Neuroplasticity & Neurorehabilitation

Question 1

Neuroplasticity =

Answer 1

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

Question 2

Molecular: changes

Answer 2

in gene transcription, protein regulation, and/or neurotransmitter release (amount, type)

Question 3

Structural: changes

Answer 3

E.g., growth of dendritic spines

Question 4

Physiological: changes

Answer 4

in neuronal excitation/inhibition; increased functional complexity of motor neurons

Question 5

Newly learned information =

Answer 5

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

Question 6

Neuroplasticity Types:

Answer 6

developmental

habituation

learning and memory

recovery from central nervous system (CNS) injury

Question 7

Developmental =

Answer 7

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

Question 8

Amount of neurons at age 2-3 is about 2X adult brain:

Answer 8

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

Question 9

You develop what you do or know by:

Answer 9

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)

Question 10

Neurons MUST have a purpose or:

Answer 10

they die (apoptosis – programmed cell death)

Question 11

developmental NEUROREHAB IMPLICATION:

Answer 11

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

Question 12

Habituation =

Answer 12

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)

Question 13

Habituation NEUROREHAB IMPLICATION:

Answer 13

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

Question 14

Learning and Memory =

Answer 14

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

Question 15

During initial stages of motor learning:

Answer 15

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

Question 16

Forms of synaptic plasticity that contribute to learning and memory:

Answer 16

Long-term potentiation (LTP) or facilitation

Long-term depression (LTD)

Question 17

Long-term potentiation (LTP) or facilitation–

Answer 17

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

Question 18

Long-term depression (LTD)–

Answer 18

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

Question 19

Need both LTD and LTP –

Answer 19

if not, eventually synapses would reach some level of maximum efficacy, making it difficult to encode new information

Question 20

Learning and Memory NEUROREHAB IMPLICATION:

Answer 20

Essential component of motor learning, which is a main focus of neurorehabilitation

Question 21

Recovery from CNS Injury =

Answer 21

involves both spontaneous and activity-dependent plasticity

Neurologic recovery occurs through complex combination of spontaneous and learning-dependent processes.

Question 22

Spontaneous plasticity =

Answer 22

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

Question 23

Spontaneous plasticity - processes include:

Answer 23

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)

Question 24

Activity-dependent (or training-induced) plasticity:

Answer 24

involves functional training to direct and enhance plasticity to restore function

Treatment factors to consider include task complexity, specificity, difficulty, intensity

Question 25

Recovery from CNS Injury NEUROREHAB IMPLICATION:

Answer 25

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

Question 26

Neuroplastic Changes and Motor Impairment/ Recovery After Stroke:

Answer 26

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)

Question 27

Changes to existing neuronal pathways =

Answer 27

Wallerian degeneration Alterations in white matter

Question 28

Wallerian degeneration -

Answer 28

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

Question 29

Alterations in white matter -

Answer 29

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

Question 30

Formation of new neuronal connections =

Answer 30

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

Question 31

Overactivation of primary and association motor areas (perilesional and contralesional) =

Answer 31

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

Question 32

Task-specific training leads to:

Answer 32

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)]

Question 33

Various events depress motor function after SCI:

Answer 33

Direct damage to the spinal cord (severed, bruising) spinal shock inflammation

Question 34

Spinal shock =

Answer 34

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

Question 35

Inflammation =

Answer 35

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)

Question 36

Neuroplastic changes occur throughout the ___ following SCI

Answer 36

neuraxis (spinal cord, brainstem, cortex)

Question 37

Neuronal dysfunction below the lesion primarily occurs due to:

Answer 37

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

Question 38

Cortical reorganization occurs due to:

Answer 38

decreased afferent-related cortical excitation due to direct damage to ascending pathways along with decreased movement-related afferent input

Question 39

More specific neuroplastic changes include:

Answer 39

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.

