Neuroplasticity
Dr. Michael P. Gillespie
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Neuroplasticity
 Neuroplasticity is the ability of the brain to change, for better
or for worse, throughout the individual’s life span.
 It involves forming neuronal connections in response to
information derived from experiences in the environment,
sensory stimulation, and normal development (Doidge, 2007;
Merzenich, 2001; Nudo, 2008).
Dr. Michael P. Gillespie
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Neuroplasticity
 Neuroplasticity refers to the moldable structure of the brain
and nerves that results from changes in neural pathways and
synapses. These changes stem from changes in behavior,
environment, neural processes as well as changes from bodily
injury.
 The brain does change throughout life.
Dr. Michael P. Gillespie
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Neuroplasticity
Dr. Michael P. Gillespie
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Girl Living With Half Her Brain
 http://www.youtube.com/watch?v=2MKNsI5CWoU
Dr. Michael P. Gillespie
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Positive Outcomes of Neuroplasticity
 New skills
 Better cognition
 More efficient communication between sensory and motor pathways
 Improved function of the aging brain
 Slowing down pathological processes
 Promoting recovery of sensory losses
 Improved motor control
 Improved memory
 (Mahncke, Bronstone & Merzenich, 2006; Mahucke & Merzenich, 2006; Nudo 2007; Stein &
Hoffman, 2003).
Dr. Michael P. Gillespie
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Negative Outcomes of Neuroplasticity
 Decline in brain function
 Altered motor control
 Impaired performance of activities of daily living
 Amplified perception of pain
Dr. Michael P. Gillespie
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Neuroplasticity
 http://www.youtube.com/watch?v=iAzmyB9PFt4
Dr. Michael P. Gillespie
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Structural Changes in the Brain
 Synaptic plasticity
 Synaptogenesis
 Neuronal migration
 Neurogenesis
 Neural cell death
Dr. Michael P. Gillespie
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Synaptic Plasticity
 Synaptic plasticity refers to changes in the strength of
connections between synapses.
 Long-term potentiation (LTP)
 Long-term depression (LTD)
 Changes in the number of receptors for specific
neurotransmitters
 Up-regulation
 Down-regulation
 Changes in which proteins are expressed inside the cell
Dr. Michael P. Gillespie
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Neuroplasticity – Brain Remodeling
 Steps to remodel the brain based upon experiences:
 1. Repetition
 2. Correct fundamentals
 3. Authentic environment
Dr. Michael P. Gillespie
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Neuroplasticity – Brain Remodeling
 http://www.youtube.com/watch?v=VvZ9ofM7Go&feature=related
Dr. Michael P. Gillespie
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Synaptogenesis & Synaptic Pruning
 The creation and removal of entire groups of synapses.
 This builds and destroys connections between neurons
respectively.
Dr. Michael P. Gillespie
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Neuronal Migration
 Neuronal migration is a process whereby neurons extend
from their place of birth to connect to far reaching areas of
the brain.
Dr. Michael P. Gillespie
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Neurogenesis
 Neurogenesis is the creation of new neurons.
 It largely occurs in the developing brain.
 Limited neurogenesis occurs in the adult brain.
Dr. Michael P. Gillespie
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Neural Cell Death
 Neurons die.
 This can happen from either damage, over-excitation, or
disease.
 Natural programmed cell death including apoptosis also
occurs.
Dr. Michael P. Gillespie
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Functional Reorganization
 As the brain develops, certain areas of the brain become
specialized for specific tasks.
 If your experience changes dramatically or parts of the brain
are damaged, areas previously specialized for a certain
function can take on the work of other areas.
Dr. Michael P. Gillespie
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Brain Functions / Brain Regions
 Contrary to common
understanding, brain
functions are not strictly
confined to specific fixed
locations as identified in this
picture.
Dr. Michael P. Gillespie
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Previously Held Beliefs
 Brain functions were confined to specific fixed locations of
brain tissue.
 Brain structure is relatively immutable after a critical period
during early childhood.
 * New research reveals that many aspects of the brain remain
plastic in adulthood. *
Dr. Michael P. Gillespie
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Levels of Neuroplasticity
 Cellular changes (result of learning)
 Cortical remapping (response to injury)
Dr. Michael P. Gillespie
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Synaptic Pruning
 Synaptic pruning is a neurological regulatory process that
facilitates a change in neural structure by reducing the overall
number of neurons and synapses.
