Term
| if the CNS cant or doesn't regenerate, how can function be recovered? |
|
Definition
ecovery of function could be due to parallel
pathways to activate motoneurons
• In PNS –only one motoneuron contacts a single muscle fibers
• In CNS ‐ motoneurons receive inputs from multiple afferent
pathways, interneuronal circuits and descending inputs |
|
|
Term
Clinical Presentation with CNS vs. PNS
injury
• Upper vs. Lower motoneuron injury |
|
Definition
Damage to corticospinal tract = UMN
injury
• Damage to motor (and sensory)
peripheral axon = LMN injury |
|
|
Term
| what is the basic mechanism of an ischemic stroke? |
|
Definition
Blood flow deficits, low ATP
levels and energy stores
• ionic disruption, metabolic
failure
• cell death in minutes
•Ischemic penumbra
• mild damage due to collateral
vessels but still metabolically
and ionically challenged
• Dies slowly and lesion
expands |
|
|
Term
| with an UMN vs LMN injury, do you have intact or impaired spinal reflexes? |
|
Definition
LMN injury –hyporeflexia, flaccid
paralysis, denervation atrophy
• UMN injury – hyperreflexia, spastic
paralysis, disuse atrophy |
|
|
Term
what are the general Signs and symptoms associated
with UMN/LMN injury? |
|
Definition
Loss of voluntary movement and conscious sensation
•Autonomic functions (CV, BP effects)
•Reflexes (PNS vs CNS)
•General health
• Cardiovascular deconditioning, earlier disease onset?
• Obesity, diabetes/metabolic syndrome
• Depression, decreased return to work, decreased socialization
• Wheelchair/bedridden/dependent – decubiti (wounds) |
|
|
Term
| Multiple sclerosis: What is it? |
|
Definition
Autoimmune disorders selectively attacking oligodendrocytes
• UMN – corticospinal/CNS axons through body |
|
|
Term
|
Definition
Autoimmune attacking Schwann cells
• LMN – peripheral nerve degeneration |
|
|
Term
|
Definition
Selective degeneration of corticospinal pathways and ventral horn
neurons
• Both, eventually more LMN signs |
|
|
Term
| what are the different types of spastic hypertonia? |
|
Definition
Constellation of involuntary motor signs following damage to
pyramidal/descending tracts
Presentation may vary by lesion types
Spasticity - velocity-dependent resistance to passive muscle stretch
Dystonia – abnormal posturing
Spasms – single or multi-joint, prolonged motor behaviors
Other types
Autonomic dysreflexia (SCI with T6 or higher)
Abnormal co-contraction (anti-gravity muscles)
Bowel and bladder spasticity/incontinence |
|
|
Term
| how long does spastic hypertonia take to appear? |
|
Definition
Typically DOES NOT APPEAR IMMEDIATELY
Takes days/weeks, sometimes months to develop
Indicative of gradual changes in motor system |
|
|
Term
| what is the prevalence of spastic hypertonia? |
|
Definition
ncreased in patients following cerebral damage (stroke, TBI, CP) – approximately 80% of patients
Variable presentation in patients with SCI (treated in 50%
patients |
|
|
Term
| is spaciticity the major component of a patients motor deficit? |
|
Definition
| no. strength has much more to do with it. |
|
|
Term
|
Definition
“Velocity-dependent increase in response to passive muscle stretch or
joint rotation”
Increased during high speed movements
tendon taps increase |
|
|
Term
| what is dystonia or hypertonia? |
|
Definition
abnormal posturing/tonic drive to muscle
often still velocity-dependent |
|
|
Term
| how do you measure spasticity or hypertonia? |
|
Definition
Biomechanical measures to controlled joint rotation
Clinical (Ashworth Scale, Pendulum tests, Tendon taps |
|
|
Term
| does the muscle spindle contribute to spasticity? |
|
Definition
| yes. the faster you pull someones arm the more they will contract. this must be spindle mediated |
|
|
Term
|
Definition
Hip and knee flexion, ankle dorsiflexion to innocuous stimuli
Similarities to normal flexion reflex (low threshold, long-lasting
