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Chapter 8 Brain Damage and Neuroplasticity Can the Brain Recover from Damage? <ul><li>This multimedia product and its cont...
Causes of Brain Damage <ul><li>Brain tumors </li></ul><ul><li>Cerebrovascular disorders </li></ul><ul><li>Closed-head inju...
Brain Tumors <ul><li>A tumor (neoplasm) is a mass of cells that grows independently of the rest of the body – a cancer </l...
Brain Tumors <ul><li>Most brain tumors are infiltrating </li></ul><ul><ul><li>Grow diffusely through surrounding tissue </...
Cerebrovascular Disorders <ul><li>Stroke – a sudden-onset cerebrovascular event that causes brain damage </li></ul><ul><ul...
Cerebrovascular Disorders <ul><li>Cerebral hemorrhage – blood vessel ruptures </li></ul><ul><ul><li>Aneurysm – weakened po...
Damage due to Cerebral Ischemia <ul><li>Does not develop immediately  </li></ul><ul><li>Most damage is a consequence of ex...
Damage due to Cerebral Ischemia <ul><li>Influx of sodium and calcium   triggers: </li></ul><ul><ul><li>the release of stil...
 
Closed-Head Injuries <ul><li>Brain injuries due to blows that do not penetrate the skull – the brain collides with the sku...
Concussions <ul><li>While there is no apparent brain damage with a single concussion, multiple concussions may result in a...
Brain Infection <ul><li>Invasion of the brain by microorganisms </li></ul><ul><li>Encephalitis – the resulting inflammatio...
Brain Infections - Some Causes <ul><li>Bacterial </li></ul><ul><li>Syphilis – may produce a syndrome of insanity and demen...
Neurotoxins <ul><li>May enter general circulation from the GI tract, lungs, or through the skin </li></ul><ul><li>Toxic ps...
Neurotoxins <ul><li>Some antipsychotic drugs produce a motor disorder caused tardive dyskinesia </li></ul><ul><li>Recreati...
Genetic Factors <ul><li>Most neuropsychological diseases of genetic origin are associated with recessive genes. Why? </li>...
Programmed Cell Death <ul><li>Apoptosis – cell suicide – involved in all forms of brain damage discussed thus far </li></u...
Neuropsychological Diseases <ul><li>Epilepsy </li></ul><ul><li>Parkinson’s disease </li></ul><ul><li>Huntington’s disease ...
Epilepsy <ul><li>Primary symptom is seizures, but not all who have seizures have epilepsy </li></ul><ul><li>Epileptics hav...
Epilepsy <ul><li>Types of seizures </li></ul><ul><ul><li>Convulsions – motor seizures </li></ul></ul><ul><ul><li>Some are ...
Epilepsy <ul><li>Seizures often preceded by an aura, such as a smell, hallucination, or feeling </li></ul><ul><ul><li>Aura...
Partial Seizures <ul><li>Simple </li></ul><ul><ul><li>symptoms are primarily sensory or motor or both (Jacksonian seizures...
Generalized Seizures <ul><li>Grand mal </li></ul><ul><ul><li>Loss of consciousness and equilibrium </li></ul></ul><ul><ul>...
Parkinson’s Disease <ul><li>A movement disorder of middle and old age affecting ~ .5%of the population </li></ul><ul><li>P...
Parkinson’s Disease <ul><li>Associated with degeneration of the substantia nigra whose neurons use dopamine </li></ul><ul>...
Huntington’s Disease <ul><li>Also a progressive motor disorder of middle and old age – but rare, with a strong genetic bas...
Multiple Sclerosis <ul><li>A progressive disease that attacks CNS myelin, leaving areas of hard scar tissue (sclerosis) </...
Multiple Sclerosis <ul><li>Epidemiological studies find that incidence of MS is increased in those who spend childhood in ...
Alzheimer’s Disease <ul><li>Most common cause of dementia – likelihood of developing it increases with age </li></ul><ul><...
Familial Forms of Alzheimer’s Disease <ul><li>Several genes identified as involved in early onset AD </li></ul><ul><li>All...
Neuropsychological Diseases - Recap <ul><li>Epilepsy – abnormal electrical activity </li></ul><ul><li>Parkinson’s disease ...
What Is an Animal Model? <ul><li>A condition in a nonhuman animal that is similar in some respects to a human disease </li...
