Neuro Final

Motor components of the human basal ganglia (A) Basic circuits of the basal ganglia pathway: (+) and (-) denote excitory and inhibitory connections.

(+) excitatory glutamatergic synapses (-) inhibitory GABAergic projections GABA and Glutamate are the major neurotransmitters in the brain Glutamate- excitatory GABA- inhibitory

Effect of stimulation rate on muscle tension

(A) At low frequencies of stimulation (red arrows), each action potential in the motor neuron results in a single twitch of the related muscle fibers. (B) At higher frequencies, the twitches sum to produce a force greater than that produced by single twitches. (C) At a still higher frequency of stimulation, the force produced is greater, but individual twitches are still apparent. This response is referred to as unfused tetanus. (D) At the highest rates of motor neuron activation, individual twitches are no longer apparent—a condition called fused tetanus.

Structures involved in the basal ganglia pathway

(B) Idealized coronal section through the brain showing anatomical locations of structures involved in the basal ganglia pathway. Most of these structures are in the telencephalon, although the substantia nigra is in the midbrain and the thalamic and subthalamic nuclei are in the diencephalon. The ventral anterior and ventral lateral thalamic nuclei (VA/VL complex) are the targets of the basal ganglia, relaying the modulatory effects of the basal ganglia to upper motor neurons in the cortex. Subthalamic nuclei are in the diencephalon and substantia nigra at the midbrain level

Muscle spindles and Golgi tendon organs The two types of muscle receptors, the muscle spindles (1) and the Golgi tendon organs (2), have different responses to: (A) passive muscle stretch (muscle lengthen) ◦ Spinal spindle respond more ◦ Golgi tendon organ

(B) active muscle contraction (tension ↑)(muscle shorten) ◦ Spinal spindle ◦ Golgi tendon organ respond more, leading to an increase in the firing rate of Ib fibers

Sensitization - allodynia

(Pain due to a stimulus which does not normally provoke pain, such as pain caused by light touch to the skin) The induction of pain by what is normally an innocuous stimulus is referred to as allodynia (Pain that results from a non-injurious stimulus to the skin, (állos) meaning "other" and οδύνη (odýni) meaning "pain"). - pain evoked by a normally INNOCUOUS stimulus Mechanisms ◦ Activation of voltage dependent L-type calcium channels ◦ The removal of Mg block of NMDA receptors ◦ à Increase the sensitivity of the dorsal horn neuron to glutamate, the transmitter in nociceptive afferents. ◦ Microglia release cytokines à promote transcription of COX-2 à production of prostaglandins in dorsal horn neurons à increase neuronal excitability ◦ Sustained depolarization of the dorsal horn neurons ◦ WindUp (a progressive increases in the discharge rate of dorsal horn neurons) An injury site where a person may feel pain by a stimulus that doesn't normally invoke pain (ex. Domestic violence) - ex. Like pain experienced from light touch to the skin

Spinocerebellar pathway which carries proprioceptive information from the body Occupies the peripheral of the lateral and carries proprioceptive and cutaneous information from GTO and muscle spindles to the cerebellum for coordination of movement So you can see it's the muscle spindle, and still goes through DRG, dorsal horn of SC, means there are also some branches to other parts of SC, but primary info continues to go up, synapses and continue to go up and to the cerebellum Believe there is 4 individual pathways of the Spinocerebellar tract Posterior spinocerebellar tract - Carries proprioceptive information from the lower limbs Anterior spinocerebellar tract - Carries proprioceptive information from the lower limbs Cuneocerebellar tract - Carries proprioceptive information from the upper limbs Rostral spinocerebellar tract - Carries proprioceptive information from the upper limbs

****Important message from this slide is that prioprioception of body reaches to not the other side of the brain, but the ipsilateral cerebellum In contrast, touch and pressure sensation cross over at the medulla and to the other side of the brain So clinically, if one has a stroke in the right hemisphere, then have impaired sensation of the left side of the body but if have a R side stroke in the cerebellum, they will have the same side of body that will have impaired proprioceptive sensation

The Major Afferent Pathway for Mechanosensory Information 1. The Dorsal Column-Medial Lemniscus Track: Sensory of the body 2. The Trigeminothalamic Tract: Sensory of the face 3. The Dorsal Spinocerebellar Tract: Proprioceptive information from the body 4. The Somatic Sensory Components of the Thalamus 5. The Somatic Sensory Cortex 6. Higher-Order Cortical Representations

***This slide summarizes almost everything The Dorsal Column-Medial Lemniscus Track carries sensory info of the body (means it will travel to the dorsal column from the spinal cord and when it reaches the brainstem, it will travel through the structure called the medial lemniscus and go up) The Trigeminothalamic Tract carries sensory of the face (here trigeminal means origin trigeminal cranial nerve and the thalamic means it reaches to the thalamus) The Dorsal Spinocerebellar Tract carries Proprioceptive information from the body (so spino- means spinal cord, cerebellar means cerebellum) ***ALL sensory info will travel to the THALAMUS Then will arrive at the somatic sensory cortex Higher-Order Cortical Representations (Your brain will integrate information from your sensation and then the special relationships, objects, environment and has a higher order cortical representation to integrate and process info and will later form a response)

(A) The dorsal column-medial lemniscus pathway carries mechanosensory information from the posterior third of the head and the rest of the body. (B) The trigeminal portion of the mechanosensory system carries similar information from the face

***Very important to understand sensory pathways Summarizes sensory info from the body and from the face - Picture on the left is from the body - The dorsal column-medial lemniscus pathway - The figure on the right carries info from the face and is the trigeminal thalamic pathway - The dorsal column-medial lemniscus pathway - the first order neuron carries sensory info regarding, touch, proprioception, or vibration from the peripheral nerve to the medulla oblongata - Signals from the lower limb below T6 travel passing through dorsal root ganglia going into dorsal horn of spinal cord, then travels to dorsal side of spinal cord, specifically the fasciculus gracilis, medial part of dorsal column and continues to travel upwards - Sensory from T6 and above from skin goes through dorsal root ganglia, goes through dorsal horn of spinal cord and then goes to back of spinal cord and specifically will be fasciculus cuneatus, the lateral part of dorsal column and continue to travel upwards - Second order begins in the cuneatus nucleus or gracilis and that will be the dorsal column - The fibers receive info from the preceding neurons and deliver to the third order neurons in the thalamus - Neurons cross over the midline of brain, continue to travel upwards - Within the medulla the fibers decussate, cross to the other side of the CNS and then they travel on the contralateral side to reach the thalamus - Third order neuron transmits the sensory signals from the thalamus to the primary sensory cortex of the brain, posterolateral nucleus of the thalamus the VPL and travels through the internal capsule then terminate at sensory cortex - Trigeminalthalamic pathway - Remember its cranial nerve number 5- the trigeminal nerve responsible for sensation of the face- have 3 branches, V1, V2, and V3 - That is the cell body and this is the trigeminal ganglia - it is the ganglia b/c it is a collection of cell bodies located in the PNS - Sensory neurons carry sensation of the face by the trigeminal cranial nerve - When it travels in, it is already at the mid pons level - The fibers cross to the other side of the CNS RIGHT AWAY and then they travel in the medial lemniscus to reach the thalamus and then to the sensory cortex

Key takeaways from this slide: Proprioceptive nerve fibers muscle spindles and Golgi tendon organ have the largest axon diameter and the fastest conduction velocity of 80-120 m/s

**remember conduction velocity b/c helps you understand why myelination is such an important factor and why MS and Guillen Barre Syndrome are so harmful b/c attack myelination Touch nerve fibers like Meissner and Merkel cells are the next largest axons and have a conduction velocity of approximately 35-75 m/s Pain, temperature- free nerve endings only have a conduction velocity of 5-30 m/s- means that you'll be able to identify the location and be more aware of the sharp painful sensation Pain, temperature, itch; non-discriminative touch- sensations that are more diffuse you cannot identify the exact location of these- these are usually unmyelinated free nerve endings and have the lowest conduction velocity of 0.5-2 m/s

Lesion in the right inferior parietal lobe: Hemispatial neglect Hemispatial neglect

, also called hemiagnosia, hemineglect, unilateral neglect, spatial neglect, a deficit in attention to and awareness of one side of space is observed. Hemispatial neglect results most commonly from strokes and brain unilateral injury to the right parietal lobe, with rates in the critical stage of up to 80% causing visual neglect of the left-hand side of space. Parietal lobe deals with your body's attention to space Patient has simultaneous stimulation and patients only recognize R side of finger and ignore the left side of the finger Use the drawing the clock test - Ask patient to draw a complete circle and number it 1-12 and patients with spatial neglect will draw a complete circle but then numbers 1-12 will be clustered on the right side Star cancellation test Ask patient to draw a flower or other figure and they will draw half of those things

Levels of SCI and dysfunction?

- C1-C3- no function maintained from the neck down; ventilator needed for breathing, electric wheelchair with breath, head or shoulder-controlled device required - C4- C5: diaphragm, which allows breathing - C6-C7: some arm and chest muscles, which allows feeding, some dressing, and manual wheelchair required - T1-T3: intact arm function - T4-T9: control of trunk, above the the umbilicus - T10-L1: most thigh muscles, which allows walking with long leg braces - L1-L2: most leg muscles which allows walking with short leg braces

Most significant component of the basal ganglia= corpus striatum

- Divided into two parts - Dorsal striatum and ventral striatum - Dorsal striatum =associated with motor function- further divided into internal capsule- inside internal capsule is caudate nucleus and putamen - ventral striatum- further divided into nucleus accumbens and olfactory tubercle- associated with cognition, rewards and reinforcement but NOT motor function

Week 0 - 3

- Early embryogeneis- cleavage, blastulation, gastrulation, and neurulation

Somatotopic order in the human primary somatic sensory cortex Cartoon of the homunculus constructed on the basis of such mapping. Note that the amount of somatosensory cortex devoted to the hands and face is much larger than the relative amount of body surface in these regions. A similar disproportion is apparent in the motor cortex, for much the same reasons.

- Homunculus= distorted representation of the human body based on the neurological map areas of the human brain dedicated to processing motor functions or sensory functions for different parts of the body

So the caudate and putamen - The putamen will be the starting point to send the output signals to the other part of the brain

- Let's see how the direct V1 pathway and the indirect V2 pathway works - Direct pathway: - From the putamen - The purple region is the globus pallidus - There are 2 parts: the external segments and the internal segments (globus pallidus internal (GPI) and globus pallidus external (GPE) - It will send information form the putamen to the GPI and then it will go to the VL nucleus in the thalamus and the thalamus will send the information to the motor cortex - ***Final outcome is to see whether the thalamus is excitatory, to send signals to the motor cortex or not - If the thalamus sends more signals to the motor cortex, more movement and activities will occur - If the thalamus turns silent (is inhibited) no signals will be sent to the motor cortex- so movement activities will be decreased - In the indirect pathway, signals from the putamen will go to the globus pallidus external (GPE) first, it is indirect because the signals will travel to OUTSIDE of the basal ganglia to the subthalamic nucleus first - Then the following signals, the green lines will send it back to the globus pallidus internal (GPI) then you will travel the same to the thalamus and then to the motor cortex

Opioid painkillers Another is the synaptic transmission, you need Ca+ to go in so that vesicles filled with

- NT can fuse with the presynaptic membranes and the NT will be released to the synaptic cleft and pass through to initiate another AP of the next neuron - ***SO can REDUCE Ca+ ion entry - OR increase outwards K+ current so that you shorten the repolarization time and duration of AP - So fundamentally want to reduce the number of AP that happen so you can reduce the brain signals to your brain

VERY IMPORTANT SLIDE!!! ***Larger diameter axons have a higher conduction velocity Less resistance facing the ion flow which means they are able to send signals faster Nerve fibers are classified as group A, B, C, nerve fibers

- Nerve fibers of the A group have a LARGER diameter, high conduction velocity and are myelinated - Fibers of group B are myelinated with a small diameter and have a low conduction velocity - Fibers of group C are unmyelinated, with a small diameter, and have a low conduction velocity Lack of myelination in the C group is a primary cause of their slow conduction velocity Group A comprises the largest and the fastest axons - Group A is further broken down into alpha- the fastest, beta, gamma and delta which is the slowest Group C is the smallest and the slowest Some of the non-discriminative touch is free nerve endings, they're unmyelinated and they belong to the class C nerve fibers For proprioceptive information from the muscle spindle and the golgi tendon organ, you will see there is sensory nerve type 1 and type 2 of group A nerve fibers

To make you happy and pain free- OPIOIDS

- Opioids are happy elements - In brain and SC certain chemicals called opioids (enkephalins, endorphins, and dynorphins) - Opioids are LIGANDS which means they are part of protein that will bind to the receptors to produce a morphine-like affect (makes you happy) - ****SO just remember, in order to be happy, you want opioids - You do NOT want anything that has "P" in it, substance P and prostaglandin - To reduce the intensity of pain, first, you don't want the pain signals traveling to the brain - if you can block the pathway, you can reduce the signals to the brain - Second, you could reduce the amount of pain signals if you could not actually block them

4. The Somatic Sensory Components of the Thalamus Each of the several ascending somatic sensory pathways originating in the spinal cord and brainstem converge on the thalamus. Somatosensory information from the body and posterior head à Medial lemniscusà ventral posterior lateral (VPL) nucleus of the thalamus. Mechaosensory from the face à trigeminal lemniscus à ventral posterior medial (VPM) nucleus of the thalamus. Proprioception from the body à ventral posterior lateral (VPL) nucleus of the thalamus. * Proprioception from the body à ipsilateral cerebellum

- Remember, nucleus is a collection of cell bodies within the CNS - Proprioception from body reaches to the SAME side- ipsilateral cerebellum

5. The Somatic Sensory Cortex Ventral posterior complex of the thalamusà cortical neurons (primarily in layer IV of the somatic sensory cortex). Primary somatic sensory cortex ◦ Brodmann's areas 3b and 1: cutaneous stimuli ◦ Brodmann's area 3a: proprioceptors ◦ Brodmann's area 2: both tactile and proprioceptive stimuli. ◦ 3b à a single finger ◦ 1 and 2 à multiple fingers ◦ Particular directions of skin stimulation à 1 ◦ More complex stimulation à 2 ◦ Deficits in 3b àTexture and shape discrimination ◦ Deficits in 1 à texture discrimination ◦ Deficits in 2 à finger coordination, shape and size discrimination

- Sensory info from thalamus will continue to travel to somatic sensory cortex - ***Key point is that your brain is a very organized system - - A variety of info will reach to different parts of sensory cortex for processing and information integration

LMN Syndrome Once you damage lower motor neuron show muscle weakness or paralysis - often receive abnormal info or lack of information from your motor cortex

- Severe atrophy develops b/c LMN will innervate your skeletal muscles and if they are injured, your muscles receive much less signal stimulation so muscle atrophy will develop over time - Patient will have hypoactive superficial and deep reflexes - Muscles will show some spontaneous firing such as fasciculations and fibrillations - And will have some geographic distribution impairment (reflecting distribution of affected spinal segments, cranial nuclei, or spinal/cranial nerves) (ex. If you have a very specific median nerve injury- then your injured regions will be associated with the sensory deficits and the motor innervations for those muscles innervated by the median nerve) - Impairments of reflexive and gross and/or fine voluntary movements

Upper row is the muscle activities when muscle is at rest - So a muscle at rest, you can usually detect a very minimal electric activity

