Brief Summary

  • when there is significant recovery of function it is associated with a remodeling of the cortical circuitry; when there is no recovery, there is also a lack of cortical change or a dendritic atrophy of the remaining neurons

Definition of Plasticity

  • the brain’s capacity for continuously changing it structure, and ultimately its function throughout a life time; allows the brain to respond to environmental changes or changes within the organism itself. Plasticity can include:
    • maturational/developmental changes
    • change with experience – for learning and remembering information
    • recovery after brain injury – brain must reorganize at least in part to recover fxn
    • maintaining function despite aging (response to natural cell death)

Concepts regarding recovery of function (must be differentiated from compensation)

  • More extensive for language function than most other cognitive functions
    • re: there appears to be limits to recovery
  • Recovery may be reversible
    • as patients age the mechanisms that promoted recovery earlier in life may be called on to compensate for neuronal deterioration (due to aging)
      • may lead to a return of the symptoms of the earlier brain injury
  • Recovery varies with the age at assessment; cortically injured subjects may grow into or out of deficits depending on the area damaged, the behavior measured and the extent of injury
  • Not all plasticity is valuable – it may take away from the development of other skills
  • Enriched environments
    • increase: cortical thickness, dendritic branching and the number of synapses in the cortex; so does training an animal on specific tasks!
  • Three possible outcomes in behavioral functioning following brain injury
    • compensation – change in strategy or a substitution of a new behavior for the lost one
    • diaschesis – restitution of the original behavior; recovery from some sort of nonspecific effect of the injury (e.g., swelling)
    • recovery associated with neurological changes
  • Three neurological implications of brain damage
    • Death
      • many neurons that are not directly injured lose their synaptic inputs which can lead to death
    • Survival w/reduced total input
    • Reinnervation (either in whole or in part)
    • In most cases all three events occur
    • Atrophy is not an inevitable result of cortical injury; synaptic remodeling may be more common than previously thought

Some basic neuroanatomy info

  • all species have the same number of neurons in a “column” of cortex, despite having brains of different thickness. The difference in cortical thickness is due to dendrites, axons, blood vessels, and glial cells – which allow the brain to have more synapses.
  • increasing the processing capacity is associated with an increase in synapses
  • mechanism behind neuronal migration:
    • re: cells develop along the walls of the ventricle, and must traverse the cells and fibers of the inner layers
    • neurons migrate along specialized filaments, known as radial glial fibers
    • after cell migration is complete these glial fibers disappear and may be transformed into another type of glia – astrocytes
      • b/c these glial are not present in the mature, neural repair or regrowth is difficult since a dividing cell will have no way to get to an injured area
  • it may be possible that damage early in life may occur when these glial cells are still there, making recovery more possible
    • Kolb has shown that it is very difficult to make cortical lesions in infant rats b/c the brain seems to regrow the lost region.
  • B/c the developing brain goes through different processes the same lesion at different times may have different effects; there may be more plasticity during the period of overproduction of synapses as the brain could just keep the needed synapses that might normally have died

General Methods of plasticity

  • Sources of plasticity include
    • spontaneous recovery
      • resolution and absorption from hematomas, decrease in swelling and return of electrolyte and neurochemical balance
    • neurostructural changes as discussed below
    • Specific mechanisms likely underlie more than one form of change (b/c the nervous system is likely to be conservative in its construction)
      • so the mechanism for learning may also form the basis of other behavioral changes such as recovery from brain injury
      • cortex is more likely to be plastic than other areas of CNS. Within the cortex, some structures are likely to be more plastic than others. e.g., language fxns are probably more plastic than spinal reflexes (b/c more advantageous)
      • significant recovery in behavior is associated with growth in the dendritic trees – and thus the number of connections
      • Enriched environments have been shown to increase the rats’ synaptic connections and decrease their dendritic spine density – so, the changes were not merely due to a growth in more connections, but also a remodeling of the dendrites, with the synapses farther apart
      • decreasing spine density may allow for more room for future experience-dependent synapses to be formed so, animals with “enriched neurons” would be able to change more quickly as they learn new things; i.e. learning makes the brain more responsive to subsequent experiences; i.e., plasticity has made the brain more plastic.
      • w/o some areas of afferent and efferent connectivity the remaining cortex is unable to compensate for the loss (no matter how many new synapses are formed)
    • neocortical activity influences plasticity so, in experiments studying fxnl recovery the very act of testing the animals may actually alter the recovery process!

More Specific Methods of Plasticity

  • re: the main way the brain modifies itself is through change at the synapse which may occur in
    • changes in axon terminals
    • dendritic arborization
    • spine density or
    • altering existing synapses
  • so, aspects of recovery include:
    • diaschisis
    • axonal growth – from damaged axons and collateral sprouting from intact axons. Some axonal growth merely involves an increase in the amount of transmitter available
    • dendritic growth – refers to the expansion of the dendritic surface, which again implies the formation of new synapses. expansion can occur by the development of more dendritic material or in an increase in the number of spines, or an increase in receptor activity
    • glia changes – glial cells may play a key role in stimulating plasticity in the neuron; there is a correlation b/t the intensity of the astrocyte response to injury and the extent of fxnl recovery (rats with frontal lesions on day 10 have an exaggerated astrocyte response, while those with day 1 lesion have no astrocyte response. It is proposed that astrocytes may produce some type of trophic factor(s) that may contribute to synaptic growth and fxn recovery
    • synapse supersensitivity – compensates for loss of presynaptic elements – remaining dendrites b/c hypersensitive to incoming stimuli
    • substitution – existing intact brain structures assume fxns previously held by lesioned areas
      • substitution of fxn – active reorganization of brain-behavior relationships
      • redundant representation of some structural systems