 The resulting synaptic connections are more efficient.
 Pruning is believed to represent the learning process.
 Synapses that are frequently used have strong connections
whereas those that are rarely used are eliminated.
 “Neurons that fire together, wire together. Neurons that fire
apart, wire apart”.
Dr. Michael P. Gillespie
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Synaptogenesis / Synaptic Pruning
 http://www.youtube.com/watch?v=tJ93qXXYRpU&feature=re
lated
Dr. Michael P. Gillespie
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Cortical Maps
 Sensory information from certain parts of the body projects
to specific regions of the cerebral cortex.
 As a result of this somatotrophic organization of sensory
inputs to the cortex, cortical representation of the body
resembles a map (or a homonculus).
Dr. Michael P. Gillespie
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The Learning Brain
 http://www.youtube.com/watch?v=cgLYkV689s4&feature=rel
ated
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Homunculus
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Removing Sensory Inputs
 If a cortical map is derived of sensory input, the adjacent
segments it will become activated by adjacent sensory inputs.
 Merzenich’s 1984 study involved the mapping of owl monkey
hands before and after amputation of the third digit.
 Before amputation, there were five distinct areas corresponding
to each individual digit.
 After amputation of the third digit, the area of the cortical map
formerly occupied by the third digit was invaded by the
previously adjacent second and fourth digit zones.
 Only the regions bordering a certain area will invade it will alter
the cortical map.
Dr. Michael P. Gillespie
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Sensory Site Activation
 Sensory sites that are activated in an attended operant
behavior increase their cortical representation (Merzenich
and William Kenkins (1990)).
 When a stimulus is cognitively associated with reinforcement,
its cortical representation is strengthened and enlarged
(Merzenich and DT Blake (2002, 2005, 2006).
 Cortical representations can increase two to threefold in 1-2
days at the time in which a new sensory motor behavior is
first acquired and changes are largely finished within a few
weeks.
Dr. Michael P. Gillespie
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Phantom Limbs
 Phantom limbs are experienced by people who have
undergone amputations.
 Cortical reorganization appears to play an important role in
phantom limb sensation.
 Mirror box therapy developed by Vilayanur Ramachandran
has shown great promise in treating phantom limb pain.
Dr. Michael P. Gillespie
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Phantom Limb Pain
Dr. Michael P. Gillespie
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Mirror Box
 A diagrammatic explanation of
the mirror box. The patient
places the good limb into one
side of the box (in this case the
right hand) and the amputated
limb into the other side. Due to
the mirror, the patient sees a
reflection of the good hand
where the missing limb would
be (indicated in lower contrast).
The patient thus receives
artificial visual feedback that
the "resurrected" limb is now
moving when they move the
good hand.
Dr. Michael P. Gillespie
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Mirror Visualization Therapy
 http://www.youtube.com/watch?v=Pe8Y3YETnuY&feature=r
elmfu
 http://www.youtube.com/watch?v=hMBA15Hu35M&feature=
related
Dr. Michael P. Gillespie
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Spatial Coupling
 Marian Michielsen suggested that Ramachandran’s Mirror
Box therapy worked by enhancing spatial coupling between
limbs.
Dr. Michael P. Gillespie
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Treatment of Brain Damage
 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.
Dr. Michael P. Gillespie
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Neurogenesis
 Neurogenesis is the process by which neurons are generated
from neural stem cells.
 Recent studies show that neurogenesis occurs 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 dies, but cannot be
recreated.
Dr. Michael P. Gillespie
Rehabilitation Techniques That
Precipitate Cortical Reorganization
 Constraint-induced movement therapy
 Functional electrical stimulation
 Treadmill training with body weight support
 Virtual reality therapy
Dr. Michael P. Gillespie
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Constraint-induced Movement
Therapy (CIMT)
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 This therapy improves upper extremity function in stroke victims
and other victims with central nervous system damage.
 The purpose is to combine restraint of the unaffected limb and
intensive use of the affected limb.
 Types of restraints:
 Sling
 Triangular bandage
 Splint
 Half glove
 Mitt
Dr. Michael P. Gillespie
Constraint-induced Movement
Therapy (CIMT)
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 The use of the affected limb is called shaping.
 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
 Concentrated and repetitive practice of the affected limb.
