Download BIOPSYCHOLOGY 8e John PJ Pinel

BIOPSYCHOLOGY 8e
John P.J. Pinel
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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 unrestrained and
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
•  Most brain tumors are infiltrating (like
tree roots)
•  About 10% of brain tumors are
metastatic – the originate elsewhere,
and are carried in bloodstream
FIGURE 10.3 An MRI of Professor
P.’s acoustic neuroma. The arrow
indicates the tumor.
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Cerebrovascular Disorders
•  Stroke – A sudden-onset cerebrovascular
event that causes brain damage
• Infarct – area of dead and dying tissue
• Penumbra – dysfunctional area
surrounding the infarct tissue
–  Cerebral hemorrhage (bleeding in
the brain)
–  Cerebral ischemia (disruption of
blood supply)
•  More next slide…
3rd leading cause of death in Canada
too
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Cerebral Hemorrhage!
Cerebrovascular Disorders
•  Cerebral hemorrhage (bleeding in the brain)
–  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
and blocks blood flow
–  Embolism – a plug forms elsewhere
and is transported in blood to a smaller
vessel
–  Arteriosclerosis – wall of blood vessels
thicken, usually due to fat deposits
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Damage Due to Cerebral Ischemia
•  Does not develop immediately
•  Most damage is a consequence of
excess neurotransmitter release –
especially glutamate (excitatory)
•  Blood-deprived neurons become
overactive and release glutamate
•  Glutamate overactivates its
receptors, especially NMDA
receptors leading to an influx of Na+
and Ca2+
•  lnflux of Na+ and Ca2+ triggers
•  the release of still more glutamate
•  a sequence of internal reactions
that ultimately kill the neuron
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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 but with no detectable evidence of
structural damage
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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 (e.g. rabies)
•  Others have no special affinity for neural
tissue (e.g. herpes)
•  Some can lie dormant for years
n
eurotoxins"
• May enter general circulation from the GI tract or lungs, or
through the skin
• Toxic psychosis – chronic psychosis (insanity?) produced by a
neurotoxin
• The Mad Hatter – hat makers often had toxic psychosis due to
mercury exposure during felt preparation
• http://www.youtube.com/watch?v=26RTlPgg-tA
• Older antipsychotic drugs produce a motor disorder called
tardive dyskinesia
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• http://www.youtube.com/watch?v=t_NKRS8lLWA
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Genetic Factors
•  Most neuropsychological diseases of
genetic origin are associated with recessive
genes--why?
•  Dominant genes that disturb neuropsychological
function tend to be eliminated from the gene pool
•  Down syndrome:
•  0.15% of births, probability increases
with advancing maternal age
–  Far more common in pregnant women
under the age of 35 –why?
•  Extra chromosome 21 created during
ovulation
•  Characteristic facial features, cognitive
impairments, other health problems
(premature aging, increased risk of
Alzheimer’s)
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Programmed Cell Death
• All six causes of brain
damage produce damage, in
part, by activating apoptosis
• Programmed cell death
• Neat and organized
• Essential to early
development
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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 (not
secondary to some other problem such
as high temperature or viral infection)
•  Difficult to diagnose due to the
diversity/complexity of seizures
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Epilepsy
•  Types of seizures
•  Convulsions – motor seizures, tonus and
clonus, loss of balance and/or consciousness
•  Some are merely subtle changes of thought,
mood, or behaviour
•  Causes
•  Brain damage
•  Genes – over 70 known so far
•  Faults at inhibitory synapses (e.g. GABA)
•  Diagnosis
•  EEG – electroencephalogram
•  Seizures associated with high amplitude spikes
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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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Epilepsy
•  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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Parkinson’s Disease
• Movement disorder of middle
and old age affecting 1-2% of
the population
• 2.5 times more prevalent in
men
• Tremor at rest is the most
common symptom of the fullblown disorder
• Other symptoms: rigidity,
difficulty initiating movement,
slowness, masklike face
• Dementia is not typically seen
• No single cause
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Parkinson’s Disease
• Associated with degeneration of
the substantia nigra; these neurons
release dopamine to the striatum of
the basal ganglia
• Almost no dopamine in the
substantia nigra of long-term
Parkinson’s patients
• Autopsies often reveal Lewy
bodies (protein clumps) in the
substantia nigra
• Treated temporarily with L-dopa
• Linked to about 10 different gene
mutations
• Deep brain stimulation of
subthalamic nucleus reduces
symptoms, but effectiveness
slowly declines
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Multiple Sclerosis
•  A progressive autoimmune disease that
attacks CNS myelin, leaving areas of hard
scar tissue (sclerosis)
•  Onset earlier in life
•  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)
•  Seems to have both a genetic and
environmental component (interaction effect)
…
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Multiple Sclerosis
•  Epidemiological studies find
that incidence of MS is
increased in those who spend
childhood in a cool climate
•  MS is rare among Africans and
Asians
•  Rates are three times higher in
women
•  Smokers higher risk
•  Higher concordance rate in
monozygotes (25%), than
dizygotes (5%)
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Alzheimer’s Disease
• Most common cause of dementia – likelihood of
developing it increases with advancing old age
• Progressive, with early stages characterized by confusion
and a selective decline in memory
• Definitive diagnosis only at autopsy – must observe
neurofibrillary tangles (tangles of protein in neural
cytoplasm) and amyloid plaques (clumps of scar tissue
comprising a amyloid protein and degenerating neurons)
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Alzheimer’s Disease
•  Amyloid plaques are found
diffusely in the extracellular
neural environment.
