Neuroplasticity & Neurorehabilitation Flashcards
Neuroplasticity =
ability of the nervous system to adapt and reorganize, often as a result of injury, learning, and/or experience
involves the sum of molecular, structural, and physiological neuronal changes
Molecular: changes
in gene transcription, protein regulation, and/or neurotransmitter release (amount, type)
Structural: changes
E.g., growth of dendritic spines
Physiological: changes
in neuronal excitation/inhibition; increased functional complexity of motor neurons
Newly learned information =
encoded as new dendrites sprout to connect neurons to specific sites, producing a new pathway that represents the experience
There can be adaptive (e.g., increased motor output) and maladaptive (e.g., neuropathic pain) neuroplastic changes
Neuroplasticity Types:
developmental
habituation
learning and memory
recovery from central nervous system (CNS) injury
Developmental =
Different regions of the brain become heavily myelinated during pre-programmed sensitive periods, which opens up windows of opportunity for developing specific skills or competencies
After a region is myelinated, a performance permanence sets in
ex)nLanguage-learning
Amount of neurons at age 2-3 is about 2X adult brain:
as we age, the old connections are deleted through synaptic pruning, which is the process of removing weakened or ineffective connections
Stronger connections are kept and strengthened
What synapses are kept is determined by experience – most frequently activated are preserved
You develop what you do or know by:
repetition and stimulating the areas of the brain for those specific functions; initially use large part of brain, then less as refine behavior (e.g., athletes, musicians)
Neurons MUST have a purpose or:
they die (apoptosis – programmed cell death)
developmental NEUROREHAB IMPLICATION:
Neuroplasticity = clear age-dependent component
Certain types of plasticity are more prevalent during different periods of life (e.g., babies working on motor control versus speech development)
Training-induced plasticity also occurs more easily in younger brains
Habituation =
Decrease in response to a repeated, benign stimulus reflecting a decrease in synaptic activity and/or reduced amplitude of synaptic potentials
With prolonged stimulus repetition, more permanent structural changes occur (e.g., decreased number of synaptic connections)
Habituation NEUROREHAB IMPLICATION:
Applied to therapeutic approaches that are intended to decrease the neural response to a stimulus
In vestibular rehabilitation patients are asked to move repeatedly in fashions that typically make them dizzy or nauseous
Also used for tactile defensiveness (i.e. extreme response to cutaneous stimulation) and sensory integration problems with kids, and for helping with phantom limb pain
Start with gentle tactile stimulation, then gradually increase the intensity in an effort to achieve habituation
Learning and Memory =
Learning involves the ability of the brain to acquire new knowledge through instruction or experience
memory is the process by which that knowledge is retained over time
During initial stages of motor learning:
large and diffuse brain regions show synaptic activity
eventually, once a task is learned, only small, distinct brain regions show increased activity with performance of the task
Forms of synaptic plasticity that contribute to learning and memory:
Long-term potentiation (LTP) or facilitation
Long-term depression (LTD)
Long-term potentiation (LTP) or facilitation–
a progressive and persistent increase in synaptic strength that occurs with repeat stimulation (can lead to enhanced motor output)
produces long-lasting changes in signal transmission (e.g., greater neurotransmitter release, increase in number of synapses and dendritic connections) associated with learning, makes neurons more “sensitive” to each other
Long-term depression (LTD)–
a reduction in the efficacy of synaptic transmission
Serves to selectively weaken certain synapses, as well as recalibrate their set point for further excitation
Also protects synapses from overexcitation by making them less sensitive to an ongoing stimulus
Need both LTD and LTP –
if not, eventually synapses would reach some level of maximum efficacy, making it difficult to encode new information
Learning and Memory NEUROREHAB IMPLICATION:
Essential component of motor learning, which is a main focus of neurorehabilitation
Recovery from CNS Injury =
involves both spontaneous and activity-dependent plasticity
Neurologic recovery occurs through complex combination of spontaneous and learning-dependent processes.
