brain - iste · learned indicating possible contribution of other brain structures rather than...

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ISTE 2012

Copyright@ Pradip Ghosh 2019 1

Brain: Important Facts

• CNS begins from 2 weeks gestation

• At birth, human brain weighs 350 g, at 1 year 1000 g

• 10% of the cells are neurons (100 billion)

• Each neuron makes 1,000 to 20,000 connections

• Uses 20% of the body energy

• Consume 20 % of the body oxygen

• All parts of brain are involved in learning, some more than other


Tractography of Whole Brain


Brain Growth

• The number of neurons that a child is born with is largely fixed around four months before birth.

• The most important mechanisms involved in the massive brain spurt that occurs in the early years of life are:

– Myelination

– Production of glial cells

– Synaptogenesis: Formation of new synapses


Neuroplasticity • It can be described as brain’s ability to reorganize

itself by forming new neural connections throughout the life.

• Neuronal connections are continuously being created and broken and all modeled by our experiences, and our states of health or diseases.

• Neuroplasticity allows neurons in the brain:

– To adjust neural activities in response to new situations or to changes in their environment (developmental plasticity)

– To compensate the loss from injury and neural diseases (adaptive plasticity)


Developmental Plasticity vs Adaptive Plasticity Developmental Plasticity Adaptive Plasticity

Definition Changes in neural connections as a result of interactions with the environment (our experiences during childhood) as a consequence of developmental processes. e.g. Development of visual cortex

The brain’s ability to compensate for lost functionality due to brain damage as well as in response to interaction with the environment by reorganizing its structure

Occurs in response to

It is predetermined and occurs in response to the initial processing of sensory information by the immature brain

Compensation for brain injury and in adjustment to new experiences.

Neuronal changes

Synaptogenesis, synaptic pruning, neural migration, myelination

Sprouting Rerouting

When it occurs Over the lifespan, but diminishes with age

Over the lifespan, but is more efficient and effective during infancy/early childhood


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Neuroplasticity

• It involves forming neuronal connections (synapses and pathways) in response to information derived from experiences in the environment, sensory stimulation, and normal development.

• Plasticity occurs on a variety of levels:

– Cellular changes involved in learning – Large-scale changes involved in cortical remapping in

response to injury • Widely recognized forms of plasticity are learning,

memory, and recovery from brain damage


Neuroplasticity in Normal Brain

• It is now clear that mammalian brain is capable of change throughout the life time in response to the environment and subsequent sensory experience.

• Numerous research studies examined the effects of sensory and social stimulation through enrichment of environment on the rodent brain.


Neuroplasticity in Normal Brain Environment and Neuroplasticity

• Environmental stimulation and exercise has significant influence in neuroplastic changes in the brain.

• Van Praag and his group have shown increased number of neurons in the hippocampus when mice were housed in enriched environment with free access to the running wheel.

• Van Praag H, Kemperman G, Gage FH. Nature Neurosci 1999; 2: 266-270


Neuroplasticity in Normal Brain: Synaptogenesis

• Black et al in 1990 examined the cerebellar neurons of rats after placing them in 4 housing conditions. – Obstacle course (AC)

– Forced treadmill exercise (FX)

– Voluntary running wheel (VX)

– In a cage (IC)

• Observations: – increased capillary density in the cerebellum of rats from FX and VX.

– increased synapses per neuron of the Purkinje cells of cerebellum of rats from AC

Black JE, Isaacs KR, Anderson BJ, Alcantara AA, Greenough WI. Proc Natl Acad Sci 1990; 87: 5568-72


Neuroplasticity in Normal Brain Synaptic Configuration

• Plastic changes in the brain are associated with changes in synaptic configurations.

• Comery et al conducted studies by housing one group of rats in a toy- and object-filled environment and by keeping the other group in the standard cages for 30 days.

• They observed an increased number of bifurcating and multi-headed spines in neurons of the caudate nucleus of rats housed in enriched environments.

