Neuroscience Research Methods 3 Flashcards
(141 cards)
1
Q
In neuropharmacology, what is meant by affinity? (1)
A
How tightly a drug binds to its target
2
Q
Give three research techniques which could be used to assess a drug’s affinity. (3)
A
- Radioligand binding
- Fluorescent ligand binding
- Fluorescent/bioluminescent Resonance Energy Transfer (FRET/BRET)
3
Q
Briefly describe how radioligand binding studies would be caried out. (4)
A
- Cells/membranes/homogenated tissue incubated with radiolabelled ligand
- During incubation ligand binds to target
- Then either centrifuge (bound ligand forms pellet) or filter (bound ligand trapped in filter) to separate tissue+ligand from unbound ligand
- Measure radioactivity
4
Q
When using radioligand or fluorescent ligand binding studies to test drug affinity, describe a method which could be used to differentiate between specific binding and non-specific binding. (4)
A
- Add labelled ligand to sample and allow it to bind (as normal)
- Then add another unlabelled ligand for same target
- Unlabelled ligand will displace specific binding but will leave non-specific binding
- So any signal left over will be from non-specific binding
5
Q
Give two ways to perform radioligand/fluorescent ligand binding studies. (2)
ie. will produce two different sets of results
A
- Saturation binding
- Competition binding
6
Q
Describe how you would produce a dose-response curve based on radioligand/fluorescent ligand saturation binding studies. (1)
A
Vary concentration of ligand and measure response
7
Q
What is the meaning of Bmax, when applied to radioligand/fluorescent ligand saturation binding studies. (1)
What can you infer from Bmax? (1)
A
Bmax = maximum specific binding
Can infer the total number of binding sites in tissue sample.
8
Q
What is the meaning of KD, when applied to radioligand/fluorescent ligand saturation binding studies. (2)
How would a KD value be interpreted? (1)
A
KD = equilibrium dissociation constant
Concentration that occupies 50% binding sites
Higher KD = lower affinity
9
Q
Give a disadvantage of using saturation binding as opposed to competition binding when performing a radioligand binding study. (1)
A
Can only be used if the drug of interest has a radioactive form.
10
Q
Describe how you would produce a dose-response curve based on radioligand/fluorescent ligand competition binding studies. (3)
A
- Add a radioligand to the target and allow to bind
- Add varying concentrations of ligand of interest, which is non-labelled
- Ligand of interest will compete for binding sites and displace radioligand
11
Q
What is the meaning of IC50, when applied to radioligand/fluorescent ligand competition binding studies. (1)
How would IC50 results be interpreted? (1)
A
IC50 = concentration which causes 50% displacement
Higher IC50 = lower affinity
12
Q
In what circumstances might it be more beneficial to use competition binding when performing a radioligand / fluorescent ligand binding experiment. (1)
A
Can be used to test a new/rare drug which doesn’t have a radiolabelled form.
13
Q
Give two advantages of performing radioligand binding studies as opposed to fluorescent ligand binding studies. (2)
A
- Radiolabel is stable and not light sensitive
- Small size of radiolabel shouldn’t interfere with binding
14
Q
Give three disadvantages of performing radioligand binding studies as opposed to fluorescent ligand binding studies. (3)
A
- Safety and practicality issues of radioligands
- Need high quantity of tissue (can’t study single cells)
- Can only measure a single time point (if you want to measure a response over time you have to perform separate assays for each time point)
15
Q
Right now, go to neuropharmacology notes, and look at table under radioligand binding.
Answer the questions.
A
I hope you did this and didn’t skip this card.
16
Q
Briefly describe how fluorescent ligand binding studies are carried out. (4)
A
- Cells/membranes/homogenated tissue incubated with fluorescently labelled ligand
- During incubation ligand binds to target
- Then either centrifuge (bound ligand forms pellet) or filter (bound ligand trapped in filter) to separate tissue+ligand from unbound ligand
- Measure fluorescence
17
Q
Give two advantages of performing fluorescent ligand binding studies as opposed to radioligand binding studies. (2)
A
- Fewer safety / practicality concerns than radioactive
- More versatile detection options (eg. can view structure with fluorescent microscopy)
18
Q
Give two disadvantages of performing fluorescent ligand binding studies as opposed to radioligand binding studies. (2)
A
- Light sensitive specimens
- Fluorophores used are large - can influence ligand binding
19
Q
Complete the sentence relating to fluorescent/bioluminescent resonance energy transfer (FRET/BRET) affinity studies. (1)
FRET/BRET are both techniques based on ……………………………..
