brainstem is affected

Three points of clinical value:

1. Bilateral cortical connections exist in most cranial nerves (except facial nucleus for the lower part of the face and the

hypoglossal which supplies the genioglossus)

2. Impairments will usually affect more than one functions

3. Sensory cranial nerve afferents have ganglia (organized like spinal nerves)

Sensory afferents are found in ganglia just like posterior root ganglia and receive input from several CN (diff for motor nuclei)

Sensory nuclei integrate the same sensation. For example taste comes from different CN (facial, glossopharyngeal, vagus nerves) but end

up at the same nuclei in the end (solitary nucleus)

Some of the main neurotransmitters in brain stem include: Noradrenaline, Dopamine, Serotonin, Monoamines

CRANIAL NERVES

Olfactory

Test for smell

Anosmia: Disorder of smell

o Bilateral anosmia = is usually due to a disease of the membrane (like having a cold)

o Unilateral anosmia= usually something affecting the nerve, bulb or tract

Fractures of cribiform plate could tear nerves leading to unilateral anosmia

Lesion to olfactory cortex can cause a unilateral lesion because you have fibers from each olfactory tract which travel to each hemisphere

Oculomotor

Innervates all extraocular eye muscles + levator palpebrae superioris + accommodation muscles (sphincter pupillae and ciliary muscles)

Lesion: eye cannot move upward, down or medially so the eye rests in lat/down (external strabismus)

o Diplopia –double vision b/c 2 eyes don’t see the same image so they often tilt head (ocular tilt)

o Ptosis- droopy eyelid

o Dilated pupil – no reaction to light & accommodation

Lesions can be incomplete so you can have different types of opthalmoplegia

o Internal opthalmoplegia

o External opthalmoplegia

Lesions can occur possibly because of superficial parasympathetic issues

Diabetics have impaired nerve conduction so they can have issues with the eyes

Superficial nerves are less likely to be affected

Other causes: aneurysm, tumor, trauma, inflammation, vascular disease

Trochlear

Supplies superior oblique

Lesions will cause diplopia because we lose an aspect of the eye

At rest eye turns medially and upwards

Caused by: head injuries, Diabetes, Vascular lesions, Anyeurysms, thrombosis

Abducens

Supplies the lateral rectus

Lesions: unable to turn eye laterally

At rest the eye is turned medially

Called an internal strabismus

Diplopia can result as well

Caused by: same as trochlear causes

Trigeminal

Sensory and motor roots

Lesions will cause loss of sensation to side of face

Muscles of mastication will also be affected

There are 3 divisions: ophthalmic, maxillary, mandibular

Trigeminal neuralgia:

Most common facial pain syndrome

Severe, unilateral and episodic stabbing pain over the lateral portion of the face

Mostly mandibular and maxillary division affected (rarely in the ophthalmic division)

Common age onset 50-70’s and often secondary to tumors or multiple sclerosis

Most likely cause: vascular compression

Damaged nerve (due to vascular compression) is hyper-excitable and normal sensory impulses affect pain fibers much more (normal

sensations now cause pain)

The medical management is effective at first but then the therapeutic effectiveness decreases over time so patients often discontinue

medical therapy due to side effects (they often seek CAM)

There are no reported cases of successful chiropractic treatment for trigeminal neuralgia but adjustments are not contra-indicated

Interventions:

Microvascular decompression is surgery in posterior fossa is often done so the

blood vessel can be moved or decompressed

This is the most successful intervention but it is costly, lengthy, invasive and

entails a long recovery

However risk is fairly low for the surgery but it is not suitable for medically unfit

Facial nerve

Controls facial expression, the anterior 2/3 of tongue and secretions

Lesions can occur by deep lacerations

Bell’s Palsy- damage/dysfunction of CN VII as it courses/lies in the facial canal

Usually unilateral

The cause is unknown but the nerve in the compartment will often swell

Some think this could be caused by cold drafts

Many times it is short-lived so the patient doesn’t suffer from any long term damage (doctors take a wait-and-see type of approach)

Vagus

Innervates many organs into the thorax and abdomen

The easiest way to test CNX is to test the gag reflex (if it is diminished or absent then you have a problem)

Vagus nerve stimulation is often used to treat symptoms of depression (because depression is linked to vagus nerve problems)

Vagus nerve stimulation basically repeatedly stimulates the vagus nerve

Treatment resistant

Accessory

Supplies SCM and trapezius

Hypoglossal

Innervates intrinsic muscles of tongue

The best way to test this is to get the patient to stick out their tongue

QUICK TEST

1. H-Gaze – tests CN III, IV, VI and potentially II

2. Facial expression –tests for CN VII and potentially CNV

3. Tongue to cheek with palm resistance—tests for CN XII, CNIX, V

4. Shoulder shrug—tests CN XI

5. Swallow—tests CNX

OCULOMOTOR COMPLEX

Oculomotor Complex

Controls all eye movements

Involves 3 cranial nerves: oculomotor, trochlear, abducens

Sits in the anterior portion of the midbrain

Innervates 4 of the 6 muscles outside the eye and structures inside the eye (has a role is almost everything having to do with the eye)

Strictly motor via two nuclei (one for the somatic motor and one for the parasympathetic)

o Oculomotor nucleus (somatic motor)

o Edinger-Westphal nucleus (preganglionic parasympathetic)

Edinger Westphal

Accessory parasympathetic nucleus controls supplies the constrictor pupillae and ciliary muscles

Functions- Adapts to light, Blink reflex, Accommodation to near/far

Location- posterior to the main motor nucleus

Axons of this nucleus will travel with motor fibers however they are preganglionic

It receives information from:

o Cortical fibers (accommodation)

o Pretectal fibers (light reflex)

Motor control of: sphincter muscles of the iris and ciliary muscles to change lens curvature

Inputs: Vestibular, Pretectal region, Cortex

Oculomotor Nucleus

Main motor nucleus

Receives information from the superior colliculus and visual cortex via the MLF (also receives from CN IV, VI, VIII)

Eye movements include

o Vestibular ocular reflex

o Smooth pursuit

o Saccades (ability to jump from one visual field/point to another)

o Convergence (eyes are moving in a non-conjugant manner)

Outputs consist of muscles of the eye (both intraocular and extraocular)

o Medial rectus: med

o Lateral rectus: lat

o Superior rectus: up/in

o Inferior rectus: down/in

o Superior oblique: down/lat

o Inferior oblique: up/lat

Oculomotor Reflexes

Vestibular ocular reflex is the fastest reflex in the body– very short delay

He explained it as “when you’re head moves right, it turns your eyes left”

Essentially this whole response aims to do 2 things in the eyes :

1. Activation of contralateral eye muscles

2. Inhibition of antagonist muscles on ipsilateral side (to inhibit turning in the same direction of the head)

The reflex is continuously ready but only turned on when you foveate (when you focus on an object). Its suppressed prior to this.

This reflex is about 14 ms (faster than the blink reflex)

Three neuron system (there are only 3 involved which allows it to be a very fast reflex)

Deficits to vestibular nerve = nystagmus

Turn your head semi circular canals will detect movement on the same side of rotation superior vestibular nucleus activates/inhibits

appropriate muscles for the eye to be able to go the opposite direction of head movement (so if you turned left then the eyes will go right)

Example:

Left head rotation will cause a positive signal to be transmitted from the left semicircular canals to CN 8 which then:

o Activates: contralateral CN 6 (lateral rectus) and ipsilateral CN3 (medial rectus)

o Inhibits: ipsilateral CN6 and contralateral CN3

So we have 2 main muscles contracting (lateral rectus on the right side and the medial rectus on the left side) making the eyes move in

the opposite direction of the head

Left head rotation left SC canal activates vestibular nuclei signal to CN8 activation of contralateral CN6 (lateral rectus) and ipsilateral

CN3 (medial rectus) so eyes move right CN8 sends inhibitory signal to ipsilateral CN6 and contralateral CN3 (prevent eyes from going left)

KNOW THIS DIAGRAM

Intraocular Eye Muscles

Ciliary eye muscles control the thickness of the lens

Circular and radial eye muscles control the amount of light entering the eye by determining the size of the diaphragm ( size of the pupil)

Pupillary Light Reflex

Parasympathetic controls this

Controls pupil diameter to determine the light entering eye

Projects to the pretectal nucleus then goes bilaterally to the EW nucleus and onto the ipsilateral ciliary ganglions

Light enters eye pretectal nucleus bilateral to the parasympathetic nuclei (Edinger Westphal) ipsilateral ciliary ganglion

Due to the bilateral projections of the pretectal nucleus this causes the light reflex to be direct or consensual

Research: Sun-sneezers

The reason people tend to sneeze when looking at the sun is because the pupillary light reflex will come close to the same reflexes that

cause you to sneeze (so there may be cross talk or cross communication between these reflexes) About 25% of the population has this

phenomenon

A lot of these circuits are involved in the light reflex. The brown circuit is the pupillary light reflex circuit.

Accommodation Reflex

Combines main motor and parasympathetic pathways (as opposed to the other two which either have one or the other)

Involves 2 of the components of CN 3 so one set projects to the oculomotor complex and the other projects to the EWN

Co-ordination of three events need to occur for this reflex to happen:

1. Eyes moving medially together

2. Lens thickens

3. Pupils constrict

Causes: increase in curvature of lens, pupillary constriction and convergence of eyes

Information enters afferents travel via optic nerve lateral geniculate nucleus visual cortex frontal cortex cortical fibers

oculomotor nuclei (main) other fibers will project to parasympathetic nuclei (EWN) allowing for the lens to become fatter and puipils to

constrict synapse on ciliary muscles constriction of pupillary muscles

Visual Physiology

Refraction occurs when light passes through different types of media (air and water) which causes light to bend

The light bends as it passes through these medias and it converges at a specific point

The focal distance is the distance to the particular object.