 The unaffected limb must be constrained 90% of the waking
hours.
Dr. Michael P. Gillespie
Constraint-induced Movement Therapy
(CIMT)
Dr. Michael P. Gillespie
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Constraint-induced Movement Therapy
(CIMT)
 http://www.youtube.com/watch?v=MMTh2hWvB2g
Dr. Michael P. Gillespie
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Functional Electrical Stimulation
 Functional electrical stimulation uses electrical currents to
activate nerves innervating extremities affected by paralysis
resulting from spinal cord injury, head injury, stroke, and
other neurological disorders.
 Sometimes it is referred to as Neuromuscular electrical
stimulation (NMES).
Dr. Michael P. Gillespie
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Functional Electrical Stimulation
Dr. Michael P. Gillespie
Contralaterally Controlled Functional
Electrical Stimulation Stroke Therapy
 http://www.youtube.com/watch?v=boz0HQXQhKg
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Treatment of Learning Difficulties
 Michael Merzenich developed a series of plasticity based
computer programs known as Fast ForWord.
 The programs consist of seven brain exercises to help with the
language and learning deficits of dyslexia.
 The software also improved cognitive function in adults with
age related cognitive decline (ARCD).
Dr. Michael P. Gillespie
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Chronic Pain
 Some people suffer chronic pain at sites that were previously
injured, but are currently healthy.
 Chronic pain happens as a result of maladaptive
reorganization of the nervous system both peripherally and
centrally.
 During the period of tissue damage, prolonged nociceptive
input from the periphery to the central nervous system results
in somatotopic organization and central sensitization.
Dr. Michael P. Gillespie
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Meditation
 Meditation has been linked to cortical thickness and the density of
gray matter.
 Richard Davidson performed experiments with H.H. the Dalai Lama
to examine the effects of mediation on the brain.
 Long term and short term practice of meditation resulted in
different levels of activity in brain regions associated with qualities
such as attention, anxiety, depression, fear, and anger.
 Mediation also demonstrated an effect on the ability of the body to
heal itself.
 Changes in the physical structure of the brain appear to be
responsible for these differences.
Dr. Michael P. Gillespie
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Exercise Induced Neuroplasticity
 All forms of exercise appear to produce neuronal changes in
the brain; however, different forms of exercise produce
changes in different brain regions.
 More demanding forms of exercise seem to promote change
in more diverse areas of the brain.
Dr. Michael P. Gillespie
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Neuroplasticity & Occupational Therapy
 Learning and memory are the result of experience driven
alterations of the synaptic structures of neurons.
 “Occupational Therapy practitioners set up the circumstances
and situations that modify the environment and the degree of
challenge for a skill set (just the right challenge) that creates
an adaptive response that originates at the cellular and
molecular level” (McCormack, 2009).
 Neuroplasticity reflects the brain’s ability to grow and
change into old age as long as it is engaged in meaningful
occupations. This is the basis of occupational therapy
(Christiansen & Baum, 2005).
Dr. Michael P. Gillespie
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Types of Neuroplasticity
 Practice-Dependent Plasticity
 Competitive Plasticity
 Positive Plasticity
 Negative Plasticity
Dr. Michael P. Gillespie
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Practice-Dependent Plasticity
 A person performs a task repeatedly to learn or re-learn a
skills set.
 “The neurons that fire together, wire together” (Hebb’s
concept).
 http://www.youtube.com/watch?v=5iyodWeFkLE
 You can incorporate constraint induced OT as well to “force”
neurons to fire together and “unmask” latent neurons to
activate those neuronal pathways.
Dr. Michael P. Gillespie
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Competitive Plasticity
 Use or disuse of a neuronal pathway will lead to natural
selection of the pathways utilized.
 “Use it or lose it”
 The cerebral cortex is constantly remodeling itself according
to influences from the environment (Bear et al, 2007;
Mahncke, Bronstone et al, 2006).
Dr. Michael P. Gillespie
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Positive Plasticity
 Compensatory changes occuring at the cellular and molecular
levels (dendritic sprouting).
 Temporal changes (speed of action potentials).
 Release of neuromodulators.
 Influence of second messengers (i.e. producing new
postsynaptic membrane receptors).
 Formation of alternative pathways that make new functional
connections in the cortex and tract systems.