Hint: answer is a phrase
A
energy transfer between paired dyes on a receptor and a ligand
20
Q
Briefly describe the principle behind the FRET/BRET technique. (2)
How can this imply affinity? (1)
A
When in close proximity, the donor dye (eg. on a ligand) transfers energy to an acceptor dye (eg. on a receptor) and alters the emitted wavelength.
*BRET is the same but a donor light-emitting enzyme produces a photon, then transfers energy to an acceptor rather than a dye
This implies affinity because the energy transfer will only take place if the ligand and target are in very close contact (ie. they are bound to each other).
21
Q
What is the difference between FRET and BRET? (2)
A
FRET uses fluorescent dyes
whereas BRET uses light-emitting enzymes
22
Q
Give three advantages of FRET/BRET techniques. (3)
A
- High sensitivity
- High throughput (many tests can be done at once)
- Kinetic (time course) assays possible (as signals can be recorded without disrupting cells)
23
Q
In neuropharmacology research, what is meant by the term ‘efficacy’? (1)
A
How effective a drug is at activating its target
24
Q
Define the term ‘agonist’. (1)
A
Binds to a receptor and activates it
25
Define the term 'antagonist'. (2)
Binds to a receptor without activating it
and prevents the effect of an agonist.
26
Define the term 'partial agonist'. (3)
Binds to a receptor
but only partially activates it
so reduces the effect of the full agonist.
27
Define the term 'inverse agonist'. (1)
Binds to receptor and reduces existing activity.
28
Describe the effect on a dose-response curve of adding a reversible, competitive antagonist. (1)
Parallel right shift - antagonist can be overcome by increasing agonist concentration.
29
Describe the effect on a dose-response curve of adding a non-competitive or an irreversible antagonist. (1)
Reduced maximum response
30
Give three possible research techniques that could be used in efficacy studies. (3)
- 'Classical' efficacy assays
- Fluorescent/bioluminescent resonance energy transfer (FRET/BRET)
- Uptake/release assays
31
Which of the three common techniques used to study efficacy are used for receptors, and which are used for transporters? (2)
RECEPTORS:
- Classical efficacy assays
- FRET/BRET
TRANSPORTERS:
- Uptake/release assay
32
Describe how classical efficacy assays can be used to measure drug efficacy. (2)
Measure downstream production of intracellular signalling messengers
eg. cAMP, IP3, reporter genes
33
Complete the sentence relating to fluorescent/bioluminescent resonance energy transfer (FRET/BRET) efficacy studies. (1)
FRET/BRET are both techniques based on ...................................
Hint: answer is a phrase
energy transfer between paired dyes on different parts of the same receptor.
34
Briefly describe how FRET/BRET techniques can be used to determine drug efficacy. (3)
- Receptor activation causes conformational change
- Proximity of donor and acceptor dyes changes
- Emitted wavelength of dye is altered
35
Give three advantages and two disadvantages of FRET/BRET studies for efficacy. (5)
ADVANTAGES:
- High sensitivity
- High throughput
- Can get time-course assays
DISADVANTAGES:
- Interference from autofluorescence
- Photobleaching (light sensitive)
36
Describe how to perform an uptake assay to
test efficacy of a ligand binding to a transporter. (3)
- Incubate cells expressing target transporter, test ligand, and radiolabelled/fluorescent substrate for the transporter
- During incubation, substrate either taken up by transporter or not depending on test ligand
- Wash sample to remove extracellular substrate, and measure radioactivity/fluorescence in cells
37
Describe how to perform a release assay to
test efficacy of a ligand binding to a transporter. (4)
- Pre-incubate cells expressing target transporter and radiolabelled substrate for transporter, and cells will take up substrate
- Wash to remove extracellular substrate
- Incubate with test ligand
- Collect samples of extracellular fluid to measure release of radioactive substrate
38
When performing uptake and release assays to test efficacy, describe the effect of MDMA on uptake and release of 5-HT and dopamine. (4)
- Inhibits uptake of DA
- But inhibits uptake of 5-HT more
- Increases release of DA
- Increases release of 5-HT to same extent
39
When performing uptake and release assays to test efficacy, describe the effect of methamphetamine on uptake and release of 5-HT and dopamine. (4)
- Inhibits uptake of DA
- Inhibits uptake of 5-HT (but not as much as dopamine)
- Increases release of DA
- Increases release of 5-HT (but not as much as dopamine)
40
Describe how affinity of an antipsychotic for the D2 receptor affects what dose will be required for a therapeutic effect. (1)
Lower affinity = higher dose needed
41
Describe what is meant by 'biological response' in neuropharmacology. (1)
The physical/therapeutic consequences of drug activity.