Short and far focal distances will change the shape of the lens.

o Closer the object = rounder/fatter the lens

o Further the object = flatter/skinnier the lens

Oculomotor Lesions

Causes of lesions: Strokes, Tumors, Diabetes, Inflammation/inflammatory diseases, CNS syphilis

CNS syphilis (Argyll Robinson pupil) – pupillary light reflex is compromised because the pupil is constantly dilated

Tumors: herniation of the temporal lobe causes pressure which causes cerebellar peduncles to herniate and stretch the oculomotor nerve

Strokes: occulsion of the posterior cerebellar artery, midbrain structures, medial lemniscus or red nucleus

Symptoms: Loss of accommodation and convergence, Droopy eyelids, Stabismus (diplopia), Down and out gaze (external strabismus)

LMN vs. UPN

Always look to see if both eyes are affected to tell if it is an UMN lesion

Superior rectus is innervated from the opposite side of the brain so as a result if you get:

1. Peripheral lesions: down and out gaze, you affect 4 different neurons

2. UMN (central) lesions: effects neurons going to extraocular eye muscles AND the nucleus on the same side (both superior

rectus are involved), one eye will be down/out and the other can’t elevate well

Ocular Tilt Reaction

Ocular tilt reaction is when someone manually tilts their head to correct for torsion of eye

Less common in humans and more common in dogs and cats (they will walk around with a tilted head which indicates a lesion in CN3)

Testing: observation if eyelids are drooping, visual inspection, looking for ptosis, seeing if there is an eye which rests down and out

Test for the motor integrity by testing a combination and convergence

Saccades testing (point to nose and point to my finger), allows eye to move from point to point very quickly (cerebellar test as well)

Smooth pursuit is tested via H-gaze and making sure it is smooth without any nystagmus

Accommodation/Convergence testing

Intrinsic Muscles (Intraocular)

Ciliary muscle- regulates the shape of the lens

Inserts via the suspensory ligaments on the periphery of the lens capsule

Circular muscle of Iris- dilates the pupil when it contracts

VESTIBULAR FUNCTION

Vestibulocochlear Nerve

Responsible for hearing and head movements

Has input from the vestibular apparatus which has 2 main structures:

1. Utricle and saccule—linear movement

2. Semi-circular canal—rotational acceleration

Any movement of the head will trigger a signal from one of these sources in the vestibular apparatus to tell you where your head is being

held in space

Neurons

We can divide the neurons into 1st and 2nd order neurons

Hair cells primary sensory neurons in the vestibular ganglion vestibular tract enter anterior brain stem (through a groove formed

by the pons and medulla) synapse on vestibular nuclear complex (floor of 4th ventricle)

Vestibular nuclei inputs:

1. Utricle and saccule

2. Semicircular canals

3. Cerebellum (flocculonodular lobe)

Vestibular nuclei receive information from all these areas (depends on vestibular apparatus and the rest of the body via the cerebellum)

Vestibular Nuclei

ALL NUCLEI are crossed & travel bilateral to cranial nerve nuclei via the Medial vestibulospinal tract/MLF

Regardless of the division, the nuclei as a whole will project bilateral to both sides CN 3, 4, 6 to control ocular movements via the MLF

1. Lateral – uncrossed to Lateral VST (to LMNs in spinal cord)

2. Superior – cortex via thalamus

3. Medial - cerebellum

4. Inferior – cerebellum

Dysfunction of the apparatus or nerve can cause dizziness, nausea, falling, abnormal eye movements

SEMICIRCULAR CANALS

The end of the vestibular apparatus is called the semicircular canals or the utricle or saccule

There are three semi-circular canals (kinetic) which are circles on each side of your head

They detect angular rotation so they are often called kinetic labyrinths (tangle)

As long as there is acceleration there will always be movement along the hair cells. Once this increased movement stops then

you no longer have movement stimulating the hair cells.

Therefore, there MUST be ACCELLERATION to have continuous stimulation.

If you keep moving at the same speed (constant velocity) then this nulls out and your vestibular apparatus will no longer give you that

feedback.

o Vestibular system’s hair cells detect acceleration. If no acceleration, than there is no feedback. Spinning around fast will

cause the fluid in your ears to move and cause the hair cells to move, giving you feedback that there is angular acceleration,

when there isn’t.

If you are moving and then suddenly stop then momentum will cause fluid to move in the opposite direction (like when you spin around

on a baseball bat). You body will tell you there is angular rotation going on when there actually isn’t

Endolith fills the semicircular canals

Crista ampullaris is a cone-shaped structure, covered in receptor cells called "hair cells".

Covering the crista ampullaris is a gelatinous mass called the cupula.

Upon angular acceleration (rotation), the endolith within the semicircular duct deflects the cupula against the hair cells of the crista

ampullaris. The hair cells respond by stimulating neurons that innervate them

Meniere’s Disease Dysfunctional drainage of the Endolith (Fluid in semicircular canals)

Endolith is secreted by endothelial cells and there is a continuous secretion

Drainage of endolith is from inner ear occurs via venous sinus

If drainage cannot be met for some reason then Meniere’s disease occurs

Due to the fullness of fluid in the ear you no longer have proper function of the vestibular apparatus and symptoms like dizziness and

nausea can result

MAIN CAUSE: dysfunction in drainage of endolith

UTRICLE AND SACCULE

Counter-current movement of fluid (fluid pushes hair cells to bend)

Gel bends as long as there is a difference between fluid speed and body speed (one will be in an

excitatory direction and the other will be an inhibitory direction)

At constant speed (i.e. no acceleration) there is no bending

If no hair cells are firing then there will be no perception of rotation (from vestibular system)

Stop rotation = fluid spins backwards

Caloric Stimulation

Cold & hot water

Irrigate (drain) the person’s ear with cold water to reduce the temperature of the entire region

Then drain the whole ear with hot water

This creates a convection in the ear which causes the fluid in the inner ear to spin

Result in a NON-PATHOLOGICAL case you will see a NYSTAGMUS!

If you DON’T see this then you should suspect a lesion at the vestibular apparatus or the nerve itself

Nystagmus is absent when this is done on the affected side

EXAM: nystagmus will result in a non-pathological case

Detection of Movement

This tells you where your head is in respect to gravity (opposed to detecting based on

acceleration like in the SC canals)

These would be considered static labyrinths as opposed to kinetic

Sensory receptors located in the macula

Ciliated hair cells are covered by a gelatinous mass with crystals of calcium carbonate on

top called otoliths

Otoliths (calcium carbonate crystal on top) help to bend hair cells with position change

The utricle is fairly good at detecting movement in the horizontal plane and saccule is

good at detecting vertical

o Utricle = horizontal

o Saccule – vertical

Discharge tonically in the absence of head movement is due to pull of gravity

Basically: The hair cells are suspended in a gelly like substance which is different than those in the SC canals due to the otolinths weighing it

down. The saccule and utricle are topped with these calcium carbonate crystals called otolinths which cause the hair cells to be top heavy.

BPPV

Most common form of vertigo

Has an easy and effective therapy

Diagnose: put the head in different positions and see which one causes the nystagmus

o Nystagmus in the absence of stimulus tells you that this could be BPPV

o Elicited by head turning to the affected side (semi-circular canal)

Posterior canal most common one affected in BPPV

Etiology is hypothesized that the otoconia (crystals) can become dislodged for some reason (usually due to trauma or whiplash) and

enter into the gel (most often get trapped in the posterior SC canal)

As a result we get a weighing of the water that is different and can affect the “water

level” (the added crystal makes it more full)

o Vertigo – illusion of movement (world is spinning, whirling, tilting)

o Dizziness – lightheadedness (wooziness, floating, unsteadiness)

Always ask them is the world around them is spinning (vertigo) or if they feel like

they are spinning/unsteady (dizziness)

Treatment

Dix-Halpike

o Head in lateral position

o Re-produce vertigo

o Eyes beat quickly towards affected ear

AUTONOMIC NERVOUS SYSTEM

Peripheral Nervous System

Divided into:

1. Somatic (voluntary)

2. Autonomic (involuntary)

a. Sympathetic (stress)

b. Parasympathetic (peace)

c. Enteric (gut nervous system)

Autonomic Nervous System

Controls organs and tissue

Relatively rapid control and very widespread

Large collections of afferent/efferent fibers = plexuses

Plexuses reside in the thorax, abdomen, pelvis

Key features:

The ANS puts your body into an environmental context to adapt your body

Sympathetic nervous system over-rides all other actions (shuts down all other actions of the parasympathetic system). So the

parasympathetic system only comes into play as a default.

SYMPATHETIC PARASYMPATHETIC

SYMPATHETIC

All sympathetic neurons are localized in the thoracic and upper lumbar segments (T1-L2/L3)

Exit with somatic motor neurons

Lateral grey regions of the spinal cord will have cell bodies called pre-ganglionic sympathetic neurons which have thin myelination

So basically your sympathetic nervous system cell bodies are in the lateral grey regions of T1-L3

The preganglionic parasympathetic neurons leave the intermediolateral cell column to synapse on the ganglion outside the spinal cord

They branch from the spinal nerve and become more myelinated (whiter appearance) so they are called the white communicating rami

Neurons synapse on the paravertebral sympathetic chain, are then called sympathetic post-ganglionic which then travel to target organ

These neurons are non myelinated, appear grey are called grey communicating rami

o Preganglionic = comes from lateral regions to the ganglion

o Postganglionic = after the ganglion

Neurotransmitters

Preganlionic fibers release ACH which is received by a cholinergic receptor on the ganglia

Activation of these receptors will lead to depolarization

Post-ganglionic fibers release norepinephrine to the target organ (One exception: sweat glands – ACH.)

