HPE630

- Advanced Motor Control

An Overview of the Nervous System

Functions of the nervous system:
1. Sensory input
– Information gathered by sensory receptors about
internal and external changes
2. Integration
– Interpretation of the sensory input
3. Motor output
– Activation of effector organs (muscles and glands)
produces a response


Central and Peripheral Nervous System
• The central nervous system (CNS) is the integrative
and control centre of the nervous system
• Consists of the
– Brain
– Spinal cord
• The peripheral nervous system (PNS) is composed of
all the nervous structures located outside of the CNS
• The PNS consists of
– Spinal nerves
– Cranial nerves


Motor (efferent) Division of PNS
1. Somatic (voluntary) nervous system
– Conscious control of skeletal muscles
2. Autonomic (involuntary) nervous system (ANS)
– Visceral motor nerve fibers
– Regulates smooth muscle, cardiac muscle, and glands
– Two functional subdivisions
• Sympathetic
• Parasympathetic













Role of the each division
• Sympathetic
– Mobilizes the body during activity; is the
“fight-or-flight” system
– Promotes adjustments during exercise, or
when threatened
• Parasympathetic
– Promotes maintenance activities and
conserves body energy
– Its activity is illustrated in a person who
relaxes, reading, after a meal



Histology of Nervous Tissue
1. Neurons—excitable cells that transmit electrical signals
2. Neuroglia (glial cells)—supporting cells:
• Astrocytes (CNS)
• Microglia (CNS)
• Ependymal cells (CNS)
• Oligodendrocytes (CNS)
• Satellite cells (PNS)
• Schwann cells (PNS)


Neurons (Nerve Cells)
Special characteristics:
Long-lived (→ 100 years or more)
Amitotic—with few exceptions
High metabolic rate—depends on continuous supply of oxygen
and glucose
Plasma membrane functions in:
Electrical signaling
Cell-to-cell interactions during development
















Classification of neurons
• Multipolar
– Most multipolar neurons are interneurons
– Conduct impulses within the CNS, and integrate
sensory input or motor output
– A chain or a single neuron connecting sensory
and motor neuron
• Bipolar
– All bipolar neurons are sensory neurons, located
in some special sense organ
– Eg. Bipolar cells of the retina
• Unipolar
– Most are sensory
– Conduct impulses along afferent pathways to the CNS for interpretation

Astrocytes
• Support and brace neurons
• Help determine capillary permeability, important for BBB
• Guide migration of young neurons

Microglia
• Microglia are of mesodermal origin
• They are derived from the cell line which also gives rise to monocytes, i.e. macrophage
precursors
• In the case of tissue damage, microglia can proliferate and differentiate into phagocytotic
cells
• Phagocytize microorganisms and neuronal debris

Ependymal and satellite cells
• Ependymal
– The ventricles of the brain and the central canal of the spinal cord are lined with
ependymal cells.
– They form tight junctions and control the exchange of substances between these
regions and surrounding nervous tissue or cerebrospinal fluid
• Satellite cells
– Surround neuron cell bodies in the PNS

Oligodendrocytes (CNS)
• Oligodendrocytes provide the same functionality as the insulation on a household
electrical wire
• Oligodendrocytes form myelin sheath around axons in the CNS
• Have shorter processes

Schwann Cells (PNS)
• Schwann cells (neurolemmocytes)
– Surround peripheral nerve fibers and form myelin sheaths
– The myelin sheath formed by the Schwann cell insulates the axon and improves its
ability to conduct
– Important in axonal injury repair!

Regeneration in PNS
Neurons in the PNS can regenerate their axons
1. After degeneration of distal axon
and myelin, macrophages clean up
debris.
2. Macrophages release mitogens that
induce Schwann cells to divide
3. The myelin-forming Schwann cells
repopulate the nerve sheaths;
Reaction to
4. Schwann cells make Nerve Growth
Factor.
5. Axons sprout, and some sprouts
enter new Schwann cell tubes

Axons sprout into

HEALTHY' DENERVATION' NEUROPATHY'

muscle is no longer stimulated during denervation which causes atrophy
neuropathy is demyalining which
Lecture objectives
• Understand the organization of the nervous system
• Recall the functions of the central nervous system
• Ability to describe the roles of different parts of the peripheral nervous system
• Ability to describe the cells which are part of the nervous system
• Explain the way in which myelination occurs in both the CNS and PNS
• Describe axonal injury and how the PNS can repair peripheral nerves
Basic Neurophysiology
• All cells have a resting membrane potential but not all tissues are excitable
• The RMP of neurons is -70 mv
• Nerves are excitable tissue, that is, they are able to generate an action potential and
transmit them as nerve impulses along the length of the axons

Electrical Signaling in Neurons
• Electrical signaling occurs only in excitable tissues (nerves and
muscle)
• Occurs via changes in membrane potential, which becomes
less or more negative
• Related to opening or closing of various types of ion channels
• Associated with increase or decrease in number of ions
moving into or out of cell





What effect do ion channels have on Vm?

Types of membrane potential changes

Sub-threshold Potentials in Neurons
• Small changes in Vm
• Occur when ligand- or mechanically-gated ion channels
open or close in response to stimulus on neuron
• Decrease over distance
• Sum of sub-threshold potentials determines if neuron is
depolarised above threshold for generation of AP


Temporal summation vs Spatial summation
Temporal
• The stimuli producing the graded potential at the same
location come together
• So rapidly the postsynaptic membrane does not have time to repolarize before the next
stimulus is received.
Spatial
• The graded potentials produced at different locations of the cell membrane add together.
• It is important to remember that the graded potentials can be inhibitory as well as
excitatory

End result – Action potential
• When Sum of Sub-threshold Potentials Exceeds Threshold Potential, Action Potential is
Generated in Axon

Give Axons Myelin!
• In myelinated axons, myelin sheath acts as electrical insulator, reduces loss of current
• Nodes of Ranvier are sections of axon membrane not covered by myelin
• AP’s “jump” from node to node
• Allows increase in AP velocity without increase in axon diameter
• Myelination provides saltatory conduction

Neuronal communication

A synapse is a region at which a neuron communicates with its target cell.
The synapse is composed of 3 parts: (a) the axon terminal; (b) the synaptic cleft, the space
between the cells and (c) the membrane of the postsynaptic cell.
Myelin allows for more coordinated movement as you grow, without it is disjointed movement
(CP)

Chemical Synapses
• Neuron secretes neurotransmitter that binds
to specific receptors on cell membrane of
second neuron
• Most common way in which neurons
communicate
• Axon terminal contains packets of chemical
neurotransmitter



Signal Transmission at Chemical Synapse
1. AP’s arrive at axon terminal
2. Voltage-gated Ca2+ channels open
3. Ca2+ enters cell
4. Ca2+ signals to vesicles
5. Vesicles move to membrane
6. Vesicles dock and release neurotransmitter by
exocytosis
7. Neurotransmitter diffuses across synaptic cleft and
binds to specific receptors
8. Binding of neurotransmitter to receptor activates
signal transduction pathway




There are multiple combinations of neurotransmitters and receptors

Postsynaptic Receptors: Ionotropic – Fast Response
• Ligand-gated ion channels
• Neurotransmitter binding opens channel
• Allows ions to move across membrane of postsynaptic
cell
• Evokes postsynaptic potential (PSP)
• Depending on receptor, PSP’s may be excitatory
(EPSP’s) or inhibitory (IPSP’s)



Postsynaptic Receptors: Metabotropic
• Neurotransmitter binds to receptor that is coupled to G-
protein
• G-protein modulates ion channels directly or indirectly via
intracellular effector enzymes and/or second messengers
• Depending on receptor, produces either EPSP or IPSP
• At slow excitatory synapses, neurotransmitter binds to
receptor, activating G-protein
• Initiates sequence of events that leads to K+ channel
closure by phosphorylation
• K+ channel closure reduces K+ leakage from cell →
depolarisation produces EPSP

Chemical classification of neurotransmitters
1. Acetylcholine
2. Biogenic Amines
– Dopamine, norepinephrine (NE), and epinephrine
– Serotonin and histamine (5-Hydroxytryptamine or 5-HT)
3. Amino Acids
– GABA, Glycine
– Glutamate
4. Neuropeptides
– Endorphins and Enkephalins
– Somatostatin, gastrin, CCK, oxytocin, ADH
5. Purines
6. Gases and Lipids
Acetylcholine (ACh)
• First neurotransmitter to be discovered
• ACh is synthesized from choline and acetyl CoA
• Where does the cell source these?
• ACh formation is mediated by cholineacetyltransferase
(CAT)
• As soon as acetylcholine is synthesized, it is stored within
synaptic vesicles
• Storage and concentration of ACh in vesicles requires
energy

Cholinergic receptors
• Cholinergic receptors respond to acetylcholine
• They can be divided into two distinct types:
– Nicotinic receptors
• Sympathetic ganglia + NMJ
– Muscarinic receptors
• Parasympathetic organs
• Activation results in adenylate cyclase inhibition, phospholipase-C
stimulation and opening of K channels

Nicotinic Cholinergic Receptors
• ACh binds to nicotinic receptor
• Ligand-gated channel opens, allowing passage of both Na+
and K+
• More Na+ moves in than K+ moves out and EPSP results
• Nicotine interferes with nicotinic receptors
• Binding to these receptors lock the ion channels in an
open position
• Causing initial hyper-stimulation and then paralysis
• An active component of cigarettes and the dangerous
patches/gum


Muscarinic Cholinergic Receptors

• Acetylcholine (ACh) binds to muscarinic receptor
and mediates effect via G-proteins
• Effects on postsynaptic cell variable (cell specific)
= Generation of either EPSP’s or IPSP’s
• Present on many end organs (smooth muscle
cardiac muscle, and glands)
• Activated by muscarine and blocked by plant alkaloids such as atropine (belladonna), and
drugs such as ipratropium (used to manage asthma)


Biogenic (mono) amines
• There are four neurotransmitters in this class all distributed
widely throughout the brain:
– Dopamine
– Epinephrine
– Norepinephrine
– Serotonin
• They act as modulators - decreasing or increasing various brain
activities
• As they are all chemically very similar many drugs can affect
their activity
• There are three subclasses of monoamines: catecholamines,
indoleamines and histamine


Catecholamines
• Two Catecholamines are generally associated with the
sympathetic nervous system:
– Epinephrine
– Norepinephrine
• These hormones prepare the body to deal with short-term
stress
• Most sympathetic postganglionic neurons are adrenergic
• Two types of receptors
– Alpha receptors
– Beta receptors

Catecholamines – Dopamine
• Dopamine is present in several brain regions, mainly the corpus striatum
• Plays a role in movement, pleasure and motivation
• Loaded into vesicles via a vesicular monoamine transporter
• Dopamine action is terminated via glial uptake and a Na+ dependent re-uptake
mechanism

Indoleamines – Serotonin
• Serotonin (5-Hydroxytryptamine or 5-HT): The precursor of serotonin
is the amino acid tryptophan
• At most serotonergic synapses this transmitter produces IPSP’s and
its behavioural effects are also inhibitory
• It plays a key role in mood; eating; pain; sleep and dreaming; and
arousal
• At least 7 different receptors

Amino acids as neurotransmitters
• Normally considered when discussing translation and the formation of a polypeptide chain
• Some neurons use amino acids as transmitter substances, the most important being:
• Glutamate and GABA

Glutamate
• Also known as glutamic acid and is found throughout the
brain.
• It produces EPSP's in the postsynaptic membrane but also
directly affects axons by lowering their threshold of
excitation
• Some Oriental foods contain high levels of monosodium
glutamate and this can cause mild neurological symptoms
• Several ionotropic (NMDA, AMPA) and metabotropic
glutamate receptors
• The ionotropic NMDA receptor is involved in the synaptic changes underlying learning and
memory

Gamma-aminobutyric acid (GABA)
• GABA (gamma-aminobutyric acid): Produced from
glutamic acid by the actions of an enzyme called
glutamic acid decarboxylase (GAD)
• It is inhibitory and is widely distributed throughout
the brain
• Two GABA receptors have been identified - the
ionotropic GABAA and the metabotropic GABAB
• The GABAA receptors contain bindings sites for at least
3 different substances, one being for GABA, the
second being for benzodiazepines and third being for
alcohol and barbiturates each of which have inhibitory effects.