type II nerve fibers (A betas) get are getting the same response as a type III or IV nerve fiber. the system is hypersensitive |
|
|
Term
| what is an extensor spasm? |
|
Definition
ip co-contraction, knee and ankle extension
Triggered by hip and knee extension, possibly increased with dorsum loading
type II nerve fibers (A betas) get are getting the same response as a type III or IV nerve fiber. the system is hypersensitive |
|
|
Term
|
Definition
Distal rhythmic muscle contraction/joint oscillation with quick stretch (velocitydependent component)
Potential stretch reflex hyper-excitability vs. spasms
type II nerve fibers (A betas) get are getting the same response as a type III or IV nerve fiber. the system is hypersensitive |
|
|
Term
| what is denervation supersensitivity? |
|
Definition
ncreased neurotransmitter receptors and receptor sensitivity
Similar to Ach receptor changes at muscle following nerve
damage – except at the motoneuron |
|
|
Term
| what receptors are responsible for denervation supersensitivity? |
|
Definition
|
|
Term
how is Sprouting/strengthening of afferent inputs to
motoneurons a potential mechanism for hyperreflexia? |
|
Definition
Remaining connections remain intact
Residual neurotrophic support (was used by descending inputs)
Primary afferents sprouting to spinal interneurons (Krenz and
Weaver 1998 |
|
|
Term
| how are Changes in spinal neuronal excitability a potential mechanism for hyperreflexia? |
|
Definition
BRAIN DAMAGE – INCREASED BRAINSTEM DRIVE TO MOTONEURONS
SPINAL DAMAGE - Loss of inputs (descending or modulatory) cause changes in
motoneuron excitability - Generation of plateau potentials without modulatory
inputs |
|
|
Term
| Mechanisms in stroke vs. spinal cord injury may be different. why? |
|
Definition
1) Receptor supersensitivity and enhanced firing
capability in SCI
2) Possibly increased tonic brainstem drive to stroke |
|
|
Term
MODELS OF STROKE–DECEREBRATE
RIGIDITY IN THE CAT.
bulbar = brainstem |
|
Definition
Corticobulbar and corticospinal lesions
1) Release of brainstem inhibition from higher cortical centers
2) Impaired volitional (cortical) control of spinal activity |
|
|
Term
| Descending bulbospinal pathways regulate spinal excitability? How? |
|
Definition
| they turn on that long lasting firing. more monoamine release |
|
|
Term
| what do we see in decerebrate cats? |
|
Definition
| decreased IN/afferent excitability, and we see increased Motor neuron excitability. |
|
|
Term
| what happens with decerebrate posturing? |
|
Definition
"stiffening” of extensor> flexor musculature
Heightened stretch reflex excitability |
|
|
Term
| is extensor tone necessary for locomotion? |
|
Definition
Such extensor “tone” necessary for locomotion with stimulation of brainstem
centers
Too little – decreased weightbearing/ambulation
Too much – decreased stepping (too much extensor tone, limitations in swing phase
This behavior is abolished by spinalization/returns with serotonin or
norepinephrine administratio |
|
|
Term
| what is a decorticate posture in humans? |
|
Definition
vampire sleeping. presumed
disinhibition of rubrospinal
input (UE flexors) and
lateral vestibulospinal (LE
extensors) |
|
|
Term
| what is decerebrate posturing in humans? |
|
Definition
brainstem
damage below red nucleus
– all four limbs extend |
|
|
Term
| what is a model of spinal cord injury with loss of corticospinal and bulbospinal inputs? |
|
Definition
Impaired volitional (cortical) control of spinal activity
2) Decreased neuromodulatory (5HT/NE inputs)
So we get increased IN/afferent excitability and DECREASED MN excitability |
|
|
Term
|
Definition
24 hrs -1 week post-SCI –
substantial depression in
volitional/reflex excitability
Recovery of volitional
activity/reflexes from flaccid
condition
Plasticity of descending
commands
Alteration in reflex function??