Norepinephrine or noradrenaline will be received by either:

o Alpha adrenergic receptor

o Beta-1 adrenergic receptor

Receptors

Activates second messenger mechanisms

Alpha receptors - found on most sympathetic targets and have a strong response to NE (epinephrine has an effect, but its weak)

Beta-1 receptors - found on heart muscle and kidney and respond equally strong to epinephrine and NE

Fate of the Neurotransmitter

Metabolized (e.g. Acetylcholinesterase), Re-uptake and broken down

Mono-amino oxidase (MAO) are found in the mitochondria and will only break down those NT’s which have one amine group on them

(i.e. those NT’s derived from amino acids)

Sympathetic cholinergic receptors can also be stimulated by nicotine (so smoking stimulates our sympathetic nervous system)

So we receptors which are meant to bind ACH but that can also bind nicotine so they are called nicotinic-cholinergic receptors

Nicotine applied exogenously (from external environment) can also stimulated them

Effects of smoking- the constant bombardment of nicotine every time someone smokes is eliciting a stress response and activating the

sympathetic nervous system so everything is working a little harder because the organs are being bombarded with adrenaline

You never actually allow your body to relax in the parasympathetic state when smoking

So essentially nicotine is an agonist and has the same effect as ACH. This causes the body to down regulate (pulls receptors away from

the surface so instead of 100 receptors on the surface there will only be 50 or so) Over time down regulation becomes greater and greater

Receptor Regulation

General rule of thumb:

o Exogenously applied agonists = cause down-regulation (less receptors on surface)

o Opposite of exogenously applied antagonists: causes up-regulation (more receptors on surface)

Nicotine receptors

The exception to the rule! This is why is it so difficult to quit

Chronic use of nicotine causes up-regulation of receptors (this is the opposite of the normal response)

Your body will begin to create more nicotine receptors

Up-regulation causes tolerance (you will need more) and once you try to quit you get withdrawal

Three states:

1. Unbound and inactive

2. Bound and active

3. Bound and inactive

During chronic exposure, receptors are in the bound and inactive state so even if it is bound the receptor has just given up and doesn’t

want to act anymore

Once the body starts to see inactivity, nicotinic cholinergic receptors then get put to the cell surface again (become up-regulated)

Once you start to take away the nicotine you cravings because you want to have these receptors doing something (and there are so many)

Once you take nicotine away permanently you get this complete withdrawal because you have tons of unbound receptors and a huge

drop in norepinephrine/adrenaline

So the whole reason smoking is so hard to quit is because nicotine is an exception to the general rule

Exposure to nicotine bound inactive up regulation

The Nicotine Patch

It aims to slowly wean you off of the nicotine by giving you the balance you need initially so all the receptors can still have some

substrate rather than stripping it away all at once

Adverse side effects can occur with excessive use of the patch

Neuromuscular junctions have nicotinic-cholinergic receptors and high doses can cause the muscle to remain depolarized

This can cause problems with the muscles of the diaphragm (cannot function) and you can get shortness of breath or respiratory failure

Sympathetic Pathology

Viscera are innervated by autonomic nerves

The viscera that are hollow usually have a dedicated pain pathway (GI) and anything

that is not hollow do not have a dedicated pathway but rather have sympathetic control

(kidney, liver).

If the organ is devoid of any direct pain pathway then it relies on the sympathetic nerves

to bring signals back to the spinal column

Pain is conducted along afferent autonomic nerves

Recall: referred pain is poorly localized because it is referred to skin areas innervated

by the same segments of the spinal nerve (so kidney pain may be presenting as upper

back pain)

General rule of thumb: referral pattern for cardiac dysfunction is in the left arm but for

women it can also be in the right arm (much more diffuse for some reason)

Intermittent Claudication

Arterial occlusive disease of the leg (common in men)

Ischemia of leg muscles produces cramp-like pain on exercise.

It can be caused by abnormal vaso-spasms which can lead to clots so sympathectomy is performed in severe cases (upper three lumbar

ganglia removed) so they are no longer sending any signals.

Essentially the arteries are not being sent enough blood/oxygen which causes the vaso-spasms

Schwanomas

Uncommon and very uncommon in the cervical sympathetic chain

Caused by a prolific growing of the Schwann cells (uncontrolled).

o Nerve sheath – Schwann cell

o Tumors – Schwanomas

Difficult to dissect out fully in surgery so common side effect is Horner’s disease

Cervical Sympathetic Trunk

Post-ganglionic nerves travel to ganglia in their respective regions

First three thoracic project to the cervical sympathetic trunk

Three ganglia in the cervical region

1. Superior

2. Middle

3. Inferior

Superior is the largest and any time this is damaged you can get the following conditions: Horner’s syndrome, Pupillary miosis, Ptosis,

Endopthalamus, Facial anhydrosis (patients do not realize these symptoms usually)

Horner’s Syndrome

Sympathetic disruption:

o Ptosis (droopy eyelid)

o Miosis (small pupils)

o Facial anhydrosis (dry skin)

o Endopthalamus (sunken eyes)

Sympathetic Response

Ciliary muscles relax so you can see distance

Capillaries constrict on the skin to send more to muscles)

Lung vessels dilate to allow for more gas exchange

Pancreas vessel decrease

Liver vessels constrict

Heart and coronary arteries will dilate for increased blood flow

Erector pilli on the skin will contract (hair on end)

Kidneys have decreased urine production (bladder constricts as well)

Gut will inhibit secretion of gastric fluid because digestion is not 1st priority anymore

Sphincter will contract

Creutzfeldt-Jakob Disease (Mad Cow)

Bacteria travels to the GI system, travels backwards and makes its way through the BBB into the CNS

How does it lead to neurological compromise? Sympathetic nerves

PARASYMPATHETIC

Parasympathetic

Peaceful state (exact opposite of sympathetic)

Aids to restore processes in the body and focuses on rest, conservation and restoring energy, increasing digestion and also results in

decreased cardiac output, slower respiration and increased urine

Craniosacral division of ANS

Origin: oculomotor (3rd), facial (7th), glossopharyngeal (9th), vagus (10th) and the sacral cord

Vagus supplies the thorax and upper abdomen (entirely parasympathetic)

Sacral neurons are found in grey matter around 2nd to 4th segments and are mostly myelinated

Pelvic splachnic nerves innervated various organs

Pre-ganglionic neurons PROJECT TO the target organs and anything located within the target organ are called postganglionic because

ganglia are located WITHIN the organs (different from sympathetic)

o Pre-ganglionic neurons project to the target organ

o Post-ganglionic neurons located in the organ

Afferent nerves project back to the cell body

Post-ganglionic parasympathetic neurons are more sensitive to stretch and lack of oxygen (not heat/pain)

Neurotransmitters

Preganglionic: releases ACH at its terminals

Postganglionic: releases ACH as well

Postganglionic receives via muscarinic-cholinergic receptors

Muscarine is a poison found in mushrooms, it has a very similar chemical structure to ACH so postsympathetic neurons will also be

suseptable to muscarine (the antidote is a shot of adrenaline for the sympathetic neurons can take over again)

Poisoning resembles parasympathetic over-activation

Sympathetic:

Pre: ACH

Post: Norepinephrine, Nicotinic cholinergic receptors

Parasympathetic

Pre: ACH

Post: ACH, Muscarinic-cholinergic receptors

Exceptions

Male reproduction system- instead of ACH you have nitrous oxide (not your typical NT) which activates the G protein for erection

Some men who have erectile dysfunction may use Viagara which prevents cyclic GMP breakdown

Some drugs function to activate Guanyl cyclase or increase production of cGMP (in some instances the two work against each other)

o Ach/parasympathetic tone is always on (dilation)

o Sympathetic activation over-rides (constriction)

Research

Pupillary Light Reflex:

There was a study done in 2005 looking at smokers: one group kept smoking and the other group stopped (abstained for 12 hours)

They then looked at the pupillary light reflex speed/kinetics

Pupillary light reflex was faster when you smoked, slower for those who did not smoke

This also occurred in a step-wise progression, so as the intensity of the light increased the then pupillary light reflex was faster and more

pronounced as well.

Nicotine stimulated the nicotinic cholinergic receptors, the eyes were constantly dilated and their sympathetic nervous system took over.

Results suggests enhanced parasympathetic suppression with smoking (cholinergic activation is very strong). Therefore, the pupillary

light reflex can be used to determine the amount of nicotine in the body.

Heart:

Sympathetic activation of SA node causes heart to pump quicker

Ventricles need parasympathetic tone to allow more blood to fill

All innervations of ANS go to SA node

BUT ventricle tend to have greater parasympathetic innervations

Male Reproductive Organs

Parasympathetic required for erection

Sympathetic required for ejaculationPS

SYMPATHETIC PARASYMPATHETIC

Environment Stressful (fight/flight) Peaceful (rest/digest)

Neurotransmitter Preganglionic – ACH

Postganglionic – NE

Pre and Postganglionic – ACH

Location of Postganglionic Neuron Paravertebral sympathetic chain Target organ

ACH (cholinergic receptors) Nicotinic-cholinergic Muscarinic-cholinergic

Spinal origin T1-L3 From CN 3,7,9,10 and spinal nerves S2-4

Hypothalamus

Head ganglion of ANS

Initiation of fight or flight and controls many different systems

Posterior and lateral regions are the primary areas involved in sympathetic functions

Stimulation causes:

o Increased cardiac function

o Increased adrenal activity

o Increased dilation of muscular blood vessels

Has reciprocal connections with other brain regions (cortex and brain stem) and stimulation of those regions may also lead to

sympathetic activation

The presence of a parasympathetic center in the hypothalamus is questionable

Pathologies of ANS

Rare

Caused by direct hypothalamic damage, systemic disease (cancer, diabetes)

Parkinson’s can also cause dysfunction in the ANS

Most disease will have the greatest effect on the cardiovascular system (heart!)