42
Give five potential things that can be looked at to assess the biological response of a drug. (5)
- Transcriptomics
- Cell morphology
- Calcium signalling
- Electrophysiology
- Immunocytochemistry
43
Describe three uses of human induced pluripotent stem cells in assessing the biological response of a drug. (3)
- Measure biological responses
- Understand disease mechanisms
- Test drug efficacy in groups of patients (ultimate goal is personalised medicine)
(Can test drugs on neurones/cells which have specific genetic mutations or cells from specific patients to see whether they have the desired response)
44
Give one advantage and two disadvantages of using humans iPSCs to assess the biological responses of drugs. (3)
ADVANTAGE:
- Can be used to study genetic contributions to a disease
DISADVANTAGES:
- Little insight into environmental contributions
- Cells remain immature so little insight into effects of ageing
45
Give three reasons why animal studies are essential to neuroscience research. (3)
- Ethics of going straight to humans
- Allows tighter control of variables than in humans
- Can give mechanistic insight
46
Give four advantages and one disadvantage of using animal studies to research neuroscience and neurological illnesses. (5)
ADVANTAGES:
- Similar neuroanatomy to humans
- Same neurotransmitters as humans
- High receptor homology with humans
- Rodents and humans share core behaviours related to feeding, pain, etc
DISADVANTAGE:
- Rodents don't develop complex mental illnesses (but may be able to show some aspects such as cognitive and affective changes)
47
Define what is meant by 'behavioural test'. (1)
Observing an animal and measuring an outcome
48
Name three types of validity that can be applied when producing animal models. (3)
- Face validity
- Construct validity
- Predictive validity
49
Describe 'face validity', as applied to animal models. (1)
Changes in the model resemble those in the disease.
eg. behavioural changes seen mimic aspects of the symptoms
50
Describe 'construct validity', as applied to animal models. (1)
Mechanism used to induce the model reflects known cause of the disease.
eg. genetic basis for genetic disorder
51
Describe 'predictive validity', as applied to animal models. (1)
Drug effects in model predict those in the disease
ie. true positives and negatives without false positives and negatives
52
Give three ways that behavioural tests alone (not paired with an animal model) can be used in neuroscience research. (3)
- Investigate basic biology (eg. effect of age/sex on behaviour)
- Target validation (eg. looking at role of a molecule in specific behaviour)
- Mechanistic insight (eg. neuroanatomical substrates of behaviour; what area of brain causes specific behaviours)
53
Give three ways that combining animal models with behavioural testing can be used in neuroscience research. (3)
- Give new insight into disease mechanisms (eg. risk exposure)
- Test new therapeutics for symptom management and prevention
- Move towards patient stratification for personalised medicine (eg. induce same faulty gene in animal as seen in patient and see which drug works best)
54
Suggest three behavioural tests which could be used to assess anxiety. (3)
Describe generally how these tests might be able to indicate anxiety in a rodent. (1)
- Open field
- Elevated plus maze
- Light-dark box
Measure a rodent's innate desire to explore a novel environment vs evolutionary avoidance of bright/open spaces.
55
Briefly describe how a rodent open field test would be performed and how the results would be interpreted. (4)
- Animal placed into open area
- Tracked for locomotor activity and time in peripheral and central zones
- Increased time in periphery = more anxiety
- Increased time in centre = less anxiety
56
Briefly describe how a rodent elevated plus maze test would be performed and how the results would be interpreted. (4)
- Animal placed on elevated maze with open and closed arms
- Tracked for locomotor activity and time in open and closed arms
- More time in closed arms = more anxiety
- More time in open arms = less anxiety
57
Describe a large confounding factor when using rodent behavioural tests for anxiety. (1)
How is this controlled for? (1)
Sedation or motor impairment from interventional treatments and/or animal models may affect results.