Lecture Objectives:
• Describe a Graded and Action potential, how they work, and what main differences exist
between them
• Explain, with particular reference to the major ions involved, how action potentials are
generated and propagated in nerves
• Describe in detail how chemical synaptic transmission occurs
• Compare the slow and fast responses at chemical synapses
• Describe each of the types of neurotransmitters, giving an example and function of each







 Lecture Two: Vertebrate Brain Structure and Function

Early stages of embryonic development
• Begins with fertilization and continues as the embryo travels through the uterine tube
– By 7 days the ICM has become a bi-layered embryonic disc

Organogenesis
• Endoderm
– Epithelial layer of digestive system and organs of the GI tract
• Mesoderm
– First evidence is the appearance of the notochord
– Somites are paired mesodermal blocks and are present by
week 4
• Ectoderm
– Neurulation causes the differentiation of the ectoderm to brain and spinal cord

Primary brain vesicles
• Development at the rostral end of the neural tube
• 3 swellings are present
• The entire human brain develops from these structures
• Prosencephalon
– Forebrain
• Mesencephalon
– Midbrain
• Rhombencephalon
– Hindbrain


Forebrain differentiation
• Involved in conscious awareness and cognition
• Voluntary actions and movements
• Requires interactions between sensory and motor neurons
• Houses the:
– Cerebrum, Cerebral cortex, Diencephalon
• Secondary vesicles sprout off either side of the proencephalon
• Optic vesicles begin to invaginate
• Telenchephalic vesicles
– Consist of the two cerebral hemispheres
– Grow posteriorly and laterally
• The remaining structure is now the diencephalon



Midbrain differentiation
• Involved in the relay and processing of information passing from the
cerebral cortex to the spinal cord
• Consists of three different regions
• Tectum
– Dorsal surface of the mesencephalon
– Houses the superior and inferior colliculi
• Tegmentum
– Houses the substantia nigra and red nucleus
– Damage at the substantia nigra is parkinsons
• Cerebral aqueduct
– Fluid filled space in the middle of the midbrain




Hindbrain differentiation
• Medulla contains neurons that perform both sensory and
motor functions
• Cerebellum plays a role in
– Control of movement
– Understanding the body’s position in space
– Calculating the best sequence of muscle contraction
• Rostral portion of hindbrain develops into cerebellum and
pons = metencephalon
• Myelencephalon houses the Medulla oblongata
• Fluid filled lumen in the centre is the 4th ventricle
• White matter system on the ventral aspect known as the
medullary pyramids






Summary of neural tube development ******* remember this slide******

The adult human brain
• Average mass of 1600 g in adult males and 1450 g in adult
females
• Average weight between 1400-1600g
• Estimated 100 billion plus neurons
• Can generate more than ~20 watts when awake
• Takes up to 25% of blood flow and oxygen
• Nearly 300,000km of blood vessels and no pain receptors
• Correct terms for the brain!

Rostral = towards the head
Caudal = towards the tail


Comparative anatomy

 Basic Neuroanatomy revision
• The cerebrum is the largest division of the brain
• Gyri - Elevated ridges that wind around the brain
• Sulci - Small grooves that divide the gyra
• Fissures - Deep grooves that divide large regions/lobes of the brain

Neuroanatomy
• Today we will focus on the following structures:
a. Cerebral hemispheres
b. Diencephalon (Tween brain)
c. Brainstem (Midbrain, Pons, Medulla Oblongata)
d. Cerebellum

 Frontal lobe
• Primary motor cortex
– Allows conscious control of precise, skilled,
voluntary movements
– Motor homunculi: upside-down caricatures
representing the motor innervation of body regions
• Pre-motor cortex
– Controls learned, repetitious, or patterned motor
skills
– Mirror neurons fire during goal-directed actions as
well as the observation of similar actions
• Brocas area
– Is active as one prepares to speak



Frontal lobotomies
• Pioneered by Dr Moniz
• Adapted surgical techniques were also developed (ice-pick)
• Desired effects
– Diminished rage and aggression
– Poor emotional responses
• Side effects
– Epilepsy
– Poor emotional responses
– Uncontrolled repetitive actions/gestures



Parietal lobe
• Somatosensory cortex
– Receives sensory information from the skin, skeletal
muscles, and joints
– Capable of spatial discrimination: identification of body
region being stimulated
• Somatosensory association cortex
– Integrates sensory input from primary somatosensory
cortex



Occipital lobe
• Its primary function is the processing, integration, interpretation,
etc. of vision and visual stimuli.
• Primary visual (striate) cortex
– Receives visual input from the retina via optic nerve
• Visual association area
– Uses past visual experiences to interpret stimuli


 Temporal lobe
• Primary auditory cortex
– Interprets information from inner ear as pitch, loudness, and
location
• Auditory association area
• Hippocampus
– Major component of the brains of humans and other mammals
– Part of the limbic system
– Implicated strongly in memory
• Wernicke’s Area
– Language comprehension
– Located on the Left Temporal Lobe


Diencephalon (Tween brain)
• Thalamus
– Gateway to the cerebral cortex
– Sorts, edits, and relays information
– Mediates sensation, motor activities, cortical arousal, learning, and
memory
• Hypothalamus
– Autonomic control center for many visceral functions
– Center for emotional response
– Regulates body temperature, food intake, water balance, and thirst
• Epithalamus
– Contains pineal gland

Diencephalon - The hypothalamus
• The hypothalamus is involved in pituitary gland function, emotional and homeostatic
regulation
• Secretes several important hormones
– Anti-diuretic hormone (ADH) + oxytocin
– Growth hormone-releasing hormone (GHRH)

Hypothalamus and aggression
• Removal of cerebral hemispheres but not hypothalamus -> sham rage
• Behavior reversed with small lesions in hypothalamus
• Hypothalamus may normally be inhibited by telencephalon?
• Stimulation of hypothalamus alone could result in aggression
• Medial Vs. Lateral hypothalamus studies on cats + dogs
• Predatory versus affective aggression


 The Brainstem: 3 major divisions

The Midbrain
• Located between the diencephalon and the pons, minimal differentiation
• 2 bulging cerebral peduncles on the ventral side of the midbrain
– Contain descending fibers that go to the cerebellum via the pons
– Descending pyramidal tracts
• The roof of the aqueduct (the tectum) contains the corpora quadrigemina
– 2 superior colliculi
– 2 inferior colliculi
• On each side, the midbrain contains a red nucleus and a substantia nigra

The Pons
• Wedged between the midbrain and the medulla
• Contains
• Sensory and motor nuclei for 4 cranial nerves
• Respiratory nuclei
– Apneustic & pneumotaxic centers work w/ the medulla to maintain respiratory
rhythm
• Nuclei & tracts that process and relay info to/from the cerebellum
• Ascending, descending, and transverse tracts that interconnect other portions of the CNS

Medulla Oblongata
• Contains choroid plexus of the fourth ventricle
• Just above spinal cord-medulla junction fibers
cross over (decussation of the pyramids)
• Cranial nerves VIII, X, and XII are associated with
the medulla
• Autonomic reflex centers
• Cardiovascular center
• Respiratory centers


The Cerebellum
• Dorsal to the pons and medulla
• Subconsciously provides precise timing and appropriate
patterns of skeletal muscle contraction
• Sensory feedback on movements compared with intended
movements
• Signals continuously “inform” the cerebellum of the body’s
position and momentum
• A “blueprint” of coordinated movement is sent to the cerebral
motor cortex and to brain stem nuclei
• Plays a role in word association and puzzle solving

Functional divisions of the cerebellum
• Vestibulocerebellum
– It collects inputs from the visual and vestibular
system
– Consists of flocculus and nodulus
• Spinocerebellum
– Collects information from the muscle and skin
carried by the spinal cord
– Sends efferent output through extrapyramidal
system
• Cerebrocerebellum
– Input comes from the area of the cerebral cortex
controlling sensory and motor functions.


Cerebellar ataxia
• Can result in affected movement from the trunk to the limbs
• Results in clumsy speech patterns, affected eye movements and affected gait
• Bleeding, MS or infections can all be a cause of cerebellar ataxia
• All cerebellar lesions do not manifest in ataxic motor syndromes


LECTURE OBJECTIVES:
• Recall the 3 primary germ layers and explain what they become
• Describe the embryonic stages of brain development from primary and secondary vesicles
• Define the terms gyrus, sulcus and fissure
• Recall the 4 lobes of the brain hemispheres and discuss regions of major significance
• Describe the structures of the diencephalon, specifically the main functions of the
hypothalamus
• Recall the brain regions which are parts of the brainstem and describe their features
• Ability to describe the functions of the cerebellum.


Cerebral white matter – Overview
• White matter contains axons
• Communicating tracts that connect areas
of gray matter
• Projection tracts
– Extend vertically
• Commissural tracts
– Cross from one cerebral
hemisphere to another
• Association tracts
– Connect different regions within
the same hemisphere


White matter in the spinal cord
• Divided into three funiculi – posterior, lateral, and anterior
• Fibers run in three directions
– Ascending fibers, Descending fibers, Commissural (transverse) fibers

Gray Matter of the spinal cord



The big four pathways!
• Corticospinal tract – Voluntary motor
• Dorsal columns/medial lemniscus – Discriminative touch + Conscious proprioception
• Spinocerebellar tract (dorsal and ventral) – Unconscious proprioception
• Spinothalamic tract – Pain/temperature

Descending pathways
• Descending tracts deliver motor instructions from the brain to the spinal cord via a
complex sequence of events
• Some are direct, some involve several higher brain centres
• Motor pathways involve two main neurons
– Upper motor neuron (UMN)
– Lower motor neuron (LMN)
• Divided into Pyramidal and Indirect pathways

Corticospinal tracts
• Originate in the precentral gyrus of brain (aka, primary motor area)
• Pyramidal neuron is the UMN
– Its axon forms the corticospinal tract
• LMN (anterior horn motor neurons)
– Exits spinal cord via anterior root
• Regulates fast and fine (skilled) movements
• Anterior corticospinal tract
– 10%: Axons don’t decussate at the medulla
• Lateral corticospinal tract
– 90%: Axons decussate and form this tract


Corticobulbar tracts
• The nerve fibers of the corticobulbar tract initially follow the same
pathway as the corticospinal tracts
• However, these will begin to synapse with the motor nuclei of the
cranial nerves beginning at the level of the upper pons
• Of interest is that the nuclei of the facial nerve receive bilateral
innervation for some muscles and unilateral representation for others.




Extrapyramidal motor tracts
• Includes all motor pathways not part of the pyramidal
system
• Upper motor neuron (UMN) originates in nuclei deep in
cerebrum (not in cerebral cortex)
• LMN is an anterior horn motor neuron
• This system includes
– Rubrospinal
– Vestibulospinal
– Reticulospinal
– Tectospinal tracts


Vestibulospinal, reticulospinal, tectospinal
• Pathways from vestibular nuclei are important in balance
• Reticular formation has many functions
• Reticulospinal pathways involved in proximal limb control
• Tectospinal important in head and neck movement post
stimulus




Rubrospinal in animals
• Rubrospinal has neurons beginning in the red nucleus and terminating in
the lateral region of the ventral horn
• Innervates arms and forearms not the lower limbs
• Important in animals and non-human primates but debateable in
humans





Role of the Basal ganglia
• Basal ganglia send output directly to
– primary motor cortex
– supplementary motor area
– premotor cortex
– Sent via the thalamus
• Basal ganglia smooth movements by
– facilitating outputs to thalamus
– inhibiting outputs to the thalamus
• Especially active during complex movement
sequences
– Involved in learning about motor sequences
– Inability to learn motor sequences




Basal ganglia
• Selection and initiation of willed movement, but do not
directly project to LMN’s
• Refers to large diverse set of nuclei



Input to basal ganglia
• From the cerebral cortex via corticostriatal
• Large dendritic trees of medium spiny neurons
• Processes converge on globus pallidus and substantia nigra pars
reticulata
• These then make their way to caudate and putamen


Indirect and direct pathways
• The direct pathway - Makes excitatory connections on the
thalamic neurons, exciting motor and cognitive areas of the cortex
• Indirect pathway - Produces the net effect of inhibiting thalamic neurons

Motor neuron lesions
• Upper or lower motor neuron lesion can be distinguished by examination and specific
attributes
• Upper motor neuron lesions
– Above the anterior horn neurons
– Spasticity
– Babinski sign is present
– Loss of dexterity and voluntary skillful movement
• Lower motor neuron lesions
– Flaccid paralysis
– Fasciculation
– Hypotonia
– Babinski is absent

Main Ascending pathways
• The nonspecific and specific ascending pathways send impulses to the sensory cortex
– These pathways are responsible for discriminative touch, pain, temperature,
conscious proprioception (body position sense) etc.
• The spinocerebellar tracts send impulses to the cerebellum and do not contribute to
sensory perception









Dorsal column medial lemniscal pathway
• Detect discriminative touch and body position
• Sensory nerve endings in the skin etc. relay to sensory neurons
• Reach DRG and fibres run only in dorsal column (posterior funiculi)
• Topographically organised spinal cord dorsal columns
• Sensory decussation in medulla, relayed to VPL nucleus prior to input to
somatosensory cortex



Trigeminothalamic pathway
• Cutaneous mechanoreceptor information from the face sent via this
pathway
• Branches of trigeminal nerve (CN V) carry information
• Terminate in appropriate region of the trigeminal brain complex before
relayed to thalamus





Spinothalamic pathway
• Afferent fibres of nociceptors are lightly myelinated or
unmyelinated
• Pain has been divided into a sharp or more diffuse type of
pain
• Include the lateral and anterior spinothalamic tracts
• 1st order neuron: sensory neuron
• 2nd order neuron: interneurons of dorsal horn; synapse
with 3rd order neuron in thalamus
• 3rd order neuron: carry impulse from thalamus to
postcentral gyrus






Spinocerebellar pathway
• Plays a role in reflex and perception
• No conscious sensation
• Transmits information about trunk and lower limb muscles to
cerebellum
• Afferent fibres bifurcate and branch in spinal cord
• Afferent fibres synapse at Clarke’s nucleus and then ascend





Phantom limb syndrome
• Phantom limb syndrome is the perception of sensations, usually including pain, in a limb
that has been amputated
• Patients with this condition experience the limb as if it were still attached to their body as
the brain continues to receive messages
• Does not appear to be affected by where amputation occurs, some patients experience
repressed memories in their phantom limbs
• Case study = ipsilateral receptive fields on the face
• Precisely mapped to the region of the amputated hand


Lecture objectives:
• Explain how sensory and motor nerves are associated travel within the spinal cord
• Ability to describe the organization of white matter, relative to gray matter and other
significant structures within the spinal cord
• Describe the major motor pathways and their function
• Describe the different ascending sensory pathways, the structures involved and their
specific functions
• Explain the role of dermatomes and how they can assist in spinal cord injury diagnosis































Lecture 3: Motor Learning, Memory & Developmental Coordination Disorder

What Is Motor Control?
“The ability to regulate or direct the mechanisms essential to movement.”
Involves the integration between:
1. Physiological
2. Perceptual
3. Cognitive

Closed Loop Control of Movement
The four components of closed loop control systems:

1. Executive:
Makes decisions regarding corrective actions needed
2. Effector:
Carries out those decisions by producing movement
3. Feedback:
Information regarding the actual state of the system
4. Comparator:
Compares expected feedback from the desired state to actual feedback from the present state
and relays any difference (ie. error) to the executive






























Motor control theories:
1. Systems Model
Movement results from the interaction of multiple systems working in synchrony to solve
a motor problem.
Advantage: accounts for adaptability of a variety of environmental conditions
Functional goals, environmental & task constraints play a major role in determining
movement.
Example: Patient A
• Sustained a brain injury. Their goal is to attempt to put on a shirt while seated.
• To be successful at performing this task BOTH Internal and External factors must be
considered
“What are some internal & external factors?”