Raynauds Syndrome

Vasospastic response initiated by cold causing decreased blood supply to hands and feet

Gangrene may set in and can be potentially fatal

Treatment is to decrease sympathetic tone with sympathetoctomy or norepinephrine blockers

Autonomic Hypertension

Sudden spikes in BP (250/120) possibly caused by a tumor of adrenal medulla

Too much NE is being released

Orthostatic Hypotension

Decreased BP upon standing

Baroreceptors initiate a reflex originating from cervical sympathetic chain and the heart temporarily increases stroke volume

Long term standing causes aldosterone and ADH changes (hormones which regulate bodily fluids)

Research

Study 1 Does SMT have a better effect on hypertension that dietary counselling?

o They looked at two groups: one with a diet by dietician and the other with a diet and SMT by chiropractors

o They found no significant change between the groups

Study 2 Do upper cervical adjustment decrease BP in healthy subjects?

o The adjustments has a drastic and immediate effect on BP (it dropped)

o Weakness: study was done on healthy people so we can’t apply this to people with hypertension

Study 3 Can SMT of the T-spine decrease sympathetic activation or increase parasympathetic activation?

o They found the adrenal medulla (which releases adrenaline) calmed down after SMT

1. SMT decreased sympathetic activation

2. Adrenals diminished as a result of SMT

Implications: maybe SMT could be used to treat heart disease

ENTERIC NERVOUS SYSTEM

The ENS is often considered the third branch of the ANS

Originates from the upper esophagus sphincter and all the way down to the outer anal sphincter

Controls digestion but not exclusively

ENS controls

1. Motility

2. Microcirculation

3. Secretion

4. Immune/inflammatory response

Neurons are organized into plexuses which all have their own network of nerves. There are 8 in total:

1. Subserosal plexus

2. Longitudinal muscle plexus

3. Myenteric plexus (auerbach’s) **

4. Circular plexus

5. Deep muscular plexus

6. Submucosal plexus (meissners) **

7. Smooth muscle plexus at the external surface

8. Mucosal plexus

Plexuses

There are two main/important plexuses that you can’t really function without:

1. Submucosal (a.k.a. Meissner’s) – secretions (closer to the lumen)

2. Myenteric (a.k.a. Auerbach) –muscular control

These 2 plexuses will often control the other plexuses to an extent

Only these two are ganglionated (other plexuses have smaller ganglion like structures but are not true ganglia)

Just like the brain these plexuses have many interconnections therefore sometimes when studies are too risky to be performed on the

CNS, they will be tested on the ENS instead because they are closely related in their arrangement

Each different layer of the GI tract has its own plexus (picture from top to bottom is going from the outer surface to inner lumen)

Myenteric/Auerbach’s Plexus

Located between the longitudinal and circular smooth muscle below

Muscular control/contraction

Controls motility

Submucosal/Meissners

Located in the connective tissue under mucosa

Controls secretion

Controls absorption (how materials are absorbed from the GI tract) and blood flow

ENS Neurological Makeup

We can divide the neurons of the ENS into 2 different groups

1. Extrinsic neurons

Long reflexes

e.g. the reflexes associated with sight/sound/smell of food

Long reflexes come from various centers of your brain and are associated

with the sight/sound/smell of food which can elicit many GI responses

2. Intrinsic neurons

Short reflexes

They can mediate the reflexes within themselves and don’t need help

from the outside long reflexes

Motility, Secretion, Growth/repair

3. Intrinsic neurons

These aren’t part of the 2 main ones

Intrinsic primary afferent neurons (IPANs)

Interneurons/Motor neurons

These are sensory neurons of the GI tract which detect any stretch/dysfunction

Sensory neurons with their endings in the mucosa

Responds to tension (sensory) and then controls how the bolus moves (motor aspect)

Similarities with CNS

The ENS seems to have its own blood brain barrier

Support cells are the oligodendroglia which are very similar to the ones in the CNS

Neurotransmitters

As the food bolus is moving through the gut the IPANS are ready and sense the stretch in the wall. Once this stretch is detected there is a feedback

to the other neurons and the extrinsic neurons will contract while the intrinsic neurons will relax. So there is this coupled effect of contraction and

relaxation so the food bolus can only move in a unidirectional way towards the anus.

ENS Neuron Targets

1. Smooth muscle

2. Mucosal secretory cells

3. GI endocrine

4. GI vasculature

5. Immune cells (inflammatory)

Motility

Intestinal movement is a combination of 3 different movements:

1. Propulsion – pushing the bolus through

2. Mixing – mix things up to allow digestion

3. Restricting (sphincters) – to compartmentalize digestion and control it

For example if you have a very fatty meal, you often feel that the food is stuck in your stomach and not passing through. Once you ingest

fats they illicit a hormonal change which slows down propulsion and restricts sphincters so the absorption and breakdown can take place

Movement can be static or dynamic

o Static just mixes things up

o Dynamic moves the digested food along the GI tract (perstalsis)

Peristalsis

This is the process of the bolus moving from one end to another and was once called the “Law of Intestines”

Denervated gut could still show contractions (without any innervations)

The bolus only ever moves in one direction so it was often called a polarized/unidirectional movement

2 stage event

1. Stage 1: arrival of bolus

2. Stage 2: activation of reflexes

Speed:

o Normal = 1-2 cm/min, Fast = 3-5 cm/min

Polarized Peristalsis

Three pathways must exist in the myenteric plexus:

1. Inhibition towards the anal end

2. Excitatory stimulus orally

3. Accommodation/stretch reflex at the site

Mechanical irritation, chemical irritation (salts and acids) can illicit this response

Research

Pediatric research looked at peristalsis early in life is vital for proper ENS development

Babies who had intestinal atresia (blocked intestines) had dysfunction even after surgery

It’s almost as if the babies did not have a learning process early on

If you don’t teach the ENS early on then it will have decreased plasticity and learning later on (there is a small window of opportunity

early on to train the GI tract)

Current evidence suggests you can enterically feed the child to induce peristalsis and stimulate the GI tract to maintain proper ENS

development

Secretions

Any sort of detections from the intrinsic neurons will elicit a secretory effect from the mucosal cells

Stimulated mechanically (peristalsis)

IPAN can detect glucose

Usually exclusive to submucosal plexus

Myenteric ganglion are only activated when cholera toxin is present

They can also elicit responses from myenteric ganglia when cholera toxin is present

ENS Pathology

Inflammatory reaction

Clostridium difficile Toxin A

This bacterium will lead to secretion of many inflammatory mediators

Secretions are mediated by the ENS and can be blocked by blocking the NTs

Plasticity from Inflammation

Lomax et al. (2005) Neurogastroenterol Motility

Inflammation has far reaching effect (will affect the secretions of other regions)

Attributed to glial cells and other interneurons

ENS neurons will discharge in a different pattern

Possibly indicative of plastic changes

Main point when there is any inflammatory response in the GI tract, the inflammation itself and agent can have an effect on the ENS

and change the way the normal discharge pattern is set up. This may be indicative of any learning process the ENS is undergoing to

know what substances are bad and how to respond to various inflammatory agent going down the road. So the ENS can result in some

learning/plasticity from inflammation so it can better process it and manage it going forward

Achalasia

Lower esophageal sphincter is contracted due to loss of myenteric neurons

The sphincter remains constantly contracted and you lose control and food backs up

Can be congenital

Dysfunction of inhibitory neurons which release vasoactive intestinal peptide (VIP)

Can also be secondary to other neurological disorder (i.e. Parkinson’s)

Hirschsprungs

Absence of both Meissners and Auerbach’s plexuses (entire nervous system is not developed)

All of the neurons remain tonically contracted

1:5000 live births and 4:1 in males

Other diseases can be present

It results in toxic mega-colon because food accumulates and have nowhere to go

Diarrhea

Involves the myenteric plexus

Stimulated by: Toxins (cholera) and chemical irritants (ethanol)

Cholera activates adenylate cyclase which increases cAMP

End result is increased chloride secretion

Water follows

Hypersecretion can be blocked by TTX (found in the puffer fish)

ENS Summary

Is it our second brain because it has organization and integration

It has its own set of sensory, interneurons and motor neurons (self sustaining unit)

How did the ENS come to be?

1. Dissociation theory – maybe a long time ago the ENS was part of the CNS and over time is separated from it (similar to an

evolution theory)

2. Endocytosis theory- the ENS may have been its own organism itself and by one organism ingesting another the 2 organisms

merged and became one

LEARNING AND MEMORY

Higher Order Functions

Phrenology

o Analyzing the skull (contours and depressions) and relating it to brain function (which was completely unrelated)

o This was one of the first concepts of neuroscience

Psychology

Learning and memory

o Short term vs. long term

o Conscious vs. unconscious/subconscious

o Retrieval vs. forgetting

Learning and Memory

Your memory will always be there but your access/retrieval to that memory may be cut off with time

or with age

o Conscious = explicit

o Unconscious = implicit

The ability to turn short term into long term memory is the concept of rehearsal where your mind is a

stage. You rehearse on this stage for a period of time and your memory will commit this rehearsal. If

you don’t rehearse or practice then when you exit the stage the memory will not remember.