MPTP Model of Parkinson’s Disease (PD) <ul><li>The Case of the Frozen Addicts </li></ul><ul><ul><li>Synthetic heroin produ...
Neuroplastic Responses to Nervous System Damage <ul><li>Degeneration - deterioration </li></ul><ul><li>Regeneration – regr...
Degeneration <ul><li>Cutting axons is a common way to study responses to neuronal damage </li></ul><ul><li>Anterograde - d...
Neural Regeneration <ul><li>Does not proceed successfully in mammals and other higher vertebrates - capacity for accurate ...
Neural Regeneration in the PNS <ul><li>If the original Schwann cell myelin sheath is intact, regenerating axons may grow t...
Neural regeneration
Why do mammalian PNS neurons regenerate? <ul><li>CNS neurons can regenerate if transplanted into the PNS, while PNS neuron...
Neural Reorganization <ul><li>Reorganization of 1° sensory and motor systems has been observed following damage to: </li><...
How/why does damage lead to reorganization? <ul><li>Strengthened existing connections due to a release from inhibition? </...
Recovery of Function after Brain Damage <ul><li>Difficult to conduct controlled experiments on populations of brain-damage...
Treating Nervous System Damage <ul><li>Reducing brain damage by blocking neurodegeneration </li></ul><ul><li>Promoting rec...
Reducing brain damage by blocking neurodegeneration <ul><li>Various neurochemicals can block or limit neurodegeneration </...
Promoting Recovery by Promoting Regeneration <ul><li>While regeneration does not normally occur in the CNS, experimentally...
Promoting Recovery by Neurotransplantation <ul><li>Fetal tissue </li></ul><ul><ul><li>Fetal substantia nigra cells used to...
Promoting Recovery by Rehabilitative Training <ul><li>Constraint-induced therapy – down functioning limb while training th...
Can the brain recover from brain damage? <ul><li>Consider what you now know about the brain’s ability to adapt following b...
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Pinel basics ch08

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Transcript of "Pinel basics ch08"

  1. 1. Chapter 8 Brain Damage and Neuroplasticity Can the Brain Recover from Damage? <ul><li>This multimedia product and its contents are protected under copyright law. The following are prohibited by law: </li></ul><ul><li>any public performance or display, including transmission of any image over a network; </li></ul><ul><li>preparation of any derivative work, including the extraction, in whole or in part, of any images; </li></ul><ul><li>any rental, lease, or lending of the program. </li></ul>
  2. 2. Causes of Brain Damage <ul><li>Brain tumors </li></ul><ul><li>Cerebrovascular disorders </li></ul><ul><li>Closed-head injuries </li></ul><ul><li>Infections of the brain </li></ul><ul><li>Neurotoxins </li></ul><ul><li>Genetic factors </li></ul>
  3. 3. Brain Tumors <ul><li>A tumor (neoplasm) is a mass of cells that grows independently of the rest of the body – a cancer </li></ul><ul><li>~20% of brain tumors are meningiomas – encased in meninges </li></ul><ul><ul><li>Encapsulated, growing within their own membranes </li></ul></ul><ul><ul><li>Usually benign, surgically removable </li></ul></ul>
  4. 4. Brain Tumors <ul><li>Most brain tumors are infiltrating </li></ul><ul><ul><li>Grow diffusely through surrounding tissue </li></ul></ul><ul><ul><li>Malignant, difficult to remove or destroy </li></ul></ul><ul><li>About 10% of brain tumors are metastatic – they originate elsewhere, usually the lungs </li></ul>
  5. 5. Cerebrovascular Disorders <ul><li>Stroke – a sudden-onset cerebrovascular event that causes brain damage </li></ul><ul><ul><li>Cerebral hemorrhage – bleeding in the brain </li></ul></ul><ul><ul><li>Cerebral ischemia – disruption of blood supply </li></ul></ul><ul><li>3 rd leading cause of death in the US and most common cause of adult disability </li></ul>