The Developing Cortex

  • studies have shown that many cortical areas are capable of assuming the structure and fxns of virtually any other area. But, as the cortex develops its plasticity decreases and it b/c constrained by its gross connectivity.
  • the stages of development: cell proliferation, cell differentiation, dendritic and axonal growth, synaptogenesis, cell and synaptic death, and gliagenesis
  • cell proliferation appears to be largely complete by the 5th month of gestation
  • cell migration may continue even postnatally

The Aging Brain

  • As we age there is a continual loss of neurons, but also a continual increase in the number of connections in each of the remaining cortical neurons
    • this allows us to maintain functioning w/o behavioral loss well until old age.
  • in dementing diseases this increase in synapses fails to occur, so there is behavioral loss much sooner
  • this suggests that plasticity following injury may be more successful in younger animals than in older ones b/c there are more remaining neurons to change. Clinically this suggests that those people with brain damage early in life may not be as successful in putting off the effects of age on the brain
    • older rats who are lesioned have difficult recovering and in fact show significant atrophy in dendritic arborization
    • but older rats who have been placed in an enriched environment still show increased dendritic arborization (i.e., plasticity) – no studies to date on enriched and then lesioned rats

The role of the type and extent of injury on plasticity

  • patients with closed head injuries show more complete and rapid recovery from aphasia than do stroke patients
    • perhaps because stroke damages larger regions of both cortical and subcortical tissues within the language areas
  • there is marked variability in the extent to w/c recovery occurs depending upon type of injury
  • we can predict that in the case of small lesions there may be changes in the remaining cortex that can underlie the recovery of fxn, but in larger lesions there may be changes in other cortical regions that allow the compensatory mechanisms to be more efficient with practice (i.e., if behavior after injury is compensatory there must be some underlying changes in the brain to accommodate this)
  • unilateral lesions allow more dendritic growth and behavioral recovery than bilateral lesions (even very small lesions in contralateral hemidecortication interferes with recovery and dendritic growth)
  • factors that affect outcome of lesions:
    • timing of lesion during development; once a brain region has b/c fxnl the same damage may produce very different results
    • gender

The Effect of Brain Damage in Infants

  • cognitive deficits associated with lateralized brain insult are generally less specific in children than in adults; therefor expression of deficit may be different (or transient); e.g., children rarely demonstrate aphasia (and even if they do, it resolves rapidly)
  • some believe that “plasticity” is due to the capacity to form or substitute new strategies to successfully fulfill a lost skill
  • Lennenberg proposed that language develops rapidly during ages 2 -5 and then more slowly during puberty. If damage occurred during the rapid development, it may be possible to shift language fxns to the intact right hemisphere – so no chronic aphasia; damage after this time would not permit reorganization thus poorer prognosis
  • but children with left-hemisphere damage in speech zones often show deficits in right-hemispheric fxns as well as an overall drop in IQ
  • lesions occurring before the age of 1 yr. produce more severe impairments in IQ than those occurring later in life
  • Effects of Lesions in Children
    • damage to children’s frontal lobes could have more severe results than similar damage in adults
    • Kolb has found that mean IQ may be compromised by early frontal injuries – mean IQ about 85; (preliminary data suggests that IQ may be even worse if damage occurs in first year of life)
  • Effects of Lesions in Rats (who do not have epilepsy following brain damage)
    • lesions during the end of the mitotic phase or during cell migration is particularly damaging (in humans this period likely begins during 3rd trimester up to about 6 days of age) but, injury during dendritic growth allows for better recovery (in humans – may include up to the 2nd year of life)
      • may depend on area since for example, the visual cortex develops more quickly than the frontal area
      • this principle was true regardless of the location of damage
      • so, there appears to be a time in early development when injury is devastating and a later time when there is substantial recovery of fxn (has been seen in cats and monkeys too)
      • even restricted frontal lesions on postnatal days 1-5 lead to a wide range of behavioral abnormalities not seen in similar lesions in adulthood
      • unilateral lesions allow substantially more recovery than bilateral lesions (even if the lesions are rather large); it is suggested that as long as one fxnl system is intact, the brain is able to recruit recovery mechanisms, but if both systems are damaged, it is more difficult

Effects of Hemidecortication

  • regardless of age, after the complete removal of the left hemisphere most people are capable of some language and do not experience the dense global aphasia seen in patients with large left hemisphere strokes
  • full scale IQ is usually at least one standard deviation below the mean (but surprisingly normal considering the extent of the removal) – but there is variability (some patients have had above average IQ’s)
  • Left hemisphere “recovery” is more complete than right hemisphere “recovery” – in fact, left decorticates show surprisingly good language, but visuospatial and constructional capacities are compromised with removal of either hemisphere
  • damage to the remaining hemisphere (no matter how small) can significantly impair recovery
  • age effects of hemidecortication
    • the age relationship is reversed (compared to cortical damage); thus, behavioral outcome is better in animals with earlier lesions (rather than 7-10 days); this actually makes sense, b/c it is believed that poor behavior outcome after cortical lesions is due to a compromise in the remaining hemispheric growth; in hemidecorticated brain there is no compromise
    • thus, the absence of the hemisphere early may have some “beneficial” effect on the growth and development of the remaining, normal hemisphere

Other Theories of Temporal Effects of Brain Damage

  • Kennard – earlier rather than later damage is preferable in sparing function
  • Dobbing – later rather than earlier damage is preferable in sparing function
  • In reality, outcome is multifactorial and neither of above holds true in every case
  • Integration of above two says that brain damage during infancy and early childhood may prove less devastating in outcome than damage either during fetal development or in the mature brain