This stage theory in a sense kind of means “practice makes perfect”

There are actual electrical and physical plastic changes which you can see when a person is trying to

make a long term memory change

You are also able to commit to memory the ability to search memory store

Traumatic events disrupt the system and people can either block out certain parts of their life or

remember it even more vividly

Forgetting = deletion of a memory or information that was once stored

Retrieval = recalling information. Impaired retrieval occurs when the pathways for recalling

these memories aren’t there

Figure 1. Plot of local maxima within the lateral PFC reported in 33 fMRI studies of LTM formation

Dr. L just wants us to notice the DLPFC associated with working memory establishment

Research:

There is an area of the brain that commits memory to the stage

DLPFC (dorsal lateral pre frontal cortex) is really active when individuals are given a working task so this area is thought to be where

working memory is located

So this working memory is like a stage and is necessary to promote long term memory formation

Any time this area was damaged, long term memories were less likely to be formed

Amnesia

Forgetting

Sometimes this is completely normal and not necessarily pathological (like when you’re a young child and you can’t remember things

from 0-2 years but usually you begin forming memories around 2 years of age)

There are also many pathological cases of amnesia

1. Anterograde amnesia – memories from that day on forward (Groundhog Day)

2. Retrograde amnesia – past memories

Hippocampal Man

Hippocampal Man was a nickname given to a man who had their hippocampus removed in order to cure him from having seizures

The hippocampus was removed and as a result the patient could remember things from the past (retrograde) but could not form new

forward memories (anterograde amnesia)

If you gave HM the same puzzle day after day he would claim that he had never seen the puzzle before however every day he would get

better at the task although he claimed he did not remember it

This could be due to the fact that the hippocampus is responsible for conscious memory however he could have been storing some

memory unconsciously (implicit memory)

Different regions store different memories:

1. Rhinal cortex: object memory

o They could put the rats in milky water so the rats could no longer use spatial cues throughout the room to navigate where

they are going. Therefore they could not complete the maze very well.

2. Hippocampus: spatial memory

o They did an experiment on rats where they put them in a water maze (rats hate water) so they would try to get to the platform

as quick as possible. Once the rat learned the maze they got to the platform very quickly. After having their hippocampus

removed the rat could not find the platform anymore.

3. Amygdala: emotional memory

o He did not discuss any way to test/determine that this area is related to emotions.

The Hippocampus

Located behind the temporal region

Greek for seahorse (because it looks like a seahorse)

Right and left hippocampi are connected by the short hippocampal commissure

Responsible for spatial, conscious and short-term memory

Much larger in rodents than humans

The 4 major parts contain a tri-synaptic circuit because there are 3 synapses within

this circuit (one between each part)

Major Parts of Hippocampus

1. Entorhinal cortex

Input region

Information is carried in via 2 pathways which penetrates a specific part of the detate gyrus:

a. Lateral perforant pathway – carries mainly olfactory info (smells we need to remember)

b. Medial perforant pathway – carries everything else (non- olfactory)

2. Dentate gyrus (DG)

Relay station from enteorhinal cortex to hippocampus proper

It extends dendrites to synapse with the medial and lateral perforant pathways

Extended axons meet with the medial pathway first and then the lateral (which may be why we learn other senses before smell)

Contains round granular cells (type of stem cells) which are constantly being produced and grow in a “stacked” manner

(new cells added to the bottom layer and old cells are on top)

Scientists record activity from the granule cells. They inject the cells with CSF to keep them alive, stimulate them with an

electrode and record how the hippocampus reacts

Projects axons called mossy fibers to the CA regions to synapse with pyramidal cells there

Axons exit the dentate gyrus through the hilus which is the hollow cavity in the concavity of the C to synapse on the dendrites of the

hippocampus proper

3. Hippocampus proper

Processes information

Divided into 4 sections: CA 1, CA2, CA3, CA4

CA1-CA3 are the main regions

Also called choro-amon (devils horn) because the 4 sections are horn shaped

As you go from CA4 to CA1 the cell bodies get bigger

CA4 = smallest cell bodies, largest dendrites

CA1= largest cell bodies, smallest dendrites

All CA regions are connected to one another

Advantages: if part of the horn is damaged the hippocampus can still function

Disadvantage: an abnormal electrical event in one location will affect all other areas due to complex neural interconnectivity between

the 4 sections of the hippocampus proper (making it very susceptible to seizures)

4. Fornix/Subiculum

Output region

Receives everything that has been processed by the CA regions

Projects the information to the contralateral thalamus, hypothalamus and the ipsilateral nucleus of the septum

Entorhinal cortex – on the right side of the hippocampus with the lat/med perforant pathways (LPP/MPP)

Dentate Gyrus – labelled DG

Hippocampus proper- middle diagram with the CA regions

Fornix/Subiculum – on the left side

Flow of information through the hippocampus – far right diagram

Plasticity

The ability of neurons to adapt or change how they are functioning

Neurons change how they behave through adaptation via changes in synaptic efficacy, alterations in gene expression, and changes in

neuronal structure

We can observe plasticity through:

1. Electrophysiology – electrical input/output changes

2. Immunohistochemistry – inject fluorescent marker into the cell and note any changes

3. Genetics – use protein markers

Hippocampus Plasticity

The hippocampus is the center for learning and memory so lesions will cause deficits in this

It is a highly plastic area, especially the DG

Granules cells in the hippocampus are constantly regenerating (slows down as we age)

Theta burst/rhythm is the high frequency wave that the hippocampus gives off while we’re trying to learn/remember something (only

lasts a few seconds)

High frequency burst induced changed in the DG neurons causing them to become potentiated (fire at a higher level for a long

period of time; new baseline) and this was called Long Term Potentiation

Long term potentiation is induced with high frequency stimulation (tetanus)

o Stimulate cell with normal/constant intensity = 5mV

o Stimulate with high/short frequency (pulses of tetanus) = 25mV

LTP - One Side vs. Both Sides

The did an experiment where they induced tetanus with a high stimulus on rats

Rats with LTP on one side = did the task a bit better

Rats with LTP on both side = didn’t do task as well

When both sides of the brain has LTP induced artificially they didn’t learn as well because there was no more potentiation that

could occur (no room to grow since scientists already maxed them out)

So the theta burst must be elicited by the organism itself in order for the organism to learn (potentiation cannot be done for the

organism)

Other regions can exhibit LTP as well (its not exclusive to hippocampus)

Cellular Changes

1. Post-synaptic

NMDA-mediated increase in calcium

NMDA receptor is a Ca2+ channel closely related to LTP

Under normal conditions there is a magnesium in the NMDA channel which blocks Ca2+ from getting in

When tetanus stimulation occurs (when learning) it causes magnesium to remove itself leading to more Ca2+ coming into the

cell (more NTs released and activity)

If a NMDA blocker is applied this effect will not occur and inducing tetanus will do nothing

2. Pre-synaptic

Not know as well as post-synaptic changes

Glutamate release can be increased along with protein synthesis in the dendrites

Stress and LTP

Acute stress causes LTP in many brain regions to be inhibited

When exposed to stress you have a lessened ability to learn (traumatic events lead to aversion to learning)

Amygdala (emotional center of the brain) is inhibited the least which allows us to make an emotional connection to the incident causing

us to remember to avoid it in the future

Chronic stress causes atrophy of apical dendrites so the synapses start to die off causing LTP suppression

48 hours after chronic stress is alleviated there is still enough LTP suppression to continue degeneration

Stress also elevates the sympathetic nervous system NTs (elevation of adrenal steroids) which can suppresses plasticity and decreases

feedback inhibition making the person more prone to seizures

Time of Day Differences

There are natural chemical in the body that act as suppressants for LTP

Adenosine a potent inhibitory neuromodulator and increases your drive to sleep

Adenosine follows a cardiac rhythm (low as 7am levels rise peak at 2pm levels drop increase again up to 10pm-midnight

drop back to original levels at 7am). Adenosine levels are therefore the highest at ~3pm and ~10pm

o As the adenosine levels rise your hippocampus doesn’t work as well since adenosine inhibits LTP in the hippocampus

o Therefore we learn better in the early mornings when adenosine levels are low (7am)

o Some people claim to study better at night, but this is largely attributed to the influence of behavioral and social factors

Effects of adenosine can be blocked by caffeine (or other caffeine analogues like taurine)

Pathology

Alzheimer’s disease has a focal effect on the hippocampus

Alzheimer’s results when nicotinic-cholinergic receptors in the hippocampus start to decline rapidly

Cholinergic drugs (e.g. nicotine) are often used

Nicotine applied to hippocampus in vitro increases glutamate release

Research

LTP in humans- it was found there does not have to be direct stimulation in order to induce LTP response

Visual cortex can be stimulated by flashed of light into the eye and this will induce LTP in the cells

Auditory cortex and spinal neurons can do the same

For some reason some chemotherapy treatments for cancer have shown to increase LTP

LTD/LTP

LTD = neuron firing that is depressed and less excitable

LTP = neurons potentiated and firing at about double the intensity (much more excitable)

Discovery of LTD precipitated by LTP (they are the exact opposite)

o LTP requires short burst of high frequency stimulation

o LTD requires long bursts of low frequency stimulation

LTD may not be just for forgetting (removing memory) and LTP may not be just for remembering

