1. Neuroplasticity
Dr. Fred Clary

2. Man's brain rewires itself after 19 years in coma
CTV.ca News
Wed. Jul

3. Neuroplasticity Research
Our brain is a dynamic system that has the capability of significant growth.
Rudraprosad Chakraborty, M.D.
J Indian Med Assoc 2007;105(9)
Neuroplasticity research
Lets you rewire and remodel your rain
Judy Willis

4. Neuroplasticity Research
Neuroplasticity research has established, beyond doubt, that instead of being a static cell mass, our brain is actually a dynamic system of neural networks that has the capability of significant growth under favorable circumstances.
Rudraprosad Chakraborty, M.D.
J Indian Med Assoc 2007;105(9)

9. Objectives At the end of this lecture, you should be able to
Understand the mechanisms underlying neuroplasticity and their relevance to rehabilitation.

10. Parts & Functions of the Human Brain
Parietal Lobe
Frontal Lobe
Occipital Lobe
Corpus Callosum
Temporal Lobe
Cerebellum
Brain Stem
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11. Found under your forehead.
Frontal Lobe
Found under your forehead.
Center of reasoning, planning, some parts of speech, movement (motor cortex), emotions, and problem solving.
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12. Found on the top of your head.
Parietal Lobe
Found on the top of your head.
Receives sensory input from the skin. (touch, pressure, temperature, & pain)

13. Temporal Lobe Found on the sides of your head above your ears.
Functions include speech perception, hearing, some types of memory
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14. Occipital Lobe Found at the back of your head.
Receives input from the eyes
Often referred to as the visual cortex
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15. Cerebellum Found at the at the back of your head under the cerebrum.
Means “little brain”
Responsible for movement, balance, posture.
Often takes over learned activities-
Like riding a bike!

16. Brainstem Most basic part of your brain.
Controls functions essential to life (breathing, digesting, eliminating waste, sleeping, maintaining body temperature…)
Maintains life without “thinking”
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17. Corpus Callosum Click here to find out more about split brains!
This is located centrally between the left and right hemispheres of your brain.
It is a bundle of fibers that connects the left and right hemispheres.
It is believed this area is involved in creativity and problem solving.
Click here to find out more about split brains!

18. The protection of your Brain
Your brain sits inside your skull which protects it from physical damage.
The cranium is the part of your skull that surrounds the brain.
The cranium is made up of 8 bones that have fused together. (When you were born the bones had not yet fused)

19. Protecting your brain -From the inside
The skull protects your brain from physical damage but what about damage from the inside-like bacteria or viruses?
Your brain is protected from the internal environment of your body by the blood brain barrier (BBB). Blood is responsible for moving materials around your body. You do not want all of these materials to have access to your brain. So the outside of the blood vessels in the brain are made of cells that are VERY tightly packed together. These cells prevent large, unwanted molecules from entering the brain. Unless they are lipids - then they easily pass through.
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20. Click here to see what an infant “sees”
Brain Development
At birth you had the majority of all the neurons that make up your brain! But your brain only weighed about 400grams. By now your brain weighs grams. What accounts for the huge change in weight?
This picture shows how neurons change overtime by growing in size. Neurons continue to make new synapses (connections to other neurons) throughout your lifetime.
Click here to see what an infant “sees”
Image from: Dr. Venkatesh Murthy, Harvard University. “Synapses: from vesicles to circuits” 7/12/05

21. Outline Overview Mechanisms of neuroplasticity
Hebb’s law
Synaptic plasticity
Synaptogenesis
Axon growth and regeneration
Factors affecting synaptic plasticity and axon growth
Sensory and motor reorganization
Neuroplasticity of sensory cortex
Neuroplasticity of motor cortex
Factors affecting cortical reorganization

22. Neuroplasticity
Refers to the changes that occur in the organization of the brain, and in particular changes that occur to the location of specific information processing functions, as a result of learning and experience

23. Neuroplasticity Occurs during development Occurs during learning
Occurs during recovery after injury/disease to sensory, motor and cognitive areas of the brain
Is an active area of research at many levels: molecular, cellular, system, clinical

24. Hebb’s law (1949)
“When an axon of cell A … excite[s] cell B and repeatedly or persistently takes part in firing it, some growth process or metabolic change takes place in one or both cells so that A’s efficiency as one of the cells firing B is increased.” A B