Comery TA, Stadmondia CX, Irwin SA, Greenough WT. Neurobiol Learn Mem. 1996; 66: 93-96


Neuroplasticity in Normal Brain Enriched Environment


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Neuroplasticity in Normal Brain Changes in the strength of Synaptic Connections


Neuronal changes in the Brain


Role of BDNF on Reaching Functions after Focal Ischemia

• It is also known that exercise can increase brain derived neurotrophic factor (BDNF) in the brain (Neeper et. al, 1995)

• Ploughman et al tested the hypothesis by evaluating the contribution of BDNF to motor skill relearning after endothelin-1–induced middle cerebral artery occlusion in rats.

Neeper SA, Gomez-Pinilla F, Choi J, Cotman C. Nature. 1995; 373: 109

Ploughman M, Windle V, MacLellan CL, White N, Doré JJ, Corbett D. Stroke. 2009;40:1490-1495


Role of BDNF on Reaching Functions after Focal Ischemia

Infused antisense BDNF to lateral ventricle after inducing ischemia in one group of rats while no infusion

to the 2nd group (control)

Rehabilitation (Running,

Skilled reaching)

Rats ran for 10 min in motorized running wheel followed by

reach training

Found reaching skills diminished in antisense BDNF

infused rats while reaching improved in non infused rats



Plastic Changes in Human Brain Influence of Repetitive Movements

• Motor tasks are accomplished by using repetitive sensory feedback to learn and refine the skill.

• Pascual-Leone et al trained adult human volunteers on finger/thumb repetitive movements.

• Observations: – Training groups had progressively larger cortical output to the

involved muscles along with improved performance.

– They also observed an increase in cortical map size followed by a subsequent decrease to baseline after the motor sequence was learned indicating possible contribution of other brain structures rather than primary motor cortex.

• Pascual-Leone A, Grafman J, Hallerr M. Science 1994; 263: 1287-89


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Plastic Changes in the Human Brain Deafferentiation

• Brasil-Neto and associates examined the speed and topography of cortical plasticity during short term deafferentiation using blood pressure cuff on the arm and leg of human subjects.

• They found an increased motor evoked potential (MEP) from the proximal muscles to the tourniquet within minutes.

• They also observed an enlarged cortical representation area for those proximal muscles.

Brasil-Neto JP, Cohen LG, Pascual-Leone A, Jabir FK, Wall RT, Hallett M. Neurol 1992; 42: 1302-06


Plastic Changes in the Human Brain Influence of Immobilization

• Liepert et al examined individuals with ankle immobilization following ankle injury with no peripheral nerve damage.

• They have shown a decreased cortical map representation for the tibialis anterior muscle.

• So, cortical maps change on a daily and even minute-to minute basis depending on increase or decrease in sensory input and motor activity.

• Therefore movement along with sensation from periphery is essential for maintaining cortical map.

Liepert J, Tegentoff M, Malin JP. Electroencephal Clin Neurophysiol 1995; 97: 382-86


Plastic Changes in Grey Matter Thickness

3 months of intensive juggling training is performed in a group of 12 individuals whereas 12 controls are provided as “non-jugglers” (experiment: 3-ball cascade juggling)

Voxel-based morphometry was employed to reveal fine changes of grey matter volume on anatomical MR images

Transient changes take place in grey matter in specific

motion-selective areas.

Draganski B, Gaser C, Busch V, Schuierer G, Bogdahn U, May A . Nature 2004; 427: 311-312


Plastic Changes in Grey Matter Thickness

Licensed London taxi drivers with extensive navigation experience were analyzed and compared with those of control subjects who did not drive taxis

Voxel-based morphometry was employed to reveal fine changes of grey matter volume on anatomical MR images

Key findings were: The posterior hippocampi of taxi drivers were

significantly larger Hippocampal volume correlated with the amount of time

spent as a taxi driver (positively in the posterior and negatively in the anterior hippocampus)

Maguire EA, Gadian DG, Johnsrude IS, Good CD, Ashburner J, Frackowiak RSJ, Frith CD Proc Natl A Sci 2000; 97: 4398-4403.


Two current concepts

Enhancement of existing

connections

Very active research area; concepts are continually being updated A very active research area; concepts are continually being updated

Formation of new connections

Types of Neuroplasticity Type Mechanism Duration

1. Enhancement of existing connections A. Synapse development Physiological ms-1 to hours

B. Synapse strengthening Biochemical hours to days

2. Formation of new connections A. Unmasking Physiological minutes to days

B. Sprouting Structural days to months

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Enhancement of existing connections

• Increased use of a synapse in existing pathways e.g. learning a new task .