Question 40

Impaired function of spinal inhibitory pathways:

Answer 40

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

Question 41

In general, movement disorders after SCI are due to:

Answer 41

defective utilization of afferent input, reduction in cortical input, and depressed functional state of spinal locomotor circuitries

Question 42

Spontaneous plasticity involves:

Answer 42

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)

Question 43

Training-induced plasticity and recovery:

Answer 43

The repetitive activation of particular sensorimotor pathways by task-specific training can reinforce circuits and synapses used to successfully perform the practiced movement

Question 44

Activity-dependent learning/plasticity occurs even in ____

Answer 44

Isolated spinal circuits

Question 45

Mechanisms of training-induced recovery include:

Answer 45

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

Question 46

Neurorehabilitation =

Answer 46

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

Question 47

Neurorehabilitation involves a multidisciplinary team with structured organization:

Answer 47

organized multidisciplinary rehabilitation has been shown to be associated with: reduced odds for death institutionalization dependency compared to other non-specific, general rehabilitation approaches

Question 48

Neurorehabilitation Strategies to Enhance Neural Plasticity and Recovery:

Answer 48

use it or lose it use it and improve it specificity repetition matters intensity mattes time matters salience matters age matters transference interference

Question 49

use it or lose it =

Answer 49

failure to drive specific brain functions can lead to functional degradation

Question 50

use it and improve it =

Answer 50

training that drives a specific brain function can lead to an enhancement of that function

Question 51

specificity =

Answer 51

nature of the training experience dictates the nature of the plasticity

Question 52

repetition matters =

Answer 52

induction of plasticity requires sufficient repetition

Question 53

intensity matters =

Answer 53

induction of plasticity requires sufficient training intensity

Question 54

time matters =

Answer 54

different forms of plasticity occur at different times during training

Question 55

salience matters =

Answer 55

training experience must be sufficiently salient to induce plasticity

Question 56

age matters =

Answer 56

training-induced plasticity occurs more readily in younger brains

Question 57

transference =

Answer 57

plasticity in response to one training experience can enhance the acquisition of similar behaviors

Question 58

interference =

Answer 58

plasticity in response to one experience can interfere with the acquisition of other behaviors

Question 59

When taking part in motor practice and training, patients need to be an active participant =

Answer 59

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

Question 60

Cortical maps are very dynamic:

Answer 60

We can form new routes after injury, and new connections with practice (i.e. neurorehabilitation)

Question 61

Strategies to enhance neural plasticity include:

Answer 61

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

Question 62

Combinatorial therapies –

Answer 62

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

Question 63

Rehabilitation training and pharmacological interventions can enhance ___ processes following CNS injury

Answer 63

spontaneous internal neuroplastic

Question 64

Stroke induces various cortical changes and reorganization on the anatomical and molecular level, yet the ____ remains unclear

Answer 64

optimal timing, intensity, and type of rehabilitation training to further enhance plasticity

Question 65

Optimal therapeutic approaches can only be designed with:

Answer 65

greater understanding of the neurobiology of spontaneous and training-induced recovery

Question 66

presence of critical time windows post-stroke =

Answer 66

(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

Question 67

3 step model for rehab schedules:

Answer 67

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

Question 68

Motor Recovery vs Motor Compensation

Answer 68

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

Question 69

Motor recovery - ICF: health condition (neuronal)

Answer 69

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

Question 70

Motor recovery - ICF: Body functions/Structure (performance)

Answer 70

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.)

Question 71

Motor recovery - ICF: Activity (functional)

Answer 71

successful task accomplishment using limbs or end effectors typically used by nondisabled individuals

Question 72

Motor compensation - ICF: health condition (neuronal)

Answer 72

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

Question 73

Motor compensation - ICF: Body functions/Structure (performance)

Answer 73

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

Question 74

Motor compensation - ICF: Activity (functional)

Answer 74

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

Question 75

Compensation can be adaptive =

Answer 75

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

Question 76

Use of Biomarkers to Guide Neurorehabilitation

Answer 76

(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

Question 77

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

Answer 77

prediction tools

Question 78

use of prediction tools in healthcare:

Answer 78

can assist rehabilitation and goal setting and increase equity of access to therapeutic services

Question 79

For prediction tools to be useful, they must:

Answer 79

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

Question 80

online calculator:

Answer 80

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

Question 81

scores and tables:

Answer 81

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

Question 82

graphical recovery curves for each predictor:

Answer 82

predictors: age, sex, glasgow coma sclae, NIHSS, stroke type time point: any week up to 1 yrs poststroke outcome: Barthel Index Score externally validated

Question 83

PREP2 prediction categories:

Answer 83

excellent good limited poor

Question 83

PREP2 - good

Answer 83

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

Question 83

PREP2 - limited

Answer 83

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

Question 84

PREP2 - poor

Answer 84

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

Question 84

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.

Answer 84

(e.g., TMS/MRI measures) (e.g., serum levels of BDNF, other markers associated with immune response)

Question 84

Selecting optimal treatment strategies for individual patients based not only on their clinical evaluation, but also on:

Answer 84

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