So locomotor activity is tracked and animals which do not move as much in total can be identified.
58
Name four traditional rodent behavioural tests for affective state. (4)
Forced swim test
Novelty-Supressed Feeding
Sucrose preference test
Tail suspension test
59
State how the rodent forced swim test for affective state would be interpreted. (1)
More time immobile = more depressed
60
State how the rodent novelty-suppressed feeding test for affective state would be interpreted. (1)
Anxious mice will take longer to begin eating
61
State how the rodent sucrose preference test for affective state would be interpreted. (1)
Depressed rodents would not prefer sucrose water
62
State how the rodent tail suspension test for affective state would be interpreted. (1)
More time spent immobile = more depressed
63
Describe three affective biases that are known to occur in depression, and which may be exploited in newer rodent behavioural tests for affective state. (3)
- Negative cues become more salient
- Better recall of negative information than positive information
- Neutral/ambiguous information more likely to be perceived as negative than positive
64
Name two newer rodent behavioural tests which look at affective state, and may exploit affective biases seen in depression. (2)
- Judgement bias task
- Affective bias task
65
Describe how a rodent judgement bias task would be carried out to assess affective state. (5)
- Food restricted animal put in box with little window
- Animal conditioned by two stimuli:
- Positive tone paired with food reward through window
- Negative tone paired with puff of air through window
- Play a neutral tone and see whether animal stays at window or leaves
66
Describe how the results from a rodent judgement bias task would be interpreted. (2)
When ambiguous tone is played:
- mouse leaves window = lower/depressed affective state
- mouse stays at window = higher/less depressed affective state
67
Describe how a rodent affective bias task would be carried out to assess affective state. (4)
- Food restricted animal digs in bowls to receive food reward (two bowls containing different media, only one contains food reward)
- Alternate treatment vs control days, and have a different media in food reward bowl on control days vs treatment days (eg. sawdust on treatment days, rocks on control days)
- Also alter locations of reward bowl to avoid bias
- Effects of treatment will determine which bowl mouse digs in on untreated preference test, when bowls contain media from either treatment or control day
68
Describe how the results from a rodent affective bias task would be interpreted. (3)
- If treatment improves affective state animal will dig in bowl with treatment-paired media
- If treatment worsens affective state animal will dig in bowl with control-paired media
- If treatment inactive animal will show no preference
69
Describe two difficulties in choosing a behavioural test to assess cognition in animals. (2)
- Not all behavioural tests are relevant to all disease states
- Some aspects of cognition cannot be tested in animals (eg. language and verbal memory)
70
Give a behavioural test for executive function which can be performed in:
a) humans
b) rodents
(2)
a) Wisconsin card sorting task
b) Attentional set shifting task
71
Would the Wisconsin card sorting task be better able to detect schizophrenia or generalised anxiety disorder? (1)
Explain why. (1)
Schizophrenia
Because this test assesses executive function, and deficits in executive function are seen in schizophrenia but not GAD
72
Describe briefly how to perform the attentional set shifting task to assess cognition in rodents. (4)
- Two bowls with different media and different scents (one contains food and animals are food restricted)
- Animals trained to follow either media or scent (other present but irrelevant)
- Measure how many trials it takes until 6 consecutive successful choices (animal has now learnt to associate food with specific media or smell)
- Rules changed multiple times to assess how long it takes for animal to learn new rule (eg. reversal, intradimensional, extradimensional rule change)
73
Give three confounding factors which may affect results of the rodent attentional set shifting task. (3)
- Sedation
- Appetite
- Motivation
74
Briefly describe the Morris water maze for spatial memory. (5)
- Animals swim in tank of cloudy water
- Use spatial cues (eg. symbols) around edge of tank to navigate to submerged platform
- Use tracking software to measure distance and time to locate platform
- Can conduct test without platform (track time spent searching zone where platform should be)
- Can also assess rate of relearning to an opposite zone
75
Describe a potential issue with comparing the rodent Morris water maze test for spatial memory to an equivalent test in humans. (1)
In the water maze, animals are extremely motivated to escape the water, but humans may not be as motivated to perform spatial memory tests in a clinical setting.
76
What cognitive domain does the novel object recognition test measure in rodents? (1)
Describe how this test is performed. (4)
Measures memory
- Animals habituated to test arena
- Familiarisation trial with 2 identical objects
- Choice trial with 1 novel and 1 familiar object
- Exploration assessed with stopwatches or software
77
Describe how results should be interpreted in the rodent novel object recognition test. (1)
Animals with better memory will spend more time exploring novel object.