Remember there is a difference between forgetting vs. being unable to recall

o Forgetting – old trace is completely deleted

o Recall inability- the old trace is there but the access pathway isn’t there anymore

Reasons why LTD may occur:

o Clearing out old memory traces

o Returning the potentiated neurons synapses back to normal (so the cell could learn over again)

o Critical/necessary process for allowing the CNS to recycle the learning and memory processes and bring potential back down

so neurons can learn again

LTD requires low frequency stimulation and has a long lasting effect

o LTP = elicited in most brain regions with high frequency bursts

o LTD = only really seen in the hippocampus

So the protocols vary based on the brain region (cerebellum can produce LTP but requires strong stimulation)

o Cerebellum – motor memory

o Hippocampus – clearing memory traces

Post-Synaptic Changes

One of the common things with LTD was involvement of AMPA receptors

EXAM LTD caused the density of AMPA RECEPTORS to DECREASE

LTD is less clear with clinical evidence linked to forgetting

Diagram

AMPA Receptors regulate the flow of Na+ and K+

LTP have a strong Ca2+ current involved

AMPA receptor are withdrawn from the cell membrane when low frequency stimulation occurs so you have less

afterwards and postsynaptic signals become depressed

Research

LTD may help in maintaining cognitive functions as we age

In older rats there were a varying amount of LTD. The rats that were more capable demonstrated ↑LTD and were better at eliciting it

LTD is reduced in aged rats and also established differently

Basically LTD was greater in smarter rats and lower in dumb rat

Plasticity

An adaptive process where neurons can make changes (ie. tinnitus)

Tinnitus- frequent auditory sensation (ringing) in the absence of external or internal acoustic stimulus. Chronic tinnitus appears to be due

to CNS dysfunction

Does it ever go away? No but tinnitus does seem to fade sometimes (due to plasticity)

Lee et al. (2005) Nature Neuroscience

Experiment they damaged rats auditory system to study tinnitus

Rats had part of their auditory system damaged with slicylate

These rats showed more traces of C-Fos which is a protein/genetic marker associated with detecting plastic changes occurring

o C-Fos = plastic changes are taking place

They looked at electromagnetic changes in brainwaves of people who developed tinnitus (transcranial magnetic stimulation)

People with tinnitus had brain regions that were very easily excitable (so maybe they have a hyper-excitability of the motor cortex)

This could be due to cross stimulation of auditory cells and possible increased facilitation (cells were more keen to facilitate in

excitation)

Facilitation – only giving 2-3 bursts very quick and you want to see how quick the cell responds transiently (without long term effect)

and how dramatic the jumps are

Different forms

o LTP – put on huge stimulation and remove it

o Facilitation- simulating consecutively so see the increase in jumping increments

CNS

Common thought was that CNS cells do not re-grow once damaged

Turns out that neighboring cells can help out extending processes to try to connect/reconnect cells with damage following a spinal cord

injury

A damaged spinal cord loses a lot of the supraspinal information it was once receiving – no longer has the same information coming

from high order inputs

Automaticity – reflexes within the spinal cord which can be used to enhance biomechanical processes (like walking)

Therapists use these functions to enhance recovery and function

Example of automaticity is the fact that when you walk in circles, the outer leg knows it has to take wide swings and the inner leg

supports the body more

Motor relearning following a spinal cord injury is based on:

o Training

o Pharmacological interventions

o Electrical stimulation

A combination of all the above are the most effective in chiropractic pain management

1. Altering inhibitory mechanisms in the INJURED spinal cord = enhanced motor ability

2. Altering inhibitory mechanisms in the HEALTHY (non-pathological) spinal cord = no effect

Boal and Gillette (2004) JMPT

LTP can be induced in various parts of spinal cord

LTP has been observed when dorsal horn neurons presented with noxious stimulus

One of the reasons SMT could contribute to relieving effect is because it may be contributing o LTP or LTD

o Any sort of pain stimuli could cause dorsal horn neurons to become potentiated

o If pain potentiates these neurons and you adjust the patient, maybe you’re inducing LTD and negating that painful effect

An adjustment was very similar to the time frame when LTP could be induced

Similarities exist between central pain sensitization and LTP

LTP in hippocampus and spinal neurons are very similar

It is also thought that low back pain causes LTP in spinal neurons via stimulation of a-delta pain fibers

Gate Theory of Pain vs. Plasticity

TENS and electro-acupuncture stimulation could close the gait/channel

Hypothesis: If pain produces LTP then pain is alleviated by LTD

Does SMT cause LTD by stimulating a-delta fibers? The time frame for effect and longevity of effect is similar

Relationship between modalities is speculative and needs to be further studied

We have various forms of plasticity in various places which is mainly for learning and memory but possibly for other functions as well

HIGHER ORDER FUNCTIONS

Motivation and Reward

Motivation is the idea that all organisms will gravitate towards a positive or reinforced stimuli

This allows us to associate motivation towards things that are good and a repulsion to things that are not good

The hypothalamus is the main brain region that controls motivation

Pavlovian Conditioning

Ivan Pavlov was a Russian psychologist who did conditioning experiments on dogs with meat as the reward

Whenever the dog was presented with meat it would salivate so he used the amount of salivation as a measure of motivation

Whenever the dog did something positive it was given meat as the reward

They quantified the saliva produced to measure the anticipation of the reward

Classical conditioning: they then rang a bell BEFORE they distributed the reward (meat)

The dog would associate the bell with the anticipation of the reward so it would begin to salivate

Once the meat was removed, the bell alone would cause the anticipation response and the dog would salivate

Therefore, the conditioning phase caused the dog to create an association with the bell and the reward

Substance Abuse

Consumption of addictive drugs causes a release in dopamine (which creates a good feeling)

So people who become addicted to the FEELING then become addicted to the drug (due to association)

Brain-reward circuitry contributes to this primarily through the medial forebrain bundle (hypothalamus)

People who easily become addicted to things (drugs, working out, sex, gambling) typically have less sensitive dopamine receptor or a

lower amount of dopamine receptors present

Romantic Love

Humans have an inherent motivation to find love (we like the feeling of being in love)

Involuntary motions occur and are difficult to control during this time

Initial romantic love is associated with higher dopamine levels (which is why some people jump from relationship to relationship)

Elevated dopamine levels are found mainly in the right ventral tegmentum and the right caudate regions of the brain

Appetite

Appetite is an emotionally motivated behavior

Motivation to eat (or not to eat) can override regulation based on energy needs

Controlled by external cues (juicy, smell, appearance) more than internal cues (nutritional needs, energy requirements)

External cues are controlled primarily by forebrain structures such as the amygdala and hypothalamus (basolateral and basomedial)

Regions of the hypothalamus can become activated upon presentation of food alone

The strength of this motivation depends on value of food (nutritional , perceived, emotional)

Hunger

Hunger is a physiologically motivated response (we are listening to internal cues from the body like stomach rumbling)

This is controlled more by internal cues

Hunger is more controlled by the lateral hypothalamus which responds to levels of leptin

Leptin basically tells your body when you’re full:

o Increased leptin = satiety (full)

o Decreased leptin = hunger

People who are obese tend to have a hypothalamus which is not as sensitive to leptin so they always finds the need to eat

Circadian Rhythm

The concept of the body having a clock which dictates when we sleep and regulates physiologic and metabolic processes

Circadian rhythm naturally falls into a 24 hour rhythm but if we let it free run (by taking away all clocks, taking away access to sunlight

and solely going on internal cues) then we notice we tend to do things by a 24 hour clock but it’s always off by about 15 minutes

Circadian rhythm is controlled by the “master clock” in the hypothalamus called the suprachiasmatic nucleus

This nucleus also synchronizes other things: motor activity, sleep induction, corticosteroid secretion, immunological processes

Various factors can affect this rhythm: shift work, travelling, daylight-savings time

Light-Dark Entrainment

Our body clock is typically entrained by light (sunrise/sunset) and the presentation of food

The retino-hypothalamic pathway is involved in this entrainment

Doses of light can advance our entrainment: so having no exposure to light will ensure we get a good night’s sleep and further entrain

our circadian rhythm

Bright light suppresses melatonin secretion (melatonin deficiency has been linked to increased cancer incidence)

If you do have light on in the evening make sure it is very low intensity

Study on the Blind:

They did studies on the blind in relation to circadian rhythm

They found although the blind cannot see light the retino-hypothalamic pathway still picks it up and sends signals telling us that there is

light present

It is important that the blind also implement a light-dark cycle to entrain circadian rhythm

Food Entrainment

Altering the delivery of food will allow you to adapt you circadian rhythm to other time zones

Food availability is primarily mediated by the dorsal medial hypothalamus which projects to other brain regions

This entrainment also roughly follows a 24-hour clock

ATP and Entrainment

This is one of the newer concepts

Increased adenosine levels (through breakdown of ATP) will cause greater entrainment in a circadian rhythm

Increased adenosine levels will cause you to want to sleep

o Adjusting your clock FORWARD = easier

o Adjusting your clock BACKWARDS = harder

It is easier to move forward is because it is always easier to accelerate chemicals in the body (adenosine) rather than suppress them

Sleep

You can train your body to deal without sleep however your body keeps a tally/running total of your sleep so if you deprive yourself then

it will try to make up for it later

Sleep deprivation will cause a sleep debt to accumulate

So sleep is not an evolutionary relic, it is something we still need and cannot do without

Sleep is a restorative process, it allows us to regenerate energy and replenish chemical/clean metabolites

Non-REM Sleep

Also called slow wave sleep (SWS)

