Plasticity

Question 1

Neural Plasticity

Answer 1

• Lifelong ability of the brain to reorganize neural pathways and neural activities based on new experiences • Ongoing process of change, in response to new experiences • Brain level: glial/vascular • Network: reorganization of cortical maps and patterns • Inter/intracellular • Biochemical • Genetic

Question 2

Neural plasticity after injury can be

Answer 2

•Restorative: Direct; Resolution of temporary changes and recovery of the injured tissue. •Compensatory: Indirect; Different neural circuits enable the recovery of lost or impaired function.

Question 3

How does CNS respond to damage?

Answer 3

•Early: depress brain function; local response (edema and diaschisis); synaptic effectiveness •Intercellular responses: denervation supersensitivity, etc •Changes in cortical maps Remapping after peripheral lesions (amputations)

Question 4

Early Transient Events

Answer 4

oEdema •Cytotoxic: accumulation of fluid •Vasogenic: leakage of proteins and fluids •Compression of axons, affects conduction oDiaschisis •Temporary disruption/depression of function in an intact brain area •Affects neuronal process far from the primary site of lesion •Caused by reduced blood supple, reduced metabolism, edema oSynaptic Effectiveness •Spontaneous recovery/resolution of neural shock because of Reduction of edema Resolution of diaschisis Absorption of necrotic tissue

Question 5

Denervation supersensitivity

Answer 5

• Occurs when critical # of neurons destroyed • Postsynaptic membrane of a neuro becomes hyperactive to a released transmitter • Supersensitive because it doesn’t get the normal amount of stimulus.  Increases number of available receptors, increases their responsiveness  Parkinson’s causes a loss of dopamine producing neurons in the substantia nigra. Due to the denervation, the postsynaptic target neurons become hypersensitive to the dopamine that is released.

Question 6

Recruiting/Unmasking of silent synapses

Answer 6

o Normally not functioning, masked under normal conditions o Facilitated by injury, drugs, experiences

Question 7

Synaptic Hypereffectiveness

Answer 7

Presynaptic changes •Increased release of NTs Postsynaptic changes • Changes in postsynaptic membrane sensitivity  Ex: increased sensitivity to Acetylcholine

Question 8

Neural Regeneration (regenerative synaptogenesis)

Answer 8

o Seen in PNS o Begin sprouting 3-7 days after injury o Can travel long distances, but grows 1 mm per day

Question 9

Collateral Sprouting (Reactive Synaptogenesis)

Answer 9

o 4-5 days after injury o Neighboring normal axons sprout to innervate synaptic sites that were previously activated by the injured axons

Question 10

Experience Dependent Plasticity

Answer 10

o Cortical maps w/in one brain area are DEPENDENT o Can be modified by activity and experience • Learning an instrument at a young age change the strength of neural connection o Experience can also change the strength of neural connections between brain areas.

Question 11

Experience Dependent Plasticity and Motor Learning

Answer 11

o At first, practice sequential finger tapping skill increases activation of sensory and motor cortical areas M1, M2, S1, S2 o When they get better, activation of motor area decreases, activation of thalamic pathways to other brain regions increases. o Constant shifting of which tasks require the most intense activation in which brain areas

Question 12

Changes in Cortical Maps after Lesions: Peripheral

Answer 12

o Occurs after Peripheral nerve lesions, amputation, prolonged immobilization o Cortical maps are use dependent, if not used it will be replaced

Question 13

· Changes in cortical maps after CNS Lesions

Answer 13

o Brain reorganization can occur following deafness or blindness

§ These area can be reprogrammed to respond to other sensory stimuli

§ Area still performs original function but responds to different mode of stimulation

o Reorganization of affected hemisphere through:

§ Redundant pathways OR

§ New regions taking over function of damaged area

§ Damage to primary motor causes activation of secondary motor areas

ú PMC, SMC, Cingulate Cortex

Question 14

· Changes in Cortical maps after lesion: Contributions of Ipsilateral Pathways

Answer 14

o Uncrossed pathways play an important role

o Contralateral primary motor cortex (cortex on the side opposite to affected area) may play a role

Question 15

· Changes in Cortical maps after lesions: Cerebellar contributions to Recovery from Ctx. Injury.

Answer 15

o Cerebellum enhances motor learning

o Generates new pathway b/w cerebellum and CTX that support more automatic performance of skilled movement

o Contralateral cerebellum is important

Question 16

Clinical Implications

Answer 16

o Experience is very important in shaping cortical maps

o Effect of training

§ Reorganization of sensorimotor cortex can result from training

§ Optimal timing and intensity of training to maximize neural plasticity

§ Cortical stimulation through behavioral changes may facilitate motor recovery.