- So a muscle at rest, you can usually detect a very minimal electric activity - So basically you don't contract any muscle - People with LMN lesion- when they insert electrical pole to the muscles, they will detect SPONTANEOUS electrical activity - the fasciculation is muscle twitch- is a small local involuntary muscle contractions and then the fibrillation is a rapid irregular and unsynchronized contraction of the muscle fibers

Ruffini's corpuscles

- Stretching of skin Encapsulated Oriented along stretch lines Aδ Slow adapting Low threshold Locations: all skin, ligaments and tendons Is oriented parallel to the stretch lines in skin Account for 20% of the receptors in the hand

Somatosensory afferents convey information from the skin surface to central circuits

- The information is first detected at a sensory receptor, transmitted by the peripheral nerve, and up to the cerebral cortex

The spinothalamic track is part of the anterolateral system - So may use spinothalamic system and anterolateral system interchangeably

- The painful signals travel through the nerve fibers to the spinal cord - Group A delta nerve fibers- which are responsible for first sharp pain - And C fibers which are responsible for dull, longer-lasting second pain - These have parallel pathways to reach to the dorsal horn of the spinal cord

OT use Modified Ashworth Scale to evaluate the severity of spasticity - Use passive stretch - Stroke patients tend to have hypertonia - Usually exhibit flexor synergy in their upper arm (flexor synergy means that when they can do some movement they will just increase their muscle tone and all move together flexion over multiple joints) - This is the pattern you usually will see in stroke patients is the UMN lesion

- When therapist start to stretch passively fast, suddenly the muscle spindle sense the change of the muscle fibers and send changes to the CNS which will misinterpret the info - This is where the therapist will suddenly see a "catch" and go at a certain degree Patient has hypertonia post stroke - Has very rigid movement - Takes a lot of strength by therapist to passively stretch - Shortening and hardening of muscle tendon - Not much control of fine movement - Will also see clonus - Patient with SCI - Leg bounces uncontrollably - Have to hit bottom of your foot to stop it - Clonus is a series of involuntary rhythmic muscular contractions - Happens when you stretch plantar and dorsiflexion muscles b/c sudden change of muscle length evoke muscle contractions of those muscles - And long-term spasticity

The neurons do not act alone, a complex model is needed so that your brain can regulate the activities of a specific brain region Proper dynamics in a neural network can only be maintained if excitatory forces can counteract the affect of inhibitory forces

- Which means if Neuron A is active, it will suppress the neural activities of neuron B - Neuron C is sending the excitatory information to neuron D, therefore if neuron C is active, then it will facilitate neuron B to be more active

- Example: #4 is lesion in DCML pathway - in the dorsal part of the spinal cord- then this individual will have impaired??

- individual will have impaired touch and proprioception

Example #5 is lesion at corticospinal pathway-then this individual will have impaired??

- then descending motor pathway is impaired

Failure of the caudal end of the neural tube to close by day 27, the baby will be born with spina bifida ---what are the different types of spina bifida??

--Occulta is the most common and mildest form so baby is born with abnormal hair or birth mark on back --Meningocele spina bifida may have few or complete dysfunction with bowel and bladder dysfunction Meningomyelocele - symptoms will be more severe- will have partial or complete paralysis of part of body below the spinal opening - may not be able to walk and have bowel and bladder dysfunction - may also have deformed feet and uneven hips --Myeloschisis- severest form of spina bifida - spinal cord is unfused and remains open - leaving spinal cord exposed- will have motor and sensory deficits- prone to infections and disturbances in bladder and bowel function

Ectoderm The surface ectoderm develops into

--The surface ectoderm develops into: epidermis, hair, nails, lens of the eye, sebaceous glands, cornea, tooth enamel, the epithelium of the mouth and nose. --The neural crest of the ectoderm develops into: peripheral nervous system, adrenal medulla, melanocytes, facial cartilage, dentin of teeth. --The neural tube of the ectoderm develops into: brain, spinal cord, posterior pituitary, motor neurons, retina.

Germ Layer A germ layer is a primary layer of cells that form during embryogenesis.

1. The ectoderm 2. The mesoderm 3. The endoderm Week 3 is frequently referred to as the week of threes as it is the week where the three germ layers are formed

- The primary somatosensory cortex is located right behind the central sulcus Three-Neuron Chain: 1st, 2nd, and 3rd Order Neurons

1st order neuron ◦ Located at the dorsal root ganglion ◦ Function: Conduct impulses from cutaneous receptors and proprioceptors to the brain and spinal cord 2nd order neuron ◦ Located at the dorsal horn/medullary nuclei (spinal cord) ◦ Function: Transmit impulses to the thalamus and cerebellum 3rd order neuron ◦ Located at the thalamus ◦ Function: Conduct impulses to the somatosensory cortex of the cerebellum

Neurulation occurs during the third week of development and continues into the fourth week Video - Primary neurulation develops CNS

3 primary portions of the brain during development Prosencephalon- telencephalon, diencephalon Mesencephalon- midbrain Rhombencephalon- metencephalon, myelencephalon- pons, cerebellum, medulla

Classifying (sensory) axons according to the conduction velocity- A, B, C

A (the largest and fastest axon) ◦ Aα (the fastest) ◦ Aβ ◦ Aδ (the slowest) B C (the smallest and slowest) Muscle afferent axons are usually classified into four additional groups—I (the fastest), II, III, andIV (the slowest)—with subgroups designated by lowercase roman letters

The Motor Unit A single motor neuron and its associated muscle fibers do what?

A single motor neuron and its associated muscle fibers together constitute the smallest unit of force that can be activated to produce movement.

Damage to Descending Motor Pathways: The Upper Motor Neuron Syndrome Damage to the motor cortex or the descending motor axons in the internal capsule causes an immediate flaccidity of the muscles on the contralateral side of the body and face. The initial period of "hypotonia" after upper motor neuron injury is called spinal shock, and reflects the decreased activity of spinal circuits suddenly deprived of input from the motor cortex and brainstem.

After several days, however, the spinal cord circuits regain much of their function for reasons that are not fully understood. The Babinski sign Spasticity A loss of the ability to perform fine movements Patients with UMN lesion may show muscle weakness increased Tendon reflex Spasticity Babinski sign And also impairment of fine voluntary movement

Amyotrophic Lateral Sclerosis (ALS)

Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease and motor neuron disease (MND), is a progressive neurological disease that causes dysfunction of the nerves that control muscle movement. Over time, this leads to muscle weakness, gradually affecting how the body functions. In the late stages of ALS, the condition affects nerves that control breathing and other vital bodily functions, resulting in death. ALS is characterized by stiff muscles, muscle twitching, and gradually worsening weakness due to muscles decreasing in size. This results in difficulty speaking, swallowing, and eventually breathing. ALS is a progressive disease where the motor neurons gradually deteriorate and die Etiology is b/c of motor neuron dying Over time this leads to muscle weakness gradually affecting how the body functions Affects both UMN and LMNs (get UMN primitive reflexes, spasticity) (LMN hypotonia, hyporeflexia, fasciculations) Most people get generalized weakness No sensory symptoms Starts very faint until patient finally comes in No cure for ALS

Transduction of Nociceptive Signals The transduction of nociceptive signals is a complex task Variety of stimuli: mechanical, thermal, and chemical For example, vanilloid receptor (VR-1 or TRPV1) is found in C and Aδ fibers and is activated by moderate heat (45°C—a temperature that is perceived as uncomfortable) as well as by capsaicin (chili peppers).

Another type of receptor (vanilloid-like receptor, VRL-1 or TRPV2) has a higher threshold response to heat (52°C), is not sensitive to capsaicin, and is found in Aδ fibers. - Some receptors can be responsive to multiple types of signals - Ex. Vanilloid receptor is receptive to moderate heat AND capsaicin (chili peppers) - - Not surprising then, that people feel hot and get sweaty after eating chili peppers Since the same receptor is responsive to heat as well as capsaicin, it is not surprising that chili peppers seem "hot."

The number of active motor units and their rate of firing both increase with voluntary force The lowest-threshold motor units generate the least amount of voluntary force and are recruited first.

As the individual generates more and more force, both the number and the rate of firing of active motor units increase.

Spinal Region Syndromes Tethered cord syndrome (not illustrated) ◦ During early development, infrequently, the spinal cord becomes attached to surrounding structures (e.g., scar tissue, a fatty mass).

As the vertebral column elongates, the tethered spinal cord becomes stretched, which damages the spinal cord and/or cauda equine. ◦ Symptoms: ◦ Low back and lower limb pain ◦ Difficulty walking ◦ Excessive lordosis ◦ Scoliosis ◦ Problems with bladder and/or bowel control ◦ Foot deformities ◦ Lower motor neuron signs (weakness, flaccidity) occur if the anterior cauda equine is stretched ◦ Upper motor neuron signs (abnormal reflexes, paresis, and changes in skeletal muscles) occur if the spinal cord is excessively stretched.

Co-activation of the α and γ motor neuron The smaller γ motor neurons control the functional characteristics of the muscle spindles by modulating their level of excitability.

As was described earlier, when the muscle is stretched, the spindle is also stretched and the rate of discharge in the afferent fibers increased. When the muscle shortens, however, the spindle is relieved of tension, or "unloaded," and the sensory axons that innervate the spindle might therefore be expected to fall silent during contraction. However, they remain active. The γ motor neurons terminate on the contractile poles of the intrafusal fibers, and the activation of these neurons causes intrafusal fiber contraction—in this way maintaining the tension on the middle (or equatorial region) of the intrafusal fibers where the sensory axons terminate. Thus, co-activation of the α and γ motor neurons allows spindles to function (i.e., send information centrally) at all muscle lengths during movements and postural adjustments.

Functions at the Level of Spinal Cord At that level, the individual can do...

At that level, the individual can do... Respirator (C2), can chew & swallow (C3) Breathing (C4) Self-care independent (C8-T1) Depression transfers (C8-T1) w/c -> floor & floor -> w/c w/ standby assist (C8- T1) (T2-T6) has some cough ability, walk w assist (T7-T12) abdominal & lower back muscles, improved cough (L1) Hips movements (L2) Hip flexion, straight leg kick (L3) Knee extension, bent knee kick (L4) Ankle dorsiflexion, use of knee flexors and extensors (L5) Use of ankles, long toe extensors (S1) Ankle plantar flexors (S2) Legs, ankle & foot muscles, sit (S3) Bladder (S4) Bowel (S5) Sexual function

Regeneration of a nerve fiber in a peripheral nerve

Axons become fragmented at the site of injury The macrophages- big "eat" Will clean out the dead axon distal to the injury Axons sprouts or filaments grow through a regeneration tube formed by Schwann cells in time, the Schwann cells will form a new myelin sheath So remember myelin is formed by Schwann cells in the PNS and oligodendrocytes in the CNS - Here we are talking about regeneration in the PNS - Nerve regeneration in CNS is a completely different story

Damage and Repair in the PNS Myelinated axons in the peripheral nervous system may be repaired if the cell body remains intact and if Schwann cells remain active. Wallerian degeneration: Degeneration of the distal portion of the axon and myelin sheath.

Axons grow at a rate of about 1 mm/day Axons will continue to grow and find their way into the distal regeneration tubes and grow toward the distally located receptors and effectors

Huntington's Disease

Basal ganglia dysfunction in the suppression of unwanted movement Rare neurodegenerative disorder of the CNS Typically inherited from a person's parents - Caused by an autosomal dominant mutation - so child of a person with Huntington's has a 50% chance of getting the disease

Brief Summary Direct Pathway: Putamen (D1) à Globus pallidus, internal segment (GPi) à ventral anterior and ventral lateral nuclei (VA/VL thalamic nuclear complex)à Frontal cortex (motor area) Indirect Pathway: Putamen (D2) à Globus pallidus, external segment (GPe) à Subthalamic nucleus à Gpi Caudate à Substantia nigra pars reticulate à Superior colliculus (command eye movements)

Because the efferent cells of both the globus pallidus and substantia nigra pars reticulata are GABAergic, the main output of the basal ganglia is inhibitory.

EMG Fasciculations and Fibrillations: The muscle at rest shows spontaneous electrical activity

EMG Fasciculations and Fibrillations: The muscle at rest shows spontaneous electrical activity Fibrillation: rapid twitching of individual muscle fibers with little or no movement of the muscle as a whole Fasciculation: A coarser form of muscular contraction, consisting on involuntary contraction of a group of muscle fibers.

Effects of spinal region dysfunction on pelvic organ function - Bowel Damage to S2-S4, or the afferents or parasympathetic efferents

Bowel control is very similar to urinary control Need parasympathetic nerve to S2 and S4 to be able to be able to have the muscle contraction force in order to have a bowel movement - If S2 and S4 spinal region is damaged, then this reflex of emptying the bowel is lost - There is no contraction force - In contrast, if the lesion is above the S2 S4, means that the reflex arc is intact - So in this scenario when the column is being stretched, and suddenly, the rectal stretch can elicit the reflexive action and therefore accidents happen

Language Areas- Broca's vs. Wernicke's

Broca's area - speech formation, speaking ability: left frontal lobe Wernicke's area - language comprehension: left superior temporal gyrus

One of the most important areas affected by stroke = motor skills Brunnstrom Stages of Stroke Recovery

Brunnstrom Stages of Stroke Recovery - breaks down how motor control can be restored throughout the body after suffering a stroke Stage 1 is the most serious - immediate stage after stroke During motor recovery from stage 4 and above, patients will be able to generate more different kinds of combinations of movement and will break flexor synergies - As you go higher in the stages, the impact of spasticity usually decreases

Intracerebral Hemorrhage

Cause ◦ Intracerebral hemorrhage occurs when a diseased blood vessel within the brain bursts, allowing blood to leak inside the brain. (The name means within the cerebrum or brain). Pathology ◦ The most common cause of intracerebral hemorrhage is high blood pressure (hypertension)

Spinal Cord Circuitry and Locomotion The mammalian cycle of locomotion is organized by central pattern generators in the spinal cord.

