1. Prepared by Jeffrey W. Grimm Western Washington University
PowerPoint Presentation for Biopsychology, 8th Edition by John P.J. Pinel
Prepared by Jeffrey W. Grimm
Western Washington University
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2. Can the Brain Recover from Damage?
Chapter 10
Brain Damage and Neuroplasticity
Can the Brain Recover from Damage?
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Causes of Brain Damage
Brain tumors
Cerebrovascular disorders
Closed-head injuries
Infections of the brain
Neurotoxins
Genetic factors
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Brain Tumors
A tumor (neoplasm) is a mass of cells that grows independently of the rest of the body – a cancer
20% of brain tumors are meningiomas – encased in meninges
Encapsulated, growing within their own membranes
Usually benign, surgically removable
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5. Brain Tumors Continued
Most brain tumors are infiltrating
Grow diffusely through surrounding tissue
Malignant, difficult to remove or destroy
About 10% of brain tumors are metastatic – they originate elsewhere, usually the lungs
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FIGURE 10.3 An MRI of Professor P.’s acoustic neuroma. The arrow indicates the tumor.
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7. Cerebrovascular Disorders
Stroke – a sudden-onset cerebrovascular event that causes brain damage
Cerebral hemorrhage – bleeding in the brain
Cerebral ischemia – disruption of blood supply
Third leading cause of death in the U.S. and most common cause of adult disability
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8. Cerebrovascular Disorders Continued
Cerebral Hemorrhage – blood vessel ruptures
Aneurysm – a weakened point in a blood vessel that makes a stroke more likely; may be congenital (present at birth) or due to poison or infection
Cerebral Ischemia – disruption of blood supply
Thrombosis – a plug forms in the brain
Embolism – a plug forms elsewhere and moves to the brain
Arteriosclerosis – wall of blood vessels thicken, usually due to fat deposits
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9. Damage Due to Cerebral Ischemia
Does not develop immediately
Most damage is a consequence of excess neurotransmitter release – especially glutamate
Blood-deprived neurons become overactive and release glutamate
Glutamate overactivates its receptors, especially NMDA receptors leading to an influx of Na+ and Ca2+
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10. Damage Due to Cerebral Ischemia
lnflux of Na+ and Ca2+ triggers
the release of still more glutamate
a sequence of internal reactions that ultimately kill the neuron
Ischemia-induced brain damage
takes time
does not occur equally in all parts of the brain
mechanisms of damage vary with the brain structure affected
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FIGURE 10.5 The cascade of events by which the stroke-induced release of glutamate kills neurons.
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Closed-Head Injuries
Brain injuries due to blows that do not penetrate the skull – the brain collides with the skull
Contrecoup injuries – contusions are often on the side of the brain opposite to the blow
Contusions – closed-head injuries that involve damage to the cerebral circulatory system; hematoma (bruise) forms
Concussions – when there is disturbance of consciousness following a blow to the head and no evidence of structural damage
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13. Closed-Head Injuries Continued
While there is no apparent brain damage with a single concussion, multiple concussions may result in a dementia referred to as “punch-drunk syndrome”
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FIGURE 10.6 A CT scan of a subdural hematoma. Notice that the subdural hematoma has displaced the left lateral ventricle.
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15. Infections of the Brain
Encephalitis – the resulting inflammation of the brain by an invasion of microorganisms
Bacterial infections
Often lead to abscesses, pockets of pus
May inflame meninges, creating meningitis
Treat with penicillin and other antibiotics
Viral infections
Some preferentially attack neural tissues
Some can lie dormant for years
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Neurotoxins
May enter general circulation from the GI tract or lungs, or through the skin
Toxic psychosis – chronic insanity produced by a neurotoxin
The Mad Hatter – hat makers often had toxic psychosis due to mercury exposure
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17. Neurotoxins Continued
Some antipsychotic drugs produce a motor disorder called tardive dyskinesia
Some neurotoxins are endogenous (produced by the body)
e.g. Auto-immune disorders
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Genetic Factors
Most neuropsychological diseases of genetic origin are associated with recessive genes--why?
Down syndrome
0.15% of births, probability increases with advancing maternal age
Extra chromosome 21 created during ovulation
Characteristic disfigurement, mental retardation, other health problems
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Programmed Cell Death
All six causes of brain damage produce damage, in part, by activating apoptosis
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20. Neuropsychological Diseases
Epilepsy
Parkinson’s disease
Huntington’s disease
Multiple sclerosis
Alzheimer’s disease
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Epilepsy
Primary symptom is seizures, but not all who have seizures have epilepsy
Epileptics have seizures generated by their own brain dysfunction
Affects about 1% of the population
Difficult to diagnose due to the diversity and complexity of epileptic seizures
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Epilepsy Continued
Types of seizures
Convulsions – motor seizures
Some are merely subtle changes of thought, mood, or behavior
Causes
Brain damage
Genes – over 70 known so far
Faults at inhibitory synapses
Diagnosis
EEG – electroencephalogram
Seizures associated with high amplitude spikes `
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Epilepsy Continued
Seizures often preceded by an aura, such as a smell, hallucination, or feeling
Aura’s nature suggests the epileptic focus
Warns epileptic of an impending seizure
Partial epilepsy – does not involve the whole brain
Generalized epilepsy – involves the entire brain
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Partial Seizures
Simple
Symptoms are primarily sensory or motor or both (Jacksonian seizures)
Symptoms spread as epileptic discharge spreads
Complex
often restricted to the temporal lobes (temporal lobe epilepsy)
Patient engages in compulsive and repetitive simple behaviors (automatisms)
More complex behaviors seem normal
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FIGURE 10.8 Cortical electroencephalogram (EEG) record from various locations on the scalp during the beginning of a complex partial seizure.