• Internal Factors:
– Strength - Balance
– Flexibility - Cognition
– Coordination - Motivation
– Pain Level

• External Factors:
– Type of Shirt
– Surface of the seat
– Availability of assistance devices
– External distractions

Dominant theories:
2. Generalized motor program
Central control of movement.
- States there is a neural storage of generalized motor programs for a large class of similar
actions
- GMP are NOT muscle specific however contain variant & invariant features

Example: Patient A
- During initial learning –Manipulate the environment in which the patient practices the
movement (changeable feature!!)
- Begin: Seated on a hard stable surface with options for balance support (reduce
risk of falling)
- Progress: unstable surface

3. Dynamical Systems Theory
Dynamic self-organisation of multiple sub-systems to control movement.
- Proposes there is a neural storage of a sequence of motor steps
- Physical movement is constrained by:
- Individual: Cognition, Motivation etc.
- Environment: Light, Gravity etc.
- Task: Goals, Rules etc.
- While certain movement patterns are preferred they are NOT set. Therefore, new patterns
of movement can emerge.

Dominant theories summary:
• BOTH theories = movement outcome is stored or represented as a motor plan, distributed
at different levels of the CNS.
o Learning or Re-learning è interaction of multiple systems è develop strong
neural connections è viewed as a representation of movement.

Stages of Skill Learning
• Skilled or Learned actions are those that demonstrate:
– Consistency: Repeatable performance
– Flexibility: Adaptability of movement
– Efficiency: Capabilities of the system to perform over various durations
• These vary dependent upon the different skill levels

1. Cognitive
- Early identification & understanding of the skill
- Focus is on “what to do”
- Simple instruction, keep motivation high, feedback is key!
- Creating an environment with emphasis on the key aspects of the movement = positive
learning environment.

2. Associative
- Emphasis is practice “how to perform” the skill
- Longest stage of skill learning
- Errors become less frequent as the synchronization of the mind and muscle occurs
- Demonstrate greater flexibility in performing the skill under multiple environmental
conditions.

3. Autonomous
- Task is executed automatically with minimal thought
- Rates of improvement during this stage are smaller
- Learning is still occurring through new strategies to perform the movement


Learning Style
• Learning occurs through two processes:
– Implicit (passive process): New information acquired through exposure
– Explicit (active process): Seek new information through structure that is presented.
• Occur at different stages and overlap during the learning process

Explicit Learning
Example: Patient A
- Cognitive stage of learning must understand the movements that can be performed with
ê ROM & Strength
- Simple cues should be provided as patient navigates through problem solving
- Explicit learning: Movement patterns constantly adapted by the patient





Implicit Learning
Example: Patient A
- Associative stage of learning = merging of successive movements & regulation of internal
factors (e.g. force) required for the task.
- For example: amount of force & muscle activation required to balance on the chair
- Implicit learning: Modulation and recognition of internal mechanisms within the
movement & environment

Measurement of Learning
Assessed in three ways:
1. Acquisition - Initial practice of skill
2. Retention - Ability to demonstrate attainment of skill
3. Transfer - Performance of a skill with slight variation (e.g. timing and force)
“Skill is not learned until transfer is demonstrated”

Promoting Acquisition
• Practice is required to promote immediate performance, long term retention & skill
transfer
• Things to consider:
– Type of Practice
– The amount of Practice
– Schedule of Practice
• Amount of Practice: More structured practice the better
*However be sure to account for physical & mental fatigue
• Type of Practice:
– Whole: Performing the movement/task as a whole
– Part: Breaking the task into segments to practice
– Massed: Practicing the task in one whole block
– Distributed: Separating practice into multiple sessions throughout the day
– Constant: Task is performed the same way each time
– Variable: Each repetition of the task is altered slightly
• Specificity & Location: Environment or task may need to be modified to ensure some early
level success is achieved
– E.G: Using a foam cup (easier to grasp) instead of glass
• Role of Mental Practice: Cognitive rehearsal & imagery of the task without physically
performing the task (visualize & feel the movement)
– Research shown a combination of mental & physical practice results in greatest
improvements in motor output.
Mental Practice
• Blood flow experiments show mental practice stimulates same areas of brain as does
performance of actual movement
– Pre-frontal areas, supplementary motor cortex, basal ganglia & cerebellum
– Mental practice leads to same plastic changes in cortical output maps as does
actual practice

Case study example:
Child with DCD demonstrates difficulty maintaining balance – for example when walking in a heel
to toe straight line they often fall/stumble.


Developmental Coordination Disorder
“Developmental coordination disorder (DCD) is the term used to describe a range of difficulties 6-
8% of children experience with posture, movement and coordination, without there being a
specific medical reason for these difficulties. These difficulties are severe enough to adversely
affect their everyday function and school activities.”

Prevalence:
• Generally identified between the age of 6 and 12
• 10-19% of school aged children (1993)
• With a more precise definition of DCD, prevalence is estimated to be between 5% and 8%
of all school-aged children (2003)
• Current research suggests this has remained consistent with DCD being prevalent within 5-
9% of school aged children (2013)

Pathophysiology
• Research suggests due to a immaturity of neuronal development in the brain affecting
they way new skills are learned & performed
– The way information is received
– Using this information to organization a specific motor task
= movement appearing awkward & difficulty performing new motor tasks.

• Cerebellum: Develops later compared to other cortical areas = vulnerable to
developmental disorders
• Basal Ganglia: Responsible for force control & motor sequencing
• Parietal region: Considered to be involved with visuospatial processes during motor skill
learning.
• Appears to be multifactorial and often observed with other developmental conditions:
• ADD
• Dyslexia (reading difficulty)
• Asperger's Syndrome
• Current research is investigating pre-natal factors including:
• Genetic Causes
• Premature birth
• Low birth weight

Signs & Symptoms
• Difficulties controlling their posture & proprioception.
• Poor timing
• Impaired Balance
• Difficulty sequencing movements
• Left to Right confusion
• Poor Proprioception
• Impaired dexterity and manipulation
• Poor Handwriting
• Difficulty performing daily life activities
• Speech Impairment (childhood apraxia of speech) and uncontrolled salivation




 • Children with DCD can suffer from severe, long term consequences
– Poor social competency
– Academic and behavioural problems (inattention)
– Low self-esteem
– Withdrawal from social situations
– Anxiety
• These problems worsen overtime, as such early diagnosis and intervention is crucial

Diagnosis
• Requires comprehensive assessment that includes a valid and reliable evaluation of a
child's motor skills.
• There is no ‘gold standard’ test or screening measure that can be solely used to identify
DCD.
• American Psychiatric Association documents the essential features of DCD under four
criteria, all of which should be met for a diagnosis of DCD to be made.

Criterion A: Performance of daily activities require motor coordination is below average given
persons age & mental intelligence.
Criterion B: Poor motor coordination interferes with academic achievements &/or ADL.
Criterion C: Not due to other medical condition (e.g. cerebral palsy, muscular dystrophy).
Criterion D: If other mental condition is observed motor difficulties in are excess then what is
typically observed.

Bruininks-Oseretsky Test of Motor Proficiency
• Consists of 46 items
• Designed to assess children between 4.5 and 14.5 years old
• One item assesses coordination of upper limb
• Seven items assess sequential and simultaneous coordination of upper limbs and lower
limbs
• Each item varies in scoring system, ranging from a pass/fail to a 16 point scale.

Movement Assessment Battery for Children (MABC)
• Most commonly used test of motor impairment
• Performance test includes 32 items, divided into four sets
• Total score = overall measure of motor ability and is referred to as the total impairment
score [TIS]
• Comprised of subtests related to three areas of motor performance:
– Manual Dexterity
– Ball skills
– Static and dynamic equilibrium
– Score resulting in the 5th percentile is indicative of motor impairment

McCarron Assessment of Neuromuscular Development (MAND)
• Standardised Assessment Tool
• 10 items, consisting of 5 fine motor and five gross motor tasks
• Administered to children of all ages
• Neuromuscular Developmental Index [NDI] = measure of overall motor skills, with a mean
of 100 and a standard deviation of 15.
• A score of 85 or less, indicative of DCD.


Considerations
Movement Patterns
– Does the child appear weak at the “core”?
– Walk with normal heal to toe action with symmetrical arm swing?
– Run or jump with explosive muscle power?

Postural control
– Rise from a supine position without the use of hands?
– Can maintain 4-point kneeling while moving one limb?
Action Sequence
– Carry out a series of actions?
Assess ability to perform unilateral vs. bilateral actions


Fitness Assessment Tools (not limited to):
• Leger’s 20m Shuttle Run
• Incremental Treadmill or Cycle Ergometer Protocol
• 6 Minute Run
• Half mile Run
• 1-RM
• Grip Strength
• Curl Up Test
• Push Up Test
• Ball Throw Distance






Prescription
1. Resistance Training
• Strength and power may be underlying deficits that contribute to motor difficulties.
• Recommended minimum of one set of 8 to 10 repetitions, focusing on both multi and
single joint exercises
• Rest intervals of 30 to 120 seconds
• Twice a week training frequency, allowing rest days
• Session should run for at least 20 – 40 minutes, including a warm up and cool down.
• At least, for a 12 week period.
2. Aerobic Training
• Children with DCD often have low cardiorespiratory fitness
• Demonstrate decreased aerobic power compared to their peers
• Implement aerobic exercises that are enjoyable for the child
• Hydrotherapy – reduces any joint/loading pain, increases mobility, assists in developing
muscle power
• Recommended 2-3 times a week for 30-60min
3. Other Modalities
• Implementing technology – promote skill learning and increase stability, balance and
aerobic capacity
– Wi-Fit
• Neuromotor Task Training – Involves function skill training to assist the development of
ADL’s

Safety Considerations
• Each child has different presentations and progressions
• Use machine weights rather than free weights
• Avoid any action/activity that may harm the child
• Ensure before loading the muscle, the child can execute the exercise with the proper
technique
• Judge progression based on level of fatigue.




















Lecture 4: Spinal Cord Dysfunction

Spinal cord dysfunction relates to acquired spinal cord injury (SCI) or spina bifida (SB)
• SCI: usually from trauma, results in compression, contusion or severance of spinal cord or
arteries
• SB: is a congenital neural tube defect; posterior arch of spine fails to close during first month
of pregnancy
Prevalence:
• Most SCI caused by trauma, approx. 10 000 per year in U.S.
• Greatest in 16-30 age group (median age 26 year), and 80% male
• Largely caused by motor vehicle accidents (44%), violence (24%), falls (22%) and sports
(8%) in U.S.

Types:

Epidemiology and pathophysiology

Classifying SCI

SCI: Pathophysiology
SCI Secondary Damage
1. Reduced blood flow to site (largely affects grey matter) = cord swell & cell death
2. Excessive release of neurotransmitters (esp. glutamate) causes neuronal death
3. Blood-brain barrier broken by damage allows immune cells into spinal cord tissue =
development of scar tissue

Autonomic Dysreflexia
• Life threatening reflex action mostly affecting patients with injuries at OR Above level of
T6.
• Causes an imbalanced reflex sympathetic discharge, leading to potentially life-threatening
hypertension.
• Excessive response to pain (infection, full bladder, skin burns) below the injured site when
the individual feels no pain.