25. Synaptic strengthening
Strong Connection
Synaptic strengthening
Structural plasticity
Weak Connection
Strong Connection

26. Changes in synaptic strength
strengthening of synapses: potentiation (LTP)
weakening of synapses: depression (LTD) A B

27. Mechanisms of LTP/LTD Increased/decreased release of neurotransmitter
Increased/decreased number of neurotransmitter receptors
Increased/decreased sensitivity of neurotransmitter receptors
All these mechanisms are used in the brain, but not all at the same type of synapse

28. Synaptogenesis The formation of new synapses Occurs during development
Axon sprouting leads to new terminals which then induce synapse formation

29. Synaptic splitting
synaptic strengthening can result in larger synapses
which then become “perforated synapses”
these then split into two synapses

30. Axon Growth and Regeneration

31. Axon Growth and Regeneration
regeneration: damaged axons regrow and re-establish their original connections
axon sprouting: axons from undamaged portions of neurons form new branches
reactive synaptogenesis: synapse formation in response to a stimulus such as damage to a neuron
PNS neurons support robust axon regeneration and sprouting because Schwann cells have a stimulatory effect
In the CNS, axon regeneration and sprouting is more difficult because oligodendrocytes have an inhibitory effect

32. Axon sprouting in the CNS
e.g. remove entorhinal cortex
80% of synapses degenerate
sprouting and reactive synaptogenesis from remaining fibers (inputs from other areas of the brain)
sprouting in the adult brain results in an increase in inputs already present without new pathway formation

33. Axon sprouting

34. Factors affecting synaptic plasticity and axon growth
Growth factors – promote neurite outgrowth
e.g. nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF)
Inhibiting factors
from oligodendrocytes
from external sources e.g. alcohol
Cell-adhesion molecules in extracellular matrix – stimulate neurite growth and stabilize new synapses as they form
Critical periods
Location: CNS vs. PNS
Gene expression & protein synthesis

35. Neuroplasticity of sensory cortex

36. Constant modification based on use

37. Neuroplasticity of motor cortex
Use-dependent: Motor learning alters body representation in the motor cortex. Areas used most have largest representation.
Connection-dependent: After deafferentiation (e.g. limb amputation), reorganization of cortex so muscles adjacent to amputated area have larger cortical representation.
After damage to brain, adjacent areas or contralesional areas can take over motor control

38. Use-dependent cortical reorganization
Monkeys trained to perform task using fingers:

39. Connection-dependent cortical reorganization (after peripheral nerve injury)

40. After damage to brain, the motor map reorganizes based on use
After damage to brain, the motor map reorganizes based on use. Why has the finger representation disappeared from the undamaged area?

41. Adjacent areas or contralesional areas can take over motor control
Adjacent areas or contralesional areas can take over motor control. Rehabilitation can help preserve the motor map and aid functional recovery

42. Ipsilateral motor representation
Hemispherectomy shows there can be motor control of ipsilateral side
ipsilateral representation increases with use
important in recovery from stroke
especially important in recovery from dysphagia after stroke

43. Factors affecting cortical reorganization
Exercise
growth factors, e.g. BDNF increased after only a few days of exercise
axon sprouting
enhances synaptogenesis
increased blood vessel density
Motor learning
Exercise alone not enough
Need learning of new skills
Age: younger brains are more plastic
Injury can “unmask” secondary connections
E.g. premotor cortex can act for motor cortex

44. Neuroplasticity: summary
Cellular mechanisms:
Changes in synaptic strength: LTP and LTD
Structural changes:
Synaptogenesis
Axon sprouting
Cortical reorganization:
Constant changes based on use
Remapping after injury: adjacent areas take over
Rehabilitation helps preserve map
Rehabilitation helps strengthen secondary connections

45. Theoretical Mechanisms of Recovery (MOR) from Brain Injury
Neuroplastic Changes
Motor Learning Practice
Recovered and Compensatory Function

46. Rehab…Now What…
Neuroplasticity-guided rehabilitation approaches have been examined and shown to be effective in research of patients with TBI.

47. Topics for Discussion
What is recovery of function? At what point should you encourage compensation or development of alternative motor strategies rather than recovery of original function?
What does “learned non-use” imply for treatment following stroke?
Discuss different types of rehabilitation approaches and how they encourage neuroplasticity.
At what point after a lesion to the CNS should rehab begin?
Discuss the effects of massed vs. distributed training sessions.