Neuroplasticity

Principles

  1. Experience-dependent changes interact: metaplasticity
  1. Plasticity is related to intensity or frequency of experiences
  1. Similar behavioral changes can correlate with different plastic changes eg. when learning one task, synapses in one brain part could increase and in the other part they could decrease
  1. Plasticity is age-dependent: if older age, learning new motor tasks becomes more difficult
  1. Two general types of plasticity derive from experience: experience-expectant (during development), experience-dependent (use-dependent)
  1. Plastic changes are time-dependent
  1. Plasticity can be analyzed at many levels: behavior (people can adapt to a visually rearranged world), cortical maps (topographic representations of external world, experience modifies sensory maps), physiology (LTP, kindling), synaptic organization, mitotic activity (new neurons produced in injured cortex), molecular structure
  1. Plasticity is related to an experience's relevance to us
  1. Plasticity is common to all nervous systems (even non mammals)

Adaptive aspects

Maladaptive aspects

Phantom Limb

Factors affecting neuroplasticity

people don't actually recover lost behaviors but they develop new way of functioning to compensate --> the problem of "three-legged cat"

compensating strategies are not consciously learned but they occur spontaneously

some functional recovery is possible in the infant brain but even this recovery isn't complete

plastic changes after cerebral injury could actually make functional outcome worse

Focal hand dystomia: loss of motor control of one or more digits because of increased muscle tone eg. musical training caused the mapped representations of the digits to fuse

lesion size

age, sex, intelligence, personality (often neglected in research)

time-dependent factors e.g., period of a coma

optimistic, extraverted, easygoing people

premorbid functioning

mechanisms of injury e.g. type of injury, local vs, global

overall environment & genetics

speed at which total damage was inflicted e.g.. one event or repeated events

Tactile stimulation --> dendritic growth, neurotrophic factors increased, acetylcholine increased

Nicotine

choline supplement --> increased dendritic growth

hormone depletion --> blocks dendritic changes

noradrenaline depletion --> blocks dendritic hypertrophy

experience-dependent plasticity situations eg. drugs --> alterations in dendritic length & spine density

development of pathological pain, pathological response to sickness, epilepsy, dementia

Phantom pain (experienced by 60-80%)

sensation that an amputated limb is still attached but majority of the sensations is painful (continuous or intermittent) --> clenching spasm

Mechanism? still unclear

irritation in the severe nerve endings

Neuromatrix: the experience of the body is created by a wide network of interconnecting neural structures

Ramachandran: sensations due to reorganization of somatosensory cortex

pain is a result of "junk" inputs from the peripheral NS

Treatment

Antidepressants, spinal cord stimulation, accupuncture, hypnosis --> lack of evidence, lack of effectiveness

Mirror Box/ Mirror Visual Feedback: effectiveness is related to ability of the patient to internalize the reflection of the limb as their own limb

Mechanisms

Adjusting sensitivity (inputs from different regions)

eg. disinhibition of one area that was previously inhibited

Sprouting

Regrowth, Regeneration

modality-specific referral from face to phantom limb (topographically face is next to arm representation)

Remapping hypothesis: sensations emerge as a consequence of the changes in topography following deafferentiation

  • effects are based partly on unmasking of preexisting connections rather than sprouting

over time, the phantom limb becomes frozen/paralyzed (perhaps because of a continuous absence of visual and proprioceptive confirmation that the command have been obeyed)

why is research on phantom limb important?

topography is extremely labile

even in adult brain, massive reorganization can occur over extremely short periods

sensations can be used as a "marker" for plasticity in th eadult brain

we can relate quail (subjective sensations) to the activity of brain maps--> to test assumptions of neurophysiology & sensory psychology

understand how neural activity leads to conscious experience

may be useful in alleviating abnormal postures and spasms in phantom limbs

other neurological syndromes e.g. hemiparesis following stroke, focal dystopias, dyspraxia maybe could also benefit

implication: suggests that body image is a purely transitory internal construct

mismatch between motor output and visual feedback from the arm

restores the congruence between motor output and sensory input

vision dominates touch & proprioception

neural mechanism: mirror neurons, interactions between different modalities eg. vision & motor commands