– The more we do something (ex: practice for skilled activity), the more synapses will be used and more synapses can be developed

• Alternative pathways following damage

– If one pathway gets damaged, the alternative pathways will be activated and used to compensate.

Increased afferent input Increased afferent input

New synapses evolve leading to increased excitation

New synapses evolve leading to increased excitation

+

+

+

Ragert et al., 2004

A study looked at cortical plasticity in piano players and found that the fingers and hand were over represented in the sensorimotor cortex . Copyright@ Pradip Ghosh

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Synapse strengthening

Effectiveness of a synapse can be increased due to

change in the structure to enhance transmission

1. Seconds and minutes (short-term memory)

2. Hours and days (intermediate-term memory)

3. Months and years (long-term memory)

Such changes can take place at

three cellular locations:

1. Presynaptic terminal

2. Postsynaptic membrane

3. Postsynaptic nucleus

Kidd et al., 1992 Copyright@ Pradip Ghosh 2019

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Two point discrimination threshold in

pianists index finger

R L

Ragert et al., 2004

Comparison of musicians to non-musicians

Findings were long-lasting piano practising resulted in lower spatial

discrimination thresholds in the index finger of piano players in

comparison to non-musicians.

This decrease in threshold was related to the number of hours practiced per

day (>3 hours), not to the number of years they had been playing Copyright@ Pradip Ghosh

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Formation of new connections

Unmasking of pre-existing pathways

Sprouting of new pathways

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Possible reasons for some silent synapses

Inhibited by dominant pathways

Too little transmitter

Too few receptors on post-synaptic membrane

Don’t fire with other inputs

Subservient pathway Subservient pathway

Parallel pathway; neurons with a comparable role Parallel pathway; neurons with a comparable role

Dominant pathway Dominant pathway

+ +

Lesion to dominant pathway

Lesion to dominant pathway

Subservient pathway is unmasked Subservient pathway is unmasked

Activity is continued despite lesion

Activity is continued despite lesion

+ +

Cell body Cell body

Axon Axon

Sprouting occurs following damage or denervation to the nervous system and is the growth of new axons from from adjacent neurons forming new pathways

lesion

Nerve Growth Factor (NGF)

Nerve Growth Factor (NGF)

Following denervation, neurotrophic factors or nerve growth factors are released, they are polypeptides capable of promoting neuronal survival.

INJURY

lesion

NGF

Neurite induced

to sprout by

NGF

The release of nerve growth factors stimulates neurites or new axons to sprout and look for the source of the NGF

INJURY

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Cell is re-innervated from alternative stimulus

Cell is re-innervated from alternative stimulus

Sprouting may be a means of recovery; it may also produce unwanted effects For example spinal cord injury patients may

experience strange sensations.

Sprouting may be a means of recovery; it may also produce unwanted effects For example spinal cord injury patients may

experience strange sensations.

Injury results in cell death Injury results in cell death

Changes in the Brain

• Structural change • Synaptic plasticity

• Synaptogenesis

• Neuronal migration

• Neurogenesis

• Biochemical change • Nucleic acid synthesis

• Protein synthesis


Neuronal Migration

• In the adult brain, neuroblasts (immature neurons) are continuously generated in the ventricular-subventricular zone (V-SVZ).

• These neuroblasts migrate rapidly to the olfactory bulb, where they mature and are integrated into the neuronal circuitry.

• After a brain injury, neuroblasts migrate to the injury site and differentiate into functional neurons (Yamashita et al. 2006).

Yamashita, T., Ninomiya, M., Hernandez Acosta, P. et al. J. Neurosci. 2006: 26: 6627– 6636.


Neuronal Migration


Neurogenesis

• It is the process by which neurons are generated from neural stem cells.

• Recent studies show that neurogenesis continues to occur in the adult mammalian brain and can persist well into old age.

– This appears to occur in the hippocampus, olfactory bulb, and cerebellum.

– In the rest of the brain, neurons can die, but cannot be formed.


Neurogenesis

• Under normal condition, neural progenitor cells (NPC) in the brain is less active and their numbers are less.

• NPC activity needs to be up in order to produce new neurons.