Spinal Bifida : Pathophysiology
• Results from failed closure of the caudal end of the neural tube.
• Results in an open lesion or sac that contains dysplastic spinal cord, nerve roots, vertebral
bodies, and skin.
SB Secondary Damage
• About 80% of SB affects lumbosacral nerve roots = sensorimotor and autonomic
impairment to lower body
– Hydromyelia – fluid cavity in central canal of spinal cord, requires surgery
– Tethered cord – stretching of spinal cord with movement/exercise, surgical
correction needed
• SB is a life-long disease
• Overuse injuries (carpel tunnel, tendinosus, arthritis) and osteoporosis common
• Skin care, hygiene important – prevent pressure sores
• Lifestyle diseases typical of non-exercisers
• 30% may have mild-moderate cognitive or learning disabilities
• Low self-esteem, immature social skills, depression

Medical/Surgical Treatment
• Surgery after SCI, may require bone screws, splints, plating or spinal fusion
• Re-Learning of bowel, bladder hygiene
• May have implanted devices: cardiac pacemakers, and functional electrical stimulation
(FES) devices

Pharmacology
Three classes of drugs
• Antispasticity (baclofen/diazapam)
– Side effects include tachycardia, hypotension, CNS/CV depression,
sedation/weakness
– Anticoagulants (warfarin)
– Side effects include haemorrhage, increased bruising
– Antibiotics (Bactrim)
– No important side effects
– Neurogenic bladder treatment may require alpha-blockers – Hypotension
Must check effects of all drugs!!!
• After SCI, serotonin (5-HT) and noradrenaline (NA) levels greatly reduce brain stem-
derived descending neuromodulatory pathways.
• Lack of NA would normally reduce motor neurone excitability, but after some weeks
spasticity increases.

Spasticity
What is Spasticity?
- Velocity dependent increase in muscle tone or muscle stiffness as a result of increased
reflex activity.
Can Result in:
- Involuntary muscle contractions/spasms
- Stiffness or tight muscles when trying to move limbs
- Pain and Weakness



Neuro-diagnostic Testing: Reflexes
• Reflexes require some type of sensory (afferent) signal, and some motor response. Two
types --à
– Direct synapse between the sensory fiber and the motor neuron (monosynaptic)
– Several neurons interposed (polysynaptic reflexes).

• Most of the pathways that descend the spinal cord have a inhibitory effect on spinal
reflexes.
• Damage of the descending tracts = facilitation of reflexes that are mediated at level of the
spinal cord = hyperactive
• After acute damage, spinal reflexes often pass through an initial stage of hypoactivity.

Muscle Stretch “Deep Tendon” Reflex
• Simple reflex, with the receptor neuron having direct connections to the muscle spindle &
alpha motor neurons in the CNS
• Normal muscle stretch reflexes result in contraction only of the muscle whose tendon is
stretched. There is also inhibition of antagonist muscles.

• Peripheral Nerve: Stretch reflexes are depressed, usually out of proportion to weakness
(which may be minimal).
• Spinal cord and brain stem: Stretch reflexes are hypoactive at the level of the lesion and
hyperactive below the level of the lesion.



Considerations affecting the involvement in exercise
• Chronic pain, spasticity, depression, obesity, urinary tract infections and pressure sores
• Dependence on upper extremities (wheelchair/crutches) predisposes overuse injuries,
joint degeneration
• Severe spasticity reduces range of motion
• Standard health issues with inactivity
• ~70% of SB patients have allergic hypersensitivity to latex (natural rubber)
• Exercise, clinical or research equipment with latex (e.g. rubber bands, rubber-
coated dumbbells, latex gloves, blood pressure cuffs)
• Causes allergic symptoms, including wheezing, itching, hives and life-threatening
anaphylaxis

During exercise
• Inability to stimulate autonomic/cardiovascular systems: lack of adrenaline &
thermoregulation difficulties
• Exercise hypotension
• Autonomic dysreflexia – extreme hypertension (>300/200 mmHg), headache, flushing,
goose pimples, sweating/shivering, nasal congestion

Contraindications

Exercise Testing: Endurance
• University of Toronto Arm Crank Protocol – Submax protocol to predict max VO2
o Perform 3 x 5-min stages with 2-min rests
o Predict max VO2 from 12-min wheelchair propulsion test
o Measure RPE & HR
• Stretching prior to exercise testing may help achieve appropriate ROM & warm up
increase aerobic metabolism

Exercise Testing: Strength
• Can use standard strength testing procedures
• May need to watch for stability, pressure sore problems
• May need trunk stabilisation or securing of hands to handles
• Empty bladder prior to maximal performance


General Exercise Testing Considerations
• May need trunk or limb stabilisation (straps, etc.)
• Skin protection (seat cushion and padding)
• Prevent bladder over-expansion (empty before test)
• Environmentally controlled or cool area to compensate for impaired
thermoregulation/sweating
• Use incremental protocols that allow monitoring of HR, BP, RPE and exercise tolerance
• Care for post-exercise hypotension – rest, recline, leg elevation, fluid ingestion

Exercise Prescription: Aerobic
• May utilise wheelchair propulsion on extra-wide treadmill or rollers
• Vigorous sports such as wheelchair basketball, rugby, racing provide extra health
benefits/motivation
• Arm powered cycling enjoyable
• Body weight supported treadmill training shown to be therapeutic in in-/complete SCI
patients.
• But few data to compare physiological outcomes – good improvements in fitness and
capacity, but not better than other training.

• Normal progression requirements, but focus on work large muscle groups where possible
• Heart rate may be hard for patient to record, and may not predict muscle fatigue.
• Be aware of overuse injuries (shoulders) – vary exercises from normal daily movement
patterns
• Increases in power output expected, but increases in max VO2 harder to obtain
• 3-5 days per week, 20-60min per session

Exercise Prescription: Strength
• Strength training in spastic muscles may help manage contractures
• Muscles respond better to slow, controlled movements
• Increase exercise capacity leads to cardiovascular benefits and fatigue resistance for daily
movement
• Standard rules of progression, overload and specificity apply

• Target shoulders, upper arms, back and postural muscles to aid movement capacity
• Ensure bladder is empty before heavy lifting as increased intra-abdominal pressure may
cause damage
• Supervision (for falls, autonomic dysreflexia, etc.) important at all times
• May train balance and coordination with strength training, under supervision
• 2-3 sets of 8-12 reps, 2-4 days per week

Exercise Prescription: Flexibility
• Twice-daily stretching sessions concentrate on shoulder and upper back (thoracic)
flexibility
• Normal stretches held for 15 s (or 30 s), but contractures or postural stretches for up to 20
min
• Continual activity helps maintain ROM, and may also stretch after exercise
• May require special equipment to help improve ROM



 Week 5: Stroke: Causes & Molecular Mechanisms
Definitions:
• Ischemia: lack of circulating blood deprives the neurons of oxygen and nourishment
• Haemorrhage: extravascular release of blood causes damage by cutting off connecting
pathways, resulting in local or generalized pressure injury
• Stroke: occurs when blood flow to the brain is interrupted by a blocked or burst blood
vessel
- Rapidly developing clinical signs of focal or global disturbance of cerebral functions
- Symptoms lasting 24 hours or longer, or leading to death, with no apparent cause other
than a vascular origin
• Transient ischaemic attack (TIA): ischaemic events < 24 hours without apparent
permanent neurological deficits

Background:
Ø Cerebral ischaemia occurs when there is a reduced blood supply to the brain
Subdivided in:
• Focal ischaemia (Stroke)
reduced blood supply to a localised brain region
• Global ischaemia
reduced blood flow to the entire brain (e.g. cardiac arrest)

Stroke can be further subdivided into two categories
Ischaemic stroke (85%)
• Blood clot in a brain artery
(thrombosis or embolism)
• Blocks blood flow to an area of the brain
• Permanent (80%) or transient (20%)

Haemorrhagic stroke (15%)
• Rupture in a brain artery
• Bleeding within the cerebral parenchyma




Ischaemic stroke
Ø Main predisposition when arteries in the brain become narrowed
Ø Ischaemic damage starts when an artery to the brain is blocked
Ø In some cases cerebral vessels form anastomoses
• Protect the brain from infarction
• Limit the amount of damage
Ø Causes of ischaemic stroke
• Thrombosis
• Embolism
• Hypoperfusion
Ø The result is a decrease in cerebral blood flow (CBF)

Haemorrhagic stroke
Ø Represents about 15% of all strokes
Ø Occurs when a weakened blood vessel ruptures
Ø Two types of weakened blood vessels
• Aneurysms
• Arteriovenous malformations (AVMs)
• Most common cause of haemorrhagic stroke is
uncontrolled hypertension
Ø Tumours and injury represent other causes of haemorrhagic stroke

Brain changes induced by ischaemia
• The brain is extremely sensitive to the effects of reduced blood supply requires 500cc of
O2 and 75-100mg of glucose per minute

Ø Central core: brain tissue most severely affected by ischaemia exposed to the most dramatic
blood flow reduction subsequently undergoes acute brain injury
Ø Penumbra: less severely affected by reduction in blood supply delayed injury over several
hours
• Potentially salvageable tissue via post-stroke therapy















Excititoxicity
• Pathological process where neurons are killed by excessive stimulation
• Glutamate is an amino acid and a neurotransmitter which acts by “exciting” neurons
• Excess glutamate is the primary cause for activating the molecular cascade of stroke
resulting in a large calcium influx within the neurons
•

Necrosis
• Death of living cells or tissues, it is not reversible
• Causes: ischaemia, trauma, infection, cancer
• Post ischaemia there is a loss in mitochondrial membrane potential

• Earliest irreversible change: swelling and eventual collapse of the inner
and outer mitochondrial membranes
• The opening of the mitochondrial permeability may also lead to apoptosis

Apoptosis
• Apoptosis is the process of programmed cell death
• Component of the normal cellular life cycle and tissue turnover
• Can occur in neuronal cells post ischaemia
• Occurs hours to days afterwards the apoptotic pathway is initiated
(caspace proteolytic enzymes)
• Features of apoptosis include
o Cell shrinking
o Marked condensation of chromosomes
o Nucleosome fragmentation





What about regaining lost function?

Epidemiology
Ø 16 million strokes each year in the world
Ø Second leading cause of death and a leading cause of disability in the Western World
• 60,000 Australians suffer a stroke per year
• 50% of strokes occur in people over 75
• 20% of strokes occur in people under 55
• Outcome is directly correlated to the length and severity of stroke
• Estimated cost in Australia: $2.6 billion/year

Non-modifiable risk factors:

Risk factor Evidence

Increasing age The incidence of stroke increases dramatically after age 65
Gender Males show an incidence rate of 1.25 compared to women
Family history A positive family history of cerebrovascular disease is often considered a
risk factor for stroke
Prior stroke Someone who has had a stroke is at higher risk of having subsequent stroke
Ethnicity The probability of stroke in black individuals is nearly twice that of white,
while hispanics fall between these two groups

Risk factor Evidence

Hypertension Most important modifiable risk factor for the demonstrated correlation with
cardiovascular and cerebrovascular complications
Diabetes mellitus Increased incidence of stroke in people with diabetes mellitus
Obesity and inactivity Obesity and lack of physical inactivity are major risk factors for cardiovascular
diseases
Cigarette smoking The relative risk for stroke is between 1.5 and 3
Alcohol abuse Alcohol abuse raises blood pressure and increase the risk of stroke
Atherotromboembolia Complications of atheroma (thrombosis or embolism) are the most common
causes of ischaemia and cerebral infarction
Atrial Fibrillation (AF) AF causes the blood to pool and clot, increasing the risk of stroke
Modifiable risk factors (by life style or medication)




Clinical aspects
• 25% of stroke patients die within the first month
• Unilateral sensorimotor impairment
• Paralysis
• Sensory deficit
• Loss of balance and vertigo
• Confusional state
• Headache
• Vision loss
• Speech impairment
• Swallowing disturbance

Diagnosis
Ø Brain Computed Tomography and Magnetic Resonance Imaging
• Gold standard
• Detect brain tissue damaged by ischaemic stroke or haemorrhage
• Carotid Ultrasound = fatty deposits (plaques) in the carotid arteries
• Cerebral angiogram= detailed view of arteries in the brain and neck

Available treatments that improve stroke outcomes
Ø Admittance to a specialised Stroke Unit
• Provides best patient care
• Allows the medical staff to stabilise the physiological parameters
Ø Thrombolytic therapy using tPA (tissue plasminogen activator) and more recently the
thrombectomy
• To be effective needs to be administered within 4.5h after stroke onset
• Brain scan to exclude any haemorragic stroke
• 7% risk of intracranial haemorrhage
Ø Hemicranectomy
• Surgical procedure performed to reduce the effects
of severe intracranial hypertension

Modelling stroke in vitro
• Several injury models that mimic the effect of stroke
• Cortical neurons can be placed within an anaerobic incubator
• Deprivation of oxygen and glucose
• We can then assess the cellular changes and viability
• Glutamate addition to primary neurons
• Glutamate is a severe insult – small concentrations will result in neuronal excitotoxicity
• Used to assess the efficacy of numerous therapeutic compounds

Modelling in vivo
• Currently rat models are used frequently
• The stroke model severity/type is dependent on where the occlusion is and how long it
occurs for
• Success of the treatment is measure by functional assessment of the animal:
– Neurological scale
– Sticky tape test
– Rota-rod test
 – Infarct size following staining
Methodology used during stroke
• Laser Doppler probe attached to the skull to measure the cerebral blood flow
• Cannula inserted in the tail artery to monitor BP, blood gases (pO2, pCO2), pH and glucose
• Through a longitudinal cervical skin incision the ICA, ECA and CCA arteries are exposed
• Silicon filament advanced into the ICA to occlude the MCA
• Treatment administered via the right internal jugular vein
• Animal’s body temperature maintained between 37 – 37.8°C

Global cerebral ischaemia
• EEG probes inserted SC over the skull to record the electrical activity of the brain
• A cannula inserted in the tail artery to monitor BP, blood gases (pO2, pCO2), pH and
glucose
• Through a longitudinal cervical skin incision the transient global cerebral ischaemia is
induced by occluding both CCAs
• Withdrawing arterial blood until the arterial pressure reaches 35 - 40mmHg


Measurement of ischaemic stroke damage































Stroke: Part 2: Exercise Prescription
Range of functional assessment tests:
• Berg Balance Assessment Scale
• Fugl-Meyer Assessment of Stroke
• Action Research Arm Test (ARAT)
• Stroke Rehabilitation Assessment of Movement Measure (STREAM)

Berg Balance Assessment Scale
• Quantitatively assess balance and risk of falls in older adults or stroke patients.
• However, not very useful in more active patients or severely impaired patients due to
ceiling effects.
• 14 item scale (approx. 10-15min to complete)
• Scoring: Global score out of 56

Fugl-Meyer Assessment (FMA)
Post-stroke hemiplegia patients to measure:
• Motor functioning
• Balance
• Sensation & Joint functioning
• The FMA has 5 Domains with a total of 155 items:
• Motor functioning
• Sensory functioning
• Balance
• Joint range of motion
• Joint pain
• Restricted to only assessing gross motor skills rather than complex and fine motor
movements & coordination.
• It takes approx. 50-60min to complete

Upper limb recovery following stroke is poor!!!

