Neuroplasticity 2 Flashcards
1
Q
Neuroplasticity is the basis for….
A
Both learning in the intact brain and relearning in the damaged brain (the occurs through physical rehab)
2
Q
What is the best and most contemporary hope for treating damage in the nervous system?
A
Active motor learning
3
Q
Traditional neurotherapeutic approaches:
A
abnormal movements result from the lesion; we can facilitate normal movement patterns by applying specific patters of sensory stimulation
4
Q
There is overwhelming evidence that ….
A
the brain continuously remodels its neural circuitry in order to encode new experiences and enable behavioral change
5
Q
what drives neuroplasticity?
A
changes in behavioral, sensory, and cognitive experiences
6
Q
Process of axonal remodeling
A
- intact CST to lumber MN (green)
- targeted DC inflammatory lesion (orange) interrupts CST and local spinal circuits (red)
• Extensive remodeling occurs leading to restoration of damaged connections and functional recovery. - local interneurons near lesion (red) sprout.
• Descending CST is remodeled in two ways: spared hindlimb fibers increase their branching (6); above lesion, (4) damaged CST fibers extend new collaterals contacting preserved spinal interneurons (eg long propriospinal neurons (red) connecting to lumber motor regions.
• Lastly, there is cortical reorganization (3)
7
Q
Spontaneous Recovery
A
recovery in the absence of intervention
8
Q
Restorative (direct):
A
Resolution of temporary changes and recovery of the injured neural tissue itself.
• Additionally, nearby neural tissue takes over identical neural functions to the original damaged tissue, resulting restitution of function.
9
Q
Activity- Induced Recovery
A
Improvements associated with specific activities and training
10
Q
Compensatory (indirect)
A
Different circuits enable recovery of lost or impaired function
11
Q
Function-enabling plasticity
A
changes in cortical representation as a function of forced use paradigms (CIMT)
12
Q
Function-disabling plasticity:
A
changes in cortical representation associated with disuse that reduce motor capabilities and phantom limb sensation or pain after amputation that is attributable to cortical reorganization and sensory-disabling plasticity.
13
Q
Disuse
A
• Learned disuse or nonuse may lead to maladaptive changes in a
recovering CNS.
• Reliance on a less-affected limb after CVA is associated with major
restructuring and neural growth in the contralesional cortex.
• Self-taught adaptive strategies may be adaptive or maladaptive
• Principle of Interference
14
Q
Overuse
A
• Musicians who perform repetitive and prolonged fine finger
movements (pianists), can develop maladaptive focal hand dystonia with abnormal hand and finger postures, muscle cramping, and difficulty coordinating hand and finger movements.
• Bad plasticity in S-M brain areas?
• Principle of Intensity
15
Q
CIMT Principles
A
•Providing extended concentrated practice in using the impaired limb
by scheduling intensive training.
•Increasing use of impaired limb in the treatment and home setting by
reinforcing and forcing its use.
•Emphasizing training of tasks instead of small components (individual
movements).
•Implementing methods for transferring gains made in treatment to
daily life.
•Principles of Use it and Improve it, Specificity, and Repetition
16
Q
Does PNS or CNS regrowth have better outcomes?
A
PNS regrowth
17
Q
Reasons why PNS regrowth has better outcomes than CNS
A
- Central myelin contains inhibitory components that inhibit neurite outgrowth
- Central axons less capable of regenerating with age
- Secondary changes following axotomy –astrocyte proliferation, microglia activation, scar formation, inflammation, invasion by immune cells (These likely minimize trauma to surrounding areas)
18
Q
Central myelin inhibitory components
A
- Nogo
- Myelin-associated glycoprotein (MAG) - structural component of myelin that is capable of promoting the outgrowth of some neurons and inhibiting outgrowth of others.
- Oligodendrocyte myelin glycoprotein (OMgp) –inhibit growth of some neuronal types.
19
Q
Cortical Representation of the Body
A
•Continuously modified in healthy persons in response to activity,
behavior, and skill acquisition. (basically, the definition of plasticity)
•Cortical reorganization occurs after peripheral injury such as
amputation or CNS injury (stroke, TBI)
20
Q
Explain the experiment of monkey’s after amputation
A
- Changes in somatosensory cortical representations in monkeys have been observed after specific training of one hand and after digit amputation (figure) or fusion.
- Braille readers after training (FDI muscle)
21
Q
Amputations
A
- MEPs of muscles proximal to amputation are larger than the equivalent muscles on the opposite side in persons with amputations.
- Stimulation of face or upper body in persons with UE amputation can elicit phantom limb sensation.
