Tools in Neuroscience Research (Exam 3) Flashcards

1
Q

what are event-related potentials? what do they show us?

A
  • used to study brain activity in response to specific stimuli or tasks
  • ERPs involve recording electrical activity from the brain using electrodes placed on the scalp (EEG)
  • by averaging the brain’s electrical signals across repetitions, random noise cancels out, and consistent patterns related to the task become clearer
  • with enough repetitions, the resulting averaged signal shows “waves” that correspond to the timing of neural processes involved
  • ERP waves are associated with different aspects of cognition and behavior
  • ex. certain waves might reflect attention, decision-making, or memory processes
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2
Q

what is transcranial magnetic stimulation (TMS)?

A
  • use magnetic fields to change electricity in the brain
  • can target parts of the cortex and turn them off (virtual lesions)
  • not able to interfere with deeper brain areas
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3
Q

what are the benefits of TMS?

A
  • a way to induce a loss of function without any actual damage
  • potential therapeutic effects for depression and anxiety that can’t be treated with medication
  • good at targeting higher cognitive functions that are usually harder to get at
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4
Q

why are non-human animal models valuable in research?

A
  • provide tools to observe behavior (behavioral assays)
  • cannot directly ask animals questions, so their behavior demonstrates responses
  • model human behavior effectively (make the same gambling mistakes)
  • mammalian brains share similar regions and structures
  • differences include prefrontal cortex structure/organization
  • animal cognition is sophisticated (rats can learn to drive a car in order to get reward)
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5
Q

what are some tasks that show the benefit of animal models in neuroscience research?

A
  • morris water maze: tool for learning spatial navigation
  • 5-choice serial reaction time task: tool to observe attention and motor impulsivity
  • t-maze tasks
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6
Q

what is the Morris Water Maze and what does it measure?

A
  • tool for learning spatial navigation
  • rats swim in an opaque pool with a hidden platform
  • measure: time it takes for the rat to find the platform
  • over trials, rats learn and reach the platform faster
  • task depends on hippocampal function
  • rats with impaired hippocampi struggle to find the platform
  • can use a maze like this to observe induced or reduced function related to spatial navigation
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7
Q

how does the 5-Choice Serial Reaction Time Task measure attention?

A
  • operant chamber with 5 lit-up holes
  • rats must identify which hole lit up to receive a reward (sugar)
  • measure: accuracy of finding the correct hole
  • attention is operationalized as accuracy
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8
Q

how does the 5-Choice Serial Reaction Time Task measure motor impulsivity?

A
  • rats must wait for the light before acting
  • early response = 5-second time-out.
  • psychostimulants increase impulsivity but also improve accuracy
  • task can be modified to offer harder or easier trials for varying rewards
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9
Q

what is the difference between classical and operant conditioning?

A
  • classical: learning through association
  • operant: learning through rewards and punishments
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10
Q

what is the T-maze and how is it used in research?

A
  • rats choose between two options in a T-shaped maze
  • their behavior indicates their response to a question or task
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11
Q

what does the Forced Swim Test measure, and what are its limitations?

A
  • meant to measure depression-like behavior and antidepressant efficacy in rodents
  • animals are placed in a pool they cannot escape from
  • idea was that depressive-like rats give up swimming sooner
  • this was used to justify that medication works
    limitations:
  • learned behavior: rats that repeat the task know they’ll be rescued if they stop swimming
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12
Q

what are the limitations of animal models?

A
  • quality of the model depends on the behavioral assay
  • poor assays lead to unreliable interpretations
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13
Q

what are potential routes for administering drugs to animals? what are their pros and cons?

A
  • intramuscular (IM): injected into muscle
    - pro: reaches brain quickly because muscle is close to blood flow
    - con: causes soreness due to pH difference with muscle
  • intravenous (IV): catheter in vein
    - pro: rapid effect
    - con: unsuitable for some drugs (that aren’t usually put in veins), catheter can fall out
  • subcutaneous (SC): injected into fat
    - pro: painless when injected in neck scruff
    - con: slower drug effect
  • intraperitoneal (IP): injected into abdominal cavity
    - pro: quick entry into bloodstream, painless
    - most common route
  • intraventricular: injected into brain ventricles (with catheter)
    - good for drugs that don’t cross the blood-brain barrier
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14
Q

why is using multiple doses in drug challenges important?