Cognitive Assessments
• In addition to physical disabilities, individuals can experience cognitive and/or mental
impairment.
• Problems understanding or articulating language
• Problems associated with thinking and/or memory
• Emotional Disturbances
Tests used to assess cognitive function:
- ACE-R
- MoCA
- Cambridge Cognitive Exam

Importance of Exercise
• Help integrate back into community
• Reduce depression
• Improve social inclusiveness
• Increases learning of visual and auditory tasks and improved association of shapes and
figures
• Increases synaptic plasticity!

Symptoms during exercise
• VO2 max – Approximately half that of age-matched health counterparts
• Breath harder when under exertion (reduced V02 and reduced lower maximal HR)
• Fatigue approximately 2.5 times more rapidly than health aged-matched individuals
• Lack of endurance & fatigue = sedentary lifestyle increase the risk of other co-morbidities

Endurance Exercise Testing
• Normally have lower VO2 due to hemiparalysis/paresis and loss of muscle mass
• Ramped/progressive testing can still be performed on treadmill (with safety harness), bike,
arm ergo

Methods Measures End Point of Test

AEROBIC

Cycle Ergometer (5- 12 lead ECG and/or

10W/min) HR
Volition Fatigue
Arm + Leg Ergometer SBP > 250 mmHg Useful for prescribing
DBP > 115 mmHg exercise intensity
Seated Stepper BP, HR, RPE Ischemic Threshold
Arm Ergometer

ENDURANCE 6 or 12 min walk Distance walked

Useful for clients with
Arm + Leg Ergometer Time of exercise Volition Fatigue and without assistive
above 60% peak devices
power

Strength Exercise Testing
• Strength can be assessed using standard machines, free weights or dynamometers (e.g.
grip strength)
• Proper instruction on technique important – remember patients may have hearing,
comprehension, language or learning difficulties

Methods Measures

STRENGTH

Manual Muscle Test • Force generated on

dynamometer
Isokinetic/Isometric • Peak torque normalized to
Only valid if the
Dynamometer BW
client can isolate
• Kilograms normalized to
Weight machines/cables movement
BW
• Number of repetitions




Flexibility & Body Composition Exercise Testing
• Flexibility about the spine and shoulders can be affected by hemiparesis
• Modified sit & reach tests, and shoulder flexibility (fingers to touch behind back) are useful
• ROM in elbow, wrist, knee and ankle should be monitored regularly
• Obesity a key problem – may use girths, skin folds (unless obese), DEXA and BMI to track
composition

Aerobic Exercise Prescription
• May need to monitor blood pressure during exercise
(note: walking up stairs associated with higher heart rate and blood pressure, so may not use for
some patients)
• Consider aquatic activities, under supervision
• Use of heart rate to set loads may be problematic if:
Goal:
- Improve ADL’s and increase independence
- Increase walking speed
- Decrease associated cardiovascular health risks
Various modes of activity including:
- Upper & lower body Ergometer
- Cycle Ergometer
- Treadmill
- Seated Stepper
40-70% V02peak
3-5 days per week
20-60mins per session (can break the time up across multiple sessions)

Strength Exercise Prescription
• Strength of knee extensors, ankle plantar flexors and hip flexors correlated with gait
performance in stroke patients
• Should progress slowly to reduce DOMS
• Isometric and water resistance exercises a good start
• Good evidence that strength training significantly improves gait re-training



Nature of Strength Post Stroke
1. Strength measures obtained from different muscle groups
- Tend to correlate
- Have internal consistency
- Represent a common underlying factor
2. Muscles on the non-affected side may also be weaker post stroke (60% less compared to
pre-stroke)
- Greater impairment proximal than distal
3. Muscles of the trunk may also be impaired post stroke – therefore can greatly affect
functional activities.

Goal:
- Improve ADL’s and increase independence
- Improve gait and balance
Various modes of activity including:
- Isometric exercises
- Weight machines (pins and cables)
- Free weight (later stages)

3 sets (8-12 reps)
2 days per week
Muscle fatigue may be a factor that limits the number of stets and reps. Progress accordingly

Flexibility & Balance Exercise Prescription
• Target upper and lower body groups (2 times per week)
• Stretch prior to session may help ROM and movement capacity, although it might reduce
maximum strength in muscles
• Particular emphasis on spastic muscle groups

Exercise Considerations/Safety Guidelines
• May hold stretches for up to 20 min for contractures
• Balance and stability a key issue – progress to unstable surfaces under supervision

• Heart rate monitors could be worn in all sessions
• Blood pressure should be monitored before and after training (supervise if BP high after
training)
• Psychological interventions (for depression), goal setting, social environments, etc. may
help exercise adherence
• Think about accessibility (may not drive, etc.) and enjoyment/social interaction

Constraint Induced Therapy
• Repetitive actions with unaffected arm in a sling.
• 5 days a week, 6 hours a day, for three weeks – improvement in raising affected arm and
holding an object steady
• Perform simple tasks such as building blocks, board games, pick-up-put-away
• This massed practice of skills with affected arm is likely responsible for the increase in
cortical reorganization
• Results indicate that:
• Larger shifts of the centre of motor cortical output map
• Enlargement of excitable cortical areas

Role of mental practice
• Imagery of movement which activates the same/similar brain areas that are activated
when movements are actually executed.
• Passive observation of movement has been shown to activate cortical motor areas.
• Imagining movements -> stimulate restitution & redistribute brain activity, which
accompanies recovery of motor function.
• Twelve, 45 min sessions 3 x per week mental imagery training.
• Study reported no enhanced improvement in outcome measures:
• Grip strength
• Hand function (manual dexterity)
• ADL’s (Barthel Index)











Lecture 6: Traumatic Brain Injury
Objectives:
• Define TBI and describe the causes of TBI
• Distinguish between the different types of head and brain related injuries
• Describe the cellular pathology associated with TBI

• A TBI occurs when an outside mechanical force is applied to the head and affects brain
functioning.
– The physical force can consist of a blow to the head (such as from an assault, a fall,
or when an individual strikes his/her head during a motor vehicle accident) or a
rapid acceleration-deceleration event (like a motor vehicle accident).
– It is possible for the brain to become injured even if the head has not directly
struck or been struck by another object.
– The brain can become injured whether or not the skull is fractured.
• The most common causes of TBI:
– Falls (28%)
– Motor vehicle-traffic crashes (20%)
– Being struck by or against an object (19%)
– Assaults (11%)
– Blasts are a leading cause of TBI for active duty military personnel in war zones

Pathology/Pathophysiology of TBI
• Primary brain injury secondary to trauma:
– Cerebral contusions
– Lacerations
– Hemorrhage (sometimes considered secondary)
– Diffuse axonal injury
• Secondary injury to brain tissue:
– Intracranial hypertension
– Brain shift and herniation
– Biochemical processes
– Swelling
– Cerebral ischemia

Pathology/Pathophysiology of TBI
Cerebral contusions: typically in tips/bases of frontal lobes and tips/bases/lateral surfaces of T
lobes.
Lacerations: less frequent but associated with penetrating TBI
Hemorrhage: may be epidural, subdural, subarachnoid, intraparenchymal
Diffuse axonal injury (DAI): occurs due to widespread shearing and stretching of axons and myelin
sheaths in white matter. DAI is best correlate with prolonged coma after TBI.
Intracranial hypertension: most common cause of death from TBI from those surviving initial
injury due to brainstem herniation compromising vital functions.
Brain shift: Pressure effects from bleeds, edema can cause mass effect or brain shift leading to
additional damage to brain tissue.
Brain swelling: can occur due to increased cerebral blood volume or cerebral edema. Swelling may
be localized adjacent to contusions, diffuse within a cerebral hemisphere, or diffuse throughout
both hemispheres.
Cerebral ischemia: can occur even without increased intracranial pressure and may relate to
vascular disruption and vasospasm.





Grading of Injury Severity
• Level of severity can be related to many variables, including the amount of force involved
and the speed at which the head or object was moving at the time of injury.
• Most acute hospital care is focused on limiting or eliminating secondary injury to the brain
– Relieving intracranial hypertension
– Aggressively treating intracranial hematomas
• Duration of Loss of Consciousness:
– In acute hospital settings, tracked hourly/daily often with GCS score (detailed
below).
• Glasgow Coma Scale score:
– Scale to assess responsiveness widely used.
– Evaluates eye opening (score 1-4), motor responses (1-6), and verbal responses (1-
5).
– Total scores range from 3-15 and are sum of 3 subcomponent scores.
Eye Opening Best Verbal Best Motor – 3-
8
Spontaneous 4 Oriented 5 Obeys Command 6

To Voice 3 Confused 4 Localizes 5

To Pain 2 Inappropriate 3 Withdraws 4

None 1 Incomprehensible 2 Flexion 3

None 1 Extension 2

None 1
Severe; 9-12 Moderate; 13-15 Mild injury severity
– Scale values available in website supplementary materials.

Glasgow Coma Scale score:















Common Sequelae following Mild TBI
• Every brain injury is different, with heterogeneity of sequelae being a hallmark of TBI.
• Most common sequelae of a mild TBI (in order of frequency) include:
– Headache
– Fatigue
– Dizziness
• Somatosensory:
– Headaches, fatigue, dizziness, blurred vision, visual field cuts, sensitivity to
light/noise, anosmia
• Motor:
– Hemiparesis, spasticity; slowed performance; poor coordination; dysarthria
• Cognitive:
– Attention/concentration problems; memory problems; slowed information
processing; visuospatial difficulties; executive functioning impairments
• Emotional/Behavioral:
– Decreased initiation; impaired self-awareness; impulsivity; inappropriate or
embarrassing behaviors; depression; irritability/anger
Types of trauma to the CNS
• Blunt force trauma of the brain is the most common
– Induced by transference of Kinetic Energy to the brain by an object or surface with
a relatively broad surface (Bat or Floor)
• Penetrating Force Trauma of the Head
– E.g.: Stab or incised wound
• Gunshot/ Firearm Wounds of the Head
– E.g.: Hand-guns, rifles, shot-guns etc
• Asphyxiation [Diffuse Hypoxic-Ischemic Cerebral Injury]
– E.g.: Hanging, smothering, Carbon Monoxide intoxication etc
• Toxic Injuries e.g. mercury, arsenic, methotrexate

Contusions of brain
• Blunt impacts of the brain on the inner skull plate due to unidirectional inertia of the brain
to violent motion of the skull
• Coup contusions: contusions located beneath point of impact and caused by direct impact
• Contre-coup contusions: contusions located in an area opposite to side of impact

Laceration vs blunt force to the scalp
• A tear of the fibroadipose and aponeurotic scalp due to perpendicular or glancing blunt
force impact (Does it affect nervous tissue?)
• Edges are usually undermined and accompanied by marginal abrasions
• Fractures typically occurs when a mobile head impacts a stationary flat surface

Intracranial hemorrhages
• Neurons are the most sensitive cells, although glial cells (oligodendrocytes and astrocytes)
are also vulnerable
• The most susceptible cells to global ischemia:
– Pyramidal cells of the Sommer sector (CA1) of the
hippocampus
– Purkinje cells of the cerebellum
– Pyramidal neurons in the neocortex

Subdural hemorrhage (SDH)
• Usually occurs without a skull fracture
• Commonly occurs as a result of translational shearing forces on the bridging subdural veins
• May occur without significant blunt force impact
• ↑ proclivity in the elderly due to cerebral atrophy and accentuated subdural space

Subarachnoid hemorrhage (SAH)
• Traumatic SAH commonly occurs around the cerebral fissures
• May accompany cerebral contusions
• Fatal basal SAH can follow severe blunt impacts on the face and forehead; and severe
hyperextension of the head and neck
• The basilar and/ or vertebral arteries are lacerated in such a scenario
• Acute ethanol intoxication and heavy use of alcohol carry an increased risk of SAH
following trivial blunt impact



DAI: Diffuse Axonal Injury
• DAI caused by global disruption of axons due to severe shearing forces
• Results in:
• Immediate primary axotomy
• Delayed secondary axotomy principally due to ischemia
• Example: severe blunt force impacts in any direction
• Immediate loss of consciousness following impact
• No lucid interval
• Sustained unconsciousness and vegetative state until death
• Focal axonal injury may occur in milder forms with recovery of consciousness