  6. 6. Cerebrovascular Disorders <ul><li>Cerebral hemorrhage – blood vessel ruptures </li></ul><ul><ul><li>Aneurysm – weakened point in a blood vessel that makes a stroke more likely. Congenital or due to poison or infection. </li></ul></ul><ul><ul><li>Congenital – present at birth </li></ul></ul><ul><li>Cerebral ischemia – disruption of blood supply </li></ul><ul><ul><li>Thrombosis – plug forms </li></ul></ul><ul><ul><li>Embolism – plug forms elsewhere and moves to the brain </li></ul></ul><ul><ul><li>Arteriosclerosis – wall of blood vessels thicken, usually due to fat deposits </li></ul></ul>
  7. 7. Damage due to Cerebral Ischemia <ul><li>Does not develop immediately </li></ul><ul><li>Most damage is a consequence of excess neurotransmitter release – especially glutamate </li></ul><ul><li>Blood-deprived neurons become overactive and release glutamate </li></ul><ul><li>Glutamate overactivates its receptors, especially NMDA receptors leading to an influx of sodium and calcium ions </li></ul>
  8. 8. Damage due to Cerebral Ischemia <ul><li>Influx of sodium and calcium triggers: </li></ul><ul><ul><li>the release of still more glutamate </li></ul></ul><ul><ul><li>a sequence of internal reactions that ultimately kill the neuron </li></ul></ul><ul><li>Ischemia-induced brain damage </li></ul><ul><ul><li>takes time </li></ul></ul><ul><ul><li>does not occur equally in all parts of the brain </li></ul></ul><ul><ul><li>mechanisms of damage vary with the brain structure affected </li></ul></ul>
  9. 10. Closed-Head Injuries <ul><li>Brain injuries due to blows that do not penetrate the skull – the brain collides with the skull </li></ul><ul><ul><li>Contrecoup injuries – contusions are often on the side of the brain opposite to the blow </li></ul></ul><ul><li>Contusions – closed-head injuries that involve damage to the cerebral circulatory system. A hematoma, a bruise, forms. </li></ul><ul><li>Concussion – when there is a disturbance of consciousness following a blow to the head and no evidence of structural damage. </li></ul>
  10. 11. Concussions <ul><li>While there is no apparent brain damage with a single concussion, multiple concussions may result in a dementia referred to as “punch-drunk syndrome” </li></ul><ul><li>When might this occur? </li></ul><ul><li>Can it be prevented? </li></ul>
  11. 12. Brain Infection <ul><li>Invasion of the brain by microorganisms </li></ul><ul><li>Encephalitis – the resulting inflammation </li></ul><ul><li>Bacterial infections </li></ul><ul><ul><li>Often leads to abscesses, pockets of pus </li></ul></ul><ul><ul><li>May inflame meninges, creating meningitis </li></ul></ul><ul><ul><li>Treat with penicillin and other antibiotics </li></ul></ul><ul><li>Viral infections </li></ul><ul><ul><li>Some viral infections preferentially attack neural tissues </li></ul></ul>
  12. 13. Brain Infections - Some Causes <ul><li>Bacterial </li></ul><ul><li>Syphilis – may produce a syndrome of insanity and dementia known as general paresis </li></ul><ul><li>Syphilis bacteria are passed to the noninfected and enter a dormant stage for many years. </li></ul><ul><li>Viral </li></ul><ul><li>Rabies – high affinity for the nervous system </li></ul><ul><li>Mumps and herpes – typically attack tissues other than the brain </li></ul><ul><li>Viruses may lie dormant for years </li></ul>
  13. 14. Neurotoxins <ul><li>May enter general circulation from the GI tract, lungs, or through the skin </li></ul><ul><li>Toxic psychosis – chronic insanity produced by a neurotoxin. </li></ul><ul><li>The Mad Hatter – may have had toxic psychosis due to mercury exposure </li></ul>
  14. 15. Neurotoxins <ul><li>Some antipsychotic drugs produce a motor disorder caused tardive dyskinesia </li></ul><ul><li>Recreational drugs, such as alcohol, may cause brain damage </li></ul><ul><li>Some neurotoxins are endogenous – produced by the body </li></ul>
  15. 16. Genetic Factors <ul><li>Most neuropsychological diseases of genetic origin are associated with recessive genes. Why? </li></ul><ul><li>Down syndrome </li></ul><ul><ul><li>0.15% of births, probability increases with advancing maternal age </li></ul></ul><ul><ul><li>Extra chromosome 21 </li></ul></ul><ul><ul><li>Characteristic disfigurement, mental retardation, other health problems </li></ul></ul>