Non-REM sleep causes low-frequency brain waves (hence slow wave sleep)

SWS increases after sleep deprivation and decreases with sleep

SWS is a marker for restorative and homeostatically regulated sleep processes

Stages of Non-REM sleep:

1. SWS 1 – high frequency / low amplitude / easier to wake up

2. SWS 2 ↓

3. SWS 3 ↓

4. SWS 4- low frequency / high amplitude / hard to wake up

Each progressive stage corresponds to a deeper sleep and can occur within 30-45 minutes of each other

Stages are later retraced in reverse order (ie. progress from stage 1 234321)

In these stages of sleep the muscles relaxed BUT somatic activity is not absent (therefore you can still move)

Parasympathetic activity predominates: ↓ HR and BP, ↑ GI motility

Threshold for arousal in SWS varies inversely with EEG frequency (so as the ECG activity increases then I is harder to wake someone)

REM Sleep

Also referred to as active sleep

Onset is usually within 90 minutes

EEG is haphazard in REM sleep (low voltage, fast activity which is similar to when we are awake)

Hippocampal EEG highly is very synchronized during REM sleep (maybe because memories are being converted from short term to

long term during this time)

Loss of muscle tone occurs because the muscles are atonic during this time (with the exception of the male penis)

Prolonged periods of awakeness can cause accumulation of heat shock proteins and if we don’t sleep then the body never has a chance to

cool down so we develop an inability to regulate body temperature

During REM sleep our stimulation threshold is increase so it is extremely difficult to wake someone

Severe pupillary contraction occurs as well

REM is the deepest stage of sleep however you are more likely to awake spontaneously during this time and recall dreaming

You are constant switching (4-6 times) back and forth during the night between REM and Non-REM

As the night goes on the following occurs:

1. Successive REM intervals decrease

2. Length of REM episode increases

So the longer you sleep, the more REM sleep intervals you accumulate and the longer the REM intervals become

REM occupies 25% of sleep

REM Deprivation Experiment

Rats were placed on a platform (half filled with water and the other half which they could stand on)

After a few hours of standing on this platform they get tired and fall asleep

When they were in non-REM sleep they could maintain an upright posture but when they dipped into REM sleep they slipped into the

water (which they hate)

The rats would have a REM deprivation

When the rats were then allowed to sleep freely they developed REM rebound which had the following characteristics:

1. Earlier initiation of REM stage (they fall into REM sleep almost right away)

2. Marked lengthening (REM sleep lasts much longer)

3. Increased frequency of REM periods (more REM periods throughout the night)

The longer the REM deprivation = longer the REM rebound

When this happens we wake up without feeling refreshed

This experiment shows us that we have a physiological necessity for REM sleep

Locus Ceruleus Experiment

Paralysis during REM sleep is controlled by the locus ceruleus within the pons

They looked at cats in REM sleep who had a lesion in their pons and found that the cats moved in their sleep

This also revealed species typical patterns (chasing motions in cats, sport specific motions in athletes etc.)

This shows us that we have an internal programming of behaviors

Adenosine

Sleep induction is caused by accumulation of adenosine (which accumulates during the day as we break down ATP)

Increased adenosine = increased propensity to sleep by acting on/inhibiting our arousal centers

Caffeine is a potent blocker of adenosine

This suggests that we can advance body’s desire to sleep with exercise (physical activity will give us a better night’s sleep)

Sleep Regulation

Sleep quantity/quality is primarily monitored by the locus ceruleus which compares sleep motivation and sleep quantity (do I want to

sleep vs. do I need to sleep)

REM sleep is necessary in development so it is much higher in infants and declines during early development

o Age 2- declines 30-35%

o Age 10- stabilizes at 25%

o Age 10+ -little change until 70-80

REM sleep levels off during middle years and declines more with old age

Dementia patients show greater decline of sleep time

The need for REM sleep begins in utero as we can see with the sleep patterns of premature infants

o Infants 10 weeks premature = 80% of time is spent sleeping

o Infants 2-4 weeks premature = 60-65% of time spent sleeping

o Full term infant= 50% of their sleep is REM

Need for REM sleep roughly parallels cerebral myelinization

Does REM sleep play a role in the development of the nervous system and muscles?

Is REM sleep a potent source of internal stimulation proper maturation of brain?

REM sleep uses more oxygen than intense physical exercise

REM sleep is increased during learning sessions

REM sleep deprivation affects learning and memory

REM sleep deprivation also affects LTP

Research They preformed a sterotaxic experiment where they induced a 5-day REM deprivation and after the 2nd day LTP was non- existent. This shows that LTP is inhibited with REM sleep deprivation

Longer the deprivation = longer the LTP inhibition

Deprivation also affects the immune system

Sleep Inertia

Sleep inertia is a physiological state characterised by a decline in motor dexterity and a subjective feeling of grogginess[1] immediately following an abrupt awakening.

The impaired alertness may interfere with the ability to perform mental or physical tasks.

Sleep inertia can also refer to the tendency of a person to want to return to sleeping.

Impaired cognition

Grogginess

Disorientation

Research Cognition is impaired up to 35% upon first waking, 15% impairment between first half hour to full hour, Sleep inertia is also

proportional to depth of prior sleep

Deeper the sleep, the more likely you will have greater cognitive impairments

Startle Response

The startle response is the response of mind and body to a sudden unexpected stimulus, such as a flash of light, a loud noise (acoustic

startle reflex), or a quick movement near the face.

In human beings, the reaction includes physical movement away from the stimulus, a contraction of the muscles of the arms and legs,

and often blinking. It also includes blood pressure, respiration, and breathing changes.

Startle reflex is a motor reflex in infants

Mediated by the midbrain (superior colliculus) which is the major sensory-motor hub

Lesions to the midbrain can result in abnormal reflexes (ie. hyper or hyporeflexia)

Cognition

Cognition is a mixture of perception, reason, intuition and judgment

The higher the species the more complicated our ability is for cognitive function

Cortical regions exists to assist in various levels of cognition

Greater complexity of cortex = higher cognitive ability

Noam Chomsky is thought to be the father of cognition

He believed that cognition was hard wired/built-in (e.g., all kids start to talk at about the same age regardless of culture; “our thoughts

are confined to what we are capable of”)

Cognition is localized to the cortex (the cortex is important for the maintenance of cognition)

Research Growth Hormone Releasing Hormone is known to facilitate cortical development. The subjects were senior citizens (gave

them GHRH and over 6 months they had improved cognition vs. control group)

Research 2 There is an inverse relationship in early childhood (smarter you are the smaller the cortex) and in late childhood and

beyond the size and intelligence are proportional

o Early childhood = inverse relationship with size of cortex and intelligence

o Later development = proportional relationship

Therefore, cognition is endocrine dependent and is dependent on dynamic processes

Cerebral Cortex

1. Frontal Cortex

Almost 20% of the neo-cortex (aka motor cortex)

Motor functions

Many cognitive functions controlled by frontal lobe primarily by pre-frontal cortex

Primary motor cortex is arranged in a somatotopic organization

Frontal Lobe compromise produces:

Working memory issues

Movement programming issues (organization/sequencing of events or movements)

Divergent thinking issues, Task management problems

Increased risk taking and rule breaking (impaired social behaviour; don’t follow social norms)

Impaired sexual behavior, Response inhibition (moving on), Delayed spatial responses

2. Parietal Cortex

Damage causes impairment of higher order senses:

Cannot learn tasks that required perception of body in space (have trouble with sidedness L vs. R)

Deficits in body image, Unable to number fingers, Unable to recognize fingers as their own, Naming fingers on hand

Confusing left to right side, Inability to write, Inability to do math

Gerstmann syndrome is characterized by four primary symptoms:

1. Dysgraphia/agraphia: deficiency in the ability to write

2. Dyscalculia/acalculia: difficulty in learning or comprehending mathematics

3. Finger agnosia: inability to distinguish the fingers on the hand

4. Left-right disorientation

Testing Parietal Cortex Function:

Astereognosis- the inability to identify an object by touch without visual input.

Graphesthesia - the ability to recognize writing on the skin purely by the sensation of touch.

Two point discrimination- ability to tell 2 areas apart on the body

Challenge their ability to know their body (i.e. left hand to right foot)

The parietal lobe is mostly sensory but not exclusively

Left parietal lobe = arithmetic

Right parietal lobe = drawing/art

3. Temporal Cortex

Not unitary in function (not just auditory sense)

Also has secondary visual and auditory input

This lobe is heavily connected to limbic system

Amygdala – adds affective/emotional tone to sensory input and memories

In the brain, the perforant pathway provides a connectional route from the entorhinal cortex to all fields of the hippocampal

formation, including the dentate gyrus, all CA fields (including CA1), and the subiculum

The temporal cortex has many has many internal connections, afferent projections from sensory systems and efferent

projections to frontal and parietal association regions

Compromise depends on which side is damaged:

Left damage – language deficit of some kind

Right damage – non-verbal memory deficit (ie. facial recollection, interpretation of facial expressions and higher

order visual processing)

Auditory perception damage can cause a disturbance of selective attention (ie. inability to focus on a sound, personality

problems and too much attention to trivial and petty details)

The temporal lobe surface area is significant and very minor effects can occur when one side has a lesion

If both sides have a lesion, the effects are greater than the sum of the individual corticies (the temporal lobe tends to have a

“take over” ability if one side gets damaged)

4. Occipital Cortex

Visual cortex

Can be divided into discrete regions:

Primary region – sorting of mail (sensory information converges on the primary region first and then goes to secondary areas

that are relatively more specialized)

Other regions will receive information that they are specialized to process

Visual agnosia- the inability of the brain to make sense of normal visual stimulus. Inability to recognize familiar objects or

faces (not the same as blindness)

Stimulantagnosia - inability to perceive more than a single object at a time. Occurs following gross bilateral damage to lateral

regions of occipital lobe (carbon monoxide poisoning)

Associative agnosia - patients can describe visual scenes and classes of objects but still fail to recognize them (ie. they may

know that a fork is something you eat with but may mistake it for a spoon). Patients are still able to reproduce an image

through copying.