PCS and depression following TBI
• Estimated 80-100% of patients with uncomplicated mild TBI experience at least one PCS
symptom in first month post-injury.
• Symptoms often accompanied with feelings of depression, anxiety, fear of permanent
brain damage.
• Most recover completely within 1-3 months after injury, but minority (roughly 10-20%)
experience more persistent symptoms.
• Set of symptoms occurring in loose cluster following mild (sometimes moderate) TBI:
– Headache
– Dizziness
– Difficulty concentrating
– Impairment of memory
– Reduced tolerance for stress, emotional excitement, and alcohol


















Traumatic Brain Injury: Part 2 Exercise Prescription
TBI: Neurological Screening (Exam)
Components of the exam include:
1. Mental Status
• Level of consciousness (may occur during acute stage)
• Orientation (level of disorientation related to severity of the injury)
• Attention & Concentration (often seen in patient with injuries to frontal lobe)
• Memory (long term and short term memory can be affected)
• Calculations (damage to parietal lobe affect mathematical skills)
• Speech & Language (due to damage of the dominant hemisphere)
• Spatial orientation/perception (result from focal injuries to non-dominant parietal
lobe)
• Affect (external facial expressions), mood (internal emotional state), behaviours

2. Cranial Nerves
• Damage or impairment to the 12 cranial nerves directly impact the structure they
innervate.
- Balance
- Vision
- Speech
- Facial expression
Cranial Nerve Innervation

1: Olfactory Sensory Nerve (Smell)

2: Optic Sensory Nerve (Vision)

3: Oculomotor Motor Nerve (Moves Eyes)

4: Trochlear Moto Nerve (Moves Eyes)

5: Trigeminal 1. Opthalmic (Tears/Sensory)

2. Maxillary (Upper Teeth/Sensory)
3. Mandibular
(Chewing/Sensory,Motor)

6: Abducens Motor Nerve (Moves Eyes)

7: Facial Motor Nerve (Facial Expression)

Sensory Nerve (Taste)

8: Vestibulocochlear Sensory Nerve (Vestibular, Cochlear)

9: Glossopharyngeal Motor Nerve (Pharynx)

Sensory Nerve (Tongue)

10: Vagus Motor Nerve (Speech)

11: Accessory Motor Nerve (Cranial & Spinal)

12: Hypoglossal Motor (Tongue)

3. Motor Assessment
• Muscle Bulk: Muscle atrophy after a period of disuse or coma
• Muscle Tone: Often observed increases in spasticity
 • Muscle Strength: Hemiparesis and tetraparesis common following TBI
• Abnormal Movements:
o Dystonia
o Dyskinesia
o Tremor
o Myoclonus

4. Sensation
- Dependant upon the location of the injury
- Thalamus = impairment of all sensory function to the contralateral face and body
- Parietal lobe = Retain pain and temperature but UNABLE to locate this sensation
- SENSORY NEGLECT – Non-dominant parietal lobe is injured

FUNCTIONAL CONSEQUENCES include:
- Inability to detect pain/soreness as a result of injury or fatigue
- Diminished joint position sense may affect individuals ability to perform ADL’s

5. Coordination
Modulated by:
• Corticospinal tracts = Muscle weakness slowing of fine & gross motor tasks
• Basal Ganglia = Slowed initiation of movement & Braykinesia
• Cerebellum = Tremors and inability to gauge speed, force etc. required for given task
• Sensory pathways (posterior columns) = Ataxia due to impaired proprioception
Can be assessed by simple tests including finger to nose and heel to toe walking

6. Reflexes
• Assessment helps to identify the brain region affected
• Hyperactive reflexes is common with corticospinal tract injuries (also associated with muscle
weakness and spasticity)

7. Posture and Gait
Spasticity, contractures and muscle weakness may result in:
• Weak hip flexors & ankle dorsi flexors = impaired swing through and toe clearance
during gait
• Decreased arm swing = due to impaired coordination
*Basal ganglia injury = stooped posture & shuffling gait







TBI: Romberg's Test
Romberg’s Test
- Used to assess the integrity of the dorsal columns of the spinal cord.
- Three inputs to the cerebellum to maintain balance (vision, proprioception & vestibular
system).
Interpretation:
1) If with the eyes open, unable to maintain balance there may be a problem with the cerebellum.
This condition is called as cerebellar ataxia.

2) If closing the eyes exacerbates this then the test is said to be positive (Romberg test positive).
It indicates that the patient is excessively reliant on vision to maintain balance. The problem may
lie in the vestibular or proprioceptive systems.

TBI: Functional Independence Assessment
• Functional Independence Measure
• 18 item, taking 20-30 minutes to administer
• Designed to assess areas of dysfunction in activities which commonly occur in
individuals with any fixed neurologic or musculoskeletal disorders.
• Limitation: With TIB individuals it is not diagnosis specific
• Functional Assessment Measure
• Developed to represent each of the disciplines in an inpatient rehabilitation
program:
• Cognitive, Behavioural, Communication and Community functioning measures
• 12 items used in conjunction with the FIM

TBI: Epilepsy
- Common chronic neurological disorder, more common in TBI patients (as high as 40-50%
post- TBI)
- Characterised by unprovoked seizures
- Due to abnormal, excessive or synchronous neuronal activity in the brain
Risk factors for chronic epilepsy include:
• Score of 8 or below on the Glasgow Coma Scale
• Intracerebral haemorrhage
• Diffuse injury
• Prolonged post-traumatic amnesia
• Depressed skull fracture

TBI: Functional Consequence
• Exercise programming might be affected by
– Deficits in judgement, memory/learning, apathy, easy frustration, loss of inhibition
(particularly if frontal lobe)
– Loss of selected, isolated movement patterns
– Loss of synergy patterns to perform functional movements
– Muscle weakness
– Hypertonia or resistance to muscle stretch
– Hyperactive deep tendon reflexes
– Sensory/perceptual changes (including special senses)

TBI: Importance of Exercise
• Help integrate back into community, reduce depression, improve social inclusiveness
• Increases learning of visual and auditory tasks and improved association of shapes and
figures
• Improves fatigue resistance to allow to return to work
• Minimise weight gain and accumulation of cardiac risk factors

TBI: Influence of prolonged bed rest on aerobic capacity & muscle strength
Cardiovascular changes:
• Postural hypotension
• Loss of aerobic capacity
• Reduction in cardiac output persists past one month
Musculoskeletal:
• Up to 40% loss of muscle strength: loss is more pronounced in the lower limbs versus
upper limbs:
• Decrease in bone density
• Shortening of soft tissues/contractures
• Effects on respiratory system, balance, cognition, sleep, psychiatric function

TBI: Exercise Testing Aerobic
• Following TBI individuals only able to achieve 60-74% of age predicted VO2 max
• Measured by submaximal progressive protocols including:
• Use bicycle, arm/leg ergo or stair climb
• 20-m progressive shuttle
• 12-min run (although typically hard to self pace)
• Treadmill (may need harness to prevent falls
• VO2 max estimated from heart rate, distance travelled (during a set time period) or
workload




TBI: Exercise Testing Strength
• Standard dynamometer tests useful
• Some individuals may have movement limitations (e.g. may only be able to extend knee if
hip is also extending)
• May demonstrate increased fatigue due to muscle weakness
• 1-min sit-up test shown to be reliable and requires little coordination
• Timed pull-up, arm flexion, etc. useful and shown reliable in this population

• Important for addressing muscle weakness
• May need to adapt movement patterns for postural stability issues
• Consider use of Velcro straps if weak grasp
• Follow standard guidelines for strength programming, but may need to progress slower
and target single large muscle groups
• ACSM =


TBI: Exercise Testing Flexibility & Balance
• Arthritic complaints more common in individuals with TBI
• Lesser range of motion
– Multiple joint trauma in addition to brain injury
– Reduced mobility in acute phase of injury (bed rest)
– Heterotopic ossification
– Muscle weakness and hypertonia
– Can often use standard flexibility tests (with goniometer), but may need to
support patient

TBI: Exercise Programming Aerobic
• Selection of mode depends on patient’s impairments
• Target large muscle groups
• Think about specificity of long-term therapeutic goals
§ Centre of mass-base of support control
§ Balance training
§ Walking/jogging - watch for foot drop (increases tripping risk)
• Consider involvement in group exercise to increase adherence and create social
environment (depression is an associated risk factor in TIB)
• ACSM = ____________________














Lecture 7: Chronic Lower Back Pain

 Lecture 8: Neuromuscular Disorders

Human motor pathways:
• The motor system is a window to brain function
• Axons descend from higher brain centres to influence local
circuits in the brain stem
• Pathways flow from the motor cortex to the spinal cord
• These pathways are mapped consistently across individuals, and
can aid in determining the location of lesions


Neurodegeneration
• Selective progressive and irreversible loss of specific vulnerable neuronal populations
• Long prodrome
• specific vulnerabilities àincreasing disability
• Loss of anatomically linked functional circuits
• Astrocytes and oligodendrocytes have a role too

Hallmarks of Neurodegeneration:
Complex disease basis
• Sporadic, familia, environmental, age
• Most will have a common sporadic and uncommon familia form

• Oxidative stress
• Apoptosis, necrosis and autophagy
• Abnormal protein folding, clearing
• Aggregate protein inclusion in surviving neurons
• Reactive glial changes






Parkinson’s Disease
• Second most common neurodegenerative disease
• QoL= Non-motor symptoms > motor decline
• Cognitive impairment: unpredictable and undertreated

Complex aetiology
Clinical diagnosis on presentation
Four cardinal symptoms:
1. Tremor
2. Bradykinesia
3. Rigidity
4. Postural instability
Management is multidisciplinary:
– PT
– OT
– Pharmalogical

Amyotrophic Lateral Sclerosis (ALS)
• Risk increasing with age
• Onset mean age: 56-63years
• Symptoms can be asymmetric
• Increased risk for developing ALS has been suggested for labourers engaged in agricultural
work, factory work, heavy manual labour, exposure to welding or soldering, and work in
the plastics industry

Signs and Symptoms:
• Increasing muscle weakness, especially in arms and legs
• Difficulty speaking
• Trouble swallowing
• Problems with breathing
• Twitching
• Cramping of muscles, mostly hands and feet


Late Symptoms:
• Extreme muscle atrophy
• Reflexes are slow to non-existent
• Excessive drooling
• Babinski’s sign: the big toe dorsiflexes and the other toes fan out
• Increased spasticity (muscle rigidity)
• Weight loss
• Choking
• Cardiac arrest due to respiratory arrest usually resulting in death

Pathophysiology of ALS
• Free radicals.
The inherited form of ALS often involves a mutation in a gene
responsible for producing a strong antioxidant enzyme that
protects your cells from damage caused by free radicals — the by-
products of oxygen metabolism.
• Glutamate.
People who have ALS typically have higher than normal levels of
glutamate, a chemical messenger in the brain, in their spinal fluid.
Too much glutamate is known to be toxic to some nerve cells.

Treatment and Diagnosis
• Diagnosis
– X-rays, MRI, Blood and urine studies
o – Muscle and nerve biopsy
o – Electomyography (EMG)
• Usually end up needing to go to a care home or have hospice
• Patients after diagnosis live usually 3 years
• Riluzole is the only scheduled treatment
• Lithium improved outcomes in SOD1 mice and in people with ALS


Peripheral Neuropathies
• Peripheral Neuropathies are common disorders
• The prevalence of non-traumatic peripheral neuropathies is estimated to be 2.4% in the
general population – 15% in people over the age of 40
• Common in diabetics (60-70% will develop neuropathy)
– Association with amputation
Acute peripheral neuropathy: Guillain-Barre Syndrome
Chronic peripheral neuropathy: Charcot-Marie-Tooth

Guillain-Barre Syndrome
• Acute inflammatory demyelinating polyneuropathy (AIDP)
• Autoimmune inflammatory demyelination
• Motor paralysis with or without sensory symptoms (pain) however sensation is preserved
• Legs > Arms
• High dose IV gamma globulin (2g/kg five consecutive days)
• Good Prognosis

Hereditary Motor and Sensory Neuropathy aka Charcot-Marie-Tooth disease type 1A
• Affects peripheral myelin protein 22
• Progressive distal polyneuropathy
– Begins in intrinsic foot muscles, and then progresses to proximal weakness
– Hammer toes, pronounced arch, thin tapered appearance of legs
• Onset in first 2 decades
First symptoms include:
• Difficulty with heel walking
• Calf atrophy
• Decreased reflexes
• Touch, pain and temperature sensation less commonly involved


Disorders of Muscle
Congenital Muscular Dystrophies
– Myotonic
– Duchenne,Becker

Duchenne Muscular Dystrophy
• DMD affects mostly males at a rate of 1 in 3,500 births.
• There are over 200 types of mutations that can cause any one of the forms of muscular
dystrophy
o Affects the dystrophin gene
• DMD is the most severe and common type of muscular dystrophy, characterized by the
wasting away of muscles.
• Diagnosis in boys usually occurs between 16 months and 8 years.
• Death from DMD usually occurs by age of 30.