A
  • start with a saline injection (no drug) to establish a baseline response
  • gradually increase drug doses: low, medium, and high
  • helps researchers create a drug response curve:
  • shows how different doses affect behavior or physiology
  • higher doses may produce stronger effects, but not always linearly (some drugs have a threshold or maximum effect)
  • this approach provides a clear picture of how the drug works across dose levels
  • giving multiple doses is difficult in humans due to ethical concerns or practical limitations
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15
Q

what are within-subject designs, and why are they useful?

A
  • each animal is exposed to all experimental conditions (saline, low, medium, and high doses)
  • allows researchers to compare how the same animal reacts under different conditions
    benefits: reduces variability caused by individual differences, requires fewer animals
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16
Q

what are the invasive electrical recording methods?

A
  • intracellular unit recording: measures activity inside a single neuron
  • extracellular unit recording: measures activity near (outside) a single neuron
  • multiple-unit recording: records activity from multiple neurons at once using extracellular electrodes
  • invasive EEG recording: done directly on or within brain tissue, reduces noise from the scalp
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17
Q

how is invasive eeg recording combined with intracellular recording?

A
  • there has been a study done with invasive EEG and intracellular recording
  • combining them is challenging because the electrode must stay in the cell as the animal moves
  • one study moved the environment around the rat to keep the electrode in place
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18
Q

what is stereotaxic surgery used for? how is it done?

A
  • precise surgical procedure used to target specific areas of the brain for experimental or therapeutic purposes (lesions, optogenetics, electrodes, etc.)
  • requires a stereotaxic atlas of the rat brain (accurate to 0.1 mm) and precise instruments
  • allows accurate placement of lesions, probes, electrodes, etc.
  • the reference point is bregma, where the skull bones fuse
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19
Q

what are the different lesion methods?

A
  1. chemical lesions: chemical spreads and destroys a spherical area in the brain by causing too much glutamate activity (excitotoxic)
  2. selective chemical lesions: target specific neurons using chemicals
    ex: 6-OHDA kills dopamine neurons, 5,7-DHT kills serotonin neurons
  3. reversible lesions (inactivations): temporarily turn off a brain region using a cannula and drugs like baclofen + muscimol (GABA agonists)
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20
Q

what are the benefits to using reversible lesions?

A
  • allow temporary inactivation of a brain region without permanent damage
  • help avoid recovery or compensatory effects seen in permanent lesions
  • use of cannulae allows us to inject drug directly into brain region
  • enable within-subject designs, allowing the same animal to be tested in both the active and inactivated conditions
  • provide more reliable data by reducing variability between subjects
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21
Q

what are the challenges of lesion methods?

A
  • researchers must kill the rat post-experiment to confirm the lesion area
  • finding the right post-surgery testing window is difficult:
    - testing too early risks confounding variables (tenderness)
    - testing too late risks brain recovery from lesions
  • complexity of interpreting lesion study results and designing experiments to address specific research questions (lesions can be unilateral, bilateral, or contralateral)
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22
Q

what are contralateral lesions used for?

A
  • contralateral lesion - damaging one brain region on one side of the brain and a different region on the opposite side
  • test if two brain areas work together in a circuit
  • example: when studying decision making, found that the amygdala and cingulate cortex work together
  • if two areas form a circuit, disrupting either will affect behavior
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23
Q

what is optogenetics?

A
  • a technique that uses light to control specific cells in the brain
  • involves channelrhodopsins, a type of ligand-gated ion channel found in bacteria and insects
  • light, not a traditional ligand, opens the channel and allows ions to flow, leading to action potentials
24
Q

how is optogenetics used in animals?

A
  • genetic animals are required to insert the gene for channelrhodopsins
  • to target specific brain regions (dopamine neurons, medulla, frontal lobe), system-specific transcription factors are used to express channelrhodopsins only in certain neurons
25
Q

how does the light activation work in optogenetics?

A
  • a fibre optic cable is inserted into the brain
  • light is shone through the cable to activate channelrhodopsins and trigger action potentials in targeted neurons
26
Q

what are the benefits of optogenetics?