Question 17

Effects of Age

Answer 17

[*] The brain reacts differently to injury at different stages of development
–Adult brains are less plastic than child
[*] The younger the age, the greater the plasticity of the nervous system
–
–Lesion during early ages causes fewer deficits than damage in the adult years
–
[*] Animal studies
[*]
[*] Language function following lesion in the dominant hemisphere

[*] Several factors must be taken into consideration:
[*]
–The area of the brain where the injury had occurred
[*]
–The maturity of the brain region rather than the age of the individual
[*]
–The loss of other behaviors
[*]
–Maturational status of the damaged area
[*] Functionally mature area
–Comparable deficits as seen in adults
[*] Functionally immature related area
–It might take over the function of damages area

Question 18

Gender

Answer 18

[*] Male versus female
–No evidence
[*]
[*] Female may be better!
–Female brain is less lateralized in cortical functions
–Effects of hormones on the formation of edema
–

Question 19

Characteristics of the Lesion

Answer 19

[*] Severity of the injury
–Evidence shows strong correlation between severity of injury and long-term functional outcomes
[*]
[*] Lesion size
–The smaller the lesion, the greater the recovery
–Remember: depends on the area of the brain involved
[*]
[*] Re-occurrence of injury
–After having sufffered brain damage (e.g., stroke), another stroke usually has significantly larger detrimental effects
[*] - Plastic reserve has been drained

How quickly does the injury occur? Slow vs. rapid lesions

[*] Slowly developing lesions create less disruption of function than sudden lesions
[*] Tumor versus gunshot or stroke
–Brain tumors or slowly develping hydrocephalus à slow destruction of brain matter, time for adaptive / plastic changes
–Brain tumors can be large before any symptoms are noticed
–Stroke: sudden loss of areas, drastic behavioral / cognitive effects
[*] Autopsy studies of people who functioned well even near death
[*] Serial small lesions in animals VS one large lesion
–For serial lesion phenomenon consider:
[*] Amount of tissue damage in each stage
[*] Time difference
[*] Age
[*] Experience

Question 21

Pre-Injury Neuroprotective Factors

Exercise

Answer 21

[*] Pre-injury exercise protects against deficits
[*] Animal studies:
–Prestroke exercises reduces infarct size
–Animal studies show that exercises may:
[*] Promote neuroplasticity
[*] Increase angiogenesis to support collateral
[*] Decrease apoptosis and edema

Question 22

PINPF

Environmental Enrichment

Answer 22

[*] Improved performance?
–Enriched infant crib
–Enriched maze for rats[*] Enrichment before brain damage
–Protects the individual from the usual results of brain damage

Question 23

Post-Injury Factors (PIF)

Effects of pharmacology

Answer 23

[*] Medications are used to …
1.Reduce nervous system’s reaction to injury
2.Promote recovery of function
–
[*] The effects of drugs include:
–Prevention of scaring
[*] Affect trophic factors, and promote regeneration
–Prevention of neurotoxicity
[*] Toxic substances released by dead or dying cells
–Restoring blood circulation
–Replacing neurotransmitters lost by cell death
–Stimulating growth

Question 24

PIF

Neurotrophic Factors

Answer 24

[*] Growth factors regulate:
–Synapse formation
–Neurotransmitter release
Neuronal excitability

Question 25

PIF

Exercises and Training

Answer 25

[*] Training improves recovery
[*]
[*] Training is more effective than enriched environments
–Training is more specific than enriched environment
[*]
[*] Specific training is better than non-specific training
–Task-specific training
–Constraint induced movement
[*]
[*] Early training after injury is better
–As long as it is not too early
–Too early may exaggerate the lesion in the perilesional area

Question 26

PIF

Environmental enrichment

Answer 26

[*] Environmental enrichment after brain damage promotes recovery of function
[*]
[*] NOTE: Environmental enrichment before injury is more effective than environmental enrichment after injury

Question 27

Implications for Therapeutic Intervention

Answer 27

[*] The brain has great capacity to change
[*]
[*] Therapist should expect recovery
–If you expect recovery … do not encourage compensation
[*]
[*] Active participation is a key factor in experience
[*]
[*] Provide early and specific training

[*] Examine the environment/Provide environmental enrichment
–Stimulating
–Varied interesting
–Challenging
–Unique
[*]
[*] Disuse and brain organization
–If patients are left without rehabilitation training for long time
[*] The brain will show changes in organization reflecting disuse

[*] The degree of function regained is determined by many factors:
–Age
–Nature of the lesion
[*] Size
[*] onset
–Experience
[*] Environmental enrichment
–Pre and post injury experience
–Training/intervention
–Pharmacological factors
–Interaction of the above factors