Gradually may become
hyperexcitable
“spasms” also become prevalent
(not common in stroke) |
|
|
Term
| why does spinal shock happen?? |
|
Definition
| serotonin and NE receptors become supersensitive. they may turn on without the drug there. |
|
|
Term
| how does behavior following chronic spinalization work? |
|
Definition
Discharge indicative of
plateau potentials
without modulation
Consistent with onset of
gross measures of
spasticity
The amount of plateau
potential activity is
similar to that observed
in “normal” conditions!!
due to long lasting Ca+2 channels |
|
|
Term
| what are some potential clinical implications of spasticity? |
|
Definition
Impaired volitional control - doesn’t impair strength, may cause antagonist activation during
concentric contractions
Impaired function?? – not much data to suggest this
strength/balance/cardiovascular capacity more related to walking
(Saraf et al 2010; Patterson et al 2007)
Upper extremities – strength is also more related to impaired arm
function (Kamper et al 2005)
Impaired self-care/burden on care-givers, particularly in those with severe weakness following neurological injury |
|
|
Term
| what is neuro-developmental technique for treating spasticity? |
|
Definition
Primitive reflex patterns emerge
following injury, similar to developing
infants
Goals: decrease spasticity, improve
function
Treatment:
Inhibit abnormal reflex/postural
responses
-Handling techniques to decrease “tone”
-Marked increase in exercise intensity
increases abnormal responses – so patients
aren’t allowed to work at high intensities |
|
|
Term
| how does the neuro-developmental technique teach someone to walk again? |
|
Definition
Facilitate production of normal
movement
-Use of handling techniques
- Guidance through proper movement
patterns, stop when abnormal
-Progress through developmental sequence |
|
|
Term
| What are some non- NDT treatments for spasticity>? |
|
Definition
temporary changes with stretching, physical activity,
longer with serial casting
Drugs at the neuromuscular junction
Botulinum toxin injection– Botox ® (lasts for 3- 6 months);
dantrolene sodium – Dantrium ®’; oral
Drugs at the central nervous system
Benzodiazepines, Valium ®; oral
Baclofen (GABA receptor B agonist) – Lioresal ®; oral or intrathecal
pump
Agents at the peripheral nerve
Phenol block (axonolysis, recovery in 1 yr, maybe)
Selective dorsal rhizotomy (permanent) |
|
|
Term
| valium and baclofen are both treatments for spasticity. are they ionotropic or metabotropic, and what receptor do they use? |
|
Definition
valium is ionotropic (gaba a)
baclofen is metabotropic (gaba b) |
|
|
Term
| how do we define motor learning? |
|
Definition
process of acquiring capability of skilled actions (simple or complex
skills)
occurs as a result of practice/experience
cannot be observed directly
produces relative permanent change in capability for skilled behavior |
|
|
Term
| how do we define performance? |
|
Definition
Measure of motor learning/skill acquisition
Ability to accomplish a desired motor behavior
Factors (motivation/mood, fatigue, context, experience, skill) |
|
|
Term
| what are the three stages of learning? |
|
Definition
Cognitive Stage
Beginner - basic concepts and
ideas
Higher levels involved -‘thinking about performance”
Associative Stage
Intermediate - awareness of
errors, not yet able to
eliminate
skills refined, errors reduced
but still occur
Autonomous Stage
Advanced – automaticity
Lower levels of brain have
taken control
premotor and dorsallateral frontal lobe help with this |
|
|
Term
| what is the difference between learning and memory? |
|
Definition
Learning “produces relative permanent change”
Memory – storage of the “learned” behavior
Process by which knowledge is encoded, stored, and later
retrieved |
|
|
Term
| what are some examples of bad motor learning? |
|
Definition
Bad: compensatory strategies to perform functional tasks
following paralysis
Inefficient movement strategies
Normal – bad running form
Abnormal - Swinging leg out to advance limb
Learned non-use
More impaired (weak) hand post-stroke
Lower extremity function in incomplete spinal cord injury |
|
|
Term
| What is non-associative vs associative motor learning? |
|
Definition
Non-associative
Habituation –decline in response to repeated benign (or
noxious) stimulus
Sensitization – enhanced response to stimuli after
presentation of a noxious stimulus
Associative –
Classical– increasing responsiveness to a previously
ineffective stimulus; pairing with an effective stimulus
Operant– trial and error learning, reinforcement |
|
|
Term
| what is the early mechanism of learning (what did we used to think about learning?) |
|
Definition
prominent role of the synapse
Mutable
specific “learned” motor behaviors generated with specific
stimuli
Able to generate other behaviors through similar efferent
pathways
Hebbian rule (Donald Hebb 1949)
“ . . . when an axon of cell A excites cell B and repeated
or persistently takes part in firing it, some growth
process or metabolic changes takes place in one or
both cells, so that A’s efficiency as one of the cells
firing B is increased . . .” |
|
|
Term
| what is the aplysia and why is it a model of learning? |
|
Definition
its a sea slug. very well studied.