• Different stimuli including sensory, chemical play a role in neurogenesis.


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Neuroplasticity: Balancing Inhibition and Excitation

• In the cortex GABA is inhibitory, glutamate is excitatory

• Reduced activity at GABAergic interneurons allows plasticity in adults

• Enhanced glutamatergic signaling leads to LTP

• So, altering the balance of inhibition/excitation is important in reopening new periods of plasticity in adult cortex


Animation of Plastic Brain


Reorganization of Brain

• Brain activity associated with a given function can move to a different location.

• This concept allows for the treatment of acquired brain injury.

• The adult brain is not hard-wired with fixed neuronal circuits.

• Cortical and subcortical rewiring of neuronal circuits happens in response to training and in response to injury.


Reorganization of Brain

• Brain remodeling: Brain remodel is based on

–Repetitions

– Functional Movement

– Environment

• Synaptogenesis and synaptic pruning:

• New connections are formed based on repetitions of tasks. If neuronal connections and pathways are not used, they will be lost.


The Role of Movement Therapy

1. Strengthen and develop normal synapses

2. Guide axonal sprouting

3. Facilitate unmasking of alternative or previously subservient pathways

Therapists need to


How? • Provide positive sensory input.

– Appropriate handling

– Sensation through purposeful movement

• Facilitate “functional” movement.

– Promote repetition of functional and goal directed movement.

– Challenge individual based on tolerance.

– Promote active participation

• Provide treatment at “optimum” time

• Education


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Cortical Reorganization

• Dendritic arbors increased in the unaffected brain and increases the number of synapses (top picture)

• Researchers found that dendritic arbor retracts when injured brain stops receiving afferent signals (bottom picture) causing maladaptive response after injury


How Does Rehabilitation Help in Regaining Functions?

• Sensory stimulation through movement that uses proprioception, kinesthetic sensation, tactile sensation.

• Supports new connections in the brain especially in the hippocampus (memory)

• Prevents secondary cascade in the brain following injury


Exercise and Activities: Role in Neuro-rehabilitation

• Exercise or functional activities

1. Reduces the rate of cognitive decline.

2. Keeps the brain cells more active

3. Increases the formation of BDNF in the brain (acts as brain fertilizer)

4. Reduces the risk of neurodegeneration

5. Reduces the risk of dementia

6. Improves stress tolerance


Vascular Injury: Stroke

52 Copyright@ Pradip Ghosh 2019

Brain Excitability after Stroke

Periinfarct cortex

Hypo-excitability

Uptake of GABA is reduced by

reactive astrocytes

Increased level of extracellular

GABA

Tonic inhibition

Decreased neuronal

excitability

Diminished recovery


Brain Excitability after Stroke

Periinfarct cortex

Stimulation (edogenous or

exogenous)

Increased neuronal

excitability

Increased BNDF signaling

Synaptogenesis Increased Recovery


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Brain Excitability after Stroke: Yin and Yang Stroke Progression

Arch Neurol. 2012; 69(2): 161-167

• It is an established fact that “adverse influences” such as stress, depression, and chronic GC treatments may cause shrinkage of the hippocampal formation [23].

• This may be due to the changes in the tissue such as reductions in neuronal dendrites.


Consequences in the Brain Following Stroke

Primary Insult (Primary damage)

Secondary Insult (Pathophysiological

Processes)

Impaired blood flow, metabolic imbalances,

Tissue damages, Membrane

permeability

Inflammation, Axon terminal depolarization,

release of excitatory neurotransmitters,

Intracellular breakdown

Cell Death


Spontaneous Recovery Vs

Training Induced Recovery


Function after Stroke

Time I


A

B

infarct 3 months

post stroke

17 days

post stroke

24 days

post stroke

31 days

post stroke

10 days

post stroke

affected

side

affected

side

Neuroplasticity After Stroke Changes in residual functional architecture


Neuroplasticity and Rehabilitation Following Stroke

• Stroke is a leading cause of chronic disability through the world.

• Impairments and movement limitations in upper extremity are more prevalent in post stroke disabilities.

• Compensatory reliance on the nonparetic hand exacerbates impairments in the paretic side by encouraging its disuse and for further inhibition on the affected brain through interhemispheric mechanisms.


http://www.hindawi.com/journals/np/2014/541870/#B20

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• Movement therapy approaches are the main tools during rehabilitation after stroke and brain injury.