78
What cognitive domain does the social recognition test measure in rodents? (1)
Describe how this test is performed. (4)
Memory
- Animals habituated to test arena
- Sociability trial with one social partner and one empty holder
- Social memory trial with 1 now familiar partner and 1 novel partner
- Track how much time animals spend around each partner
79
Apart from its main function is assessing memory, give two other cognitive domains or conditions that a rodent social recognition test will assess. (2)
How are these assessed? (1)
Stress and social dysfunction
When animal exposed to one partner animal and one empty cage, normal animals will explore partner, but stress or social dysfunction animals will avoid partner.
80
Describe how results should be interpreted in the rodent social recognition test. (1)
Animals with better memory will spend more time exploring novel social partner
81
Describe briefly how social interaction between animals can be assessed using behavioural tests. (2)
- Two animals (weight and treatment matched) which are unfamiliar to each other put in unfamiliar arena
- Assess interactions between animals (eg. time spent interacting, and aggressive vs exploratory interactions) via video recordings
82
Name two types of nuclear brain imaging. (2)
PET
SPECT
83
What is nuclear imaging mainly used for in neuroscience? (1)
Functional imaging
84
What type of electromagnetic radiation is used in nuclear imaging? (1)
Gamma
85
Describe the frequency and wavelength of gamma radiation, which is used for nuclear neuroimaging. (2)
High frequency, short wavelength
86
Describe/explain the risks associated with nuclear imaging techniques such as PET and SPECT. (3)
Uses gamma radiation
which is ionising
so has the potential to cause tissue damage.
87
What does 'PET' stand for in neuroimaging? (1)
positron emission tomography
88
Briefly describe how PET is carried out. (4)
- Positron-emitting radioisotope is incorporated into compound/molecule of interest
- Radiopharmaceutical injected and distributed in body
- Radiopharmaceutical emits positrons with annihilate with electrons
- Reaction produces 2 high energy photons (gamma rays) which are detected by detectors lying opposite each other
89
Give an example of a radiopharmaceutical used in PET imaging and explain what this would detect in the brain. (2)
Glucose with added 18F (fluorodeoxyglucose)
which would accumulate in areas of active tissue so detects brain activity.
90
Describe what is meant by 'coincidence detection' in PET scanning. (3)
2 gamma rays emitted by annihilation travel in opposite directions
and are detected by 2 detectors lying opposite each other.
This process is essential for localisation of the signal.
91
In PET imaging, what does Pittsburgh compound B (11C-PiB) detect in the brain? (1)
What disease can it detect/monitor? (1)
Binds to beta-amyloid
Used for Alzheimer's
92
Give one advantage of using MRI imaging to monitor neurological disease, and one advantage of using PET imaging. (2)
MRI:
- Better resolution and shows more detail
PET:
- Better at showing function
93
Describe the half lives of the radionuclides used in PET imaging. (1)
What is the consequence of this? (1)
Short half lives (couple of hours to minutes)
They have to be assembled on-site, using expensive machinery which can make the technique more difficult.
94
What does SPECT stand for in neuroimaging? (1)
Single photon emission computed tomography
95
Briefly describe how SPECT imaging works. (3)
- Gamma-emitting radioisotope (which directly emits photons) incorporated into compound
- Injected into subject and distributes throughout body
- Emits photons (gamma rays) which are detected singularly (do not have to detect 2 photons opposite each other)
96
The molecule 99T-hexamethylpropyleneamine (HMPAO) can be used in SPECT imaging.
What does this compound measure? (1)
Explain your answer. (1)
Detects cerebral blood flow
as it readily crosses the BBB.
97
Name four radioisotopes which can be used in PET imaging. (4)
18F
11C
15O
13N
98
Name four radioisotopes which can be used in SPECT imaging. (4)
99Tc
111In
123I
201Th
99
Describe the half lives of the radionuclides used in SPECT imaging. (1)
What is the consequence of this? (1)
Long half lives
Isotopes can be purchased instead of creating them onsite, which makes the method cheaper and easier.
100
Give one advantage of using PET imaging as opposed to SPECT imaging. (1)
Better quality images
101
Give one disadvantage of using PET imaging as opposed to SPECT imaging. (1)
Radionuclides have shorter half lives which makes the technique more difficult and expensive.