Simple synaptic circuitry - generates
“learned” motor behaviors
Similar mechanisms involved in
complex learning in CNS of higher
vertebrates
Learning in Aplysia (and other animals,
including human) demonstrate:
Short-term learning (minutes to hours)
Long-term learning (hours to persistent)
Short-term can lead to long-term changes
– but separate mechanisms |
|
|
Term
| what is the simplest learning of the sea slug and what is the mechanism?? |
|
Definition
Habituation of gill
withdrawal reflex
decline with repeated stimuli
return with long delay
Mechanism - decline in NT
vesicle release
Other potential changes
decline in afferent/neuronal
discharge
inhibitory interneurons
activated |
|
|
Term
|
Definition
|
|
Term
|
Definition
enhanced response to stimuli after
presentation of a noxious stimulus |
|
|
Term
| what is the mechanism for sensitization? |
|
Definition
Animal “learns” to respond more
vigorously to same or nonnoxious stimuli
Shock to tail enhances synaptic
transmission,
5HT from tail “facilitating”
interneurons
Increased excitability of pre- and
post-synaptic connections to
siphon-gill withdrawal circuit
Phosphorylate K+
channels, alter
membrane potential and RN
vesicles mobilized to active zone
long-lasting Ca
2+channels
activated |
|
|
Term
| what is the simplest learning of the sea slug and what is the mechanism?? |
|
Definition
Habituation of gill
withdrawal reflex
decline with repeated stimuli
return with long delay
Mechanism - decline in NT
vesicle release
Other potential changes
decline in afferent/neuronal
discharge
inhibitory interneurons
activated |
|
|
Term
|
Definition
decline in response to repeated benign (or
noxious) stimulus |
|
|
Term
| what is the mechanism for sensitization? |
|
Definition
Animal “learns” to respond more
vigorously to same or nonnoxious stimuli
Shock to tail enhances synaptic
transmission,
5HT from tail “facilitating”
interneurons
Increased excitability of pre- and
post-synaptic connections to
siphon-gill withdrawal circuit
Phosphorylate K+
channels, alter
membrane potential and RN
vesicles mobilized to active zone
long-lasting Ca
2+channels
activated |
|
|
Term
| what is the difference between short term and long term sensitization? |
|
Definition
hort term
sensitization
secs to minutes with
single shock
degrades with time
Long term sensitization
hours to days with five
consecutive shocks
requires protein
synthesis |
|
|
Term
| a high intensity stimulus to the tail of the sea slug paired with some other stimulus causes which one: hibituation or sensitization? |
|
Definition
| the shock releases serotonin, which facilitates the drive of the paired stimulus, so it gets sensitized. |
|
|
Term
| what is facilitative and depressive plasticity? |
|
Definition
Changes in anatomical connectivity/physiological function alter
rapidly
Alteration in patterns of activity can alter synaptic plasticity
Repeated, consistent stimuli vs. variable triggers
Use of modulatory pathways to alter responsiveness |
|
|
Term
| know the example of classical conditioning in the sea slug and the mechanism. |
|
Definition
Pre-synaptic mechanisms
enhanced responses = second
messengers
similar to sensitization
Post-synaptic mechanisms
use of glutamate
regular ionotropic responses –
AMPA
separate NMDA receptor
NMDA elicits long-term effects
Diffusible signals?? –
DIFFUSIBLE ONLY TO
STRENGTHEN THE
PRESYNAPTIC TERMINAL
THAT WAS ACTIVE |
|
|
Term
|
Definition
| allows K+ and Na+ through, it is ionotropic, but it can be metabotropic because it can let in Ca+2. |
|
|
Term
| how do glutamate receptors regulate synaptic plasticity? |
|
Definition
AMPA receptor utilized in normal
synaptic transmission
NMDA receptors
open via two mechanisms
presence of glutamate
depolarization removes Mg
2+
Depolarization ensures
Ca2 +