Genotype of DMD
• Females carry the DMD gene on the X chromosome.
• Females are carriers and have a 50% chance of transmitting the disease in each pregnancy.
– Sons who inherit the mutation will have the disease.
– Daughters that inherit the mutation will be carriers.
• The DMD gene is located on the Xp 21 band of the X chromosome.
• Mutations which affect the DMD gene.
• 96% are frameshift mutations
• 30% are new mutations
• 10-20% of new mutations occur in the gametocyte (sex cell, will be pass
on to the next generation).
• The most common mutation are repeats of the CAG nucleotides.

DMD Pathology
• DMD gene product: dystrophin
– Absent or nonfunctional in DMD patients
• Associated with muscle cell membranes
– In its absence, a sequence of events occurs that leads to calcium influx into the
muscle cells
• Affects Skeletal, Cardiac, and Smooth muscle

DMD Disease Progression
• Under 2 yrs old – Behave like healthy toddlers
• 2-5 yrs old
o First outward signs of muscular weakness
o Clumsiness, frequent falling, waddling gait, difficulty climbing stairs
o Calf muscles begin to look enlarged
• 6-12 yrs old
o Child walks on toes secondary to Achilles tendon tightening and to compensate for
weak quads
o Weakening pelvic and shoulder girdles -> compensatory lordosis
• 8-14 yrs old
o Lose ability to walk
o Decrease in caloric requirements -> even normal diet leads to obesity
o 95% develop scoliosis
• Adult phase
o Scoliosis + weakened respiratory muscles, inactivity, obesity -> compromised lung
expansion and function
o Vital capacity decreased approximately 50%
o Weak cough -> vulnerable to pneumonia
• Late 20’s
o 90% die of respiratory complications, 10% cardiac







Part 2: Parkinson’s
Impact of Parkinson’s
Society: Cost (AUS 8.3 billion each year, individual $6000)
Family: Caregiving (22 hrs per week)
Social: communication, embarrassment, social isolation, dependence on others (transport)
Financial: Lost wages (individual & caregivers), cost of informal care, changing roles within the
family

Types:
Ideopathic Parkinson’s disease (IPD):
Most common for of Parkinson’s (75-90% of all cases). Cause of IPD is unknown.
Secondary Parkinsonism:
Display similar symptoms as IPD but damage is the result of certain medicines, nervous system
disorder or other illness
Parkinsonism-plus syndromes:
Cause Parkinson’s related syndromes due to multiple system degenerations






Primary Signs and Symptoms
1. Tremor at Rest
- Slow and rhythmic
- Starts on one side of the body slowly spreads to other areas
- External or Internal tremor
2. Rigidity
3. Bradykinesia
- Slow movement
- Decrease in fine motor skills and coordination
4. Gait Impairments
- Decrease in natural arm swing
- Shuffling
- Freezing of gait (feet appear glued to the ground)
5. Balance & Posture Impairments

Secondary Signs and Symptoms
• Increased risk of dementia
• Autonomic dysfunction: drooling, constipation, urinary problems, erectile dysfunction,
excessive sweating, hypohydrosis (lack of sweating)
• Neuropsychiatric problems: hallucinations, delusions, cognitive decline, depression
• Sleep disorders: difficulty falling or staying asleep, restless leg syndrome, REM sleep
disorders
• Sensory disorders: pain, difficulty staying still, loss of smell

Classification
Can be classified by:
1. Stage progression
2. Age onset (<40 [Juvenile], 40-70 yrs, >70 yrs)
3. Clinical Symptoms
4. Mental Status
5. Level of Disability (assessed by screening tools)

Screening Tools
• Symptoms & Severity
• Hoehn & Yahr Scale of Disability
• Independence
• Parkinson’s Disease Questionnaire - 39
• Self-assessment Parkinson’s Disease Disability Scale
• Unified Parkinson’s Disease Rating Scale
• Functional Capacity
• Gait
• Aerobic
• Strength
• Balance
• Timed Up and Go





Screening Tools – Hoehn & Yahr Scale
Stage 1
Signs and symptoms on one side only, symptoms mild, symptoms inconvenient but not disabling,
usually presents with tremor of one limb, friends have noticed changes in posture, locomotion
and facial expression
Stage 2
Symptoms bilateral, minimal disability, posture and gain affected
Stage 3
Significant slowing of body movements, early impairment of equilibrium on walking or standing,
generalised dysfunction that is moderately severe
Stage 4
Severe symptoms, limited walking, rigidity and bradykinesia, cannot live alone, tremor may have
lessened
Stage 5
Cachectic stage, invalidism complete, cannot stand or walk, nursing care

Unified Parkinson’s Disease Rating Scale (UPDRS)
• Allows the longitudinal rating of patient’s capabilities
– Mentation, behaviour and mood
– Activities of daily living
– Motor performance
– Complications of therapy
– Hoehn & Yahr Scale
• Interview plus clinical observation

Contrindications
1. Emotional state – Depression, anxiety, fear of falling, low confidence
2. Cognitive state – Can they comprehend what it is you want them to do?
3. Physical state – Are there balance and coordination deficits and gait instability?
*Depending on stability, choose either standing or seated exercises



Exercise Testing
• Dynamic balance test: sitting and standing, functional reach (reach for object), Berg
Balance Scale, etc.
• Gait observation: stride length and frequency, heel-toe, obstacle avoidance, turn time
• Aerobic tests: Treadmill not a good option when balance and gait difficulties - use bicycle
or arm crank (sub-maximal)
• Strength tests: often done by dynamometers and isokinetic equipment
• Little research, so no clear guidelines for testing… patient specific!

Modes& Goals&& Intensity/Dura3on/
Frequency&
Aerobic(–(arm(&(leg(ergo( (Increase(work(capacity( 60980%(HRmax(
((((((((((((((((((!!!!!!!!!!((((((((((((( 3dpw(
≤60(min((conCnuous(or(
incremental)(
Endurance(–(short(walking( Improve(and(maintain(gait( 20930(min(supervised(
7dpw(
Strength(–(weight( Maintain(strength(of(arms,( Light(weights(
machines,(CKC( legs,(shoulders(&(hips( 1x8912(reps(
3dpw(
Flexibility(( Increase(and(maintain( 193dpw(
ROM( Ideally(everyday(
FuncConal(–(ADLs,(postural( Maintain(ability(to(perform(
changes( as(many(ADLs(as(possible,(
address(postural(changes(

Exercise Neuroplasticity?
• Evidence suggests enhanced neural circuitry between basal ganglia and its thalamic and
cortical connections
• Activity-dependent neuroplasticity
• May improve motor, non-motor and cognitive behaviours in patients with PD

Safety considerations
• Weight assisted treadmills, use of harness
• Recumbent bike, arm ergometer
• Begin with exercises that make the individual feel safe and offer greatest reward
• Monitor HR
• BP cuff with stethoscope
• Climate controlled environment

Neural Control of Gait
What is Gait?
• Rhythmic, alternating, symmetrical limb pattern to provide propulsion in intended
direction
• complex interactions involving the brain, spinal cord, peripheral nerves, muscles, bones
and joints
• Integrated with equilibrium control systems of the moving body - vestibular, visual,
proprioception
• Is adaptive, goal directed activity – learned during latter months of first year

Contributors to normal gait
Equilibrium = ability to assume upright posture and maintain balance
Locomotion = ability to initiate and maintain rhythmic stepping
Musculoskeletal integrity = normal bone structure, joint alignment and muscle function
Neural control = processing inputs from visual, vestibular, sensorimotor


Equilibrium Control
1. Vestibular – inner ear - semi circular canals, utricle, saccule; R&L pairs – signalling via
gravity (U,S) and inertia (SCC) = posture of head with respect to gravity
2. Sensorimotor (Proprioception) – joint, tendon, ligament, muscle and skin receptors –
respond to mechanical forces of stretch, pressure, force, pain
3. Visual – L& R eyes – rods and cones respond to wavelength of light, and light patterns =
coordinate for focusing and tracking movements

Vestibular Nerve
Neural information for posture & balance control from the hair cells of the SCC to
spinal cord
• Direct pathway - cerebellum for control of equilibrium
• Indirect pathway - via the vestibular nuclei (medulla & pons)

Vestibulospinal Tracts
From vestibular nuclei - 2 major descending pathways into the spinal cord emerge
1. Lateral vestibulospinal tract – from lateral vn
• Function: maintains posture and balance: involves neck, back, hips and leg
muscles
2. Medial vestibulospinal tract – from the medial vn
• Function: stabilising and coordinating head position, neck muscles

Central Pattern Generators
• CPG – grouping of neurons /neural circuits that can autonomously generate coordinated,
rhythmic movements.
• Exist in brain stem, spinal cord – mastication, respiration, locomotion
• Can generate movement in absence of movement-related feedback; but constantly
modified by sensory input
Sensory input from hips, knees, dorsum, sole of feet interact with CPGs in SC – to time leg
movements during stance & swing phases
• Feedback inhibition & rhythmic control -> one group excites another and the later inhibits
the former = tonic activity & rhythmic generation.

 Week 9: CEREBRAL PALSY

Epidemiology
• 1 in 400 babies in Australia and world-wide are diagnosed with CP
• Symptoms apparent by about 12 – 18 months of age, but may take until 6 years
• Damage leading to CP can occur in foetal development, during birth, or soon after birth
while nervous system developing rapidly

Pathophysiology
• Characterised by:
o Limited ability to maintain posture & balance
o Changes in muscle and spinal reflex

Category Site of injury Presentation
Pyramidal Cortical region Spastic, Hyperreflexia,
Hypertonia
Extrapyramidal Basal Ganglia & Cerebellum Ataxia, Rigidity
Mixed Combination of above Combination of above

Etiology
• Improper of failure of brain areas to develop
o Occurs within the first or second trimester of birth (embryonic development)
o Disruption in normal development
• Neurological Disorder
o Brain injury (before, during or after birth)
o Lack of oxygen, bleeding in brain, metabolic disorder, or infection of nervous
system

Diagnosis
• Severe CP can be predicted* after birth
o MRI
o Cranial Ultrasonography
o Other imaging techniques

 • Mild to Mod. Early warning signs
o Delayed motor milestones
o Seizures
o Decreased rate of head growth
o Persistently fisted hand

Signs and symptoms
• Depends on the type of Cerebral palsy
• Baby:
o Slow or delayed development (such as holding their heads up or sitting up later
than other babies)
o Unequal movements across their bodies (such as taking no notice of one hand)
o Muscle spasms or feeling stiff when you try to move their joints.
o Some babies with cerebral palsy might have been sick or premature when they
were newborns.
• Children:
o Problems with feeding, pain, sleep and communication
o Intellectual disability or learning disabilities in about 45% of children
o Behaviour difficulties in about 25% of children
o Epilepsy

Pharmacology interventions
• Anticholinergics (uncontrolled body movements)
o E.g. Benztropine
• Anticonvulsants (seizure medications)
o E.g. Gabapentin
• Antidepressants (depression medication)
o Side Effects: Dizziness, Fatigue, Nausea, Dry mouth, Blurred vision
• Antispastic (muscle relaxants)
o E.g. Baclofen
• Anti-inflammatories (pain medication)
o E.g. Aspirin

Surgical interventions
• Orthopedic Surgry
• Botox
o Injected into the muscle to weaken them by interrupting the connection between
the nerves & muscle
o Lasts 3-6 months
o Research found = Decrease in muscle stiffness allows greater ROM and ability to
perform motor tasks
o Side Effects: Blurred vision, loss of strength, fatigue, nausea, respiratory problems
• Selective Dorsal Rhizotomy (SDR)
o Involves cutting of some of the sensory nerve fibres that come from the muscles
and enter the spinal cord (typically lumbar region)
o Side Effects: Back pain, sensory loss, weakened hamstring muscles




Secondary considerations and consequences
• Chronic pain, spasticity, obesity, urinary tract infections and pressure sores
• Dependence on upper extremities (wheelchair/crutches)
• Severe spasticity reduces range of motion, may affect breathing
• Standard health issues with inactivity
• Inability to perform large muscle group exercise exacerbates problems

Screening tools
1. Gross Motor Function Classification System (GMFCS)
• GMFCS examines movements such as sitting
(posture) and walking. Provides:
o Clear description of a child’s current motor
function
o Idea of what equipment or mobility is
required to aid the child
• Classification according to five categories à

2. Communication Function Classification System (CFCS)
• Effective Sender & Receiver with unfamiliar &
familiar partners.
• Effective but slower paced Sender &/or Receiver
with unfamiliar &/or familiar partners.
• Effective Sender & Receiver with familiar
partners.
• Inconsistent Sender &/or Receiver with familiar
partners.
• Seldom Effective Sender & Receiver even with
familiar partners.

3. Manual Ability Classification Scale (MACS)
• Handles objects easily & successfully.
• Handles most objects but with somewhat reduced quality &/or speed of achievement
• Handles objects with difficulty; needs help to prepare &/or modify activities
• Handles a limited selection of easily managed objects in adapted situations
• Does not handle objects & has severely limited ability to perform even simple actions.