Prospagnosia- patients cannot consciously recognize familiar faces, sometimes even including their own. This is often

misperceived as an inability to remember names (AKA face blindness and facial agnosia). Will be able to recognize people

based on facial information (moustache, mole) but unable to recognize human from non-human faces (usually if the person has

bilateral damage)

Alexia/dyslexia - inability to read, damage to left fusiform and lingual regions

Visual spatial agnosia- -inability to navigate around familiar settings

Language

We define language as sound that has meaning based on order

Factors influencing your ability to learn a language are exposure and age

Exposure in the womb determines what languages you will be able to learn more easily

Age at which you are exposed to a language is also important (the younger you are when exposed to a

language, the easier it is to learn it)

Language is localized to two discrete areas both of which are on the LEFT hemisphere:

o Broca’s = SPOKEN words (frontal cortex)

o Wernicke’s = HEARING/INTERPRETING words (temporal cortex)

Language areas appear to be larger in male however, women have superior verbal skills

Size may be inversely related to ability

o Larger size = lesser verbal skills

o Smaller size = better verbal skills

Multi-linguals (well-known languages may have more condensed language centers and there may be more brain areas recruited if speaking a less familiar language)

Right Hemisphere and Language

The right hemisphere contributes very little to language?

It is capable of some comprehension of auditory material and can compensate for left hemisphere damage but not make up for it.

Aphasia

Aphasia is a disorder that results from damage to portions of the brain that are responsible for language

1. Wernicke’s Aphasia

Able to hear or see but unable to understand

People with this may speak in long sentences that have no meaning, add unnecessary words, and even create new words called

neologisms

Speech is fluent but not comprehensible

When spoken to, they will not able to understand, and will not be able to repeat

2. Broca’s Aphasia

Able to understand but have difficulty expressing themselves (especially verbally)

Writing difficult but maintained

Speech is non-fluent

Individuals with Broca's aphasia frequently speak short, meaningful phrases that are produced with great effort.

Also called nonfluent aphasia- affected people often omit small words such as "is", "and", and "the".

3. Anomic Aphasia

A difficulty with naming (can describe, but cannot name)

The patient may have difficulties naming certain words, linked by their grammatical type (e.g. difficulty naming verbs and not

nouns) or by their semantic category (e.g. difficulty naming words relating to photography but nothing else) or a more general

naming difficulty.

Patients tend to produce grammatic, yet empty, speech.

Auditory comprehension tends to be preserved.

Problem is localized to temporal cortex

Will use action words – frontal cortex

Transcortical: loss of cortex outside of traditional areas, able to repeat and understand and unable to speak spontaneously

Dyslexia

Inability to read

Reading is a task which requires sight and sound (even if you are not reading out loud, you are “saying” them in your head and so this

requires sound)

Various different types

1. Attentional Dyslexia

Able to name single letters

With other letters there, naming is difficult if not impossible

2. Neglect Dyslexia

Patients misread one half of the word

Weather is read as smoother

Strong is read as stroke

3. Deep Dyslexia

Patients read semantically related words in place of word

Merry is read as Christmas

4. Surface Dyslexia

Cannot recognize words directly

But will be able to understand them using letter to sound relations

Words are only understood if sounded out

Kuh! Sie Kuh! Sie Kahn der….Wer Du Ja Wanduhr?

A surface dyslexic could read this (they sound it out phonetically). Goosey, goosey gander. Where do you wander?

Language Disorders

Wernicke’s area - language processing and logic area in the left temporal lobe (dominant area)

o Wernicke’s aphasia: inability to understand language in a meaningful way (but their speech is still intact)

o Non-dominant side lesion- inability to perceive pitch, rhythm, emotion/tone of speech

Broca’s Area- allows us to express using our motor skills, frontal lobe close to primary motor cortex

o Broca’s aphasia- understanding is intact but they don’t make any sense when they speak o Broca’s aphasia is often an expressing problem: verbally and written (affected less, but still significant), speech is labored and

they can’t really express what they want to say

o Non-dominant side processes the emotional/tone in speech

What happens with complete loss of both language centers on dominant side?

Some take-over effect occurs depending on how old/how much plasticity is remaining in the brain

Right brain = controls emotions so you may have some cursive words intact(as they relate to emotion)

Disorders of Sleep

1. Initiating issues (can’t fall asleep)

2. Excessive sleep

3. Rhythm disruptions (1, 2, 3, 4, REM) 4. Parasomnias activity during sleep (not typically associated with normal sleep like sleep walking and bed wetting)

Insomnia

Insomnia: chronic inability to obtain the amount of quantity of sleep necessary to maintain adequate daytime behavior

o Normal range 4-10 hours

o Young adults 7-8 hours

Characterized by spending less time in stages 1-2 SWS/non-REM

Subjective reports alone are non-diagnostic - out of every 8 people who think they have it, only 1/8 does

Associated with an emotional disturbance: anxiety, depression

Kept awake by a physiological event: nocturnal myoclonus (jerks/moves limbs during sleep) or restless legs syndrome

Poor sleep continuity: irregular movement through sleep stages or disproportionate times in each stage

Maintain higher core temperatures- possible increased autonomic arousal maybe associated with lack of decline of body temp (recall

body temp assumes room temp during REM sleep)

Parasomnias

Include a broad set of undesired behaviors like nightmares, sleepwalking, bed-wetting and nocturnal enuresis

Incidence higher in psychologically disturbed

Nocturnal Enuresis

Nocturnal Enuresis is bedwetting at night and can be caused by dreams, slow urinary tract maturation or psychological disturbance

This occurs in stage 4 sleep usually preceded by agitated sleep

A common pattern seen = moving more before they wet the bed; then, they urinate in bed; then, they don’t move as much (tranquility)

It is very difficult to wake up the sleeper during the tranquility stage.

Chiropractic and enuresis- the literature is sparse, there are many case reports but acupuncture may help

Finding local restrictions but there is no unified location for adjustment

Narcolepsy

Irresistible sleep attacks lasting 5-30 minutes

Overwhelming feeling of drowsiness preceding the attack and nap is very refreshing (15 minutes)

Excessive daytime sleepiness is not the same thing

The disorder is characterized by cataplexy (sudden atonia in muscles, loss of muscle tone) in the jaw, head, arms drops, knees buckle

Triggered by an emotion- laughter / anger / sexual excitement or sedentary acts (driving)

Sleep paralysis can also occur- reversible episode of muscle inhibition while person is lying in bed (awake) and is conscious but unable

to move or speak (like being paralyzed while lying in bed awake)

Enters REM sleep directly (within 10 minutes) but have less time in REM and poor transition to different stages

REM is fragmented and sleep attacks may be way of restoring REM sleep

Can sleep on demand (within 2 minutes) with quick initiation

Strong genetic component and environmental factors unknown

Alzheimer’s Disease

Characterized by behavioral impairments: Communicating, Learning, Thinking, Reasoning

Warning signs are fairly self explanatory: problems with memory, tasks, language, judgment, personality etc.

As we age, Tau proteins accumulate in the brain which is normal

In Alzheimer’s, the accumulation of Tau proteins is excessive, resulting in pathology of the microtubules and neurons in the brain

causing them to become tangled.

There is neuron cell death as the cytoskeleton of the brain becomes tangled and transport in the brain is impaired.

As a result, the ventricles in the brain become enlarged and the brain shrinks.

To summarize: Tau proteins accumulate microtubules (cytoskeleton) becomes tangled decreased transport between neurons

neuronal cell death brain shrinks and ventricles enlarge

Due to the natural process of aging, beta-amyloid plaques usually accumulate in the brain (they come from myelin).

In an Alzheimer’s patient, these plaques accumulate faster. Thus, the rapid accumulation of plaques prevents synapses from being

formed and compromise communication between different areas of the brain. The plaques may also lyse and thus contribute to

inflammation

The cortex shrivels and thinking, planning and memory storage is affected

The hippocampus shrinks the MOST

Ability to form new memories is impaired and the ventricles expand

Plaques spread in cortex predictably - language compromised first and then perception of self is compromised

Onset is middle to late adulthood (1 in 10 people over 65) and it affects one person every 72 seconds

The HALLMARK of Alzheimer’s is the presence of senile plaques (extracellular beta-amyloid protein plaques) which accumulate in the

brain and the cerebral blood vessels as well

The gene coding for this protein is on chromosome 21

The bad kind of amyloid forms fibrils which become resistant to degeneration (so they build up) and they can form neurotoxic properties

Microtubule tangling occurs in large neurons (hippocampus, olfactory cortex, amygdale, brain stem nuclei) and can also occur in other

disorders (Down’s Syndrome, Dementia)

The difference is that in Alzheimer’s the patient have BOTH tangles and plaques present

Therefore, you can only really diagnose Alzheimer’s with an autopsy so you can see the tangles and plaques (clinical diagnosis is just

based on symptoms)

More women have dementia than men and Alzheimer’s is the most common form of dementia (65% of all dementias)

Over 52% of Canadians know someone with Alzheimer’s and 25% have someone in their family with it