HC 10

Question 1

What is rationale in lesion studies?

Answer 1

If a brain region is damaged and a particular behavioral deficit occurs, then that brain region plays critical role in that particular behavior in a normal healthy brain.

Assumptions:
-Modularity or localization: discrete anatomical modules deal with different cognitive functions. This is not met most of the time.

-Universality: brain regions subserve the same processes across individuals. Also sometimes not the case, because of the plasticity of an individual person.

Question 2

What is double dissociation?

Answer 2

Determine whether 2 cognitive functions are independent. When lesions have converse effects on 2 distinct cognitive functions:

Brain lesion area A => disruption cognitive function A, but not B

Brain lesion area B => disruption cognitve function B, but not A

The area of Broca and Wernicke is an example. They should work independently.

Question 3

What is lesion-symptom mapping?

Answer 3

Inferring the function of a brain area by observing the behavioral consequences of damage to that area.

fMRI: Does activity in the brain correlate with the task? All regions are associated, no dissociation.

LSM: Is the brain area necessary for a task? Only the critical regions.

Question 4

What is voxel-based lesion-symptom mapping?

Answer 4

It is a neuroimaging analysis technique used to identify the relationship between brain lesions and behavioral or cognitive deficits. It involves statistically analyzing the brain imaging data of patients with brain lesions to determine which specific brain regions (voxels) are associated with particular symptoms or deficits.

Question 5

What are the advantages of VLSM over prior lesion studies?

Answer 5

-Directly comparable to fMRI and PET findings. Common stereotactic space.
-Behavioral data can be continuous. No biased patient groups
-Wide range of lesion size and location possible. No need to predefine regions of interest
-Nuisance variables (lesion, size, age, etc.) as covariates
-Observe lesion effects on multiple regions at once

Question 6

What is the limitation of VLSM?

Answer 6

Damage may extend beyond the area of apparent injury as seen on structural scans. We cannot always see all the damage.

White matter damage (disconnection) may have broad ramifications outside the lesioned area of necrosis and can thus lead to remote dysfunction of apparently intact cortical tissue.

Question 7

What is the alternative to VLSM?

Answer 7

Network-based lesion symptom mapping. Examines statistical relationship between network injury and behavioral performance.

Example, why are some patients with lesions outside of ‘decision-making network’ impaired on decision-making tasks? Lesioned areas are connected to areas important for emotion-guided decision-making.

Can provide more systematic assessment by evaluating brain damage as a combination of necrosis as well as disconnection.

Question 8

What are some limitations on lesion studies?

Answer 8

Necessarily largely data-driven. The questions that one can investigate are completely determined by the patient population one happens to have access to.

There is differential vulnerabilty, which means some areas of the cortex are more likely to be damaged.

Damage often follows structural boundaries rather than functional boundaries.

Question 9

What are pharmacological interventions?

Answer 9

It involves the use of medications to prevent, treat or manage diseases and health conditions.

Question 10

What are on- vs off-medication conditions?

Answer 10

-Test de novo patients before and after their first medication. This allows for clean off-medication condition. A problem is the order-effect.
-Aks patients to do a day without their medication. This is to control for order effects.

This is mostly restricted to dopamine-related manipulations in Parkinson patients. Most other medications has too complicated widespread multivariate effects on neurotransmitter functions.

Question 11

What is the difference between anterograde- and retrograde tracers?

Answer 11

Tracers are injected in a specific region. Then see if it gets transported. Tracers go along monosynaptic connections (projections to the first synapse).

Anterograde: Label pathway from cell body to termination site of axons

Retrograde tracers: Label pathway from termination to cell body

Question 12

What are viruses?

Answer 12

They are polysynaptic tracers and follow a chain of connections. They are transmitted across synapses.

Question 13

Why is it unethical to use tracers in animals?

Answer 13

It gets injected in the region itself.

Question 14

Why should we use animals instead of humans?

Answer 14

-We get information on which of the 6 cortical layers receives or sends the connection. This level of detail is not possible in the human brain.

-Localization of the area to which tracers are transported is possible in humans, but the problem is the injection of tracers, which is unethical in human subjects.

-Possible to place lesion in a single cytoarchitoctonic area

-Possible to remove grey area matter while leaving underlying white matter undisturbed

-Possible to place exactly the same lesion in several animals, so reliability results

-Possible to assess cognitive function both before and immediately after lesion is induced

-Possible to record/induce activity in any area

-Possible to record/induce activity in a brain that is not abnormal

-Possible to test each cell in a variety of conditions

Question 15

What purpose do lesions and pharmacological manipulations have?

Answer 15

Allows for causal conclusions regarding the function of a region or neurotransmitter system.

Question 16

What are some permanent animal research techniques?

