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) Remove brain – Fix brain in formalin to solidify tissue and to prevent autolysis 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