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Generalized Seizures
Grand mal
Loss of consciousness and equilibrium
Tonic-clonic convulsions
Rigidity (tonus)
Tremors (clonus)
Resulting hypoxia may cause brain damage
Petit mal
Not associated with convulsions
A disruption of consciousness associated with a cessation of ongoing behavior
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Parkinson’s Disease
A movement disorder of middle and old age affecting about .5% of the population
Tremor at rest is the most common symptom of the full-blown disorder
Dementia is not typically seen
No single cause
Associated with degeneration of the substantia nigra; these neurons release dopamine to the striatum of the basal ganglia
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28. Parkinson’s Disease Continued
Almost no dopamine in the substantia nigra of Parkinson’s patients
Autopsies often reveal Lewy bodies (protein clumps) in the substantia nigra
Treated temporarily with L-dopa
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29. Parkinson’s Disease Continued
Linked to about ten different gene mutations
Deep brain stimulation of subthalamic nucleus reduces symptoms, but effectiveness slowly declines over months or years
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Huntington’s Disease
A rare, progressive motor disorder of middle and old age with a strong genetic basis
Huntingtin gene
single, dominant gene
Begins with fidgetiness and progresses to jerky movements of entire limbs and severe dementia
Death usually occurs within 15 years
Caused by a single dominant gene
First symptoms usually not seen until age 40
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Multiple Sclerosis
A progressive disease that attacks CNS myelin, leaving areas of hard scar tissue (sclerosis)
Nature and severity of deficits vary with the nature, size, and position of sclerotic lesions
Periods of remission are common
Symptoms include visual disturbances, muscle weakness, numbness, tremor, and loss of motor coordination (ataxia)
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32. Multiple Sclerosis Continued
Epidemiological studies find that incidence of MS is increased in those who spend childhood in a cool climate
MS is rare amongst Africans and Asians
Only some genetic predisposition and only one chromosomal locus linked to MS with any certainty
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33. Multiple Sclerosis Continued
Recent focus on epigenetic mechanisms
Gene/environment interactions
An autoimmune disorder – immune system attacks myelin
Drugs may retard progression or block some symptoms
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FIGURE Areas of sclerosis (see arrows) in the white matter of a patient with MS.
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Alzheimer’s Disease
Most common cause of dementia – likelihood of developing it increases with age
Progressive, with early stages character-ized by confusion and a selective decline in memory
Definitive diagnosis only at autopsy – must observe neurofibrillary tangles and amyloid plaques
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36. Alzheimer’s Disease Continued
Several genes associated with early-onset AD synthesize amyloid or tau, a protein found in the tangles
Which comes first, amyloid plaques or neuro-fibrillary tangles? Genetic research on early-onset AD supports amyloid hypothesis (amyloid first)
Decline in acetylcholine levels is one of the earliest signs of AD
Effective treatments not yet available
Immunotherapy is promising in animal models
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FIGURE The typical distribution of neurofibrillary tangles and amyloid plaques in the brains of patients with advanced Alzheimer’s disease. (Based on Goedert, 1993, and Selkoe, 1991.)
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38. Animal Models of Human Neuropsychological Diseases
Experiments regarding neuropathology are not usually possible with human subjects
Animal models are often utilized, for example:
Kindling model of epilepsy
Experimentally induced seizure activity
Transgenic mouse model of Alzheimer’s
Mice producing human amyloid
MPTP model of Parkinson’s
Drug-induced damage comparable to that seen in PD
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39. Kindling Model of Epilepsy
A series of periodic brain stimulations eventually elicits convulsions – the kindling phenomenon
Neural changes are permanent
Produced by stimulation distributed over time
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40. Kindling Model of Epilepsy Continued
Convulsions are similar to those seen in some forms of human epilepsy – but they only occur spontaneously if kindled for a very long time
Kindling phenomenon is comparable to the development of epilepsy (epileptogenesis) seen following a head injury
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41. Transgenic Mouse Model of Alzheimer’s Disease
Only humans and a few related primates develop amyloid plaques
Transgenic – genes of another species have been introduced
Genes accelerating human amyloid synthesis introduced into mice
Plaque distribution comparable to that in AD
Unlike humans, no neurofibrillary tangles
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42. MPTP Model of Parkinson’s Disease
The Case of the Frozen Addicts
Synthetic heroin produced the symptoms of Parkinson’s
Contained MPTP
MPTP causes cell loss in the substantia nigra, like that seen in PD
Animal studies led to the finding that deprenyl can retard the progression of PD
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43. Neuroplastic Responses to Nervous System Damage
Degeneration – deterioration
Regeneration – regrowth of damaged neurons
Reorganization
Recovery
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Degeneration
Cutting axons (axotomy) is a common way to study responses to neuronal damage
Anterograde: degeneration of the distal segment – between the cut and synaptic terminals
Cut off from cell’s metabolic center – swells and breaks off within a few days
Retrograde: degeneration of the proximal segment – between the cut and cell body
Progresses slowly – if regenerating axon makes a new synaptic contact, the neuron may survive
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FIGURE Neuronal and transneuronal degeneration following axotomy.