  16. 17. Programmed Cell Death <ul><li>Apoptosis – cell suicide – involved in all forms of brain damage discussed thus far </li></ul><ul><li>Apoptosis is adaptive, while necrosis involves inflammation and may lead to the damage of surrounding cells </li></ul>
  17. 18. Neuropsychological Diseases <ul><li>Epilepsy </li></ul><ul><li>Parkinson’s disease </li></ul><ul><li>Huntington’s disease </li></ul><ul><li>Multiple sclerosis </li></ul><ul><li>Alzheimer’s disease </li></ul>
  18. 19. Epilepsy <ul><li>Primary symptom is seizures, but not all who have seizures have epilepsy </li></ul><ul><li>Epileptics have seizures generated by their own brain dysfunction </li></ul><ul><li>Affects about 1% of the population </li></ul><ul><li>Difficult to diagnose due to the diversity and complexity of epileptic seizures </li></ul>
  19. 20. Epilepsy <ul><li>Types of seizures </li></ul><ul><ul><li>Convulsions – motor seizures </li></ul></ul><ul><ul><li>Some are merely subtle changes of thought, mood, or behavior </li></ul></ul><ul><li>Causes </li></ul><ul><ul><li>Brain damage </li></ul></ul><ul><ul><li>Genes – over 70 known so far </li></ul></ul><ul><li>Diagnosis </li></ul><ul><ul><li>EEG – Electroencephalogram </li></ul></ul><ul><ul><li>Seizures associated with high amplitude spikes </li></ul></ul>
  20. 21. Epilepsy <ul><li>Seizures often preceded by an aura, such as a smell, hallucination, or feeling </li></ul><ul><ul><li>Aura’s nature suggests the epileptic focus </li></ul></ul><ul><ul><li>Warns epileptic of an impending seizure </li></ul></ul><ul><li>Partial epilepsy – does not involve the whole brain </li></ul><ul><li>Generalized epilepsy – involve the entire brain </li></ul>
  21. 22. Partial Seizures <ul><li>Simple </li></ul><ul><ul><li>symptoms are primarily sensory or motor or both (Jacksonian seizures) </li></ul></ul><ul><ul><li>symptoms spread as epileptic discharge spreads </li></ul></ul><ul><li>Complex – often restricted to the temporal lobes (temporal lobe epilepsy) </li></ul><ul><ul><li>patient engages in compulsive and repetitive simple behaviors – automatisms </li></ul></ul><ul><ul><li>more complex behaviors seem normal </li></ul></ul>
  22. 23. Generalized Seizures <ul><li>Grand mal </li></ul><ul><ul><li>Loss of consciousness and equilibrium </li></ul></ul><ul><ul><li>Tonic-clonic convulsions </li></ul></ul><ul><ul><ul><li>-rigidity (tonus) and tremors (clonus) </li></ul></ul></ul><ul><ul><li>Resulting hypoxia may cause brain damage </li></ul></ul><ul><li>Petit mal </li></ul><ul><ul><li>not associated with convulsions </li></ul></ul><ul><ul><li>A disruption of consciousness associated with a cessation of ongoing behavior </li></ul></ul>
  23. 24. Parkinson’s Disease <ul><li>A movement disorder of middle and old age affecting ~ .5%of the population </li></ul><ul><li>Pain and depression commonly seen before the full disorder develops </li></ul><ul><li>Tremor at rest is the most common symptom of the full-blown disorder </li></ul><ul><li>Dementia is not typically seen </li></ul><ul><li>No single cause </li></ul>
  24. 25. Parkinson’s Disease <ul><li>Associated with degeneration of the substantia nigra whose neurons use dopamine </li></ul><ul><li>Almost no dopamine in the substantia nigra of Parkinson’s patients </li></ul><ul><li>Treated temporarily with L-dopa </li></ul><ul><li>Linked to ~10 different gene mutations </li></ul>
  25. 26. Huntington’s Disease <ul><li>Also a progressive motor disorder of middle and old age – but rare, with a strong genetic basis, and associated with dementia. </li></ul><ul><li>Begins with fidgetiness and progresses to jerky movements of entire limbs and sever dementia </li></ul><ul><li>Death usually occurs within 15 years </li></ul><ul><li>Caused by a single dominant gene </li></ul><ul><li>1 st symptoms usually not seen until age 40 </li></ul>