Central pattern generators - may have seen a baby appear to take steps when held upright with their feet touching a solid surface reflex is called stepping reflex or walking or dancing reflex This reflex will last about 2 months Theory proposed by scientists that in the SC, there must be a mechanism that causes the baby to have a stepping reflex and start to have a walking pattern even without being taught Cat SC cut but cat still walks on treadmill - So scientists proposed that the SC with a structure called a central pattern generator are the neural circuits that when activated, can produce a rhythmic motor patterns such as walking, swinging in the absence of the sensory or the descending inputs that carry specific timing information

Lesion in the cerebellum: Cerebellar stroke syndrome, ataxia gait

Cerebellar stroke syndrome is a condition in which the circulation to the cerebellum is impaired due to a lesion of the superior cerebellar artery, anterior inferior cerebellar artery or the posterior inferior cerebellar artery Account for only 2-3% of stroke Symptoms: Cardinal signs include vertigo, headache, vomiting, and ataxia Deadly D's Diplopia Dysmetria- undershoot or overshoot of intended position with the hand, arm, leg, or eye Dysarthria- slurred or slow speech Dysphonia- voice involuntarily sounds breathy, raspy, or strained, or is softer in volume or lower in pitch Dysphagia- difficulty in swallowing Some movement that is too big or too small for the distance (undershoot or overshoot) of intended position - ex. Dysmetria overshoot or undershoot in finger to nose movement

The corticospinal and corticobulbar tracts

Corticospinal tract originates in the motor cortex The UMN travels through the posterior limb of the internal corpuscle and enter the cerebral peduncle in brainstem at base of midbrain, then pons, and to medulla About 75 to 90 percent of axons at the medulla cross the midline to enter the lateral column of the spinal cord on the other side So the region of the lateral corticospinal tract is the opposite location And then they travel into the ventral horn The remaining 10% of axons do NOT cross- they form the ventral or also called anterior corticospinal tract and they continue to go downwards and land in anterior region of the SC before they enter into the ventral horn of the SC Axons that land in the medial portion region of your ventral horn will have the axons branches cross over to the other side so they terminate bilaterally Those will be muscle fibers that will go out and innervate muscle fibers of proximal and axial muscles Those that travel with the lateral corticospinal tract will usually go out from here at the lateral region of ventral horn and innervate your distal muscles such as your arm and hand Now the yellow line= the corticobulbar tract- bulbar refers to brainstem nuclei a two neuron tract that unites the cerebral cortex with cranial nerve nuclei in the brainstem that is involved with motor functions The corticobulbar tract originates in the central gyrus, the motor cortex The tract then passes down to internal corpuscle and together with the corticospinal tract The corticobulbar tract continues to descend and gives branches to the motor nuclei such as trigeminal nerves to chewing muscles and facial motor nuclei to facial muscles and vagus and hypoglossal cranial nuclei

Examination of a 3-day-old male infant reveals protrusion of his spinal cord and meninges from a defect in the lower back. Which of the following describes this congenital anomaly? Avulsion of meninges Meningitis Spina bifida occulta Spina bifida with myelomeningocele Spina bifida with meningocele

D. Spina bifida with myelomeningocele

The following organs are derived from mesoderm EXCEPT: skeletal musculature musculature of blood vessels cardiac musculature brain

D. brain

Summarizes the spinal thalamic pathway - compare this to the dorsal-column medial lemniscus (DCML) pathway Differences:

DCML pathway- For touch and proprioceptive senses of the body, the axons and neurons in the DCML pathway once they get in, they travel upwards FIRST They cross the midline at the medulla level and ascend to the thalamus Spinal thalamic (Anterolateral) pathway crossing point for info takes place IMMEDIATELY at the spinal cord level at the time of entry For touch and proprioception of the face, the axons and neurons in the trigeminal thalamic pathway Cross the midline at the midpons and ascend to the thalamus Pain and temperature stimuli from the face the axons and neurons DESCEND first to the medulla, cross the midline to the other side and ascend to the thalamus

Ectoderm

Ectoderm has several subsets of cells Neural tube of ectoderm develops into brain and spinal cord Neural crest cells- neural and glial cells consisting of sensory ganglia and dorsal root ganglia- sympathetic and parasympathetic ganglia and neural plexus within specific tissue and organs

Lower motor neuron syndrome

Damage to lower motor neuron cell bodies or their peripheral axons results in paralysis (loss of movement) or paresis (weakness) of the affected muscles, depending on the extent of the damage. The lower motor neuron syndrome includes a loss of reflexes (areflexia) due to interruption of the efferent (motor) limb of the sensory motor reflex arcs. Damage to lower motor neurons also entails a loss of muscle tone, since tone is in part dependent on the monosynaptic reflex arc that links the muscle spindles to the lower motor neurons. The muscles involved may also exhibit fibrillations and fasciculations (spontaneous contractions), which are spontaneous twitches characteristic of single denervated muscle fibers or motor units, respectively. These phenomena arise from changes in the excitability of denervated muscle fibers in the case of fibrillation, and from abnormal activity of injured α motor neurons in the case of fasciculations.

UMN Syndrome Damage to the UMN will cause the UMN symptoms such as muscle weakness

Damage to the UMN will cause the UMN symptoms such as muscle weakness Mild or no atrophy of muscles develops Patients will have hyperactive deep reflexes after initial period of spinal shock Initial period of spinal shock, then spasticity ensues Babinski's sign and clonus More widespread (nongeographic) distribution of impairment in body regions Impairment of fine voluntary movements, when involved with arm and hand, gross movements like shoulder and trunk remain relatively unimpaired

Spinal Region Syndromes Cauda equine syndrome (Figure (D)) ◦ What have been interrupted and symptoms?

Damage to the lumbar and/or sacral spinal roots ◦ What have been interrupted ◦ Ascending spinothalamic tracts (pain, temperature) ◦ Ascending dorsal column medial lemniscus tract (touch, proprioception) ◦ Descending motor tracts ◦ Lumbar and sacral spinal nerves ◦ Sympathetic and parasympathetic nerves ◦ Symptoms ◦ Paralysis (both sides) of lower limb muscles, bladder, and bowels ◦ Loss of touch and proprioception (both sides) ◦ Analgesia (the inability to feel pain) and loss of discriminative temperature sensation (both sides) ◦ Muscle hypertonia ◦ Note that hyperreflexia do NOT occur because the upper motor neurons are intact

Damage to Descending Motor Pathways: The Upper Motor Neuron Syndrome

Damage to the motor cortex or the descending motor axons in the internal capsule causes an immediate flaccidity of the muscles on the contralateral side of the body and face.

Fig. 3 Opioids have been proposed to inhibit neurotransmitter release by inhibiting calcium entry, by enhancing outward movement of potassium ions, or by inhibiting adenylate cyclase (AC), the enzyme which converts adenosine triphosphate (ATP) to cyclic adenosine monophosphate (cAMP).

Decreased Ca++ entry Voltage-sensitive channels are activated only when there is depolarisation of the neuron. Opioids inhibit N-type Ca++ channels and thus inhibit neurotransmitter release. Increased outward movement of K+ Opioids open voltage-sensitive K+ channels and thus increase outward movement of K+ from neurons. Increased outward movement of K+ is the most likely mechanism for the postsynaptic hyperpolarisation and inhibition of neurons induced by opioids throughout the nervous system.

3 main layers of the skin Epidermis, dermis, and hypodermis Cells in epidermis are constantly renewing themselves- constant shedding

Dermis does not go through this cellular turnover and DO NOT replace themselves Most nerves and sensory receptors such as the Meissner corpuscle, Ruffini and Pacinian are found in the DERMIS layer Don't want these to be damaged easily or renewed so often

Descending projections from the brainstem to the spinal cord: The indirect motor pathways

Direct motor pathway = Pyramidal tract = Corticospinal tract + corticobulbar tract The brainstem motor centers give rise to the indirect motor pathways, also known as extrapyramidal pathways, which include all somatic motor tracts other than the corticospinal and corticobulbar tracts. Image in textbook to show different tracts that help with motor control beyond corticospinal and corticobulbar Colliculospinal tract- Movement of head and eyes Rubrospinal tract- movement of arms Reticulospinal tract- muscle tone and body position Vestibulospinal tract- body position

Spinal cord injuries involve the S2-S4 level: bladder, bowel, and sex functions

Disruption of ANS following SC injury is common and can negatively affect quality of life ANS divided into parasympathetic and sympathetic nervous systems -sympathetic division emerges from SC from the thoracic and lumbar areas and terminate around L2 - Parasympathetic division has a cranial sacral outflow- means neurons begin at cranial nerves 3, 7, 10, and 9 - And from S2 and S4 will have parasympathetic nerves coming out - It will go to innervate the bladder and bowel and sex organs

Peripheral nerve injury Single neuron- dendrite, soma, axons, axon terminal, myelin sheath along axons But we have not talked about 3 layers of connective tissues around the nerve --what are they?

Endoneurium Perineurium Epineurium Within each nerve the axon is surrounded by a layer of connective tissue called endoneurium The axons are then bundled together into groups called the fascicles- each fascicle is wrapped in a layer of connective tissue called the perineurium Finally, the entire nerve is wrapped in a layer of connective tissue called the epineurium

Basal Ganglia: Role in Eye Movements A major function of the basal ganglia is the control of body movements. This is illustrated by avariety of movement disorders caused by dysfunction of the basal ganglia, such as Parkinson'sdisease and Huntington's disease. Symptoms include the inability to initiate a movement andthe inability to suppress involuntary movements

Eye movement is not an exception. A fixed, vacant facial expression of patients with Parkinson's disease, which is often called the "Parkinson's mask," is due to the paucity of movements in the face, including the paucity of eye movements. Most affected among various kinds of eye movements are smooth pursuit and saccade, which require more voluntary control. Parkinsonian patients are often impaired in smoothly pursuing a moving object (deficit in smooth pursuit). They are also often impaired in shifting their gaze from one position in space to another (deficit in saccade).

Force and fatigability of the three different types of motor units: Slow (S) Fast fatigue-resistant (FR) Fast fatigable (FF)

Fast fatigable generates more force than the fast fatigue resistant and slow motor unit Slow oxidative muscle fibers in the second picture can generate small forces for a longer duration of time Whereas fast fatigable and fast fatigue resistant will fatigue in the short term

Feedforward and feedback mechanisms of postural control

Feedforward postural responses are "preprogrammed" and typically precede the onset of limb movement. Feedback responses are initiated by sensory inputs that detect postural instability.

Primary afferents in the dorsal root ganglia send their axons via the dorsal roots to terminate in the dorsal horn of the spinal cord.

Figure 10.3 The anterolateral system. (A) Afferents branch and course for several segments up and down the spinal cord in Lissauer's tract, giving rise to collateral branches that terminate in the dorsal horn. Second-order neurons in the dorsal horn send their axons (black) across the midline to ascend to higher levels in the anterolateral column of the spinal cord. (B) C-fiber afferents terminate in Rexed's laminae I and II of the dorsal horn, while Aδ fibers terminate in laminae I and V. The axons of second-order neurons in laminae I and V cross the midline and ascend to higher centers.

Pain Pathway (pain from the body) - first, second, and third order neurons

First-order neuron ◦ Dorsal root ganglia ◦ Dorsolateral tract of Lissauer ◦ Cross the midline (spinal cord) Second-order neuron ◦ Spinothalamic tract (anterolateral system) ◦ Brainstem Third-order neuron ◦ Thalamus (VPL)

The anterolateral (spinothalamic) pathway (pain from the face)

First-order neuron ◦ Ganglia associated with nerves VII, IX, and X ◦ Brainstem ◦ Descend to the medulla, forming spinal trigeminal tract (or spinal tract of cranial nerve V) ◦ Terminate in (1) pars interpolaris, and (2) pars caudalis. Second-order neuron ◦ Cross the midline ◦ Ascend to the thalamus (trigeminothalamic tract) Third-order neuron ◦ Thalamus (VPM)

1. The Dorsal Column-Medial Lemniscus System (Tactile and proprioception from the upper and lower body, and from the posterior third of the head)

First-order neurons ◦ Dorsal root (or sensory) ganglia ◦ Synapse on neurons located mainly in Rexed's laminae III-V. ◦ Ascends ipsilaterally through the dorsal columns of the cord à lower medulla Second-order neurons ◦ Gracile and cuneate nuclei (dorsal column nuclei) ◦ Lower limbs à gracile tract ◦ Upper limbs à cuneate tract ◦ Internal arcuate tract à cross the midline (decussation) to form medial lemniscus Third-order neurons ◦ Ventral posterior lateral (VPL) nucleus of the thalamus - Just some key points of the pathways

Sensitization - hyperalgesia (An increased response to a stimulus which is normally painful)

Following a painful stimulus associated with tissue damage (e.g., cuts, scrapes, and cruises), stimuli in the area of the injury that would ordinarily be perceived as slightly painful are perceived as significantly more so, a phenomenon referred to as hyperalgesia (an exaggerated sense of pain, hyper- + algesia 'feeling of pain' ). - increased sensitivity of nociceptors due to tissue damage due to decreased threshold of nociceptors - Excessive response to noxious stimuli • Injured tissue release histamine, bradykinin, and prostaglandin and serotonin which sensitizes the nociceptors à primary afferent axon terminals in CNS release substance P that increases release of histamine from mast cells

For the LMN One characteristic to ID LMN syndrome= is

For the LMN - One characteristic to ID LMN syndrome= is FLACCID or paralyzed - b/c LMN is the one that directly synapses to travel to the innervated muscle fibers - So if the muscle fibers have no signals, then it will reveal muscle weakness and paralysis - So combined with loss of muscle tone- appear to be flaccid - Also loss of reflexes (areflexia) - And muscles may show the spontaneous activation and firing

Organization of neural structures involved in the control of movement

Four systems— local spinal cord and brainstem circuits, descending control centers in the cerebral cortex and brainstem, the cerebellum, and the basal ganglia—make essential and distinct contributions to motor control.

1. Frontal, Temporal, Parietal and Occipital Lobe Strokes

Frontal Lobe Strokes ◦ A frontal lobe stroke produces a number of effects, which may include weakness of one side of the body, behavioral changes, memory problems and trouble with self care. Temporal Lobe Strokes ◦ A temporal lobe stroke can produce trouble with communication, which is called aphasia. Language function is primarily located on the dominant side of the brain, which is the left side of the brain for right handed people, and the right side of the brain for many left handed people. Therefore, a temporal lobe stroke is more likely to produce aphasia if it occurs on the dominant side of the brain. ◦ Broca's area - speech formation, speaking ability: left frontal lobe Wernicke's area - language comprehension: left superior temporal gyrus Parietal Lobe Strokes ◦ A parietal lobe stroke produces a number vision changes, causes trouble with spatial perception, and results in problems with motor tasks. Hemispatial neglect is most frequently associated with a lesion of the right parietal lobe. Occipital Lobe Strokes ◦ The occipital lobes are vital for visual processing. A stroke of the occipital lobe can cause vision loss or partial vision loss of one eye or both eyes.

Fugl-Meyer Assessment of Motor Recovery After Stroke

Fugl-Meyer Assessment- Widely used clinical assessment of motor function of stroke patients - an assessment that reflects the Brunnstrom Stages of Motor recovery - So if they get a lower score in Fugl Meyer it means they will be in Brunnstrom stages 1-3

Acting F.A.S.T. Is Key for Stroke If you think someone may be having a stroke, act F.A.S.T. and do the following simple test:

F—Face: Ask the person to smile. Does one side of the face droop? A—Arms: Ask the person to raise both arms. Does one arm drift downward? S—Speech: Ask the person to repeat a simple phrase. Is the speech slurred or strange? T—Time: If you see any of these signs, call 9-1-1 right away. Note the time when any symptoms first appear.This information helps health care providers determine the best treatment for each person. Do not drive to the hospital or let someone else drive you. Call an ambulance so that medical personnel can begin life-saving treatment on the way to the emergency room. People who arrive at ER within 3 hours of first symptoms have less disability 3 months after stroke

Neural Tube Deficit - Anencephaly

If the cranial end of the neural tube fails to close around 25 days, the baby will be born with anencephaly Anencephaly is the absence of a major portion of the brain, skull, and scalp that occurs during embryonic development. It is a cephalic disorder that results from a neural tube defect that occurs when the rostral (head) end of the neural tube fails to close, usually between the 23rd and 26th day following conception.