Spontaneous plasticity =
entails the variable, spontaneous recovery during the first few months (typically 3 months) post-injury as a result of endogenous biological processes rather than behavioral, pharmacological, or neuromodulatory interventions
Resolution of reversible injuries to neurons and glia (such as alterations in membrane potentials, axon conduction), reversal of diaschisis, activation of cell repair, etc. occur during this timeframe
Spontaneous plasticity - processes include:
resolution of inflammation/decreased edema
molecular and cellular changes (e.g., gene expression changes important for neuronal growth activation of growth factors)
structural changes (e.g., axonal sprouting)
electrophysiological changes (e.g., alteration of excitatory/inhibitory balance, particularly in the peri-infarct cortex post-stroke)
Activity-dependent (or training-induced) plasticity:
involves functional training to direct and enhance plasticity to restore function
Treatment factors to consider include task complexity, specificity, difficulty, intensity
Recovery from CNS Injury NEUROREHAB IMPLICATION:
Training-induced plasticity and recovery is what we focus on in neurorehabilitation
We utilize neuroscience and neuroplasticity principles to develop and/or direct more evidence-based diagnostics and treatments to enhance motor output and recovery in our patients
Neuroplastic Changes and Motor Impairment/ Recovery After Stroke:
Injury to the motor cortex leads to the recruitment of motor areas that were not making significant contribution to the lost motor function before injury
1) Changes to existing neuronal pathways
2) Formation of new neuronal connections
3) Overactivation of primary and association motor areas (perilesional and contralesional)
Changes to existing neuronal pathways =
Wallerian degeneration
Alterations in white matter
Wallerian degeneration -
characterized by anterograde degeneration of the distal portion of axons after injury to the cell body/proximal nerve
Detected as early as 2 weeks post-stroke
Followed by progressive myelin degeneration and eventually fibrosis and atrophy of fiber tracts
Alterations in white matter -
microstructural integrity
Occurs not only in the lesioned area but also in brain regions and motor tracts beyond the infarction site (diaschisis)
Such alterations can contribute to behavioral deficits
Formation of new neuronal connections =
Cortical remapping – reorganization of movement representations within the motor cortex
Can entail perilesional reorganization, secondary motor area contributions, changes in neuronal activation patterns (e.g., unmasking of latent motor pathways)
Alternative and/or newly formed connections can compensate for loss of original connections
Overactivation of primary and association motor areas (perilesional and contralesional) =
In patients who demonstrate more favorable recovery, overactivations tend to diminish over time as learning occurs and it takes fewer brain regions to complete a task
Research has shown that the contralesional hemisphere undergoes neuroplastic changes after stroke, but its role in motor recovery is unclear (e.g., it may play a greater role in the presence of large ischemic infarcts)
Persistent recruitment of contralesional motor areas often appears in patients with poorer functional outcomes
Task-specific training leads to:
an increase in the area of motor cortex that controls the muscles used during the task
Therapeutic modulation of neural networks has also been shown to occur following high-intensity exercise/gait training and non-invasive brain stimulation [repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation (tDCS)]
Various events depress motor function after SCI:
Direct damage to the spinal cord (severed, bruising)
spinal shock
inflammation
Spinal shock =
state of transient physiological (rather than anatomical) reflex depression of cord function below the level of injury with associated loss of all sensorimotor functions
reflects the decreased activity of spinal circuits suddenly deprived of input from the motor cortex and brainstem
Areflexia and flaccid paralysis, including of the bowel and bladder, is observed
May last hours or up to several weeks
Early resolution is a positive sign
Inflammation =
entails both local swelling that compresses spinal tracts (impairing neural conduction) and intradural pressure (pressure created by edema and hemorrhage inside the spinal cord, which then expands against the dura)
Neuroplastic changes occur throughout the ___ following SCI
neuraxis (spinal cord, brainstem, cortex)
Neuronal dysfunction below the lesion primarily occurs due to:
immobility and decreases in appropriate afferent input, resulting in a loss of activity in neuronal circuitries below the level of injury, an imbalance in inhibitory and excitatory activity, and a change in spinal reflex behavior
Cortical reorganization occurs due to:
decreased afferent-related cortical excitation due to direct damage to ascending pathways along with decreased movement-related afferent input
More specific neuroplastic changes include:
Impaired function of spinal inhibitory pathways
Altered excitability of alpha motor neurons due to loss or reduction in brainstem-derived serotonin and norepinephrine.
Lack of soleus H-reflex depression during the swing phase of walking; disruption of sustained reflex excitability during stance.