• The efficacy of rehabilitation following stroke depends on multiple factors (age, intensity, frequency, early vs late etc).

• Ischemic injury triggers prolonged periods of both structural and functional reorganization.

• Early after stroke, changes in the brain are more dynamic and promoting functional reorganization is crucial.



• There are windows of opportunity to drive functional reorganization of brain through functional based movement training.

• As well as there are windows of vulnerability for keeping the brain less functionally active.

• So questions are

– When is the “early”?

– When is it safe?


Plastic Changes Following Stroke

STROKE

New axonal growth

surrounding ischemic area

Reduced GABA mediated inhibition

Unmasking of ipsilateral pathways

Post stroke hyper excitability

surrounding lesion area



• Considerable variability in neural remodeling time courses can be expected between individuals and across brain regions (Riley et al)

• It is important to note that earlier is not better always for everything.

• Peri-infarct tissue is vulnerable to use-dependent excitotoxicity in very early periods after stroke (Humm et al, 1998)

• Riley JD, Le V, Der-Yeghiaian L, See J, Newton JM, Ward NS et al. Stroke 2011; 42: 421-426

• Humm JL, Kozlowski DA, James DC, Gotts JE, and Schallert T. Brain Res. 1998; 783: 286-292


Skill Learning

• Manual skill learning depends on practice dependent structural and functional reorganization of motor cortex (Dayan and Cohen, 2011)

• The developing brain depends on external stimuli to shape neural circuitry patterns via mechanisms of synaptic competition.

• Here most effectively activated neural connections are selectively maintained and matured and those less well activated are eliminated

• Dayan E, and Cohen LG. Neuron 2011; 72: 443-454


Neural Remodeling

• Neuronal loss in the core of ischemic injury leaves connected region partially denervated.

• Synapse densities around infract also decline and then recover over time to varying degrees depending on proximity to the infarct core (Sigler and Murphy, 2010).

• Sigler A, and Murphy TH. Stroke 2010; 41: 117-123


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Neural Remodeling

• Goal directed ovement therapy (MT) can induce growth permissive environment that promotes axonal sprouting and synaptogenesis from remaining projections leading to re-innervation.

• Rehabilitation through MT and other treatments may also cause persistent alterations in excitatory and inhibitory activity patterns (Zeiler et al, 2013).

Zeiler SR, Gibson EM, Hoesch RE. Li MY, Worley PF, O’Brien RJ et al. Stroke 2013; 44: 483-489


Glial Remodeling

• Post ischemic reactions of neurons and astrocytes are tightly coordinated.

• Astrocytes are intricately involved in synaptic plasticity (Eroglu and Barres, 2010).

• Astrocytes release thrombospondins to promote synaptogenesis (Eroglu et al, 2009), release cholesterol to promote synapse maturation (Goritz et al, 2005).

Eroglu C, and Barres BA. Nature 2010; 468: 223-231

Eroglu C, Allen NJ, Susman MW, O’Rourke NA, Park CY, Ozkan E et al Cell 2009; 139: 380-392

Goritz C, Mauch DH, and Pfrieger FW. Mol Cell Neurosci 2005; 29: 190-201


Glial Remodeling

• Astrocytic behavior is neural activity and experience dependent (Theodosis et al, 2008).

• Astrocytic reactions to denervation in motor cortex are elevated by forced forelimb use in rats (Bury et al, 2000)

• Theodosis DT, Poulain DA, and Oliet SH. Physiol Rev. 2008; 88: 983-1008

• Bury SD, Eichhorn AC, Kotzer CM, and Jones TA. Neuropharmacol 2000; 39: 745-755


Vascular Remodeling

• Ischemic stroke results in areas of reduced cerebral blood flow (CBF) and capillary density.

• With time, proangiogenic factors elevated to promote angiogenic micro envirenment for making neuronal connections.

• Sufficient blood flow is essential for activity dependent neural remodeling.

• Whitaker et al have shown that sensory stimulation starting after 3 days of cortical ischemia in mice can promote angiogenesis and CBF recovery.