entry –second messenger
activation
Short-, long-term modulation
Diffusible signals to pre-synaptic
cells
Also thought to be the basis of
operant conditioning |
|
|
Term
| what is long term potentiation? |
|
Definition
Non-associative (sensitization)
Use of basic ionotropic receptors only (AMPA)
Dependent on presynaptic Ca influx (IC messengers)
Associative (classical conditioning)
Use of both AMPA (1-3 ms) and NMDA (100-300 ms)
Requires firing of several axons together (co-operativity)
Glutamate bound plus depolarization
IC messenger activated post-synaptically
Coincident firing (associativity)
Generation of retrograde messengers |
|
|
Term
Brief, intermittent, high frequency
stimuli results in what? |
|
Definition
|
|
Term
| what is early vs late LTP? |
|
Definition
Short term (early) – 1-3 hours, use of modulators
Long lasting (late) - > 24 hours – protein synthesis (pre and
post-synaptic) |
|
|
Term
| Consistent, low frequency stimuli causes long term depression. why is this important? |
|
Definition
| it tells us that intensity of activity is very important! |
|
|
Term
LONG TERM DEPRESSION IN CEREBELLAR
CIRCUITS does what? |
|
Definition
| helps cancel out or suppress the error signals |
|
|
Term
| how does calcium help regulate plasticity? |
|
Definition
| in normal synaptic transmission, AMPA receptors bind to glutamate,which allow sodium entry. But if we get a LOT of glutamate release, the depolarization knocks the magnesium out of the NMDA receptor, activating it and allowing calcium to enter the cell. this activates the second messenger system, which can produce nitric oxide to enhance the presynaptic cell, or it can increase availability of AMPA receptors. |
|
|
Term
| how does long term plasticity work? |
|
Definition
| growth factors like BDNF would cause new protein synthesis and new connections to form. |
|
|
Term
| intensity drives the muscle harder, but it also drives plasticity of the nervous system harder. |
|
Definition
|
|
Term
| can you differntiate between short term and long term plasticity? |
|
Definition
Short term plasticity
activation of presynaptic intracellular messenger systems
1-3 hours, no transcription factor activation, no protein
synthesis
Long term plasticity
Requires protein synthesis - synaptic vesicles/terminals
Post-synaptic modifications to accommodate |
|
|
Term
| what are diffusible retrograde messengers? why are they important? |
|
Definition
Small molecules (NO) or larger proteins (GFs??)
Think back to hypoxia article, this helps drive long term potentiation |
|
|
Term
| what types of things factor into levels of neural growth factors? |
|
Definition
Large amounts in development, reduced with age
Increased with physical activity (high intensity)
Increased immediately following injury (first hours to 2 weeks;
definitely for walking Norrie et al 2005; maybe not for upper
extremity, esp very early Kozlowski et al 1996)
Increased with caloric restriction but not calorie deprivation
inflammatory cytokines induce growth factor release as well. |
|
|
Term
| what morphological changes occur in neural cells? |
|
Definition
Dendritic
arborizations
Increased spine
density
Alteration in
synaptic contacts
and density |
|
|
Term
| what are some examples of neuroplasticity (types of recovery)? |
|
Definition
Neural shock resolution (diaschisis – cortical vs
spinal shock) – temporary disruption affecting
neurons far from lesion
Denervation supersensitivity
Unmasking of silent synapses
Redundancy: anatomy ≠physiology
Strengthening of previously little used or quiescent
synapses – “somatotopic organization”
Sprouting
Recovery of motoneuron excitability |
|
|
Term
| What interventions do we use to get someone to walk again? |
|
Definition
| SAID principle. specificity. if they want to walk, you have to walk them! |
|
|