The Physiological Basis of Pain Modulation Figure 9-7 (B) Local interactions between mechanoreceptive afferents and neural circuits within the dorsal horn can modulate the transmission of nociceptive information to higher centers. Gate theory of pain:

Gate theory of pain: the flow of nociceptive information through the spinal cord in modulated by concomitant activation of the large myelinated fibers associated with low-threshold mechanoreceptors. For example, if you crack your shin or stub a toe, a natural reaction is to vigorously rub the site of injury for a minute or two. Key message= gate control theory of pain - describes how non-painful can override and reduce painful sensation It is based on the idea of CONFUSION of neural signals Some non-painful stimulation can sometimes interfere with the experience of pain - This is the explanation behind benefits of rubbing a sore knee after a bump or use of hot and cold compresses on top of a wounded region

Modifying the Gain of Muscle Stretch Reflexes The role of γ motor neurons in regulating muscle spindle responses. (A) When α motor neurons are stimulated without activation of γ motor neurons, the response of the Ia fiber decreases as the muscle contracts. (B) When both α and γ motor neurons are activated, there is no decrease in Ia firing during muscle shortening. Thus, the γ motor neurons can regulate the gain of muscle spindles so they can operate efficiently at any length of the parent muscle.

Golgi Tendon organs are receptors that activate by stretch or active contraction of muscle and that transmits information about muscle tension Top picture When skeletal muscle is passively stretched, so the muscle did not actually contract, you just passively lengthen muscle fibers Notice muscle spindle that detects the muscle length activates GTO responds a little, but not much Bottom picture When the muscle actively contracts, muscle gets kind of loose and muscle spindle cannot actually detect the loosened muscle fibers But when the muscle contracts, and you increase tension your GTO responsible intensively

Note HAPPY (YOU WANT THIS)

HAPPY (YOU WANT THIS) Opioids are ligands/substances that act on opioid receptors to produce morphine-like effects. Opioids act by binding to opioid receptors. Open opioid receptors Opioid peptides (such as morphine) produced by the body: enkephalins, endorphins, and dynorphins Morphine is a pain medication of the opiate (drug derived from opium) variety which is found naturally in a number of plants and animals.

For the motor neuron that innervates your axial muscles such as the torso, the neurons when they travel down to the spinal cord located more medially Their axons will usually terminate bilaterally

Have branches that not only travel downwards but have branches to the other side that inform the other side of the body to coordinate the trunk movement and to maintain posture Local circuit neurons travel a shorter distance that may cross several SC levels- this provides a way for you to coordinate your trunk control and also maintain posture

Primary motor cortex is right in front of central sulcus Primary somatosensory cortex is behind central sulcus

Have the parietal lobe with a region called the posterior parietal cortex Then you have the SMA which stands for supplementary motor area And in front you have the premotor cortex Function of primary motor cortex is to generate neural impulses that passed down your SC and control the execution of the movement - This is the primary commander in chief - But before we execute the movement, we need motor information and you need motor planning before formulating those commands - So different parts of the brain contribute to motor planning and motor control mechanisms

Neural Control of the Bladder To allow bladder filling

Here we have 2 sphincters to control External sphincter is controlled by our somatic motor nerves Internal sphincter is controlled by the ANS and so is the bladder wall Bladder stores urine- bladder filling is usually not the problem

Topographic map of movement in the primary motor cortex The musculature used in tasks requiring fine motor control (such as movements of the face and hands) is represented by a greater area of motor cortex than is the musculature requiring less precise motor control (such as that of the trunk).

Homunculus- motor map shows the same general proportion observed in the somatic sensory map

Dermatomes The innervation arising from a single dorsal root ganglion and its spinal nerve

How the brain processes sensory info Dermatomes= skin regions responsible for each of the spinal cord levels

Conversely, an abnormal reduction in the tonic inhibition as a consequence of basal ganglia dysfunction leads to excessive excitability of the upper motor neurons, and thus to the involuntary movement syndromes that are characteristic of basal ganglia disorders such as?

Huntington's disease.

Golgi tendon organs and their role in the negative feedback regulation of muscle tension (A) Golgi tendon organs (GTO) are arranged in series with extrafusal muscle fibers because of their location at the junction of muscle and tendon. (B) The Ib afferents from tendon organs contact Ib inhibitory interneurons (gray neuron) that decrease the activity of α motor neurons innervating the same muscle. The Ib inhibitory interneurons also receive in- put from other sensory fibers, as well as from descending pathways.

Ib afferents also contact excitatory interneurons (purple neuron) that activate α motor neurons innervating antagonistic muscles. This arrangement prevents muscles from generating excessive tension and helps maintain a steady level of tone during muscle fatigue.

Perception of pain Pain is the unpleasant sensory and emotional experience associated with stimuli that cause tissue damage. The relatively unspecialized nerve cell endings that initiate the sensation of pain are called nociceptors (noci is derived from the Latin nocere, "to hurt"). There are fast and slow pain pathways In general, two categories of pain perception have been described:

In general, two categories of pain perception have been described: • a sharp first pain • Aδ group of myelinated axons, which conduct at about 20 m/s • respond either to dangerously intense mechanical or to mechanothermal stimuli, and have receptive fields that consist of clusters of sensitive spots. • a more delayed, diffuse, and longer-lasting sensation that is generally called second pain. • C fiber group of unmyelinated axons, which conduct at velocities generally less than 2 m/s. • Other unmyelinated nociceptors tend to respond to thermal, mechanical, and chemical stimuli, and are therefore said to be polymodal. - Group A delta nerve endings are responsible for sharp first pain - C fibers are responsible for the dull, longer lasting second pain

Weeks 4-5 cover Somatogenesis Term somatogenesis is used to describe process of segmentation of paraxial mesoderm within the trilaminar embryo body to form pairs of somites or balls of mesoderm

In humans, the first somite pair appears at day 20 and adds caudally at 1 somite pair/90 minutes until an average of 44 pairs eventually form Somite will be further divided into sclerotome, myotome, and dermatome That gives rise to the vertebral column, ribs, and skeletal muscles and the skin Neural crest cells- part of derivative= dorsal root ganglion Somites are a set of bilaterally paired blocks of paraxial mesoderm that form in the embryonic stage of somatogenesis

Effects of spinal region dysfunction on pelvic organ function - Sexual function Reflexive sexual erection can occur if the sacral cord is intact.

In some men with complete spinal lesions above the lumbar level in whom the lumbosacral cord is intact, ejaculation can be elicited reflexively because sympathetic axons from the L1 and L2 levels and somatic nerves from the S2-S4 levels control ejaculation. Fertile women with spinal cord lesions can conceive and often have a normalpregnancy, but they frequently require cesarean delivery

The Premotor Cortex Medial premotor cortex ◦ [internal cues] removal of the medial premotor area in a monkey reduces the number of self-initiated or "spontaneous" movements the animal makes, whereas the ability to execute movements in response to external cues remains largely intact. ◦ perform motor sequences from memory (i.e., without relying on an external instruction).

In summary, both the lateral and medial areas of the premotor cortex are intimately involved in selecting a specific movement or sequence of movements from the repertoire of possible movements. The functions of the areas differ, however, in the relative contributions of external and internal cues to the selection process. Medial region of premotor cortex is activated when the individual performs motor sequences from memory without relying on external instructions (ex. Dancing spontaneously)

Muscle spindles Muscle spindles consist of four to eight specialized intrafusal muscle fibers surrounded by a capsule of connective tissue. The intrafusal fibers are distributed among the ordinary (extrafusal) fibers of skeletal muscle in a parallel arrangement.

In the largest of the several intrafusal fibers, the nuclei are collected in an expanded region in the center of the fiber called a bag; hence the name nuclear bag fibers. The nuclei in the remaining two to six smaller intrafusal fibers are lined up single file, with the result that these fibers are called nuclear chain fibers. - The nerve fibers that send muscle length information from muscle spindles to the CNS is the 1a and 2 nerve fibers

Parkinson's Disease Degeneration of dopaminergic neurons reduces voluntary movement

In the midbrain of an individual with Parkinson's disease, the substantianigra (pigmented area) is largely absent in the region above the cerebral peduncles. The midbrain from an individual without Parkinson's disease shows intact substantia nigra (cf. regions indicated with red arrows).

Important slide about somatosensory pathway somatosensory pathway typically consists of 3 neurons Primary, secondary, and tertiary, also known as 1st order, 2nd order, and 3rd order neuron

In the periphery, the first order neuron is the sensory receptor that detects sensory stimuli like touch and pressure The cell body of the primary neuron is housed in the dorsal root ganglion of the spinal nerve, when in the head and neck, in the ganglia of the trigeminal nerve So that is the first order neuron Red dot in SC is the start of the second order neuron The second order neuron acts as a RELAY and is located in either the spinal cord or the brainstem This neuron's ascending axon will close, or decussate to the opposite side of the spinal cord or brainstem and travel up the spinal cord to the brain Cranial nerves will terminate in the thalamus or the cerebellum Next red dot is the third order neurons The third order neurons have cell bodies in the thalamus and projected to the posterior central gyrus of the parietal lobe, forming a sensory homunculus in the case of the touch Regarding posture, tertiary neuron is located in the cerebellum which means that part of the information will go from your brainstem region and deliver to the cerebellum

Mechanoreceptors Specialized to Receive Tactile Information Most of the nerves and sensory receptors are found in the DERMIS layer

Meissner corpuscle - are for touch and dynamic pressure when you touch the skin and remove it right away Pacinian corpuscle- detects deep pressure and we see it lies DEEPER in dermis layer Ruffini corpuscle- oriented parallel to the stretch lines in skin and detects stretching of skin Merkel's disks- is in charge of touch and static pressure when you press down in the skin and stay there for a brief moment Free nerve endings- pain, temperature and crude touch - these free nerve endings are group C nerve fibers

3 Types of Stroke Ischemic stroke (80%)

Ischemic stroke (80%) ◦ Most strokes are ischemic strokes. ◦ An ischemic stroke happens when blood flow through the artery that supplies oxygen-rich blood to the brain becomes blocked. ◦ Blood clots often cause the blockages that lead to ischemic strokes. Hemorrhagic stroke (15%) ◦ A hemorrhagic stroke happens when an artery in the brain leaks blood or ruptures (breaks open). The leaked blood puts too much pressure on brain cells, which damages them. ◦ High blood pressure and aneurysms—balloon-like bulges in an artery that can stretch and burst—are examples of conditions that can cause a hemorrhagic stroke. ◦ There are two types of hemorrhagic strokes: ◦ Intracerebral hemorrhage is the most common type of hemorrhagic stroke. It occurs when an artery in the brain bursts, flooding the surrounding tissue with blood. ◦ Subarachnoid hemorrhage is a less common type of hemorrhagic stroke. It refers to bleeding in the area between the brain and the thin tissues that cover it. Transient ischemic attack (a warning or "mini-stroke") ◦ It is different from the major types of stroke because blood flow to the brain is blocked for only a short time—usually no more than 5 minutes. ◦ A TIA is a warning sign of a future stroke.

Skin is the body's largest organ

It is about 2 meters thick and weighs approximately 6 pounds

Golgi Tendon Organs (GTOs) Senses changes in muscle tension. It lies at the origins and insertion of skeletal muscle fibers into the tendons of skeletal muscle.

It provides the sensory component of the Golgi tendon reflex. In a Golgi tendon reflex, skeletal muscle contraction causes the antagonist muscle to simultaneously lengthen and relax. This reflex is also called the inverse myotatic reflex, because it is the inverse of the stretch reflex. Clinical importance: The clasp-knife response is a stretch reflex with a rapid decrease in resistance when attempting to flex a joint. However, it is actually thought to be caused by the tendon reflex of the antagonistic muscle of that joint, which gets extended. It is one of the characteristic responses of an upper motor neuron lesion. - GTOs lies at the origin and insertion of skeletal muscle fibers into the tendons of skeletal muscle - - Senses changes in muscle TENSION

Somatotopic organization of lower motor neuron pools A cross section of the ventral horn at the cervical level of the spinal cord,illustrating that the motor neurons innervating the axial musculature arelocated medially, whereas thoseinnervating the distal musculature arelocated more laterally

Key point= the nuclei of motor neurons are located in the ventral horn and then axons will travel to your skeletal muscles Most motor neurons that innervate in the medial side - that will be innervate those proximal muscles- so more toward your trunk and proximal parts like shoulder Motor neurons located more laterally will travel to innervate distal muscles like your arm and hand

Examples of LMN and UMN Disorders

LMN Lesion Guillen-Barre Syndrome Polio Cauda equina syndrome Amyotrophic lateral sclerosis (Lou Gehrig's disease) UMN Lesion Spinal cord injury Cerebral palsy Multiple sclerosis Acquired brain injury Stroke Amyotrophic lateral sclerosis (Lou Gehrig's disease)

Hemi-injury of spinal cord: Have impaired touch and proprioception on SAME SIDE of body part below the lesion have impaired pain and temperature on OPPOSITE SIDE of body part below the lesion

Pain and temperature and touch and proprioception travel separately have different pathways - So if you go to assess one's sensation, you need to evaluate them SEPARATELY!! - Don't assume they will react the same

Flexion Reflex Pathways Stimulation of cutaneous receptors in the foot (by stepping on a tack, in this example) leads to activation of spinal cord local circuits that serve to withdraw (flex) the stimulated extremity and extend the other extremity to provide compensatory support. - Stimulated leg flexed to withdraw - Opposite leg extends to support

LMN have the flexion reflex pathways that does not require the command from the motor cortex Stimulation of the cutaneous receptors in the foot (ex. Stepping on a tac) elicits activation of spinal cord local circuits And that serves to flex the stimulated leg and at the same time extend the opposite leg to support the standing position

The Premotor Cortex Influence motor behavior ◦ axons project through the corticobulbar and corticospinal pathways to influence local circuit and lower motor neurons of the brainstem and spinal cord.

Lateral premotor cortex have responses that are linked in time to the occurrence of movements [external cues] ◦ In contrast to the neurons in the primary motor area, when a monkey is trained to reach in different directions in response to a visual cue, the appropriately tuned lateral premotor neurons begin to fire at the appearance of the cue, well before the monkey receives a signal to actually make the movement. ◦ Patients with frontal lobe damage have difficulty learning to select a particular movement to be performed in response to a visual cue, even though they understand the instructions and can perform the movements. ◦ Individuals with lesions in the premotor cortex may also have difficulty performing movements in response to verbal commands. Premotor cortex Acts to prepare the primary motor cortex for planning movement The lateral region of the premotor cortex is activated when individuals perform motor sequences from external cues such as verbal commands or individual cues

Lesion of the spinal cord Impaired touch, pressure, vibration, and proprioception on the same side Impaired pain on ...

Lesion of the spinal cord Impaired touch, pressure, vibration, and proprioception on the same side Impaired pain on the opposite side b/c of the anatomical differences in the pathways of where decussation occurs (the level where the neurons cross over to the other side) So if someone has a unilateral spinal cord lesion - it will result in a loss of sensation of the touch and proprioception on the SAME SIDE of the lesion (ex. If someone has a left side spinal cord injury at a certain spinal cord level, then the body parts below that lesion will have impaired touch and proprioception) In contrast, the person will have deficits of pain and temperature perception on the CONTRALATERAL SIDE of the body So if someone has a left side spinal cord injury, below the lesion on the right leg will have deficits of pain and temperature So touch and proprioception from the same side of the body BELOW the lesion - information will not be able to pass For pain and temperature - the neurons immediately cross over to the other side of the spinal cord upon entrance and then continue to travel upwards to thalamus So pain and temperature on the same side of the lesion stays intact But pain and temperature from the other side of the spinal cord is impaired

Local circuit neurons in the spinal cord gray matter

Local circuit neurons that supply the medial region of the ventral horn are situated medially within the intermediate zone of the spinal cord gray matter. Their axons (red) extend over several spinal cord segments and terminate bilaterally. Those local circuit neurons that supply the lateral parts of the ventral horn are located more laterally; their axons (orange) extend over just a few spinal cord segments, always terminating on the same side of the cord as the cell body. Pathways that contact the medial parts of the spinal cord gray matter are involved primarily in the control of posture and locomotion; those that contact the lateral parts are involved in the fine control of the distal extremities.