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Neural Regeneration
Does not proceed successfully in mammals and other higher vertebrates – capacity for accurate axonal growth is lost in maturity
Regeneration is virtually nonexistent in the CNS of adult mammals and unlikely, but possible, in the PNS
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47. Neural Regeneration in the PNS
If the original Schwann cell myelin sheath is intact, regenerating axons may grow through them to their original targets
If the nerve is severed and the ends are separated, they may grow into incorrect sheaths
If ends are widely separated, no meaningful regeneration will occur
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FIGURE Three patterns of axonal regeneration in mammalian peripheral nerves.
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49. Mammal PNS Neurons Regenerate, CNS Don’t
CNS neurons can regenerate if transplanted into the PNS, while PNS neurons won’t regenerate in the CNS
Schwann cells promote regeneration
Neurotrophic factors stimulate growth
CAMs provide a pathway
Oligodendroglia actively inhibit regeneration
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50. Neural Reorganization
Reorganization of primary sensory and motor systems has been observed in laboratory animals following
Damage to peripheral nerves
Damage to primary cortical areas
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
Studies show large scale of reorganization possible
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51. Cortical Reorganization Following Damage in Humans
Brain-imaging studies indicate there is continuous competition for cortical space by functional circuits
e.g. Auditory and somatosensory input may be processed in formerly visual areas in blinded individuals
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52. Mechanisms of Neural Reorganization
Strengthened existing connections due to a release from inhibition?
Consistent with speed and localized nature of reorganization
Establishment of new connections?
Magnitude can be too great to be explained by changes in existing connections
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53. Recovery of Function after Brain Damage
Difficult to conduct controlled experiments on populations of brain-damaged patients
Can’t distinguish between true recovery and compensatory changes
Cognitive reserve – education and intelligence – thought to play an important role in recovery of function – may permit cognitive tasks to be accomplished in new ways
Adult neurogenesis may play a role in recovery
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FIGURE Increased neurogenesis in the dentate gyrus following damage (These images are courtesy of Carl Ernst and Brian Christie, Department of Psychology, University of British Columbia.)
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55. Neuroplasticity and the Treatment of Nervous System Damage
Reducing brain damage by blocking neurodegeneration
Promoting recovery by promoting regeneration
Promoting recovery by transplantation
Promoting recovery by rehabilitative training
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56. Reducing Brain Damage by Blocking Neurodegeneration
Various neurochemicals can block or limit neurodegeneration
Apoptosis inhibitor protein – introduced in rats via a virus
Nerve growth factor – blocks degeneration of damaged neurons
Estrogens – limit or delay neuron death
Neuroprotective molecules tend to also promote regeneration
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57. Promoting CNS Recovery by Promoting Regeneration
While regeneration does not normally occur in the CNS, experimentally it can be induced directing growth of axons by
Schwann cells
Olfactory ensheathing cells
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58. Promoting Recovery by Neurotransplantation
Transplanting fetal tissue
Fetal substantia nigra cells used to treat MPTP-treated monkeys (PD model)
Treatment was successful
Limited success with humans
Transplanting stem cells
e.g. Embryonic stems cells implanted into damaged rat spinal cord
Rats with spinal damage with improved mobility
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59. Promoting Recovery by Rehabilitative Training
Monkeys recovered hand function from induced strokes following rehab training
Constraint-induced therapy in stroke patients – tie down functioning limb while training the impaired one – creates a competitive situation to foster recovery
Facilitated walking as an approach to treating spinal injury
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60. Promoting Recovery by Rehabilitative Training Continued
Benefits of cognitive and physical exercise
Correlations in human studies between physical/cognitive activity and resistance or recovery from neurological injury and disease
Rodents raised in enriched environments are resistant to induced neurological conditions (epilepsy, models of Alzheimer’s, Huntington’s, etc.)
Physical activity promotes adult neurogenesis in rodent hippocampus
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61. Phantom Limbs: Neuroplastic Phenomena
Ramachandran’s hypothesis: phantom limb caused by reorganization of the somato-sensory cortex following amputation
Amputee feels a touch on his face and also on his phantom limb (due to their proximity on somatosensory cortex)
Amputee with chronic phantom limb pain gets relief through visual feedback: view in mirror of his intact hand unclenching as seen in mirror box
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FIGURE The places on Tom’s body where touches elicited sensations in his phantom hand. (Based on Ramachandran & Blakeslee, 1998.)
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