Dr. Michael P. Gillespie
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Dendritic Sprouting
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Neurite Outgrowth
 http://www.youtube.com/watch?v=n_9YTeEHp1E&feature=r
elated
Dr. Michael P. Gillespie
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Negative Plasticity
 Negative plasticity occurs when dendritic sprouting and
proliferation of postsynaptic membrane receptors results in
excessive production of excitatory impulses producing hypertonicity
in muscles.
 Good motivation and attention release neuromodulators (dopamine
and acetylcholine) that promote faster synapses and positive
changes in cortical mapping.
 Poor motivation and lack of effort produces weak synaptic
connections and synapses that are slower. These neurons
sometimes undergo apoptosis.
 “Neurons that fire out of sync, fail to link” (Bear et al., 2007; Fillipi,
2002; Woolf & Salter, 2000).
Dr. Michael P. Gillespie
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Secondary Neural Pathways
 After a lesion in the central nervous system, the usual
neuronal pathways are blocked or destroyed.
 We can develop secondary neuronal pathways to send
neuronal signals around the blockage.
 We say that secondary neuronal pathways become
“unmasked” and get stronger with use.
 This is analogous to a bridge going out. We can take
secondary roads. This path may take longer, but shorter
paths will be found.
Dr. Michael P. Gillespie
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Compensation
 If a person loses one sensory modality, other senses can
compensate and take over.
 Teaching ways to adapt, modify, or change the method to perform
the task.
 This may involve modifying the environment.
 It may involve training the family members or caregivers to assist.
 Compensation involves the brain’s ability to recruit other neurons
in other regions of the nervous system. It is a form of
neuroplasticity and not just a way to modify or adapt.
Dr. Michael P. Gillespie
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Neuroplasticity in Pain Syndromes
 Neuropathic pain and pain hypersensitivity are examples of
negative plasticity.
 Activation of nociceptive pathways is the response of the
system to repeated stimuli.
Dr. Michael P. Gillespie
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Neuroplasticity in Repetitive Strain
Injuries
 Complex bio-psychosocial responses can cause undesirable
outcomes in localized injuries (Nudo, 2007).
 Therefore, it is necessary to “treat the whole person”.
 OT practitioners should stimulate practice-dependent plasticity by
facilitating adaptive responses that engage the cerebral cortex.
 Mental rehearsals and guided imagery techniques release
neuromodulators such as dopamine, norepinephrine, and
acetylcholine.
 These neuromodulators influence neuroplasticity and the formation
of new cortical maps.
Dr. Michael P. Gillespie
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Mechanisms of Neuroplasticity
 1. Diaschisis – neuronal structures that are anatomically connected
to a lesion or region damaged by stroke undergo reduced blood
supply and metabolism.
 2. Behavioral compensation – occupational therapy directs the
individual’s interaction with the environment to utilize viable
neurons surrounding the area of the lesion in order to reorganize
their capacity to compensate for damaged neurons.
 3. Adaptive plasticity – dendritic growth and angiogenesis occurs
near the damaged areas. Dendritic growth is an adaptive response
to substitute for the lost function.
 This is a critical time of OT intervention.
 Positive plasticity happens through use or doing.
 Negative plasticity happens through disuse or doing little.
Dr. Michael P. Gillespie
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OT in Cognitive Rehabilitation
 Cognitive impairments are an example of negative plasticity
that affects mood and the ability to problem solve. This in
turn can reduce motivation.
 Interventions used in occupational therapy that stimulate
change and repetition are important in strengthening
connections between neurons (Meintzschel & Ziemann,
2006).
 If the practitioner uses a novel stimulus, it should be followed
immediately by some reward or reinforcement. It should be
repeated again and again to drive synaptic change.
Dr. Michael P. Gillespie
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Compensatory Cognitive Strategies
 Changes in environmental structure and support.
 Visual aids.
 Checklists.
 Step-by-step instructions.
 Remedial cognitive interventions include repetitively practicing tasks that
require specific cognitive functions and challenges.
 Video games
 Virtual reality
 Neurofeedback training
 Brain-computer interface technology can deliver repetition, challenge, and
motivation rapidly and consistently.
Dr. Michael P. Gillespie
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Neurofeedback Training
 http://www.youtube.com/watch?v=GJRWYxEEFv0
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Brain Computer Interface
 http://www.youtube.com/watch?v=ZwuMg0FsKzs
Dr. Michael P. Gillespie