102
Give one reason why optical neuroimaging has limited clinical use. (1)
Poor penetration (cannot visualise tissues)
103
Transmitted microscopy and episcopic microscopy are both methods of imaging using visible light.
Describe the difference between transmitted and episcopic microscopy. (2)
TRANSMITTED:
- Light passes through a thin sample
EPISCOPIC:
- Light does not pass through sample, so can be used for dissection/surgery (sample can be thicker)
104
Transmitted microscopy and episcopic microscopy are both methods of imaging using visible light.
How is contrast produced in these methods in order to better visualise structures? (1)
Use of stains
105
Describe how optical coherence tomography works. (1)
What type of electromagnetic radiation is used? (1)
In what situations is it usually used? (1)
Infrared light used to obtain sub-surface 3D images by detection of reflected photons (can penetrate 2-3mm).
Infrared
Used for retinal imaging
106
Name an application of fluorescence microscopy that can be carried out in vivo, potentially in humans. (1)
Near infrared guided surgery
107
Described how near infrared guided surgery is performed. (3)
Indocyanine green is an infrared fluorophore that binds to plasma proteins.
Accumulates in injured/disrupted areas of brain (eg. tumour) due to BBB disruption.
Can be used clinically to view tumour margins during surgery.
108
Give two equations to describe how the enzyme luciferase (found in fireflies) is able to produce light. (2)
Luciferin + ATP = Luciferyl adenylate + pyrophosphate
Luciferyl adenylate + O2 = Oxyluciferin + AMP + light
109
Describe a potential mechanism by which stem cells which have modified to express the luciferase enzyme can indicate that they are able to survive and potentially proliferate in damaged areas of brain after a stroke. (2)
If the cells still show light later down the line, it indicates that they have survived in the new environment.
An increase in light signal indicates that they have proliferated.
110
True or false? Explain your answer. (1)
GFP imaging can be used in mice in vivo.
True - although mice either have to be shaved or nude mice used as the fur blocks the signal
111
Give two types of radiological neuroimaging. (2)
CT
MRI
112
What type of electromagnetic wave does CT use? (1)
Is this ionising or non-ionising radiation? (1)
X Ray
Ionising
113
Briefly describe how a CT scan works. (1)
Powerful X-rays passed through specimen from many angles.
114
Complete the following sentence relating to CT scanning. (1)
When CT scans are performed, attenuation images are reconstructed in .............................
Hounsfield Units (HU)
115
Describe what is meant by 'attenuation', in the context of CT scanning. (2)
Attenuation is the degree to which a signal is slowed down or disrupted.
Related to the radiodensity of the tissue, and affects how much X-ray is transmitted through the specimen.
116
Put the following structures in order from lowest attenuation to highest attenuation. (6)
- Fat
- CSF
- Bone
- Air
- Brain
- Blood
Where does 0 attenuation sit on this scale? (1)
- Air
- Fat
- CSF
- Brain
- Blood
- Bone
CSF has 0 attenuation.
117
Complete the sentences relating to CT scans and attenuation. (2)
When performing a CT scan, bone has ................. attenuation so will appear .....................
CSF and water have .................... attenuation so will appear ..................
High
bright white
lower
black
118
Is CT scanning more commonly used for research or clinical purposes in neuroscience? (1)
Clinical
119
MRI imaging uses what type of electromagnetic radiation? (1)
Is this type of radiation ionising? (1)
Radiowaves
No
120
Briefly describe how MRI works and what it detects. (3)
Large magnetic field
able to manipulate the magnetic fields in atoms with an excess proton (ie. hydrogen)
It picks up water
121
Describe what is meant by relaxometry, as applied to MRI imaging. (1)
Relaxometry is a measure of the signal decay after exciting a proton.
122
Why are different forms of relaxation used when performing MRI scans? (1)
They produce different images and allow you to visualise different tissues.
123
Describe the difference between MRI images produced using T1 and T2 relaxometry. (2)
T1 results in lower contrast
T2 results in good contrast (especially to visualise water/CSF, which appears bright)
124
What is diffusion MRI used for in neuroscience? (1)
What is this technique based on? (1)
Provides structural information about the brain
based on random water motion (how fast water diffuses around the brain and in which directions).