Impaired function of spinal inhibitory pathways:
can lead to increased muscle tone, stretch reflex hyperexcitability, and muscle co-contractions (commonly observed in persons with incomplete SCI)
Spastic muscle tone, however, can compensate in part for the SCI-induced loss of supraspinal drive
Secondary changes in muscle fibers lead to a regulation of muscle tone during functional movements at a simpler level, i.e. without modulated muscle activation
In general, movement disorders after SCI are due to:
defective utilization of afferent input, reduction in cortical input, and depressed functional state of spinal locomotor circuitries
Spontaneous plasticity involves:
resolution of neuropraxia (transient nerve conduction block)
changes in neuronal properties (e.g., collateral sprouting, remyelination of spared axons)
changes in cortical and spinal neuronal networks (e.g., modifications of synaptic strength, synaptic rearrangements, reflex adaptations)
Training-induced plasticity and recovery:
The repetitive activation of particular sensorimotor pathways by task-specific training can reinforce circuits and synapses used to successfully perform the practiced movement
Activity-dependent learning/plasticity occurs even in ____
Isolated spinal circuits
Mechanisms of training-induced recovery include:
up-regulation of growth and neurotrophic factors (e.g., BDNF), changes in neuronal excitability, and adaptations within spinal networks
As persons with SCI likely cannot reactivate their normal motor patterns, they may engage new motor patterns of muscle activity to perform as task
Neurorehabilitation =
interface between rehabilitation medicine and neurology
an active and dynamic process designed to help patients with neurological injury or disease increase their level of function (both at home and in the community), prevent secondary deterioration, facilitate psychological adaptation, and enhance their quality of life
Neurorehabilitation involves a multidisciplinary team with structured organization:
organized multidisciplinary rehabilitation has been shown to be associated with:
reduced odds for death
institutionalization
dependency compared to other non-specific, general rehabilitation approaches
Neurorehabilitation Strategies to Enhance Neural Plasticity and Recovery:
use it or lose it
use it and improve it
specificity
repetition matters
intensity mattes
time matters
salience matters
age matters
transference
interference
use it or lose it =
failure to drive specific brain functions can lead to functional degradation
use it and improve it =
training that drives a specific brain function can lead to an enhancement of that function
specificity =
nature of the training experience dictates the nature of the plasticity
repetition matters =
induction of plasticity requires sufficient repetition
intensity matters =
induction of plasticity requires sufficient training intensity
time matters =
different forms of plasticity occur at different times during training
salience matters =
training experience must be sufficiently salient to induce plasticity
age matters =
training-induced plasticity occurs more readily in younger brains
transference =
plasticity in response to one training experience can enhance the acquisition of similar behaviors
interference =
plasticity in response to one experience can interfere with the acquisition of other behaviors
When taking part in motor practice and training, patients need to be an active participant =
The task has to be challenging enough, and at a high enough training intensity, to induce adaptive neuroplastic changes
t is important to allow for error feedback/adjustment, so the patient learns how to monitor and adjust motor output
Cortical maps are very dynamic:
We can form new routes after injury, and new connections with practice (i.e. neurorehabilitation)
Strategies to enhance neural plasticity include:
Experience, especially enriched environments
Skill training (vs. strength training)
Cortical stimulation – E.g., TMS and tDCS. Can be used to “prime” the motor cortex for subsequent behavior-induced plasticity
Combinatorial therapies
Combinatorial therapies –
can be used to amplify the effects of single interventions (e.g., cortical stimulation or pharmacological agent + task-specific training)
Augmenting motor practice with stimulation can increase the responsiveness of the nervous system to modulatory influences that occur through motor practice and training (i.e. increased neural excitability), promoting adaptive neuroplasticity and functional recovery
Rehabilitation training and pharmacological interventions can enhance ___ processes following CNS injury
spontaneous internal neuroplastic
Stroke induces various cortical changes and reorganization on the anatomical and molecular level, yet the ____ remains unclear
optimal timing, intensity, and type of rehabilitation training to further enhance plasticity
Optimal therapeutic approaches can only be designed with:
greater understanding of the neurobiology of spontaneous and training-induced recovery
presence of critical time windows post-stroke =
(i.e. when the brain is most responsive)
for plasticity-promoting agents and training, combined with the heterogeneity of stroke
suggests that appropriate treatment onset times and individually tailored interventions are essential
3 step model for rehab schedules:
1) determine the metabolic and plastic status of the brain = state of the art imaging and biomarkers
2) enhancement of plastic status of the brain and spinal cord = applications of growth and plasticity promoting factors
3) selection and stabilization of newly formed functional connections = rehabilitative training
Motor Recovery vs Motor Compensation
Return of motor capacity following neurologic injury or in patients with neurologic disease is often a combination of recovery and compensatory mechanisms
happens at 3 levels
Motor recovery - ICF: health condition (neuronal)
restoring function in neural tissue that was initially lost after injury
may be seen as reactivation in brain areas previously inactivated by the circulatory event
although this is not expected to occur in the area of the primary brain lesion, it may occur in areas surrounding the lesion (penumbra) and in the diaschisis
Motor recovery - ICF: Body functions/Structure (performance)
restoring the ability to perform a movement in the same manner as it was performed before injury
may occur through the reappearance of premorbid movement patterns during task accomplishment (voluntary joint range of motion, temporal and spatial interjoint coordination, etc.)