Developmental Trajectories (earlier may not always be better)

Plasticity during stroke recovery (Murphy)

NS reorganization following injury (multiple levels: cortical & subcortical)

cortical representation of body parts is continuously modulated in response to activity, behavior & skill acquisition

cross-modal plasticity

eg. motor recovery from stroke: adjacent cortical areas taking over the function of the damaged areas or using alternative motor pathways

mechanism of plasticity may differ depending on the time frame: rapid (eg. modulation of GABAergic inhibition), longer (LTP, changes in voltage-gated ion channels, axonal regeneration, sprouting, synaptogenesis)

Transient deafferentiation: useful in studying short-term plasticity, rapid reorganization

cortical representation is dynamically modulated based on afferent input

changes in organization map of S1 after removal of afferent input: responsive to inputs from neighboring parts, threshold for eliciting movements reduced

rapid expansion of muscle representation (after transient deafferentiation) likely involves unmasking of latent excitatory synapses

increased excitatory neurotransmitter release, increased density of postsynaptic receptors, changes in membrane conductance that enhance the effects of weak or distant inputs, displacement of presynaptic elements to a more favorable site, decreased inhibitory inputs or removing inhibition from excitatory inputs

Importance of GABA: maintenance of cortical motor representations

Kennard Principle: sparing of function follows infant lesions

3 critical age divisions

1-5 years: reorganization of brain function eg. rescue of language --> very plastic, remapping

older than 5 years: permit little or no sparing of function --> not as plastic

before 1 year: produce more severe impairments than other

Effects on language

an injured child recovers almost fully, only short lived deficits

left-hemisphere injury (right hemiplegia): shift of language location, remapping BUT it comes at expense of visuospatial functions (crowded right hemisphere) --> slight decrease in both verbal & performance IQ

right-hemisphere lesion (left hemiplegia): no impairment of language (verbal IQ), but decrease in performance IQ

strong affinity for left hemisphere, will not abandon it unless an entire center is destroyed

Lesions & Effects

Anterior or Posterior --> language remained in the left hemisphere

Anterior-posterior--> all language moved to right hemisphere

Anterior--> anterior speech one shifts to the right hemisphere

Posterior--> posterior speech zone shifts to the right hemisphere

serial lesion effect: multiple smaller lesions less harmful than one big lesion (because of ongoing plasticity)

limited time window of neuroplasticity --> greatest recovery gains

neuroplasticity can be further augmented by rehabilitative therapy

Recovery = enhanced sensory & motor performance after stroke BUT reemergent post stroke behavior will never equal pre stroke state (recovery is rather a compensation)

stroke recovery similar to developmental mechanisms

Main Mechanisms (can operate at the same time)

  1. Homeostatic (initial stages of recovery 1-4 first weeks)
  1. Hebbian (refinement)

prenumbra --> reversible damage, rewiring possible

Therapeutic approaches

enriched rehabilitation eg. changing physical environment: moveable walls, varies activities

Stem cell therapy: replacing circuits by promoting neurogenesis or by transplantation

Constraint-induced movement therapy CIMT: enforcing use of the impaired limb by restraining the good limb --> induces cortical motor map expansion

pharmacological rehabilitation: amphetamine treatment

What enables plasticity in the adult brain? ---> diffuse, redundant connectivity in CNS & structural/functional circuits forming through remapping between related cortical regions

cortical remapping is activity dependent and based on competition

peri-infarct cortex --> situated at the border of an infarct but has sufficient blood perfusion, surviving neurons undergo active structural & functional remodelling after stroke

upregulation of the presynaptic release & postsynaptic response

negative feedback-based: restoration of synaptic structural & functional elements

reinforcing the appropriate presynaptic & postsynaptic elements

makes changes at existing synapses & new connections to reset the level of activity (to come back to baseline) --> regulate synaptic activity, could trigger formation of new synapses

Evidence: post-stroke hyper excitability, less specific receptive fields, increased spontaneous activity

engaged when pre & postsynaptic neurons are coincidently active

specific forms of use-dependent rehabilitative training can influence rewiring & functional outcome