The somatic sensory system has two major components: a subsystem for the detection of

Mechanical stimuli (e.g., light touch, vibration, pressure, and cutaneous tension) Painful stimuli and temperature - Somatosensory system is an ascending pathways- goes up from SC to brain- carrying sensory info from body to brain - Motor pathways= descending pathway - allows brain to control movement of body below the head ***Sensation of body is carried by the spinal nerves- sensation of the face is carried by the trigeminal nerve cranial nerve 2 subsystems of the somatic sensory system 1) Mechanical stimuli- light touch, vibration, pressure, and proprioception 2) Painful stimuli and temperature

A Lesion in the Spinal Region For example, (Figure) the lesion interrupts all axons in the left C5 spinal nerve.

Mixed nerveà loss of sensation and motor innervation at C5 level This produces loss of sensation form the C5dermatome and weakness of the biceps and brachioradialis, partially innervated by the C5spinal nerve. The biceps and brachioradialis are not paralyzed because C6 also supplies these muscles. Thus the losses are limited to only part of the left arm Here is the lesions that interrupt all axons in the left C5 spinal nerve, in this scenario it is OUTSIDE of the spinal cord- this is the place where you have the mixed sensory and motor nerves traveling together - In this case, the patient will have paresis of muscles innervated by C5 and C6 combined with loss of all sensory information - Have paralysis of all muscles innervated by C5 along with dermatome regions innervated by C5 - So incoming sensory info is blocked and outgoing motor info at C5 level will also be blocked - C4 is fine, the motor is fine - C6 sensory is fine, and the motor is also okay

Spinal Cord Injury - monoplegia, paraplegia, hemiplegia, quadriplegia

Monoplegia is paralysis of one limb only. Diplegia is paralysis of both upper limbs or both lower limbs. Paraplegia is paralysis of both lower limbs. Hemiplegia is paralysis of the upper limb, trunk, and lower limb on one side of the body. Quadriplegia is paralysis of all four limbs.

Motor Neuron Pool Each lower motor neuron innervates muscle fibers within a single muscle, and all the motor neurons innervating a single muscle (called the motor neuron pool for that muscle) are grouped together into rod-shaped clusters that run parallel to the long axis of the cord for one or more spinal cord segments

Motor neuron pool - For the neurons that innervate part of your rectus femoris, the motor neurons in the ventral horn will allocate across from L2 to L4 spinal levels - So all those motor neurons innervating a single muscle = motor neuron pool

Muscle spindles

Muscle spindles are proprioceptors that consist in intrafusal muscle fibers enclosed in a sheath spindle intrafusal muscle fibers -- run parallel to the extrafusal muscle fibers and act as receptors that provide info on muscle length and the RATE of change of muscle length Muscle spindles are stretched when the muscle is lessened

Upper motor neuron control lower motor neuron through two different pathways Pyramidal tract ◦ Corticospinal tract Extra pyramidal tract ◦ Rubrospinal tract ◦ Reticulospinal tract ◦ Olivospinal tract ◦ Vestibulospinal tract ◦ Corticobulbar tract: cortical to medulla oblongata ◦ Corticorubral tract: cortical to red nucleus

Need to know travel trajectories of the: Corticospinal tract Corticobulbar tract: cortical to medulla oblongata

Anatomical organization of the inputs to the basal ganglia The motor nuclei of the basal ganglia are divided into several functionally distinct groups. The first and larger of these groups is called the corpus striatum (striped appearancds), which includes the caudate and putamen. These two subdivisions of the corpus striatum comprise the input zone of the basal ganglia, their neurons being the destinations of most of the pathways that reach this complex from other parts of the brain.

Need to see where are the input zones Caudate and putamen receive all the input information

Cutaneous and Subcutaneous Somatic Sensory Receptors

Pain and temperature is carried by free nerve endings Touch, dynamic pressure - like when you push down on the skin and up is carried by the Meissner's corpuscle Deep pressure is carried by the Pacinian corpuscles- part of the reason why the Pacinian corpuscle lies deeper in the dermis level Touch and static pressure as in pushing down the skin and staying there for a short duration of time is carried by the Merkel disks Ruffini corpuscles are oriented parallel to stretch lines in the skin- and thus detects stretching of skin Muscle spindles, Golgi tendon organs, and Joint receptors all carry proprioceptive information - Muscle spindles detect muscle length - Golgi tendon organs detect the muscle tension - Joint receptors carry the joint position information

Key Points Neurulation begins in the third week of development and continues into the fourth week. The principal result of neurulation is the formation of the neural tube and neural crest cells. The baby's brain and spinal cord will develop from the neural tube.

Neural crest cells are a temporary group of cells unique to vertebrates that arise from the embryonic ectoderm cell layer, and in turn give rise to a diverse cell lineage—including melanocytes, craniofacial cartilage and bone, smooth muscle, peripheral and enteric neurons and glia. The forebrain, the midbrain (mesencephalon), and hindbrain (rhombencephalon) are the three primary portions of the brain during early development of the central nervous system. At the five-vesicle stage, the forebrain separates into the diencephalon (thalamus, hypothalamus, subthalamus, epithalamus, and pretectum) and the telencephalon which develops into the cerebrum. Midbrain, also called mesencephalon, region of the developing vertebrate brain that is composed of the tectum and tegmentum. Hindbrain, also called rhombencephalon, region of the developing vertebrate brain that is composed of the medulla oblongata, the pons, and the cerebellum.

Organization of neural structures involved in the control of locomotion

Neural structures involved in motor control So you have UMNs - Motor cortex and brainstem centers which descend to synapse with LMNs - Before generating a sequence of motor movement, your brain needs to integrate information from other parts of the brain such as from the visual cortex- the visual guidance of the movement and also need proprioceptive info from body - The basal ganglia suppresses unwanted movement and prepare UMN for initiation of movement - During the movement, the cerebral cortex also sends information to the cerebellum of what is the intended action - On the other hand, your body also sends information to your cerebellum of what is actually performed - The cerebellum detects and attenuates the differences or the motor errors between the intended movement and the movement actually performed

Peripheral nerve injury Neuropraxia (Class I) Axonotmesis (Class II) Neurotmesis (Class III)

Neuropraxia (Class I) ◦ The endoneurium, perineurium, and the epineurium are intact. ◦ Recovery of nerve conduction deficit is full, and requires days to weeks. Axonotmesis (Class II) ◦ The axons and their myelin sheath are damaged in this kind of injury, but the endoneurium, perineurium and epineurium remain intact. Neurotmesis (Class III) ◦ Neurotmesis (in Greek tmesis signifies "to cut") is the most serious nerve injury in the scheme. In this type of injury, both the nerve and the nerve sheath are disrupted.

Three classes of peripheral nervous injury From the most mild form (neuropraxia) to the most serious form (neurotmesis)

Neuropraxia (Class I)- a mild form of peripheral nerve injury - Temporary interruption of conduction, without loss of axon connuity - Ex. Of neuropraxia are entrapment neuropathies like CTS, radial nerve palsy (Saturday night palsy) caused by pressure on the arm after person fell asleep - Endoneurium, perineurium, and epineurium in this case are INTACT - Recovery of nerve conduction deficits is full and requires days to a few weeks - Axonotmesis (class II) - "Tmesis" means cutting - Axons and their myelin sheath are damaged - But the Endoneurium, perineurium, and epineurium remain INTACT - Degeneration occurs distal to the site of injury - degeneration of nerve fibers that occurs following the injury or disease and now progresses from the place of injury, along the axon away from the cell body - While the part that is between the places of injury and the cells bodies remain intact - There are sensorimotor deficits that are distal to the site of the lesion - Neurotmesis (Class III) - The most serious nerve injury among the three - Both the nerve and nerve sheaths are disrupted - it is disruption of the whole nerve - Degeneration occur distal to the side of injury - There is no nerve conduction distal to the site of injury

Opioid inhibition of neurotransmitter release

Neurotransmitter release from neurons is normally preceded by depolarisation of the nerve terminal and Ca++ entry through voltage-sensitive Ca++ channels. Drugs may inhibit neurotransmitter release by a direct effect on Ca++ channels to reduce Ca ++ entry, or indirectly by increasing the outward K + current, thus shortening repolarisation time and the duration of the action potential. Opioids produce both of these effects because opioid receptors are apparently coupled via G- proteins directly to K+ channels and voltage-sensitive Ca++ channels. Opioids also interact with other intracellular effector mechanisms, the most important being the adenylate cyclase system (Fig. 3). Approaches of how some painkillers work Decreasing activities of transmission cells reduce perceived pain - How can we reduce activities of transmission? - We want to reduce the AP from happening - so can prevent from depolarizing so you can make the cells more hyperpolarized inside

The Babinski sign Following damage to descending corticospinal pathways, stroking the sole of the foot causes an abnormal fanning of the toes and the extension of the big toe.

Normal plantar response= toes down in flexion Abnormal response= Babinski sign- fanning of toes for patients with UMN lesion

- Thalamus- the word is Greek for "chamber" Large mass of gray matter located in dorsal part of diencephalon Nerve fibers project out from thalamus to cerebral cortex in all directions allowing exchanges of information Anatomically the thalamus is a symmetrical midline structure with two halves and many nuclei Thalamus has two ends- anterior and posterior and 4 surfaces- medial, lateral, superior, and inferior

Nuclei all have different functions and maintain specific connections with nervous and limbic system Clinical importance of thalamus- lots of sensory info merges at thalamus before traveling to somatosensory motor cortex - So if someone has a stroke at the thalamus, they will have bizarre sensation and you will hear the term "thalamic pain" symptoms

Hydrocodone As a narcotic, hydrocodone relieves pain by binding to and activating opioid receptors, namely the μ- opioid receptor (MOR), in the central nervous system.

Opioid receptors are a group of inhibitory G protein-coupled receptors with opioids as ligands. The endogenous opioids are dynorphins, enkephalins, endorphins ("a morphine-like substance originating from within the body"), endomorphins and nociceptin. ◦ Vigorous aerobic exercise can stimulate the release of endorphins in the bloodstream, leading to an effect known as a "runner's high". Laughter may also stimulate endorphin production; a 2011 study showed that attendees at a comedy club showed increased resistance to pain. - Typical example of an opioid painkiller- cannot purchase over the counter

The Physiological Basis of Pain Modulation Regulating the transmission of nociceptive information arises from a number of brainstem sites. These descending projections provide a balance of facilitatory and inhibitory influences that ultimately determines the efficacy of nociceptive transmission.

Painful signals also reach to other parts of the brain - Reticular formation, midbrain, amygdala, and hypothalamus - Descending modulatory pathway will reach to several structures- one noteworthy one= Raphe nuclei - Then axon terminals reach at dorsal horn of SC and will connect to axon terminals of spinal thalamic pathway

Painkillers: work and mechanism of action Based on the type of action, they can be broadly classified into 2 major groups - Non-narcotic analgesics Narcotic analgesics painkillers

Painkiller (1) Non-narcotic analgesics Non-opioids: are analgesics that do not have CNS effects These painkillers include aspirin, Indomethacin, Mefenamic acid, Ibuprofen, Piroxicam, Diclofenac, Ketorolac and Roxicob. NSAIDS (Non-steroidal anti-inflammatory drugs): The principal therapeutic effects of NSAIDs derive from their ability to inhibit prostaglandin production. Aspirin and NSAIDs inhibit the COX enzymes and prostaglandin production. (Prostaglandins are made at sites of tissue damage or infection, where they cause inflammation, pain and fever as part of the healing process.) - P are the unhappy elements remember? Prostaglandin - So these BLOCK the prostaglandin production - Remember these are one of the things your tissue will release when you have injured tissues and cells - This will start a lot of swelling and redness which will push the free nerve endings that will convey pain sensation to your brain

Parkinson's disease= Basal ganglia dysfunction in the initiation of movement

Parkinson's disease is a slowly progressive neurologic disorder caused by the loss of dopamine (DA)-secreting cells in the substantia nigra and basal ganglia of the brain. - Neurodegenerative - Symptom progression varies from person to person due to diversity of the disease - Has less facial movement and appears less animated -is sometimes called a "poker face" - Hypokinesia- in addition to movements being slower (Bradykinesia) they are also smaller

Disorders of Basal Ganglia Conditions where things go wrong with the basal ganglia: Parkinson's disease, Huntington's Disease, Cervical Dystonia, Tourette's Syndrome, Myoclonus Dystonia

Parkinson's have resting tremor- rigidity and increased stiffness in all muscles- freezing gait turning Huntington's Disease- neurodegenerative disorder characterized by inability to suppress unwanted movement Cervical Dystonia- painful condition where the neck muscles contract involuntarily, causing the head to twist and turn to one side Myoclonus Dystonia- an abnormal muscle tone typically affecting the upper part of the body - rapid jerky movement of the upper limb Tourette's Syndrome

Helpful pneumonic- pee, poo, point and shoot

Pee is bladder Poo if bowel Point and shoot is sex function Anything that starts with "P" is parasympathetic that plays a more important role Anything start with an "S" has a more important role in sympathetic function Point is the erection- so parasympathetic plays a major role in it Shoot is the ejaculation- so the SYMPATHETIC will play a more important role in it Here we have 2 sphincters to control External sphincter is controlled by our somatic motor nerves Internal sphincter is controlled by the ANS and so is the bladder wall Bladder stores urine- bladder filling is usually not the problem

Amyotrophic Lateral Sclerosis (ALS) Etiology: An autosomal dominant form of familial ALS (FALS) is caused by mutations of the gene that encodes the cytosolic antioxidant enzyme copper/zinc superoxide dismutase (SOD1). Mutations of SOD1 account for roughly 20% of families with FALS.

Phenotype of motor neuron disease: Defects of axonal transport have long been hypothesized to cause ALS. Pathophysiological mechanisms in ALS: Among the mechanisms implicated in motor neuronal degeneration in ALS are glutamate-mediated excitotoxicity, increased oxidative stress, mitochondrial dysfunction, accumulation of toxic protein and RNA aggregates, impaired axonal transport, and activation of pro-inflammatory microglia. One cause of ALS is a mutation of the SOD1 gene Later on just destroys the motor neuron not just the axonal transport

Besides motor functions, the basal ganglia also involves many non-motor brain functions

Planning, working memory, and attention Regulate emotional behavior and motivation

Components of the motor cortex ◦ The posterior parietal cortex is sometimes also considered to be part of the group of motor cortical areas; however it is best to regard it as an association cortex rather than motor. It is thought to be responsible for transforming multisensory information into motor commands, and to be responsible for some aspects of motor planning, in addition to many other functions that may not be motor related. ◦ The primary somatosensory cortex, especially the part called area 3a, which lies directly against the motor cortex, is sometimes

Posterior parietal cortex is thought to be responsible for transforming sensory info into motor commands And to be responsible for some aspects of motor planning such as getting information from touch, proprioception, vision, special information regarding where the objects are So some patients with damage to parietal lobe may lead to some deficits in attention to space, spatial neglect, etc. Your motor planning relies on the sensory information and proprioceptive information from your body

3. The Spinocerebellar Tract (Proprioceptive information from the body) They transmit information from the Golgi tendon organs and muscle spindles to the cerebellum. Within the spinocerebellar tracts, there are four individual pathways:

Posterior spinocerebellar tract - Carries proprioceptive information from the lower limbs to the ipsilateral cerebellum. Cuneocerebellar tract - Carries proprioceptive information from the upper limbs to the ipsilateral cerebellum. Anterior spinocerebellar tract - Carries proprioceptive information from the lower limbs. The fibres decussate twice - and so terminate in the ipsilateral cerebellum. Rostral spinocerebellar tract - Carries proprioceptive information from the upper limbs to the ipsilateral cerebellum.