Answer 16

-Aspiration
-Excitotoxic

Question 17

What are some reversible animal research techniques?

Answer 17

-Pharmacological injections
-Cryogenic
-Genetic
-TMS
-FUS

Question 18

What is aspiration?

Answer 18

A permanent animal lesion technique. It is non-specific and the size is unlimited. It does not spare fibres.

Remove tissue by suction through glass pipette. It is visually-guided. Only surface areas can be reached.

Question 19

What is excitotoxic/neurotoxic?

Answer 19

A permanent animal lesion technique. It is specific and the size is small to medium. It spares fibres.

Selectively destroy cells (or neurotransmitters) and spare fibers by infusion of chemical through a cannula. Deep subcortical structures can be reached. It is difficult to ensure the precise extent of the lesion.

Question 20

What is pharmacological intervention?

Answer 20

A reversible animal lesion technique that lasts minutes to hours. It is specific and the size is small. It spares fibres.

Infusion of non-neurotoxic chemical to temporarily change neurotransmission (re-uptake, synthesis, break-down).

Virtually any brain region can be targeted while sparing fibers of passage, but difficult to assess spread and efficacy of drug.

Typically 10-20min to take full effect and wears off after a few hours.

Question 21

What is cryogenic?

Answer 21

A reversible animal lesion technique that lasts hours. It is non-specific and the size is large. It spares no fibres.

Transient cooling prevents synaptic transmission. Requires direct access to tissues, so not well-suited for deep and subcortical structure.

Question 22

What are genetic-based approaches?

Answer 22

A reversible animal lesion technique that lasts miliseconds to hours. It is specific and the size is small. It spares fibres.

Use of viral vectors to make cells express specific proteins.

Proteins are selectively activated to alter cell function.

It has a high spatial resolution, because it targets individual structures, cell types or pathways.

There is also a high temporal resolution, because there is precise control over timing of a lesion, so less reorganization by the brain.

Question 23

What is TMS (animal)?

Answer 23

A reversible animal lesion technique that lasts miliseconds to minutes. It is non-specific and the size is small. It spares no fibres.

Question 24

What is FUS (animal)?

Answer 24

A reversible animal lesion technique that lasts minutes. It is non-specific and the size is small to medium. It spares no fibres.

Question 25

What is electrolytic?

Answer 25

Pass current through electrode to head exposed tip abd destroy adjacent tissue. Areas at depth can be reached and also fiber destruction.

Question 26

What are optogenetics?

Answer 26

A reversible lesion technique on animals. A combination of genetic and optical methods to achieve gain or loss of function of well-defined events in specific cells of living tissue.

Question 27

What are chemogenetics?

Answer 27

A reversible lesion technique on animals. A combination of genetic and drug-based methods to achieve gain or loss of function of well-defined events in specific cells of living tissue.

Question 28

What does DREADDS stand for?

Answer 28

It is a part of chemogenetics.

D= Designer
R= Receptors
E= Exclusively
A= Activated
by
D= Designer
D= Drugs

Question 29

What does single-unit recording and multi-unit recording provide?

Answer 29

Activity patterns of neurons (single) and neuron clusters (multi) provide insights into a region’s function. This gives superior spatial and temporal resolution.

Question 30

What is effective connectivity?

Answer 30

Stimulating neurons in the vicinity of the electrode provides insights into the funtion of the area and its projection regions.

Question 31

What are the results of comparing neuroimaging data between primates and humans?

Answer 31

Visual areas in monkeys and humans have the same response pattern.

Question 32

How are rodent’s brain?

Answer 32

Less variable brains, means easier to place subcortical lesions. Especially for processes related to ‘old’ brain structures of neurotransmitter systems or behavioral pharmacology.

Due to eyes and paws and cognitive limitations, it is difficult to train to fixate a central point, report perceptions and decisions, manipulate joysticks or perfrom difficult attentional tasks.

Use primates to study relations between neocortical activity and higher cognitive abilities.

Question 33

What is the difference between marmosets and macaques?

Answer 33

Marmosets (new world monkeys) mature and age more quickly. This speeds up studies of diseases that affect development/aging. The brain is less furrowed and is therefore easier to record activity from the surface.

Macaques (old world monkeys) are easier to train and have better work ethics. There is better knowledge on anatomical connections. They have less smooth brain, so it is easier localize specific areas.

Question 34

What are the 3Rs principle for protection of animals used in research?

Answer 34

Replacement:
-Absolute: replace inanimate systems (tissues, cells)
-Relative: replace more sentient animals with animals with lower potential for pain perception

Reduction:
Any strategy that results in fewer animals being used to obtain sufficient data to maximize information obtained per animal. Limit or avoid subsequent use of additional animals.

Refinement:
Modify husbandry or experimental procedures to minimize pain and distress enhance welfare of animals from birth to death.