  26. 27. Multiple Sclerosis <ul><li>A progressive disease that attacks CNS myelin, leaving areas of hard scar tissue (sclerosis) </li></ul><ul><li>Nature and severity of deficits vary with the nature, size, and position of sclerotic lesions </li></ul><ul><li>Periods of remission are common </li></ul><ul><li>Symptoms include visual disturbances, muscle weakness, numbness, tremor, and loss of motor coordination (ataxia) </li></ul>
  27. 28. Multiple Sclerosis <ul><li>Epidemiological studies find that incidence of MS is increased in those who spend childhood in a cool climate </li></ul><ul><li>MS is rare amongst Africans and Asians </li></ul><ul><li>Strong genetic predisposition and many genes involved </li></ul><ul><li>An autoimmune disorder – immune system attacks myelin </li></ul><ul><li>Drugs may retard progression or block some symptoms </li></ul>
  28. 29. Alzheimer’s Disease <ul><li>Most common cause of dementia – likelihood of developing it increases with age </li></ul><ul><li>Progressive, with early stages characterized by confusion and a selective decline in memory </li></ul><ul><li>Definitive diagnosis only at autopsy – must observe neurofibrillary tangles and amyloid plaques </li></ul>
  29. 30. Familial Forms of Alzheimer’s Disease <ul><li>Several genes identified as involved in early onset AD </li></ul><ul><li>All affected genes are involved in synthesis of amyloid or tau, a protein found in the tangles </li></ul><ul><li>Not clear what comes 1 st – amyloid plaques or neurofibrillary tangles </li></ul><ul><li>Declined acetylcholine levels is among one of the earliest changes seen </li></ul>
  30. 31. Neuropsychological Diseases - Recap <ul><li>Epilepsy – abnormal electrical activity </li></ul><ul><li>Parkinson’s disease </li></ul><ul><ul><li>progressive motor disorder without dementia </li></ul></ul><ul><li>Huntington’s disease </li></ul><ul><ul><li>progressive motor disorder with dementia </li></ul></ul><ul><li>Multiple sclerosis </li></ul><ul><ul><li>autoimmune disorder that affects motor function and strikes early </li></ul></ul><ul><li>Alzheimer’s disease - dementia </li></ul>
  31. 32. What Is an Animal Model? <ul><li>A condition in a nonhuman animal that is similar in some respects to a human disease </li></ul><ul><li>While animal models only model some aspects of the human condition, they can provide insight </li></ul><ul><li>There are animal models of all five of the neuropsychological disorders discussed </li></ul>
  32. 33. MPTP Model of Parkinson’s Disease (PD) <ul><li>The Case of the Frozen Addicts </li></ul><ul><ul><li>Synthetic heroin produced the symptoms of Parkinson’s </li></ul></ul><ul><ul><li>Contained MPTP </li></ul></ul><ul><li>MPTP and its metabolites cause cell loss in the substantia nigra, like that seen in PD </li></ul><ul><li>Animal studies led to the finding that deprenyl can retard the progression of PD </li></ul>
  33. 34. Neuroplastic Responses to Nervous System Damage <ul><li>Degeneration - deterioration </li></ul><ul><li>Regeneration – regrowth of damaged neurons </li></ul><ul><li>Reorganization </li></ul><ul><li>Recovery </li></ul>
  34. 35. Degeneration <ul><li>Cutting axons is a common way to study responses to neuronal damage </li></ul><ul><li>Anterograde - degeneration of the distal segment – between the cut and synaptic terminal </li></ul><ul><ul><li>cut off from cell’s metabolic center </li></ul></ul><ul><ul><li>swells and breaks off within a few days </li></ul></ul><ul><li>Retrograde – degeneration of the proximal segment – between the cut and cell body </li></ul><ul><ul><li>progresses slowly </li></ul></ul><ul><ul><li>if regenerating axon makes a new synaptic contact, the neuron may survive </li></ul></ul>
  35. 36. Neural Regeneration <ul><li>Does not proceed successfully in mammals and other higher vertebrates - capacity for accurate axonal growth is lost in maturity </li></ul><ul><li>Regeneration is virtually nonexistent in the CNS of adult mammals and unlikely, but possible, in the PNS </li></ul>