Exercise considerations
• “Children with cerebral palsy are likely to also have other impairments in addition to their
motor disability”
• Spinal and hip abnormalities
• Epilepsy/ seizure – medications
• Vision and/or Hearing impairment
• Intellectual/ behaviour disability
• Chronic pain
• Communication issues
• Fatigue
• Secure hands and feet where necessary


Exercise testing
MODE Measures/ comments
Aerobic Arm Cranks ECG, HR, BP, RPE
Wheelchair Use slow cadence if
Cycle ergometer (mild CP) spasticity is a concern
6/12min walk/push test Use incremental protocols
Strength Free Weights Record # of RM’s
Machine Weights # of Reps in 60 seconds
Limited by ROM &
Spasticity
Flexibility Goniometry ROM limited by pain
and/or spasticity

Neuromuscular Gait\Balance Useful to assess to identify
limitation in motor
performance

Exercise programming
Mode Goals Frequency
Aerobic Increase aerobic capacity 40-85% V02 max
& endurance 3-5 days per week
20-40 min per session
Emphasis Duration over
intensity
Strength Improved muscle strength 3 sets 8-12 reps
2 days per week
Following rules of
progression
Flexibility Improve ROM Before and after aerobic
exercise




















 MULTIPLE SCLEROSIS

Epidemiology
• Neurological disease affecting both somatic and autonomic nervous systems
• ~1.7 people per 100,000 diagnosed (incidence), but prevalence is closer to 100 per 100
000 in Australia
• 2 – 3 times greater incidence in women, more likely in those who grew up further from
equator, genetic link
• More common in those with history of immune diseases

Pathophysiology
• Disease of CNS with multiple areas of inflammatory de-myelination, and damage to axons
• T- cells to attach to capillaries in brain and activate macrophages to attack and digest
myelin
• Lesions representing focal areas of inflammatory demyelination seen in cerebral
hemispheres, brainstem and spinal cord
• Diagnose by neurologic deficits and MRI scanning

Clinical subtypes of MS

85% relapsing-remitting MS (RRMS)
• Disease relapses with either a full recovery or a deficit after
recovery
• No progression of disease symptoms


10% primary progressive (PPMS)
• Disease progression from onset with infrequent plateaus
and temporary small improvements
• Continuously worsening with no distinctive relapses


5% progressive relapsing (PRMS)
• Rare type
• Progresses steadily from onset


Secondary progressive (SPMS)
• After initial RRMS may develop into secondary progressive
(SPMS) with more steady decline in function
• Begins as relapse-remitting but continually progresses either
with or without infrequent relapses, plateaus and remissions








Screening tools
1. Functional System Scores (FSS) & Expanded Disability Status Scale (EDSS)
• Based on a standard neurological examination, the 7 functional systems:
o Pyramidal
o Cerebellar
o Brain Stem
o Sensory
o Bladder & Bowel Control
o Visual & Mental Function
• These ratings are then used in conjunction with observations and gait assessments are
used to rate the EDSS.
• FSS - Scale of 0-9 (0 = normal)
• EDSS – Scale 0 (normal neurologic examination) to 10 (death due to MS) in half-point
increments.

2. Multiple Sclerosis Functional Composite (MSFC)
• MSFC is a three-part, standardized instrument for use in clinical studies & trials of MS.
• The MSFC was designed to fulfil three criteria:
o It should be multidimensional to reflect the varied clinical expression of MS across
patients and over time
o The dimensions should change relatively independently over time.
o One component should be a measure of cognitive function. The three components
of the MSFC measure leg function/ambulation, arm/hand function, and cognitive
function.

3. Trunk Impairment Scale
• To measure the motor impairment of the trunk
through the evaluation of static and dynamic sitting
balance as well as co-ordination of trunk
movements.
• Scores range from a minimum of 0 to a maximum of
23.
• If patient scores 0 on the first item, the total score on
the TIS is 0.

4. Functional Independence Measure (FIM)

5. Berg Balance Scale

6. Manual Muscle Testing

7. ROM Testing

8. Gait Assessment
Primary signs and symptoms
• Fatigue and lack of motivation
• Decreased heat tolerance, blurred vision
• Other symptoms include facial numbness
and pain, loss of taste, swallowing difficulty,
loss of coordination of lower limbs before
upper
• Bladder control (excessive urination) and
constipation a problem

Secondary signs and symptoms
• Loss of strength and mass
• Poor balance, postural stability
• Osteoporosis and weight gain from
medications
• Diabetes
• Watch for thermoregulation difficulties and
lack of pain feedback because of poor afferent conduction
• Spasticity common

Importance of exercise
• Exercise is viewed as an important component of disease management
• Early intervention can help to maximise physical abilities through neuroplastic adaptions
• Early intervention preserves neural integrity
• May accelerate the spontaneous restoration of CNS damage
• Aerobic exercise has been associated with gray matter volume and white matter integrity
in patients with MS.
• Slower accumulation of functional limitations and improvements in QOL



Aerobic exercise testing
Aerobic fitness Implementation Measures Special Considerations
tests
Arm ergometer Increase work rate BP, HR, workload Blunted HR response, attenuated BP
8-12W per stage at steady state HR response, impaired thermoregulation,
to predict VO2 fatigue, excessive muscle weakness
peak, RPE

6MWT Measure track, Total distance Spasticity, lower limb weakness and
instruct patient to walked, HP, BP & paralysis will preclude walking tests.
walk track, record RPE Normal range between 512m-640m
distance walked


Strength and endurance exercise testing
Muscular Implementation Measures Special Considerations
strength/
endurance
30 second sit-to- Normal range Number of times client is Poor flexibility, spacticity &
stand (65yr) 12-18 reps able to fully stand with arms muscle fatigue
crossed from a standard
chair



Flexibility testing
Flexibility fitness test Implementation Measures Special Considerations
Goniometry ROM of hip flexors, Contractures &
ankle plantar flexors, Spasticity
shoulders, adductors
and internal rotators
Modified bench sit and Client seated on a table, Distance reached in Contractures &
reach, one foot on floor could also conduct sit hip/trunk flexion Spasticity
other straight and reach test

Exercise prescription
Mode Goals Frequency
Aerobic Increase aerobic capacity & 60-70% V02 max
endurance 3-5 days per week
30 min per session

Strength Improved muscle strength and 1-2 sets 8-12 reps

power 2 days per week
50-70% 1RM

Flexibility Improve ROM Daily



Special considerations

Special considerations Precautions
Sensory loss and balance Perform resistance training, aerobic exercise and flexibility training in a
deficits seated position; Avoid excessive joint range and muscle spasticity
aggravation. Careful progression based on the individuals responses to
exercise & avoid excessive fatigue
Fatigue Perform resistance training on non-aerobic exercise training days

Severe Spasticity Avoid excessive joint range and muscle spasticity aggravation. Work to
correct imbalances & rest at least 1 day between sessions
Thermo sensitivity and Encourage adequate hydration, keep exercise room temperature
reduced sweating response between 20-22 degrees Celsius. Use cooling fans & exercise in the
morning when body temperature is lowest
Higher energy cost of walking Adjust workloads to maintain desired heart rate and check HR, BP & RPE
(2-3 times greater) frequently.
Daily variations in symptoms Provide close exercise supervision and make daily adjustments to
exercise program variables. Careful progression based on an individual’s
abilities.
Urinary incontinence Ensure adequate hydration and schedule exercise in close proximity to
restrooms
Cognitive deficits Provide written instructions, diagrams, frequent instructions and verbal
cues
Exacerbation of symptoms Discontinue exercises and refer client to their physician. Resume
exercise program once symptoms are stable and client is medically
cleared to continue
Unco-ordination in upper Consider using a synchronised upright or recumbent arm/leg ergometer
and/or lower extremities to ensure balance and safety





















 LECTURE 10: NEUROPLASTICITY
A plastic brain? the hurry and the hype
• functional reorganisation
• pruning and branching
• "rewiring"
• short and long term
• depression and potentiation
• cortical remodelling
• synaptogenesis and myelination

NEUROPLASTICITY
The ability for the brain to change itself White matter
What it is: versus
General term; implicated in: Grey matter
Development, learning, post-injury
• ‘Structural’ AND ‘Functional’
• Scaleable
• Applicable to rehab

What it isn’t:
• Unlimited
• Time independent
• Patient independent
• Exact repair
• Always permanent

Phases of neurodevelopment
1. Neural plate formation and induction
2. Neural proliferation
3. Migration and aggregation
4. Axon growth and synapse formation
5. Cell death and synapse rearrangement


Neuronal Death
• Between 40-75% neurons made, will die after migration – death is normal and necessary
• Neurons die due to failure to compete for neurotrophins provided by targets

Cell survival or apoptosis
• What happens to individual neurons?
• Neurotrophin signalling decides the function and fate of the neuron
• Apoptosis will result when no signalling occurs
• Plasticity can result through a glutamate/Ca2+ mediated signal cascade



Postnatal Cerebral Development in Humans
• The human brain develops more slowly than other species, not maturing until late
adolescence
• Brain volume quadruples between birth and adulthood; most of this increase in volume
comes from increased numbers of synapses (synaptogenesis), myelination of axons, and
increased dendritic branching
• In particular, the prefrontal cortex is the last part of the brain to reach maturity as late as
one’s early 20s
• Developed prefrontal cortex is thought to mediate many higher cognitive abilities such as
executive function

Postnatal myelination and synaptic pruning
• Synapses are being pruned from birth
• Synapses are created with extreme speed in the first 3 years of life
• Children have twice as many synapses than adults in the first decade of life
• Coating of myelin is not complete until about age 20
• Areas of the brain that regulate emotion, judgment, and impulse control myelinate during
adolescence

Synaptic plasticity
• Synaptic plasticity involves changes to synaptic communication, something necessary for
memory
• Short-term synaptic plasticity can occur as a result
– Facilitation
– Augmentation
– Potentiation
– Synaptic depression
• Long term synaptic plasticity can occur via long-term depression or long-term potentiation

Hebb’s postulate
• Hebb's postulate of learning (or simply Hebb's rule) (1949), is the following:
“Axons that fire together wire together”
• This rule forms the basis of much of the research on role of synaptic plasticity in memory
and learning
• Has been generalised to include decreases of strength when neuron A repeatedly fails to
be involved in activation of B and generally look at the correlation or covariance of
activities of pre-and postsynaptic neurons

Basic concepts of learning
• Learning: the process by which new information is acquired by the nervous system
• Allows us to adapt our behaviors to the environment
• Ways of learning
– Non-associative learning
– Associative learning





Non-associative learning
• Non-associative learning results when the animal is exposed once or repeatedly to a single
type of stimulus
• Habituation
– The decline in the tendency to respond to an event that has become familiar
through repeated exposure
• Sensitization
– An increase in the tendency to respond to an event that has been repeated; is
more likely when a repeated stimulus is intense

Associative learning
Classical conditioning
– Innate reflex can be modified by association of triggered stimulus with unrelated
stimulus
– Pavlov and his dog
Operant conditioning
– Associating a stimulus with a reward
• Both of these forms of learning require repetitive training prior to change in behaviour
• Learning speech/language can be an example of complex conditioning

Molecular memory
• The simplest model organism for learning and memory is the Aplysia
• Used because of simplicity, size, genetics and ease of study
• Pioneered by Kandel in the 60’s and 70’s
• Other models include C. elegans, zebra fish, frogs, and bees!

Short-term sensitisation
1. Serotonin binds to G-protein coupled receptors,
producing of cAMP
2. cAMP binds regulatory subunit of PKA
3. Phosphorylation of K+ channels, closing the channel.
Reduced K+ outflow from the cell, Prolongs the AP (and
allows more calcium to enter)
4. Opening Ca2+ channels, increase Ca2+ influx
5. Increase the amount of Glu

Long-term sensitisation
1. Prolonged serotonin-induced enhancement of
glutamate release
2. Phosphorylation of CREB (transcription factor)
3. CREB binds to CRE, changes in gene expression

Vertebrate Models of Learning
• Synaptic Plasticity in the Hippocampus
– Properties of LTP in CA1

In response to postnatal injury/change
• The adult brain has a small regenerative capacity
• This means neuroplasticity occurring following brain acute or
delayed brain injuries is remarkable

Compensatory hypertrophy
• Stimulus and paired region do not change, but responds in a
more sophisticated way
– deaf subjects having changes in their vision to
compensate
– blind people having changes in their hearing
– Tendon transfer

The role of exercise
• Exercise increases growth factors in brain making it easier to grow new connections
• Mice that ran on a wheel had twice as many new brain cells as mice housed in standard
cages.
• As a comparison, provided mice with other “enriched” environments (e.g., “free swim”)
yet only running produced the effect.
• Growth was in the hippocampus (learning and memory)

What we know about growth factors and neuroplasticity
• BDNF is important during developmental synaptic rearrangement
• Can stimulate numerous pathways involved in survival and differentiation
• Commonly used to differentiate SH-SY5Y neuroblastoma cells
• Thought to play a major role in post-injury neuroplasticity
• Can we elevate BDNF levels?

What effect does exercise have?
• Preliminary results are encouraging
• Significant improvements in fitness over very short periods of time
• Aerobic exercise has shown improvements in fitness, cognition and motor skills

Where to for stroke treatment?
• Previous work showing aerobic exercises enhancing cognitive functions
• Positive correlation between the mean value of changes in total score of ACER test and
level of serum BDNF
• Possible treatments for a number of neurodegenerative conditions

LECTURE OBJECTIVES
• Explain the term neuroplasticity
• Describe the different types of neuroplasticity and how they arise in the brain
• Describe the relationship between age and neuroplasticity
• What we haven’t covered
– Complexity in signalling relating to developmental stage and interplay with
exogenous feedback, electrophysiological frequency/timing