Neuroplasticity

Dr. Fred Clary

Man's brain rewires itself after 19 years in coma

CTV.ca News

Wed. Jul. 5 2006

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

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)

Objectives

At the end of this lecture, you should be able to Understand the mechanisms underlying

neuroplasticity and their relevance to rehabilitation.

Parts & Functions of the Human Brain

Check out

Frontal Lobe

Parietal Lobe

Occipital Lobe

Cerebellum

Brain Stem

Temporal Lobe

Corpus Callosum

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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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Parietal Lobe

•Found on the top of your head.

•Receives sensory input from the skin. (touch, pressure, temperature, & pain)

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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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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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!

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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Corpus Callosum•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!

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)

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.

Protecting your brain -From the inside

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are needed to see this picture.

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 weighs1300-1400 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

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

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

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

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

Weak Connection

Strong Connection

Synaptic strengthening

Structural plasticity

Strong Connection

Changes in synaptic strength strengthening of synapses:

potentiation (LTP) weakening of synapses:

depression (LTD)

A

B

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

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

synapse formation

Synaptic splitting synaptic

strengthening can result in larger synapses

which then become “perforated synapses”

these then split into two synapses

Axon Growth and Regeneration

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

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

Axon sprouting in the CNS

Axon sprouting

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

Neuroplasticity of sensory cortex

Constant modification based on use

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

Use-dependent cortical reorganizationMonkeys trained to perform task using fingers:

Connection-dependent cortical reorganization (after peripheral nerve injury)

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

Adjacent areas or contralesional areas can take over motor control. Rehabilitation can help preserve

the motor map and aid functional recovery

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

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

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

Theoretical Mechanisms of Recovery (MOR) from Brain Injury

Neuroplastic Changes Motor Learning Practice Recovered and Compensatory Function

Rehab…Now What…

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

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.