125
Describe what is meant by anisotropy, as applied to diffusion MRI. (1)
The property of being directionally dependent (ie. more likely to move in one axis than another).
126
Describe what is meant by the diffusion tensor, as applied to diffusion MRI. (1)
A 3D model that describes anisotropic diffusion around an XYZ axis.
127
How can tracking the random motion of water in the brain give us information about the structure of the brain? (2)
Water is much more likely to diffuse parallel to structures (eg. tracts and axons) than perpendicular to them.
So the movement of water can help to distinguish tracts and other brain structures, including oedema.
128
Describe how functional MRI is able to show neural activity. (3)
Blood oxygen level dependent (BOLD) imaging measures the difference in oxygenation of tissues between resting and activated state.
It uses blood flow and oxygen levels to infer neural activity.
Areas of more blood flow = higher activity levels.
129
Describe how task-based fMRI is carried out. (5)
Task performed at intervals to generate brain activity.
Changes in blood flow recorded throughout brain (however images produced have very low resolution).
So brain split into 3d grid (voxels) and the signal pattern (change in brain oxygenation) is compared to the activity pattern in each voxel.
Statistics carried out to confirm that the oxygenation changes in specific voxels match the activity pattern performed.
Voxel statistics can then be overlaid onto an anatomical image.
130
Describe what resting state fMRI is, and what it is used for. (2)
Searches for patterns of synchronous BOLD activity among brain regions when patient at rest.
And common patterns are interpreted as functional connectivity between regions.
*No tasks performed*
131
Complete the sentence relating to resting state fMRI. (1)
rsfMRI is able to use BOLD signal fluctuations to show that the ............................... network is active during rest.
default mode
132
Using amphetamine or PCP to model schizophrenia in animals is what type of animal model? (1)
pharmacological/genetic/lesion/surgery/neurodevelopmental
Pharmacological
133
Describe the face validity and construct validity of using amphetamine or PCP to model schizophrenia in animals. (2)
FACE VALIDITY:
- Good, because these drugs produce the same symptoms as the disease
CONSTRUCT VALIDITY:
- Poor, because amphetamine and PCP do not normally feature in the mechanism by which schizophrenia develops
134
Knocking out the DISC1 gene to model psychiatric illnesses (such as schizophrenia) in animals is what type of animal model? (1)
pharmacological/genetic/lesion/surgery/neurodevelopmental
Genetic
but also includes neurodevelopmental component as mutation is present from conception.
135
Describe the face validity and construct validity of using DISC1 knockout to model schizophrenia in animals. (2)
FACE VALIDITY:
- Good, because it produces the same symptoms as seen in disease
CONSTRUCT VALIDITY:
- Good for some patient groups (ie. groups that have disc1 mutation), but other patient groups do not have this mutation
136
Causing a neonatal ventral hippocampal lesion to model psychiatric illnesses (such as schizophrenia) in animals is what type of animal model? (1)
pharmacological/genetic/lesion/surgery/neurodevelopmental
Lesion/surgery
137
Describe the face validity and construct validity of causing ventral hippocampal lesions to model schizophrenia in animals. (2)
FACE VALIDITY:
- Generally good, as it produces symptoms of schizophrenia
CONSTRUCT VALIDITY:
- Poor, because in models the entire ventral hippocampus is ablated, which does not happen in the disease
138
Describe what is meant by a neurodevelopmental type of animal model, ie. how this type of animal model would be produced. (1)
Replicating conditions in utero or childhood which increase risk of illness.
139
Stimulating maternal immune activation or carrying out isolation rearing to create animal models of schizophrenia is known as what type of animal model? (1)
pharmacological/genetic/lesion/surgery/neurodevelopmental
Neurodevelopmental
140
Describe the face validity and construct validity of stimulating maternal immune activation or carrying out isolation rearing to model schizophrenia in animals. (2)
FACE VALIDITY:
- Generally good, and it includes developmental component - symptoms develop at right time
CONSTRUCT VALIDITY:
- Good, as it is based on epidemiological risk factors
141
Describe two general constraints of all animal models in replicating human psychiatric illnesses. (2)
- Some symptoms of complex disorders like schizophrenia or depression cannot be studied in animals (eg. suicidal ideation, delusions)
- Schizophrenia and depression are very heterogenous (many different combinations of symptoms present) - no single model can replicate all aspects of these states or be relevant to all subtypes or patient subgroups