Motor recovery - ICF: Activity (functional)
successful task accomplishment using limbs or end effectors typically used by nondisabled individuals
Motor compensation - ICF: health condition (neuronal)
neural tissue acquired a function that it did not have prior to injury
may be seen as activation in alternative brain areas not normally observed in nondisabled individuals
Motor compensation - ICF: Body functions/Structure (performance)
performing an old movement in a new manner
may be seen as the appearance of alternative movement patterns (recruitment of additional or different degrees of freedom, changes in muscle activation patterns such as increased agonist/antagonist coactivation, delays in timing between movements of adjacent joints) during the accomplishment of a task
Motor compensation - ICF: Activity (functional)
successful task accomplishments using alternate limbs or end effectors
ex) opening a package of chips using 1 hand and the mouth instead of 2 hands
Compensation can be adaptive =
characterized by the use of alternate movement patterns, or substitutive, which is characterized by the use of different effectors or assistive devices to replace lost motor components
Use of Biomarkers to Guide Neurorehabilitation
(e.g., neural markers via TMS or MRI, blood markers) may be used to predict motor recovery and response to therapy after stroke
Improve accuracy of functional motor recovery prognosis
Target therapeutic interventions (personalized medicine)
Optimize patient resources/inform discharge planning
Both clinical measures, neural and physiological mechanisms have been shown to be associated with different stroke outcomes (e.g., independence and disability, upper extremity recovery), and several ____ have been developed for these outcomes
prediction tools
use of prediction tools in healthcare:
can assist rehabilitation and goal setting and increase equity of access to therapeutic services
For prediction tools to be useful, they must:
1) be used at the beginning of recovery
2) make a prediction for a specific timepoint (rather than an outcome at discharge)
3) should be meaningful to patients (e.g., like being able to predict likelihood of achieving specific level of function
4) should combine a small number of variables in an easy way (decision tree, app) for easy use by clinicians
online calculator:
predictors: age, sex, time to admission, motor FIM score, cognitive FIM score, unilateral neglect
time point: discharge from inpatient rehab
outcome: probability of a motor FIM score > 61 points
externally validated
scores and tables:
predictors: age, NIHSS, diabetes, previous stroke, atrial fibrillation
time point: discharge from inpatient rehab
outcome: probability of each of 5 categories based on Barthel Index score
not externally validated
graphical recovery curves for each predictor:
predictors: age, sex, glasgow coma sclae, NIHSS, stroke type
time point: any week up to 1 yrs poststroke
outcome: Barthel Index Score
externally validated
PREP2 prediction categories:
excellent
good
limited
poor
PREP2 - good
34-48
potential to be using the affected hand and arm for most activities of daily living within 3 months, though with some weakness, slowness, or clumsiness
promote normal funciton of the affected hand and arm by improving strength, coordination
minimize compensation with other hand and arm and trunk
PREP2 - limited
13-31
potential to regain some movement in the affected hand and arm within 3 months, but daily activites are likely to require significant modification
unlikely to regain dextrous hand function
promote adaptation in daily activities, incorporating the affected upper limb wherever safely possible
PREP2 - poor
0-9
unlikely to regain useful hand and arm function within 3 months
may be able to use the affected hand and arm as a stabilizer in bimanual tasks
prevent secondary complications such as pain, spasticity, and shoulder instability
reduce disability by learning to complete daily activities with the stronger hand and arm
Future work is needed to investigate the potential role of neural ___ and blood ___ biomarkers in walking recovery post-stroke, and to differentiate between different levels of walking ability.
(e.g., TMS/MRI measures)
(e.g., serum levels of BDNF, other markers associated with immune response)
Selecting optimal treatment strategies for individual patients based not only on their clinical evaluation, but also on:
their neural, blood, and genetic makeup will help tailor treatment strategies to maximize therapeutic effects, helping to optimize function and quality of live in persons with stroke