• Whitaker VR, Cui L, Miller S, Yu SP, and Wei L. J Cereb Blood Flow Metab 2007; 27: 57-68


Neuro-regeneration Time

• Time courses and magnitudes of astrocytic and vascular reactions to injury are altered with age (Popa-Wagner et al 2011), injury severity (Kim and Jones, 2010).

• Aging involves brain changes including reductions in synaptic density, demyelination and increased vulnerability in synaptic connectivity (Hof and Morrison, 2004)

• Popa-Wagner A, Buga AM, and Kokaia Z. Ageing Res Rev. 2011; 10: 71-79

• Kim SY and Jones TA. Synapse 2010; 64: 659-671

• Hof PR, Morrison JH. Trends Neurosci. 2004;27:607–613.


Earlier Intervention is Better

• Several studies support the fact that motor rehabilitation training (MRT) is more effective if initiated earlier after stroke.

• Nudo and his group have reported that MRT beginning within 1 week of motor cortical infarct in monkeys spares the paretic hand representation of motor cortex compared with controls.

• This effect gets lost if training is delayed until 30 days post-infarct (Barbay et al 2006)

• Nudo RJ, Wise BM, SiFuentes F, and Milliken GW. Science 1996; 272: 1791-1794

• Barbay S, Plautz EJ, Friel KM, Frost SB, Dancause N, etal Exp Brain Res. 2006; 169: 106-116


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Earlier Intervention is Better

• In humans, initiation of interventions within 4 days of stroke are associated with reduced disability at the time of hospital discharge compared with later interventions (Matsui et al, 2010).

• Lang and her group have shown that initiation of CIMT within 3-9 months post stroke enhaces performance in several fine motor tasks compared to delayed (>9 months) initiation of CIMT.

• Matsui H, Hashimoto H, Horiguchi H et al. BMC Health Serv Res. 2010; 10: 213

• Lang KC, Thompson PA, and Wolf SL. Neurorehabil Neural Repair 2013; 27: 654-663


Early in not Better for Everything

• Researchers support the fact that highly intense physical activity very early after injury onset can be risky.

• Schallert and colleagues discovered that forced use of a paretic limb via constraint of the nonparetic limb can be detrimental if done too early (Schallert et al 2003).

• In humans, initiation of high intensity CIMT after 10 days of stroke can decrease the functional improvement compared with the lower intensity treatment (Dromerick et al, 2009).

• Schallert T, Fleming SM, and Woodlee MT. Med Rehabil Clin N Am. 2003; 14: 27-46

• Dromerick AW, Lang CE, Birkenmeier RL, Wagner JM et al. Neurology 2009; 73: 195-201


Functional Movement and Neuroplasticity

• Researchers support the fact that functional movement based therapy can promote both structural and functional organization of brain following stroke.

• Richards and colleagues have reported that functional movement based therapy induces neural changes in the sensorimotor cortex of the lesioned hemisphere (fMRI, PET and TMS) and changes accompany the gains of motor functions in the paretic upper extremity (Richards et al, 2008)

Richards LG, Stewart KC, Woodbury ML, Senesac C, Cauraugh JH Neuropsychologia 2008; 46: 3-11


Neuroplasticity and Motor Learning

• Movement therapies which induce cortical reorganization are based on the principles of motor learning.

• Sprouting of dendrites, formation of new synapse, alterations of existing synapse take place during motor learning.

• If practice is meaningful, repetitive and intensive in nature, changes will be greater and retention will be long lasting.


Neuroplasticity and Motor Learning

• If we ask our clients following stroke to reach for a glass filled with water in order to attempt to drink (meaningful) 30 times (repetitive) and 3 times daily (intensive), individual will gain more permanent elbow extension that can be used for other functional tasks.

• Therefore, stroke rehabilitation methods should consist of intensive and repetitive practice of meaningful tasks.


True Motor Recovery vs Compensatory Motor Recovery

• True motor recovery occurs when undamaged or alternative pathways send command to the involved muscles following stroke or brain injury.

• This may be due to the redundancy of motor cortical areas with unmasking of pre-existing cortico-cortical connections (Teasell et al, 2005).