Clinical Conditions Sensodyne is a brand name of toothpaste targeted at people with sensitive teeth. Sensodyne toothpastes work in different ways depending on the product's active ingredient - potassium nitrate, strontium acetate/chloride. Potassium nitrate:

Potassium nitrate: The potassium ion hyperpolarizes the nerve and stops it from firing. The nerve impulses are thus desensitized and there is no pain. - Remember need depolarization in order for an action potential to occur, potassium nitrate ingredient in Sensodyne toothpaste will cause the neurons to hyperpolarize- so will stop the neuron from firing and that desensitizes the teeth

Opioids and pain pathways Pain is normally associated with increased activity in primary sensory neurons induced by strong mechanical or thermal stimuli, or by chemicals released by tissue damage or inflammation.

Primary sensory neurons involved in pain sensation release predominantly substance P and glutamate in the dorsal horn of the spinal cord. Nociceptive information is transmitted to the brain via the spinothalamic tracts. This ascending information can activate descending pathways, from the midbrain periaqueductal grey area, which exert an inhibitory control over the dorsal horn. The opioid drugs produce analgesia by actions at several levels of the nervous system, in particular, inhibition of neurotransmitter release from the primary afferent terminals in the spinal cord and activation of descending inhibitory controls in the midbrain. - Opioids inhibit the release of the NT from the primary afferent terminals in the SC and activation of descending inhibitory controls in the midbrain. - Approach of how painkillers work

The anterolateral (spinothalamic) pathway & Affective-motivational pain pathways (unpleasant quality of pain)

Project to ◦ Lamina I à Reticular formation (arousal center) of the mid- brain (parabrachial nucleus) ◦ Thalamic nuclei (intralaminar nuclei) ◦ Amygdala (motivation and affect) à periaqueductal grey of the midbrain ◦ Areas in the frontal lobe, the insula and the cingulate cortex The perception of painful sensation and feeling is a complex system So pain perception is usually associated with emotion, alertness and also with memory So the information from the painful sensation and also the temperature information will reach to the brainstem and also will have branches that will reach to different parts of the CNS Ex. The reticular formation projects to the amygdala and hypothalamus in addition to the main pathways that reach to the somatosensory cortex The reticular formation may be known best for its role in promoting arousal and consciousness - ex. Waking up in the middle of the night with stomach pain b/c the painful sensation will stimulate the reticular formation and that will wake you up from your sleep - The amygdala helps to store memories of events and emotions so that an individual may be able to recognize similar events in the future

Basal ganglia- structures within the cerebral hemispheres

Putamen Caudate nucleus Globus Pallidus in middle part- also is divided into an external and internal part

Remember pee, poo, point and shoot Point- parasympathetic Shoot- sympathetic

Remember parasympathetic is for rest- activities for the parasympathetic will cause the dilation of the penis - as a result, the blood and tissue is increased So parasympathetic is primarily involved with sustaining and maintaining an erection The sympathetic nerves play a predominant role in the ejaculation process- so shoot is sympathetic In the case of men with complete SCI of the lumbar level in which the lumbar sacral cord is intact, the ejaculation can be elicited reflexively b/c the sympathetic axons from the L1, L2 level and the somatic nerves from S2 S4 levels control ejaculation

Descending Control of Pain Perception Perception (interpretation) of pain is subject to central modulation ◦ The pain of an injured soldier on the battlefield

Remember, interpretation of pain is subjective to central modulation - So pain perception can vary depending on context and situation - Ex. many soldiers on the battlefield do not immediately feel or suffer from the wounds they receive - **This diagram shows how your brain can modulate pain perception - Green line= ascending spinal thalamic pathway (pain and temperature) - skin, DRG, dorsal horn, cross over to other side of SC immediately at the same level and then travel upwards - Branches to reticular formation, midbrain, and VPL nuclei of the thalamus and then primary somatosensory cortex - Blue line= Spinal trigeminal tract from the face- painful signals also reach other parts of the brain like reticular formation, amygdala, and hypothalamus - Red line= something we haven't learned yet - a DESCENDING pathway where your brain can modulate and change the pain perception - Starts from places like the hypothalamus, amygdala, and frontal cortex - It travels down to structures called the Raphe nuclei and has some axon terminals connected to axons of spinal thalamic pathways at the dorsal horn of your spinal cord at region where enter the SC - Remember, if you don't want pain, you don't want the pain signals to send to the brain, you want to reduce the amount of the pain signals traveling to the brain if you can - So you want to send inhibitory action potentials here (where axon terminals of descending modulatory pathway meets the spinal thalamic pathways in the dorsal horn) to interfere with the signal transmission - So activating the descending pain modulating pathway- inhibits the activity of nociceptic projecting neurons in the dorsal horn of your spinal cord - So if you don't want pain signals, target the source of where those pain signals come in

Spinal Region Syndromes Brown-Sequard syndrome (Figure (C)) ◦ What have been interrupted and symptoms?

Results from a hemisection of the cord. ◦ What have been interrupted ◦ Ascending spinothalamic tracts (pain, temperature) ◦ Ascending dorsal column medial lemniscus tract (touch, proprioception) ◦ Descending motor tracts ◦ Symptoms ◦ Paralysis (ipsilateral side) ◦ Loss of touch and proprioception (ipsilateral side) ◦ Loss of pain and temperature sensation (contralateral side)

Signs and Symptoms of Stroke

SUDDEN numbness or weakness of face, arm or leg, especially on one side of the body SUDDEN confusion, trouble speaking, or understanding SUDDEN trouble seeing in one or both eyes SUDDEN trouble walking, dizziness, loss of balance or coordination SUDDEN severe headache with no known cause

Size principle: as the synaptic activity driving a motor neuron pool increases

Size principle: as the synaptic activity driving a motor neuron pool increases, low-threshold S motor units are recruited first, then FR motor units, and finally, at the highest levels of activity, the FF motor units. Since these original experiments were performed, evidence for the orderly recruitment of motor units has been found in a variety of voluntary and reflexive movements, including exercise activities.

Neural Tube Deficit - Spinal Bifida Myelomeningocele

◦ open spinal canal over some vertebrae, usually in the middle or lower part of the back ◦ membranes and spinal cord pushed outside the back in an exposed or skin-covered sack ◦ weak or paralyzed leg muscles ◦ seizures ◦ deformed feet ◦ hips that are not even ◦ scoliosis (curved spine) ◦ issues with the bowel and bladder

Force and fatigability of the three different types of motor units - Slow (S) motor units - Fast fatigue-resistant (FR) motor units - Fast fatigable (FF) motor units

Slow (S) motor units are especially important for activities that require sustained muscular contraction, such as the maintenance of an upright posture. Fast fatigue-resistant (FR) motor units are of intermediate size and are not quite as fast as FF units. As the name implies, they are substantially more resistant to fatigue, and generate about twice the force of a slow motor unit. Fast fatigable (FF) motor units and are especially important for brief exertions that require large forces, such as running or jumping. There are 3 types of motor units and those will stimulate the muscle fibers Slow motor unit= means its conducting a bit more slowly usually generate lower forces but they can last for a much longer duration of time So muscle fibers will fire continuously and across a longer period of time and will not get fatigued in the short term Fast fatigable motor units= will fire when we try to do something that needs large forces in a very short time like running and jumping

Slow oxidative fibers Fast-twitch glycolytic fibers - Fast oxidative-glycolytic fibers (FOG)

Slow oxidative fibers - High myoglobin, many mitochondria - Red "dark meat" - Generate more ATP as an energy source and located in muscles that contract slowly and generate relatively small forces across a longer duration of time Fast-twitch glycolytic fibers - Use glycogen as energy source - Muscle fibers contain very few myoglobin so they appear WHITE - Large diameter produce large contractile force - Break down ATP quickly - Fatigues very quickly - Fast oxidative-glycolytic fibers (FOG)

Each of the lines In the picture is one motor unit And then they record different motor units when you have increased voluntary contraction force of a specific muscle Increasing the firing rate firing frequency at which individual motor units fire So the CNS can increase the strength of muscle contractions via firing strategy either by increasing the firing rate or increasing by recruiting more motor units

So at a lower voluntary force, when a voluntary force increases, a single motor unit also increases the firing frequency So as the x axis increases, the single motor unit has a firing frequency that increases The CNS can also increase the strength of muscle contraction by increasing the number of active motor units So in a higher voluntary force, more motor units are being activated

Muscle spindles send the muscle length info to the CNS via the afferent 1 and 2 sensory fibers The muscles spindles also need to synchronize the muscle length with the skeletal muscle fibers so they can remain sensitive to the changes of the muscle length

So the CNS regulates the muscle spindle length by the efferent gamma nerve fibers So those ensure the muscle fibers and their sensory information to the CNS while type 1 and 2 nerve fibers and the CNS regulate the length of the muscle fibers while the gamma motor neurons the Info sent from the gamma motor neurons and the muscle spindles contract and shorten so that they can remain just the right length so they can detect the changes of the length of the skeletal muscles

Spasticity Physiologically spasticity is defined as

Spasticity Physiologically spasticity is defined as a motor disorder characterized by a velocity dependent increase in the tonic stretch reflexes (muscle tone) with exaggerated tendon jerks, resulting from hyperexcitability of the stretch reflexes as one component of the upper motor neuron (UMN) syndrome (Lance, 1980). Is characterized by a velocity dependent increase in tonic stretch reflexes (muscle tone) Patients with UMN syndrome they lose the suppression of reflexes at a higher level, the underlying reflexes that our body is originally born with to protect ourselves And now without the inhibition, it becomes actively involved and start to act out

Neural Tube Deficit - Spinal Bifida

Spina bifida is a birth defect where there is incomplete closing of the backbone and membranes around the spinal cord (the lower back). Failure of the caudal end of the neural tube to close by day 27, the baby will be born with spina bifida

A 1-year-old girl is brought to the clinic for a routine checkup. The child appears normal except for a dimpling of the skin in the midline of the lumbar region with a tuft of hair growing over the dimple. What is this relatively common condition that results from incomplete embryologic development? Meningomyelocele Meningocele Spina bifida occulta Spina bifida cystica Rachischisis

Spina bifida occulta

The Physiological Basis of Pain Modulation (C) The role of enkephalin-containing local circuit neurons in the descending control of nociceptive signal transmission (have a narcotic action). There are three well-characterized families of opioid peptides (such as morphine) produced by the body: enkephalins, endorphins, and dynorphins. They are present in the periaqueductal gray matter.

The enkephalins are termed endogenous ligands, as they are internally derived and bind to the body's opioid receptors. Descending input from the Raphe nuclei To the axon terminal of enkephalin-containing local circuit neuron (the HAPPY elements) And you see that inhibits the pain signals- which is why you see a minus sign The plus sign travels to the CNS

Neural Tube Deficit - Spinal Bifida Meningocele

◦ small opening in the back ◦ sack that's visible at birth ◦ membranes pushing out through the opening in the vertebrae into sack ◦ normal development of the spinal cord

Stretch reflex circuitry (A) Diagram of muscle spindle, the sensory receptor that initiates the stretch reflex. (B) Stretching a muscle spindle leads to increased activity in Ia afferents and an increase in the activity of α motor neurons that innervate the same muscle. Ia afferents also excite the motor neurons that innervate synergistic muscles, and inhibit the motor neurons that innervate antagonists. (C) The stretch reflex operates as a negative feedback loop to regulate muscle length.

Stretch reflex When you pour a drink and suddenly you feel the weight, and so you have the passive stretch lowering your arm and that then lengthens your biceps muscles the sensors that detect the muscle length is called the muscle spindles- these lie inside parallel to the muscle fibers and when the skeletal muscle fibers lengthen, so do those muscle spindles So muscle spindles detect the length of the muscle, they convey length information to the CNS and its usually while their afferent nerve fibers is type 1a and 2 sensory nerve fibers The CNS increases the motor neuron activity sending action potentials to the skeletal muscles via the alpha motor neuron causing the muscle fibers to contract and thus resist the stretching A second set of neurons also go to the triceps and cause opposing muscles to relax

PAIN (YOU DON'T WANT THE FOLLOWING...)

Substance P Prostaglandin First, you don't want the pain signals to travel to the brain. Second, you want to reduce the amount of pain signals traveling to the brain.

Cerebellar brainstem stroke Cerebellar stroke syndrome is a condition in which the circulation to the cerebellum is impaired due to a lesion of the superior cerebellar artery, anterior inferior cerebellar artery or the posterior inferior cerebellar artery.

Symptoms ◦ Cardinal signs include vertigo, headache, vomiting, and ataxia. ◦ Deadly D's ◦ Diplopia ◦ Dysmetria: undershoot or overshoot of intended position with the hand, arm, leg, or eye. ◦ Dysarthria: slurred or slow speech ◦ Dysphonia: voice involuntarily sounds breathy, raspy, or strained, or is softer in volume or lower in pitch ◦ Dysphagia: difficulty in swallowing

Flexion and extension synergy of the upper limb and lower limb

Synergy refers to abnormal stereotypical type pattern across multiple joints together Most stroke patients just show the flexor synergy in the upper limb Extensor synergy in the lower limb is more prominent

Referred pain Referred pain, also called reflective pain, is pain perceived at a location other than the site of the painful stimulus. Pain arising from an organ (viscera) is often not felt where the organ is located but is referred to the dermatomes innervated by the same spinal to which the visceral afferent fibers project.

The CNS 'misinterprets' the source of stimulation of visceral nociceptive fibers as pain in the corresponding somatic or skin region. The central nervous system (CNS) perceives pain from the heart as coming from the somatic portion of the body supplied by the T1-T4. Ex. Pain that radiates into the left arm and left chest can be a sign of the heart attack - At the light blue region in the picture

Two distinct aspects of the experience of pain

The anterolateral system supplies information to different structures in the brainstem and forebrain that contribute to different aspects of the experience of pain. 1. The spinothalamic tract (left of dashed line) conveys signals that mediate the sensory discrimination of first pain. 2. The affective and motivational aspects of second pain are mediated by complex pathways that reach integrative centers in the limbic forebrain.

Endoderm The endoderm The endoderm forms:

The endoderm The endoderm forms: the stomach, the colon, the liver, the pancreas, the urinary bladder, the epithelial parts of trachea, the lungs, the pharynx, the thyroid, the parathyroid, and the intestines. Endoderm forms the tube inside your body from your stomach, liver, pancreas, colon and bladder

Neural Tube Deficit - Spinal Bifida ◦ Myeloschisis

◦ the severest form of the spina bifida aperta ◦ The nerve tissue is here fully bare and a dermal or meningeal covering is absent. With this abnormality, the closure of the neural folds fails to occur.