Neurofibrillary tangles (NFT) on
the other hand, form inside
neurons.
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Animal Models of Human Neuropsychological
Diseases
•  Experiments regarding neuropathology are not usually
possible with human subjects
•  Therefore, essential for understanding, predicting and
treating disordered/diseased brain states
•  Animal research is usually a first and critical step prior
to human clinical trials
•  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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Neuroplastic Responses to Nervous System Damage
• The Brain is Plastic (changeable)
• Neuroplasticity is the dynamic
process of changes occurring in
the brain in response to genes
and experience (Including
damage)
• Degeneration – deterioration
• Regeneration – regrowth of
damaged neurons
• Reorganization
• Recovery
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Neural 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
•  Retrograde: degeneration
of the proximal segment –
between the cut and cell
body
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Neural Regeneration
• Not great in mammals and other
higher vertebrates (inverts are more
successful at it)
•  Capacity for accurate axonal
growth during early development is
lost at maturity
• Regeneration is virtually
nonexistent in the CNS of adult
mammals and hit-and-miss in the
PNS
•  Mammalian PNS regeneration begins
2-3 days after axonal damage - 3
outcomes possible…
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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 (this
is why limbs with nerve damage
have variable prognoses for
recovery of function)
•  If ends are widely separated, no
meaningful regeneration will
occur
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Neural Regeneration
•  Why no regeneration in the mammalian
CNS?
•  Brain and vertebrae offer good protection
•  Schwann cells have abilities oligodendroglia do not:
•  Schwann cells clear neural debris resulting from
neural degeneration and promote/guide
regeneration
•  Produce both neurotrophic factors and celladhesion molecules
•  Oligodendroglia live longer after nerve damage
and inhibit axonal regeneration
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Neural Reorganization
•  The adult mammalian brain can however,
reorganize itself in response to
experience
–  Reorganization of primary sensory and motor
systems has been observed in laboratory
animals following
– Damage to peripheral nerves
– Damage to primary cortical areas
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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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Mechanisms of Neural Reorganization
•  What accounts
neural
reorganization?
Thefor
human
brain
• 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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Mechanisms of Neural Reorganization
The human brain
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Recovery of Function after Brain Damage
•  Difficult to conduct controlled
experiments on populations of braindamaged patients because:
•  Can’t distinguish between true
recovery and compensatory changes
•  Eg decline in swelling or new strategies
•  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
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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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Reducing Brain Damage by Blocking
Neurodegeneration
•  Various neurochemicals
can block or limit
neurodegeneration
Apoptosis
inhibitor protein
Nerve growth
factor
Estrogens
•  Neuroprotective molecules
tend to also promote
regeneration
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Promoting CNS Recovery by Promoting Regeneration
• While regeneration does not normally occur in CNS,
experimentally it can be induced, directing growth of
axons by:
• Transplanted Schwann cells
• Transplanted olfactory ensheathing cells
• Caution: two studies here and recovery is only partial
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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 improved mobility
•  Again, not perfect recovery
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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 –
performance of affected arm improved + increased motor
cortex for area controlling that arm
•  Facilitated walking as an approach to treating spinal
injury
•  Cognitive and physical exercise
•  Active individuals are less likely to contract
neurological disorders (correlational finding)
•  If they do, symptoms are less severe and recovery
is better
•  Enriched environments and regular physical
activity work for animals with neurological trauma
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