- Face and upper body somatosensory representation expanded to occupy hand and arm area
- Principles of Use it or Lose it and Use it and Improve it
22
Q
Fast Mechanisms of Plasticity
A
- Unmasking –what was previously there and inhibited is no longer inhibited
- LTP/LTD: strengthening or weakening of existing synapses
- Membrane excitability change
23
Q
Slower Mechanisms of Plasticity
A
• Sprouting (reactive synaptogenesis): Principle of Use it and Improve it
24
Q
Cross- Modality Plasticity
A
- When deprived of its usual input, the part of the cortex normally responsive to that input may now be responsive to inputs from other sensory modalities
- Principle of Use it or Lose it
25
Example of Cross- Modality Plasticity
* Retinal cells (in ferrets) may be induced to project to the medial geniculate nucleus. Then, primary auditory cortex can respond to visual stimuli.
* Visual neurons to somatosensory cortex
26
Explain Cross- Modality Plasticity in persons blind from an early age
* Task-dependent activation of occipital cortex to tactile-, auditory-, memory-, and language-related
* Not as robust in persons who become blind at a later age
* Even 90 min to 5 days of being blind-folded result in improvements in accuracy during sound localization
27
Reorganization of Affected Hemisphere following Cortical Damage
Ablate somatosensory cortex finger representation in a monkey
Skin surface originally represented in that ablated area were represented in the nearby intact somatosensory area
28
Internal capsule lesion in humans:
recovery of hand function associated with ventral extension of the hand area of the cortex into the area normally controlled by the face
29
What do M1 lesions result in?
activation of secondary motor areas (premotor, SMA, cingulate gyrus)
• Use of more normal activation patterns associated with better recovery compared to overactivation of secondary motor areas.
• Small lesions –recovery may be due to undamaged parallel motor pathways
30
Contributions of Ipsilateral Motor Pathways
* Study with persons who sustained internal capsule stroke who eventually recovered --> Performed fingers to thumb movement while getting a PET scan
* For control subjects and for the unaffected hand of the patients, contralateral motor cortex and premotor areas were active during the task.
* When previously paretic hand was used, both ipsilateral and contralateral motor areas showed increased blood flow. So, ipsilateral pathways were now contributing
31
What is the role of contralesional primary motor cortex to recovery of function?
- Not clear
| • Some evidence contralesional primary motor cortex can impede recovery through increased intercortical inhibition
32
Cerebellar Role in Cortical Injury
•Cerebellar hemisphere opposite to the damaged CST may play an
important role in motor recovery
• Related to role in motor learning --> Establishment of automatic motor skills
• Considered to have an effect from 2-3 months to 6 months poststroke, further suggesting the role it plays is through motor learning processes
33
What does strengthening of brainstem inputs to spinal cord motor neurons do following damage to corticospinal system?
both contributes to and constrains recovery of function
• In monkeys, functional recovery following a CST lesion was associated with increased EPSPs in reticulospinal pathways. Origin: Medial brainstem. Synapsed onto spinal cord neurons for forearm and hand flexor (but not extensor) muscles
• This pattern of recovery (stronger flexor; weaker extensor) is commonly observed in the UE poststroke in humans
34
CST v RST innervation
• CST branch to a small number of MN pools allowing for control of small groups of synergistic muscles insuring independent control.
*** This is the hallmark of what we call individuation or fractionated movement***
35
Damage to CST =
loss of individuated movements of the hand
36
RST axons ....
branch extensively within the spinal cord and contact many MN
pools
37
Is RST bilateral or unilateral system?
Bilateral
Thus, broader, bilateral activation of muscles in the hand
and arm, (not fine, fractionated control)
38
In a non-injured system, what does the CST do to the RST?
CST suppresses activity of the REST system
39
What occurs with CST lesion?
Suppression of RST is lost
| May explain why some patients post-stroke make bilateral movements when attempting unilateral movements
40
Strategies to Enhance Neural Plasticity and Cortical Reorganization
* Principles of Use it and Improve it; Repetition Matters; Intensity Matters
* Monkeys practicing (2K times) to reach for food using middle three fingers
* Cortical map showed significant increase in the area for those fingers only.
* Training-induced reorganization of the somatosensory cortex.
* Receptive fields larger in those fingers
41
Explain cortical remapping following two weeks of intensive training of the affected
Increased size of motor output area in affected hemisphere was associated with significant improvements in motor function of the hand.
Functional improvements still present 6 months after training.
Hand area between the two hemispheres also equal suggesting a return to balanced excitability between hemispheres
42
Cortical Remapping poststroke and in CP
Principle of Specificity
43
Hand-arm-bilateral intensive training:
Progression of task difficulty, repeated practice of isolated movements that included complex motor tasks, and repetition of functional goals promoted plasticity in the motor cortex (hand motor map)
44
Does all training induce cortical reorganization?
* No
* Skill learning is associated with cortical reorganization --> Exercise (independent of skill acquisition) may affect angiogenesis
45
Early and intense forced motor behavior after a neural lesion can lead to
- Undesirable neurodegeneration in vulnerable tissue
| - Principle of Timing Matters
46
Is training in combination with pharmacological treatments good?
- It holds promise
| - Principle of Salience Matters!
47
What has been used to decrease cortical activity?