Pain pathway from the body

The first order neuron terminates at the dorsal horn The second order neuron in the dorsal horn, sends out axons across the midline and ascend on the contralateral side of the cord to their target in the thalamus and the brainstem The third order neuron travels from the VPL nuclei and reaches to the somatosensory cortex of the brain Painful sensation of temperature info from the lower body gets into the spinal cord FIRST!! And the signals from the torso and signals from the upper body continue to join the pathway and travel together This information from different parts of the body is organized in the concept of the homunculus

Medium spiny neurons in the corpus striatum The destinations of the incoming axons from the cortex are the dendritesof a class of cells called medium spiny neurons in the corpus striatum

The large dendritic trees of these neurons allow them to integrate inputs from a variety of cortical, thalamic, and brainstem structures. The axons arising from the medium spiny neurons converge on neurons in the globus pallidus and the substantia nigra pars reticulata. The globus pallidus and substantia nigra pars reticulata are the main sources of output from the basal ganglia complex.

Mesoderm The mesoderm The mesoderm forms

The mesoderm The mesoderm forms: muscle (smooth and striated), bone, cartilage, connective tissue, adipose tissue, circulatory system, lymphatic system, dermis, genitourinary system, serous membranes, and notochord. Mesoderm forms what you learned in anatomy course including muscles and bones

Nearly all regions of the neocortex project directly to the corpus striatum Regions of the cerebral cortex (shown in purple) that project to the caudate, putamen, and ventral striatum in both lateral (A) and medial (B) views. The caudate, putamen, and ventral striatum receive cortical projections primarily from the association areas of the frontal, parietal, and temporal lobes.

The only cortical areas that do not project to the corpus striatum are the primary visual and primary auditory cortices. All of these projections, referred to collectively as the corticostriatal pathway, travel through the internal capsule to reach the caudate and putamen directly Nearly all regions of the cortex project directly to the basal ganglia -from association areas of the frontal, parietal, and temporal lobe - The only area that does not project to the corpus striatum are the primary visual and primary auditory cortices

Thalamus The thalamus is crucial for perception, with 98% of all sensory input being relayed by it.

The only sensory information that is not relayed by the thalamus into the cerebral cortex is information related to smell (olfaction). Function ◦ Relaying information between different subcortical areas ◦ medial geniculate nuclei - hearing ◦ lateral geniculate nuclei - vision ◦ ventral posterior nuclei - taste and somatic sensations (pain, pressure) ◦ anterior nucleus - emotions and memory ◦ Regulating states of sleep and wakefulness. ◦ Providing the specific channels from the basal ganglia and cerebellum to the cortical motor areas.

The Placebo Effect

The placebo effect is defined as a physiological response following the administration of a pharmacologically inert 'remedy.' ◦ In a study, 75% of patients suffering from post-operative wound pain reported satisfactory relief after an injection of sterile saline. - Painful perceptions can be modulated

Components of the motor cortex 1. the primary motor cortex is the main contributor to generating neural impulses that pass down to the spinal cord and control the execution of movement.

The premotor cortex (PMA) and the supplementary motor area (SMA) function to transform the intention to perform a complex motor act into the specific sequence of movements necessary to accomplish the act.

Acetaminophen (Tylenol) Acetaminophen is a pain reliever and a fever reducer.

The primary mechanism of action is believed to be inhibition of cyclooxygenase (COX), with a predominant effect on COX-2. Inhibition of COX enzymes prevents the metabolism of arachidonic acid to prostaglandin H2, an unstable intermediate byproduct which is converted to pro- inflammatory compounds. While acetaminophen shares the analgesic and antipyretic properties of other COX inhibitors such as aspirin and the non-steroidal anti-inflammatory drugs (NSAIDs), it does not possess significant anti-inflammatory properties. Unlike aspirin, acetaminophen does not inhibit thromboxane and, as a result, does not alter platelet aggregation. - Tylenol= typical example of a non-narcotic pain killer

Differences in Mechanosensory Discrimination across the Body Surface Two-point discrimination ◦ Fingertips: 2 mm ◦ Forearm: 40 mm

The receptive field of a somatic sensory neuron is the region of the skin within which a tactile stimulus evokes a sensory response in the cell or its axon. ◦ Fingertips: 1-2 mm in diameter ◦ Palms: 5-10 mm Body areas differ in both tactile receptor density and somatosensory cortical representation Two point discrimination- the ability to discern that two nearby objects touching the skin are truly two distinct points, not one Assumed to identify how finely innervated an area of skin is Normally a person should be able to identify 2 points separate by 2-8 mm of fingertips and 30-40 mm on the shin or the back

Discriminative component of pain

The response of an organism to noxious stimuli is multidimensional Pain perception can be described by: location, intensity, and quality of noxious stimulation Pathologic pain can happen after damage to nervous system or even when there is no damage or inflammation - Largely a result of amplified sensory signals in the CNS - Conditions like fibromyalgia, tension type headaches, and TMJ - Can be pain without any noxious stimuli - Painful sensation may trigger autonomic fight or flight activation - This enables you to quickly protect yourself from perceived threat

Descending projections from the brainstem to the spinal cord: The indirect motor pathways In general, the indirect motor pathways conduct action potentials to cause involuntary movements that regulate posture, balance, muscle tone, and reflexive movements of the head and trunk. For example, the brainstem postural reflexes keep the body in an upright and balanced position (vestibulospinal tracts).

The reticular formation also helps control posture. In addition, it can alter muscle tone. The reticular formation receives input from several sources, including the eyes, ear, cerebellum, and basal nuclei. In response to this input, discrete nuclei in the reticular formation generate action potentials along the medial reticulospinal tract and lateral reticulospinal tract, both of which convey signals to skeletal muscles of the trunk, and proximal limbs. The superior colliculus receives visual input from the eyes and auditory input from the ears (via connections with the inferior colliculus). When this input occurs in a sudden, unexpected manner, the superior colliculus produces action potentials along the tectospinal tract, which conveys neural signals that activate skeletal muscles in the head and trunk. The superior colliculus is also an integrating center for saccades, small, rapid jerking movements of the eyes that occur as a person looks at different points in the visual field. The red nucleus receives input from the cerebral cortex and the cerebellum. In response to this input, the red nucleus generates action potentials along the axons of the rubrospinal tract, which conveys neural signals that activate skeletal muscles that cause fine, precise, voluntary movements of the distal parts of the upper limbs. Note that skeletal muscles in the distal parts of the lower limbs are not activated by the rubrospinal tract.

Summarizes the spinal thalamic pathway - compare this to the dorsal-column medial lemniscus (DCML) pathway Similarities:

The sensation of the body all reaches to the VPL nuclei of the thalamus For the sensation from the face, they all reach to the VPM nuclei of the thalamus

Huntington's Disease Degeneration of medium spiny neurons increases involuntary movement

The size of the caudate and putamen (the striatum) is dramatically reduced in patients with advanced Huntington's disease.

The somatosensory system The somatosensory system is arguably the most diverse of the sensory systems, mediating a range of sensations—touch, pressure, vibration, limb position, heat, cold, itch, and pain—that are transduced by receptors within the skin, muscles, or joints and conveyed to a variety of CNS targets.

The somatic sensory system has two major components: a subsystem for the detection of: Mechanical stimuli (e.g., light touch, vibration, pressure, and cutaneous tension) Painful stimuli and temperature

The somatosensory system

The somatosensory system is arguably the most diverse of the sensory systems, mediating a range of sensations—touch, pressure, vibration, limb position, heat, cold, itch, and pain—that are transduced by receptors within the skin, muscles, or joints and conveyed to a variety of CNS targets.

Pain pathway from the face

The trigeminal pain and temperature system The sensory neurons carry the sensation of the face via the trigeminal cranial nerve #5 - Enters at mid-pons level - The neurons DESCEND to the medulla first, and then cross the midline to the other side - The neurons ascend to the VPM nuclei of the thalamus, and then convey information to the primary somatosensory cortex Review (L- is from the body) (R- is from the face)

Figure 9.10 Diagram of the somatic sensory portions of the thalamus and their cortical targets in the postcentral gyrus.

The ventral posterior nuclear complex comprises the VPM, which relays somatic sensory information carried by the trigeminal system from the face, and the VPL, which relays somatic sensory information from the rest of the body. Inset above shows organization of the primary somatosensory cortex in the postcentral gyrus, shown here in a section cutting across the gyrus from anterior to posterior.

Joint Receptors Joint receptors are found in the synovial junctions between bones. The receptors detect mechanical deformation within the capsule and ligaments. They serve two main purposes: ◦ to protect the joint from potentially injurious flexion and extension, and ◦ serve as propriocepters.

There are four types of sensory endings that make up joint receptors: ◦ free nerve endings, ◦ Golgi type endings, ◦ ruffini endings, and ◦ paciniform endings. - Joint receptors are found in the synovial junctions b/w bones - - Detect mechanical deformation within the CAPSULE and LIGAMENTS thus providing proprioceptive information

Painkillers (2) Opioid (narcotic) pain medications Narcotic analgesics are the analgesics that have central nervous system effects. They bind with the opioid receptors in the CNS to block the perception of pain or affect the emotional response to pain and are much more effective.

They are of two types. ◦ Natural - Narcotic analgesics containing alkaloids of opium eg. Morphine and Codeine. ◦ Synthetic - Trimeperidine , Fentanyl, Piritramide, Pentazocine, Tramadol, Butorphanol Inhibition of neurotransmitter release is considered to be the major mechanism of action responsible for the clinical effects of opioids. - Narcotic pain medications depend on the opioid They bind to the opioid receptors in the CNS and block the perception of pain or affect emotional response to pain Remember opioids, they open up the opioid receptors - those are happy elements Opioid drugs produce analgesia by actions at several levels of the CNS

In contrast to the lateral corticospinal tract which controls the movement of the limbs, the anterior corticospinal tract controls

anterior corticospinal tract controls the movements of axial muscles (of the trunk). anterior corticospinal tract Has axon branches terminating bilaterally and have local circuit neurons that travel a short distance or travel a long distance across several spinal segments Stroke patients may see their upper or lower limb muscles are severely impaired but trunk control may be okay This is partially b/c of the anterior corticospinal tract projects terminates bilaterally and those neurons will travel and relay the proximal axial muscles So they still have some of the innervations that can send signals to both sides of the SC

To cause you pain and not happy - things with the letter "P" in it!!

To cause you pain and not happy - things with the letter "P" in it!! - Substance P - secreted by nerves and inflammatory cells like microphages, lymphocytes, and eosinophils- also nociceptors themselves release substance "P" which cause release of histamine and stimulates nociceptors - Prostaglandin - a group of lipids produced at site of tissue damage or infection - (control blood flow and clots) released by damaged cells also - These are the chemicals you do NOT want in your body

Clinical relevance: Dissociated sensory loss Axons conveying information for the anterolateral system and the dorsal column-medial lemniscal system travel in different parts of the spinal cord white matter. Touch & proprioception signals ascend in the ipsilateral dorsal column BUT But pain signals (anterolateral system) do what?

Touch & proprioception signals ascend in the ipsilateral dorsal column. But pain signals (anterolateral system) crosses immediately at the spinal level and then travel upwards.

Upper motor neurons (UMNs) vs lower motor neurons (LMNs)

UMNs arise in the cerebral cortex or brainstem, and their axons travel in descending tracts to synapse with LMNs and/or interneurons in the brainstem or spinal cord. LMNs have their cell bodies in the spinal cord or brainstem and synapse with skeletal muscle fibers. Control circuits adjust the activity of the descending tracts. The motor pathway is a descending pathway 2 types- UMNs and LMNs When LMNs get signals from UMNs they pass messages to skeletal muscles to initiate complex a special temporal sequence of controlled movement

Lesion in the thalamus: Thalamic Stroke

Usually results from hypertension and get hemorrhagic bleeding into the thalamus Loss of sensation or abnormal sensory processing - called thalamic pain syndrome- involves burning or freezing sensation in addition to intense pain, usually in the head, arms or legs Depending on part of thalamus effected, may experience difficulties with movement, or maintaining balance, speech difficulties, vision loss, sleep disturbance, loss of interest or enthusiasm, changes in attention span, memory loss b/c a lot of information passes through the thalamus before ascending to other part for processing

Phantom Limbs and Phantom Pain=Neuropathic pain

When the afferent fibers or central pathways themselves are damaged - a frequent complication in pathological conditions that include diabetes, shingles, AIDs, multiple sclerosis, and stroke - these processes (sensitization) can persist. The resulting condition is referred to as neuropathic pain. The pain can arise spontaneously (without a stimulus) or can be produced by mild forms of stimulation (e.g., gentle touch of clothing). Patients often describe their experience as a constant burning sensation interrupted by episodes of shooting, stabbing, or electric shock-like jolts. Amputees often experience sensation of the limb they are missing and experience pain from the amputee limb - Due to the fact that the nociceptors are damaged or missing and the neurons in the spinal cord that send the pain messages have become hyperactive - So brain gets messages of pain even when there is no tissue left

Neural Control of the Bladder To empty bladder (when the bladder is full)

When the bladder has a lot of urine, and its so stretched it can't fill anymore At that time we will feel the urge to go to the restroom We can still hold it b/c we have the external sphincter that is under our control Internal sphincter is involuntary - you need the parasympathetic signals elicited contraction of the bladder wall and also to relax the internal sphincter in order to urine - This is regulated at the S2 S4 spinal cord level - So you will need the parasympathetic nerve at S2 S4 spinal cord level to send signals to the bladder wall in order to contract the muscles and push the urine out - If the S2 S4 spinal cord region is damaged, that means the parasympathetic efferent is also damaged - Without the parasympathetic signals, then there is no signal to send it to the urinary bladder wall or the muscle to contract - In this case, the urine will continue to accumulate but you have no contraction force - When the bladder stretches farther, now you have a lot of urine and it will just drip out - So in this way we say the individual has a FLACCID PARALYZED BLADDER and you will continue to have the dripping issue - In contrast, if the lesion is above the S2 S4 spinal cord level, the reflex arc then is normal and intact - But the voluntary sphincter control is absent - Have no control over here so when the bladder is being stretched and suddenly the reflex from the parasympathetic will cause the bladder wall to contract - Accidents will happen b/c it triggers the reflex

Mechanoreceptors Specialized for Proprioception Low-threshold mechanoreceptors, including ◦ muscle spindles: muscle length ◦ Golgi tendon organs: tension ◦ joint receptors

Whereas muscle spindles are specialized to signal changes in muscle length, low-threshold mechanoreceptors in tendons inform the central nervous system about changes in muscle tension. These mechanoreceptors, called Golgi tendon organs, are innervated by branches of group Ib afferents and are distributed among the collagen fibers that form the tendons Meissner, Merkel and Pacinian cells are for touch and pressure Muscle spindles, GTO and joint receptors are for proprioception Muscle spindles- detect changes in muscle length Golgi tendon organ- detect muscle tension Joint receptors- carry overall joint position info

The corticospinal and corticobulbar tracts The corticospinal tract originates in several parts of the brain (30% originate in the primary motor cortex, 30% more in premotor cortex and supplementary motor areas, with the remaining 40% distributed between the somatosensory cortex, the parietal lobe, and cingulate gyrus). These upper motor neurons travel through the posterior limb of the internal capsule in the forebrain, to enter the cerebral peduncle at the base of the midbrain, the pons and then to the medulla.

a. As they course through the brainstem, corticobulbar axons (gold) give rise to bilateral collaterals that innervate brainstem nuclei (only collaterals to the trigeminal motor nuclei and the hypoglossal nuclei are shown). b. Lateral corticospinal tract (75-90%): Most of the corticospinal fibers (dark red) cross in the caudal part of the medulla to form the lateral corticospinal tract in the spinal cord. c. Anterior corticospinal tract (10-25% of fibers) Those axons that do not cross (light red) form the ventral corticospinal tract, which terminates bilaterally.