  36. 37. Neural Regeneration in the PNS <ul><li>If the original Schwann cell myelin sheath is intact, regenerating axons may grow through them to their original targets </li></ul><ul><li>If the nerve is severed and the ends are separated, they may grow into incorrect sheaths </li></ul><ul><li>If ends are widely separated, no meaningful regeneration will occur </li></ul>
  37. 38. Neural regeneration
  38. 39. Why do mammalian PNS neurons regenerate? <ul><li>CNS neurons can regenerate if transplanted into the PNS, while PNS neurons won’t regenerate in the CNS </li></ul><ul><li>Schwann cells promote regeneration </li></ul><ul><ul><li>Neurotrophic factors stimulate growth </li></ul></ul><ul><ul><li>CAMs provide a pathway </li></ul></ul><ul><li>Oligodendroglia actively block regeneration </li></ul>
  39. 40. Neural Reorganization <ul><li>Reorganization of 1° sensory and motor systems has been observed following damage to: </li></ul><ul><ul><li>peripheral nerves </li></ul></ul><ul><ul><li>primary cortical areas </li></ul></ul><ul><li>Lesion one retina and remove the other – V1 neurons that originally responded to lesioned area now responded to an adjacent area – remapping occurred within minutes </li></ul><ul><li>Studies show scale of reorganization possible is far greater than anyone assumed possible </li></ul>
  40. 41. How/why does damage lead to reorganization? <ul><li>Strengthened existing connections due to a release from inhibition? </li></ul><ul><ul><li>Consistent with speed and localized nature of reorganization </li></ul></ul><ul><li>Establishment of new connections? </li></ul><ul><ul><li>Magnitude can be too great to be explained by changes in existing connections </li></ul></ul>
  41. 42. Recovery of Function after Brain Damage <ul><li>Difficult to conduct controlled experiments on populations of brain-damaged patients </li></ul><ul><li>Can’t distinguish between true recovery and compensatory changes </li></ul><ul><li>Cognitive reserve – education and intelligence – thought to play an important role in recovery of function – may permit cognitive tasks to be accomplished new ways </li></ul><ul><li>Adult neurogenesis may play a role in recovery </li></ul>
  42. 43. Treating Nervous System Damage <ul><li>Reducing brain damage by blocking neurodegeneration </li></ul><ul><li>Promoting recovery by promoting regeneration </li></ul><ul><li>Promoting recovery by transplantation </li></ul><ul><li>Promoting recovery by rehabilitative training </li></ul>
  43. 44. Reducing brain damage by blocking neurodegeneration <ul><li>Various neurochemicals can block or limit neurodegeneration </li></ul><ul><li>Apoptosis inhibitor protein – introduced in rats via a virus </li></ul><ul><li>Nerve growth factor – blocks degeneration of damaged neurons </li></ul><ul><li>Estrogens – limit or delay neuron death </li></ul><ul><li>Neuroprotective molecules tend to also promote regeneration </li></ul>
  44. 45. Promoting Recovery by Promoting Regeneration <ul><li>While regeneration does not normally occur in the CNS, experimentally it can be induced </li></ul><ul><li>Eliminate inhibition of oligodendroglia and regeneration can occur </li></ul><ul><li>Provide Schwann cells to direct growth </li></ul>
  45. 46. Promoting Recovery by Neurotransplantation <ul><li>Fetal tissue </li></ul><ul><ul><li>Fetal substantia nigra cells used to treat MPTP-treated monkeys (PD model) </li></ul></ul><ul><ul><li>Treatment was successful </li></ul></ul><ul><ul><li>Limited success with humans </li></ul></ul><ul><li>Stem cells </li></ul><ul><ul><li>Rats with spinal damage “cured”, but much more research is needed </li></ul></ul>
  46. 47. Promoting Recovery by Rehabilitative Training <ul><li>Constraint-induced therapy – down functioning limb while training the impaired one – create a competitive situation to foster recovery </li></ul><ul><li>Facilitated walking as an approach to treating spinal injury </li></ul>
  47. 48. Can the brain recover from brain damage? <ul><li>Consider what you now know about the brain’s ability to adapt following brain damage, can it “recover”? </li></ul><ul><li>If so, what conditions promote recovery? </li></ul>
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