- Cortical stimulation to the contralesional cortex
- Reduces abnormal inhibition of the affected hemisphere by the intact hemisphere
- May need to be provided during or before training --> After training resulted in poorer outcome
48
What are combinations of charm-training or cortical stim-training typically called?
Priming
49
Strength Training the less affected side (in stroke)
Rather than seeing changes in intracortical inhibition or motor cortex excitability, it is likely that changes occurred in the spinal cord (spinally-mediated reflexes)
50
Priming Techniques
- Interventions that may prepare the sensorimotor system for subsequent motor practice, thereby enhancing its effects
- Principle of Transference
51
Priming- Mirror Therapy
- Use visual input for priming
- The patient observes specific movements or tasks performed by the therapist or by their nonparetic limb reflected in a mirror placed at the body’s midline
- Frontoparietal circuitries respond not only during one’s own
movement but also during the observation of others’ movements -->
Observation may promote activation of these circuitries
52
Active passive bilateral priming to UE task specific training
* Same activities are performed with both limbs simultaneously
* Unaffected active wrist flex/ext drives passive ROM of affected wrist
53
Active passive bilateral priming to UE task specific training Exclusion Criteria
complete sensory loss, neglect, cerebellar stroke
54
Principle 1: Use it or Lose it
* Neural circuits not actively engaged in task performance for an extended period of time begin to degrade
* CIMT poststroke would be a counter measure to this
55
Principle 1: Use it or Lose it Examples
Amputation; auditory or visual deprivation studies
• Blind subjects showing activation of visual cortex during tactile tasks such as Braille reading.
• Deaf subjects showing auditorycortical activation to visual stimuli
56
Principle 2: Use it and Improve It
• Training that drives a specific brain function can lead to an enhancement of that function
57
Principle 2: Use it and Improve It Examples
motor skill training; ‘acrobatic’ training in rats with S-M cortex damage promoting reactive synaptogenesis
58
Principle 3: Specificity
* The nature of the training experience dictates the nature of the plasticity
* Practice associated with acquisition of a novel or reacquisition of a lost skill is associated with changes in motor cortex, repetition of a movement already learned is not
* Skill learning (practice gait if you want to improve gait)
59
Principle 4: Repetition
* Induction of plasticity requires sufficient repetition.
* Repetition of a newly learned (or relearned) behavior is required to induce lasting changes
* This qualifies the previous principle
* Repetition of skilled movement
60
Principle 5: Intensity
* Induction of plasticity requires sufficient training intensity
* Sufficiently intense to stimulate experience-dependent neural plasticity
* Training must be progressively modified to match the dynamic and changing skill level of the patient –to ensure continued neural adaptation
61
• Interaction between timing and intensity during training?
- VECTOR study
• Acute stroke (2 weeks); CIMT (2hrs) vs conventional (OT also 2 hrs) vs Hi-CIMT (3hrs). CIMT and conventional best with no difference between the two. Hi-CIMT worst outcome.
• More intensity in acute phase may not be the answer. Distributed practice for acute phase
62
Principle 6: Time Matters
* Neuroplasticity underlying learning is a process, not a single measurable event
* In motor skill training, gene expression precedes synapse formation, which precedes motor map reorganization
63
Time in the recovery process
- 5-wk period of rehab started 30-days after cerebral infarct was far less effective in improving functional outcome and in promoting growth in cortical dendrites than the same regimen initiated 5-days after infarct
- Time delays may allow for greater establishment of self-taught compensatory behaviors --> But this may interfere with rehab training
64
Principle 7: Salience
• Training must be functionally relevantand significant to the individual.
• For an activity to be salient, it must be an activity that the person wants to do
- Speaks to attention and motivational processes
65
Principle 8: Age Matters
* Experience-dependent synaptic potentiation, synaptogenesis, and cortical map reorganization are all reduced with aging.
* But these things still occur!
* Considerations for prognosis
66
Principle 9: Transference
- refers to the ability of plasticity within one set of neural circuits to promote concurrent or subsequent plasticity
67
What does exercise promote?
Angiogenesis in motor cortex and cerebellum and in expression of factors (neurotrophins) that promote neuronal growth and survival of vulnerable neurons in the spinal cord, hippocampus, and other brain regions
68
Transference and Priming
Appropriately timed exercise to elevate neurotrophic factors and other plasticity-related molecules to improve outcomes
69
Principle 10: Interference
- Where plasticity impedes behavioral change
70
Example of Interference
* Some types of non-invasive cortical stimulation applied during or shortly before skill training enhance motor learning, other forms can be disruptive
* Cortical stim after training reduced the training-dependent increases in cortical excitability
* Compensatory movement patterns poststroke may induce plastic changes in the CNS that need to be overcome in order to obtain more optimal movement patterns
71
What are key principles that need more work to identify best practices
Intensity, repetition of what types of activities, and timing
72
Biggest location differences: Procedural
neocortex, striatum, amygdala, cerebellum, and for simple cases, reflex pathways
73
Biggest location differences: Declarative
medial temporal lobe and hippocampus (and some areas of neocortex)