. Higher-Order Cortical Representations a. Primary somatic sensory cortex à secondary somatosensory cortex à limbic structures (amygdala and hippocampus) à tactile learning and memory b. Tactile information à motor cortical areas in the frontal lobe à integration of sensory and motor information

a. Descending projections from the somatic sensory cortex à modulate the ascending flow of sensory information at the level of the thalamus and brainstem. - The sensory info will be used for tactile learning and memory, visual motor integration etc.

A basal ganglia syndrome called hemiballismus, which is characterized by

characterized by violent, involuntary movements of the limbs, is the result of damage to the subthalamic nucleus. The involuntary movements are initiated by abnormal discharges of upper motor neurons that are receiving less tonic inhibition from the basal ganglia.

Development of the Nervous System- Embryology

study of embryogenesis the development of an embryo from an egg cell

Lesion in the posterior parietal lobe: Apraxia Apraxia is a motor disorder caused by damage to the brain (specifically the posterior parietal cortex), in which theindividual has difficulty with??

the individual has difficulty with the motor planning to perform tasks or movements when asked, provided that the request or command is understood and he/she is willing to perform the task. Assess apraxia by asking a patient how to use certain objects like a toothbrush or hammer or spoon

Parkinson's Disease

the inputs provided by the substantia nigra are diminished (thinner arrow), making it more difficult to generate the transient inhibition from the caudate and putamen. The result of this change in the direct pathway is to sustain the tonic inhibition from the globus pallidu (internal segment) to the thalamus, making thalamic excitation of the moto cortex less likely (thinner arrow from thalamus to cortex).

the premotor cortex is responsible for??

the premotor cortex is responsible for--some aspects of motor control, including Premotor neurons become active before the onset of anticipated movements, particularly in response to external cues Lesions of the premotor cortex lead to slowing of anticipated movements but do not lead to paralaysis Thus, the premotor cortex acts to prepare the primary motor cortex for planned movements by facilitating appropriate M-1 columns. Other functions include the preparation for movement, the sensory guidance of movement, the spatial guidance of reaching, or the direct control of some movements with an emphasis on control of proximal and trunk muscles of

Components of the motor cortex the supplementary motor area (SMA), has many functions including

the supplementary motor area (SMA), has many functions including the Stimulation of SMA neurons elicits complex movements involving several muscles, particularly movements involving bilateral coordination SMA neurons become active when voluntarily executing complex movements but not when executing simple acts SMA neurons become active when thinking about complex movements even if the movement is not executed particularly in response to internal cues Lesions of the SMA inhibit the ability to perform complex movements Other functions include internally generated planning of movement, the planning of sequences of movement, and the coordination of the two sides of the body such as in bi-manual coordination. Located on the midline surface of the hemisphere anterior to the primary motor cortex Supplementary motor cortex area becomes active when our brain is planning complex movements, movements involving bilateral coordination, so the SMA is not active when executing simple movement

Basal Ganglia In contrast to the upper motor neurons in the motor regions of the cerebral cortex and brainstem, the basal ganglia and cerebellum do not directly influence lower motor neuronal circuitry; instead, these brain regions influence movement by?

these brain regions influence movement by regulating the activity of upper motor neuronal circuits.

Review Structures & Functions Related to Spinal Cord Spinal nerves

• Consist of 31 pairs: 8 cervical, 12 thoracic, 5 lumbar, 5 sacral, and 1 coccygeal. • The spinal cord is continuous with the medulla and ends at the L1-L2 intervertebral space in adults. The spinal cord ends at the L2-L3 level in neonates and infants. • Because the spinal cord is not present below the L1 vertebral level, long roots are required for axons from the termination of the cord to exit the lumbosacral vertebral column. These long roots form the cauda equine within the lower vertebral canal. • Inferior to the end of the spinal cord is the filum terminale, a bundle of connective tissue and glia that connects the end of the cord to the coccyx.

Myotomes • Testing movements at successive joints can help in localizing lesions to specific nerves or to a specific spinal cord level. • For example,

• Muscles that move the shoulder joint are innervated mainly by spinal nerves from spinal cord levels C5 and C6. • Muscles that move the elbow are innervated mainly by spinal nerves from spinal cord levels C6 and C7. • Muscles in the hand are innervated mainly by spinal nerves from spinal cord levels C8 and T1. Usually the physicians will do the clinical assessments and you will get the info from the medical chart

Myotomes • A myotome is that portion of a skeletal muscle innervated by a single spinal cord level, or, on one side, by a single spinal nerve.

• Myotomes are generally more difficult to test than dermatomes because each skeletal muscle in the body is usually innervated by nerves derived from more than one spinal cord level. Developed from the somite, the myotome is the portion of the skeletal muscles innervated at a single spinal cord level or on one side, by a single spinal nerve Ex. The deltoid- the muscles that abduct the arm are innervated by C5 and C6 spinal level

The left hemisection of the cord at C5 produces the following conditions below the C5 level:

• Paralysis on the left side • Loss of discriminative touch and conscious proprioceptive information from the left side • Analgesia and loss of discriminative temperature sensation from the right side.

Dermatome • A dermatome is that area of skin supplied by a single spinal cord level, or on one side, by a single spinal nerve.

• Testing touch in these autonomous zones in a conscious patient can be used to localize lesions to a specific spinal nerve or to a specific level in the spinal cord. Developed from the somite, the dermatome is an area of skin supplied by that spinal nerve Testing touch in these zones in conscious patients may be used to localize lesions to a specific spinal nerve However, usually SCI patients will just tell you directly where the sensation is still normal and where it is not

Corticospinal tract vs Corticobulbar tract Corticobulbar track

• The corticobulbar tract is composed of the upper motor neurons of the cranial nerves. The muscles of the face, head and neck are controlled by the corticobulbar system, which terminates on motor neurons within brainstem motor nuclei. • Corticobulbar pathway axons travel into the brainstem with those of the corticospinal tract. These axons project to cranial nerve motor neurons of the trigeminal, facial, ambiguus, and hypoglossal nucleus , and are involved in control of the muscles of the head and face, including the tongue.

Corticospinal tract

• This is in contrast to the corticospinal tract in which the cerebral cortex connects to spinal motor neurons, and thereby controls movement of the torso, upper and lower limbs. Corticospinal tract controls the movement of our torso, upper limbs, and lower limbs Corticobulbar track is composed of the UMNs of the cranial nerves - The muscles of the face, head, and neck are controlled by this which terminates on motor neurons within brainstem motor nuclei - Branches of corticobulbar - Trigeminal involves chewing muscles, facial involves facial expression muscles, ambiguous is CN involved with swallowing and muscles in your pharyngeal region and hypoglossal nucleus is the movement of the tongue

Cervical Dystonia (CD)

◦ Cervical dystonia, also called spasmodic torticollis, is a painful condition in which your neck muscles contract involuntarily, causing your head to twist or turn to one side. ◦ Both agonist and antagonist muscles contract simultaneously during dystonic movement. ◦ The pathophysiology of spasmodic torticollis is still relatively unknown. Some people who have cervical dystonia have a family history of the disorder. ◦ There is no cure for cervical dystonia. The disorder sometimes resolves without treatment, but sustained remissions are uncommon. ◦ Injecting botulinum toxin into the affected muscles often reduces the signs and symptoms of cervical dystonia. Real cause of cervical dystonia is largely unknown

Effects of spinal region dysfunction on pelvic organ function - Bladder Damage to S2-S4, or the afferents or parasympathetic efferents ◦ Complete lesions that damage any part of the reflexive bladder emptying circuits produce a flaccid, paralyzed bladder.

◦ Could not constrict urinary bladder à The flaccid paralyzed bladder overfills with urine, and when the bladder cannot stretch any further, urine dribbled out. In contrast, complete lesions above the sacral cord ◦ Reflex at the spinal level is normal but the voluntary sphincter control is absent. ◦ Interrupt descending axons that normally control bladder function but do not interrupt sacral level reflexive control of the bladder. This results in a hypertonic, hyperreflexive bladder with reduced bladder capacity. ◦ Because the reflex circuit for bladder emptying is intact, reflexive emptying may occur automatically whenever the bladder is stretched... (remember: no voluntary control due to injury)

Parkinson's disease (PD) Parkinson's disease is a slowly progressive neurologic disorder caused by the loss of dopamine (DA)-secreting cells in the substantia nigra and basal ganglia of the brain.

◦ DA is a neurotransmitter responsible for synaptic transmission in the nerve pathways coordinating smooth and focused activity of skeletal muscles. ◦ Symptoms: ◦ Resting tremor in the limb, especially of the hand when in a relaxed position; tremor usually increases during stress and is often more severe on one side of the body ◦ Rigidity or increased tone (stiffness) in all muscles ◦ Slowness of movement (bradykinesia) and inability to initiate movement (akinesia) ◦ Lack of spontaneous movements ◦ Loss of postural reflexes, which leads to poor balance and abnormal walking (festinating gait) ◦ Slurred speech, slowness of thought, and small, cramped handwriting ◦ There is no cure for Parkinson's disease. ◦ Initial treatment is typically with the antiparkinson medication L-DOPA (levodopa)

Huntington's Disease Also known as Huntington's chorea

◦ HD is a fatal genetic disorder that causes the progressive breakdown of nerve cells in the brain. ◦ HD is typically inherited from a person's parents, with 10% of cases due to a new mutation. ◦ The Huntingtin gene provides the genetic information for a protein called "huntingtin". Expansion of CAG (cytosine-adenine-guanine) triplet repeats in the gene coding for the Huntingtin protein results in an abnormal protein, which gradually damages cells in the brain. ◦ The mutated protein is toxic to certain cell types, particularly in the brain. Early damage is most evident in the striatum, but as the disease progresses, other areas of the brain are also more conspicuously affected. ◦ Symptoms Include: ◦ Personality changes, mood swings & depression ◦ Forgetfulness & impaired judgment ◦ Unsteady gait & involuntary movements (chorea) ◦ Slurred speech, difficulty in swallowing & significant weight loss ◦ There is no cure for HD. ◦ Treatments can relieve some symptoms and in some improve quality of life. The best evidence for treatment of the movement problems is with tetrabenazine.

The functions of the basal nuclei include the following :

◦ Initiation of movements. Neurons of the basal nuclei receive input from sensory, association, and motor areas of the cerebral cortex. Output from the basal nuclei is sent by way of the thalamus to the premotor area, which in turn communicates with upper motor neurons in the primary motor area. The upper motor neurons then activate the corticospinal and corticobulbar tracts to promote movement. ◦ Suppression of unwanted movements. The basal nuclei suppress unwanted movements by tonically inhibiting the neurons of the thalamus that affect the activity of the upper motor neurons in the motor cortex. When a particular movement is desired, the inhibition of thalamic neurons by the basal nuclei is removed, which allows the thalamic neurons to activate the appropriate upper motor neurons in the motor cortex. ◦ Regulation of muscle tone. Neurons of the basal nuclei send action potentials into the reticular formation that reduce muscle tone via the medial and lateral reticulospinal tracts. Damage or destruction of some basal nuclei connections causes a generalized increase in muscle tone. Regulation of nonmotor processes. The basal nuclei influence several nonmotor aspects of cortical function, including sensory, limbic, cognitive, and linguistic functions. For example, the basal nuclei help initiate and terminate some cognitive processes, such as attention, memory, and planning. In addition, the basal nuclei may act with the limbic

Muscle spindles The Ia axon terminal is known as the primary sensory ending of the spindle. Secondary innervation is provided by group II axons that innervate the nuclear chain fibers and give off a minor branch to the nuclear bag fibers. The density of spindles in human muscles varies.

◦ Large muscles that generate coarse movements have relatively few spindles; ◦ In contrast, extraocular muscles and the intrinsic muscles of the hand and neck are richly supplied with spindles, reflecting the importance of accurate eye movements, the need to manipulate objects with great finesse, and the continuous demand for precise positioning of the head.

Myoclonus Dystonia (MD)

◦ Myoclonus-dystonia is a movement disorder that typically affects the upper half of the body. ◦ Individuals with this condition experience quick, involuntary muscle jerking or twitching (myoclonus) that usually affects their arms, neck, and trunk. Less frequently, the legs are involved as well. ◦ MD is caused by loss-of-function-mutations in the epsilon sarcoglycan gene (SGCE). ◦ SGCE is an imprinted gene: Children suffering from this disease inherit the mutation from the father. If the mutated allele is inherited from the mother, the child is not likely to exhibit symptoms. ◦ No cure has been found for myoclonus dystonia. ◦ Symptoms including: ◦ Rapid, jerky movements of the upper limbs (myoclonus) ◦ Distortion of the body's orientation due to simultaneous activation of agonist and antagonist muscles (dystonia). Abnormal muscle tone associated with a movement disorder affecting upper half of the body About 30-50% of the patients have SGCE mutation So far there is no cure

Ischemic Stroke

◦ Results from a sudden cessation of adequate amounts of blood reaching parts of the brain Pathology ◦ Embolism (the lodging of an embolus. An embolus is anything that travels through the blood vessels until it reaches a vessel that is too small to let it pass. ) ◦ Thrombosis (the formation or presence of a blood clot in a blood vessel) Clinical presentation ◦ The vascular territory affected will determine exact symptoms and clinical behaviour of the lesion: ◦ anterior circulation infarct ◦ anterior cerebral artery infarct ◦ middle cerebral artery infarct ◦ posterior cerebral artery infarct ◦ lacunar infarct ◦ striatocapsular infarct ◦ posterior circulation infarct ◦ posterior cerebral artery infarct ◦ cerebellar infarct ◦ brainstem infarct: ◦ midbrain infarct ◦ pontine infarct ◦ medullary infarct

Tourette Syndrome (TS)

◦ TS is a neurological disorder characterized by repetitive, stereotyped, involuntary movements and vocalizations called tics. ◦ Symptoms: ◦ Tics are movements or sounds "that occur intermittently and unpredictably out of a background of normal motor activity" ◦ The tics associated with Tourette's change in number, frequency, severity and anatomical location. ◦ Coprolalia: the spontaneous utterance of socially objectionable or taboo words or phrases ◦ The exact cause of Tourette's is unknown. A person with Tourette's has about a 50% chance of passing the gene(s) to one of his or her children. Tics are believed to result from dysfunction in cortical and subcortical regions, the thalamus, basal ganglia and frontal cortex. There is no cure for Tourette's and no medication that works universally for all

Spinal Region Syndromes Central cord syndrome (Figure (B)) ◦ What have been interrupted and symptoms?

◦ Usually occurs at the cervical level ◦ What have been interrupted ◦ Ascending spinothalamic tracts (pain, temperature; the spinothalamic fibers crossing the midline are interrupted) ◦ Descending motor tracts (if larger lesions, the lateral corticospinal tracts may be interrupted) ◦ Symptoms ◦ Analgesia and loss of discriminative temperature sensation (both sides)

Anterior cord syndrome (Figure (A)) ◦ What have been interrupted and symptoms?

◦ What have been interrupted ◦ Ascending spinothalamic tracts (pain, temperature) ◦ Descending motor tracts ◦ Symptoms ◦ Paralysis (both sides) ◦ Analgesia (the inability to feel pain) and loss of discriminative temperature sensation (both sides)

Neural Tube Deficit - Spinal Bifida Spina bifida occulta

◦ no visible opening outside ◦ no fluid-filled sack outside the body ◦ small birthmark or dimple on the back ◦ small group or cluster of hair on the back ◦ an area of extra fat on the back