• Compensation is the use of alternative muscles to accomplish the task goal

• Teasell R, Bayona NA, Bitensky J. Top Stroke Rehabil 2005; 12: 11-26


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Task Specific Training and Neuroplasticity

• Task specific training (TST) emphasizes the practice and repetition of skilled motor performance to improve functional abilities.

• TST may restore functions by using spare parts of the brain which are generally adjacent to the lesion or by recruiting supplementary part of the brain (Nudo et al, 2000).

• TST induces long lasting motor learning through cortical reorganization (Harvey, 2009).

• Nudo RJ, Friel KM, Delia SW. Neuropharmcol 2000; 39: 733-742

• Harvey RL. Curr.Treat. Options Cardiovasc Med. 2009; 11: 251-259



• It has been observed that functional recovery is associated with the changes in cortical activation pattern.

• Researchers recorded brain activities using fMRI after TST and showed decreased activation in the unaffected brain and increase activity in the affected primary sensorimotor cortex (Jang et al 2003).

• Another group of researchers observed increased activation in the contralesional cerebrum and ipsilesional cerebellum in response to repetitive bilateral arm training (Luft et al, 2004).

• Jang SH, Kim YH, Cho SH, Lee JH, Park JW, Kwon YH. Neuroreport 2003; 14: 137-141



• Langhammer and Stanghelle compared the effects of motor relearning program between task oriented strategies and Bobath techniques using facilitation/inhibition strategies.

• They found patients showed better results on motor functions with task oriented strategies when compared to Bobath techniques (Langhammer and Stanghelle, 2000).

• Langhammer B, Stanghelle JK. Clin Rehabil 2000; 14: 361-369


TST and Environment • Environment for the training is also important in motor

learning and cortical reorganization.

• Training with enriched environment improves the performance as it provides individual with clear understanding of what is being expected of them during task specific training (Davis 2006)

• For example, an individual would stand for a longer period of time if he/she brushes his/her teeth in front of the washbasin compared to someone who stands without doing nothing.

• Davis JZ. Top Stroke Rehabil. 2006; 13: 1-11


Gait Training with Gait Training Sling


TST with FES and Repitition


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Repitition of Functional Movement using Saeboflex


TST, Repetition, Enriched Environment

• Therefore, rehabilitation program for patients with stroke should include repetitive task-specific movement training in an enriched environment in order to promote cortical reorganization, motor and functional recovery.


Mental Practice and Cortical Reorganization

• Mental practice or motor imagery is an act of producing an internal representation of a movement without generating any motor output.

• It is the imagination of movements of body parts when individual cannot move due to hemiparesis.

• Brain mapping techniques have shown the activation of the motor cortex and other associated areas during imagery as well as during execution of movement (de Vries and Mulder, 2007).

• De Vries S, Mulder T. J Rehabil Med. 2007; 39: 5-13


PET/MR Scan: Physical Movement Vs Imagined Movement

• This image illustrates that a similar network of cerebral structures (e.g., premotor cortex) is activated when normal control subjects execute physically or imagine a sequence of up-down foot movements.

• This suggests that mental practice with motor imagery can be used as a therapeutic approach to keep active the neural circuits involved during practice and hence facilitating the rehabilitation of patients who sustained damage to the brain.


Watching the Brain In Action: Functional Neuroimaging

Seeing words

Hearing words

Speaking words

Generating Verbs



• Studies have shown that mental practice (30 min therapy sessions + 30 min mental practice) can lead to activation of premotor area and primary motor cortex ipsilateral and contralateral of the affected hand as well as superior parietal cortex ipsilateral to the affected hand following stroke (Page et al, 2009)

Page SJ, Szaflarski JP, Eliassen JC, Pan H, Cramer SC. Neurorehabil Neural Repair 2009; 23: 382-388


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• It is well known that mental practice alone is not enough to induce recovery after stroke.

• It should be used as a complement or adjunct to another evidence based motor rehabilitation approaches such as repetitive task practices or CIMT (Zimmermann-Schlatter et al, 2008; Page et al, 2009).

Zimmermann-Schlatter A, Schuster C, Puhan MA, Siekierka E, Steurer J. J Neuroeng Rehabil. 2008; 14: 8

Page SJ, Szaflarski JP, Eliassen JC, Pan H, Cramer SC. Neurorehabil Neural Repair 2009; 23: 382-388


Motor Imagery Using Mirror Box


Body Weight Supported Treadmill Training and Cortical Reorganization

• BWST can reduce load on the paretic leg which can results in more straight trunk and thereby reduces the deviation during walking.

