3680Lecture8_RJS.ppt
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Transcript 3680Lecture8_RJS.ppt
Assignment
• Rules:
– Must be Human Cognitive Neuroscience
– Experimental approach may involve animal research only if
this is the best way to test your theory
• Your mindset should be that studying humans is preferable to
studying animals when you have a specific theory about
Human cognition
• One moves to animal research because of some
insurmountable constraint on Human research
• If this applies to your theory, you will make this constrain
explicit in your proposal
L
Methods of Cognitive Neuroscience
Lesion Studies
• Logic of Lesion Studies:
– damaged area plays a role in accomplishing whatever task is
deficient after the lesion
Lesion Studies
• Types of Lesions
– Animal
– Human
Stereotaxic Surgery
• A stereotaxic instrument holds
the head in a fixed position
– The instrument has an arm that
can move in 3 dimensions
– The surgeon can thus position an
electrode or other device within a
particular sub-cortical structure
• A stereotaxic atlas provides a
series of drawings of brain
structures
– Each page is a section of brain
relative to a landmark on the skull
(such as bregma)
5.6
Using a Stereotaxic Atlas to
Target a Brain Lesion
5.7
Histological Techniques
• Histological techniques are used to verify the placement of a
lesion within brain
–
Perfuse (to remove blood from brain)
•
–
Fix brain in formalin to solidify tissue and to prevent autolysis
•
–
Remove brain
Slice brain into thin sections (10-80 microns thick)
Use stains to highlight selective neural elements
•
Myelin (Weil stain)
•
Cell body (cresyl violet: Nissl substance in cytoplasm)
•
Membrane (Golgi stain)
5.8
Lesion Studies
• Animal Lesion Techniques
– Aspiration Lesions
– Electrolytic Lesions
– Problems:
• These can damage surrounding tissue - especially white matter
tracts nearby (“fibers of passage”)
• Irreversible
• eventual degradation of connected areas
Lesion Studies
• Animal Lesion Techniques
– Vascular Lesions
• endothelin-1
• good model of human stroke
• severe damage
• not pinpoint accuracy
Lesion Studies
• Animal Lesion Techniques
– Reversible Lesions – temporary inactivation
• Cooling - controllable
• Local anesthetics
• Tetrodotoxin
• Receptor specific agents: muscimol, scopolamine
Lesion Studies
• Animal Lesion Techniques
– Selective Pharmacological lesions
• damage or destroy entire pathways that have a specific
sensitivity to a particular chemical
• e.g. MPTP model of Parkinson’s Disease (frozen addicts)
• Can be selective for specific circuits but not for specific brain
areas
• can be reversible in some cases (e.g. scopolamine, but not
MPTP)
Lesion Studies
• Animal Lesion Techniques: Transgenic animals
– Gene Knock-Out, Knock-In
• can selectively block expression of specific receptor types
• animal develops differently
• Newer – regionally and temporally conditional knockouts
• Only mice
Lesion Studies
• Human Lesions
– Ischemic Events
• Stroke and Hemorrhage:
– typically due to blood clot or hemorrhage
– size of lesion depends on where clot gets lodged
– amount of damage depends on how long clot remains lodged
Lesion Studies
• Human Lesions
– Trauma
• Frontal lobes are particularly susceptible
• Some famous cases (e.g. Phineas Gage)
Phineas Gage
Phineas Gage:
From responsible,
religious respectable and
socially well-adapted
man to an irreverent,
profane and impulsive
itinerant.
Lesion Studies
• Human Lesions
– Surgery
• Often surgery done to treat epilepsy
• Occasionally corpus callosum is severed
• Problem: patient wasn’t “normal” before the surgery
Lesion Studies
• Human Lesions
– Transcranial Magnetic Stimulation
• Electromagnet Induces current in the brain
• very transient, very focal reversible “lesion”
• Believed to be safe
• sites that can be studied are limited by the geometry of the
head
Lesion Studies
• Making sense of Lesion studies
• variability
Lesion Studies
• Logic of Lesion Studies:
– damaged area plays a role in accomplishing whatever task is
deficient after the lesion
– Double dissociation
• Warning:
– This isn’t the same as saying the lesioned area “does” the
operation in question
– examples:
• normal behaviour may be altered to accommodate lesion
– e.g. sensory loss of one arm favors other arm
• lesion might cause “upstream problem” or general deficit
– e.g. attention problem “looks like” specific deficit if you only test
one specific demanding task