• In addition, due to the movement of treadmill, there will be a decrease in double limb support time and increase in single limb support time (swing phase).

• This can provide an environment for specific and repetitive training for walking.


Body Weight Supported Treadmill Training and Cortical Reorganization

• BWSTT can lead to bilateral cortical activation in individual with chronic stroke.

• A group of researchers have shown increased brain activity in the bilateral primary sensory cortices, cingulate motor areas and caudate nuclei (Enzinger et al 2009).

• This might be due to the requirement of motor control in response to environmental demand, position sense and balance during walking on treadmill.

• Enzinger C, Dawes H, Johansen-Berg H et al. Stroke 2009; 40: 2460-2467


Constraint-Induced Movement Therapy (CIMT): Cortical Reorganization

• CIMT was developed originally to reduce the phenomenon “learned non-use” in which individuals with stroke form the habit of not using their paretic upper extremity.

• In CIMT training, individual with stroke will be forced to use the affected extremity by constraining the less affected UE with mitt during waking hours.

• This therapy improves upper extremity or lower extremity function in individual with stroke and or brain injury.


Constraint-induced Movement Therapy

• Training typically involves restraining the unaffcted limb and using the affected limb for 90% of waking hours.

• Receiving CIMT early (3-9 months post-stroke) results

in greater functional gains than receiving delayed treatment (15-21 months post-stroke).

• Factors for success of CIMT – Repetitive functional practice using affected limb. – The unaffected limb must be constrained 90% of the

waking time


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• CIMT approach has evidence for the physiological and structural brain changes as well as improvement in the affected upper limb function in patients with stroke.

• A group of researchers have shown that CIMT can cause changes in cortical excitability, metabolic rate and cortical blood flow in individual with stroke (Schaechter et al, 2002).

• Schaechter JD, Kraft E, Hilliard TS et al. Neurorehabil Neural Repair 2002; 16: 326-338



• Another group of researchers have shown profuse increase in the gray matter in the sensory and motor cortical areas in both contralateral and ipsilateral brain following CIMT (Gauthier et al 2008).

• They have also shown the changes are accompanied by improvements in spontaneous arm functions.

• Therefore, CIMT may be considered as one of the important movement therapies for individual with chronic stroke

• Gauthier LV, Taub E, Perkins C, Ortmann M, Mark VW, Uswatte G. Stroke 2008; 39: 1520-1525


CIMT vs Control after Stroke Activity measured by TMS


Virtual Training and Cortical Reorganization

• Virtual training (VT) technique is an interactive intervention approach which involves real-time simulation of an environment and activities that allow user interaction.

• With VR, practice intensity and sensory feedback (visual, auditory) can be systematically manipulated to provide the most appropriate, individualized real-life motor training.

• Various types of VR devices are available to facilitate movement even for walking.


Virtual Training and Cortical Reorganization

• VR has been found to induce cortical reorganization with improved associated motor functions in individual with chronic stroke (Adamovich et al, 2009; Kim et al, 2009)

• Another group of researchers have shown fMRI changes in the sensorimotor cortex of patients with chronic stroke after locomotor VR training (You et al, 2005)

• Adamovich SV, Fluet GG, Tunic E, Merians AS. Neuro Rehabil. 2009; 25: 29-44

• Kim JH, Jang SH, Kim CS, Jung JH, You JH. Am J Phys Med Rehabil 2009; 88: 693-701

• You SH, Jang SH, Kim YH et al. Stroke 2005; 36: 1166-1171


Action Observation


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Virtual Training using Wii Game


Right Left Both

Bilateral Training

0.05

1.00

0.75

0.50

0.25

Relative

Intensity

R L

Z: + 54 mm

CS

9 days

post-stroke

28 days

post-stroke

3 months

post-stroke


Unmasking Ipsilateral Pathways


Transcranial Magnetic Stimulation


Is Neuron Repair in the Brain Possible?


THANK YOU

Dr. Pradip Ghosh, PT, PhD, DMS, MS

Professor


brain - iste · learned indicating possible contribution of other brain structures rather than...

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