A
  • allows for precise control of brain activity
  • can turn brain regions on or off
  • used for both recording and manipulation of brain activity
27
Q

what are the challenges with optogenetics?

A
  • while measuring action potentials (AP), it can also cause AP to travel in the wrong direction
  • if the channel is located on an axon, AP could propagate backwards
28
Q

what are the different types of stains and how are they used?

A
  • golgi stain: for seeing individual neurons
  • nissl stain/cresyl: for seeing grey matter (cell bodies)
  • fibre stain: for seeing white matter (myelin)
  • green fluorescent protein (GFP): used as a staining technique or genetic tool
29
Q

what are the common types of fibre stains?

A
  • luxol-fast blue (LFB)
  • toluidine blue
30
Q

what is green fluorescent protein (GFP) and how is it used?

A
  • used as a staining technique or genetic tool
  • a protein that glows, derived from jellyfish
  • can be inserted into an animal’s genome to make them express GFP, or directly inserted to living cells using electroporation
  • derivatives of GFP (e.g., YFP, BFP) stain cells in different colours for visual tracking purposes
31
Q

what is static/structural neuroimaging? what are the different types of structural neuroimaging?

A

shows a still picture of the brain, does not show brain activity (action potentials)
- CAT/CT (computerized axial tomography)
- MRI (magnetic resonance imaging)
- DTI (diffusion tensor imaging)

32
Q

what is dynamic/functional neuroimaging? what are the different types of functional neuroimaging?

A

indirectly measures brain activity (does not measure action potentials directly)
- PET (positron emission tomography)
- fMRI (functional MRI)
- rsfcMRI (resting-state functional connectivity MRI)

33
Q

what does structural neuroimaging show?

A
  • reveals brain structure
  • shows blood flow, grey matter (CTI), and white matter (MRI)
34
Q

what is an X-ray and how does it work?

A
  • uses x-ray tube, beam, and detectors
  • different type of tissue types absorb different amounts of radiation
  • does not show brain activity
35
Q

what is CT (computed tomography)?

A
  • uses x-rays from many angles to create 2D slices
  • slices are combined to form a 3D brain model
  • can see differences in fluid vs. tissue (cerebrospinal tissue darker, tissue lighter)
  • does not distinguish between white and grey matter or tissue types (tumors)
  • previously used to see strokes in the brain
36
Q

what is MRI (magnetic resonance imaging)?

A
  • takes multiple 2D images and reconstructs them into a 3D model
  • shows white and grey matter
  • has higher spatial resolution (can see 1mm³ voxels, shows 1 million voxels in the brain)
  • MRI has 3 teslas of magnetic power, and is on all the time
  • magnetic field aligns atoms, and radiofrequency (RF) signal is measured as atoms realign
37
Q

how does MRI work?

A
  1. protons in hydrogen atoms align with magnetic field (northward and southward)
  2. magnetic pulse knocks protons out of alignment (causes loud sound)
  3. radiofrequency (RF) signal from realignment is measured to create images
    - realignment is also called relaxation
38
Q

what is DTI (diffusion tensor imaging)?

A
  • a type of MRI that tracks how water molecules move in the brain
  • water moves freely in cell body and outside the cell, but water movement along axons it is limited (moves along the plane of axon)
  • DTI uses different pulse waves to record movement of water
  • shows clear photos of axon tracts (white matter)
  • useful for studying brain area connectivity and white matter dysfunctions
39
Q

what is functional neuroimaging?

A
  • shows brain activity while performing a task
  • correlational (measures activity, does not determine cause)
40
Q

what is PET (positron emission tomography)?

A
  • measures radiation from radioactive molecules in the brain
  • can create radio-labeled molecules, like radioactive cocaine
  • cocaine binds to dopamine transporters, revealing the dopamine system
41
Q

how does PET show brain activity during tasks?

A
  • uses radioactive water or glucose to track brain activity
  • more active areas need more blood, water, and glucose
  • shows which areas are metabolically active
42
Q

what is paired image subtraction?

A
  • compare control scan with scan during activity
  • subtract control from activity scan to highlight differences
  • shows activity related to the task being studied
  • individual difference image: subtraction for one person
  • mean difference image: average of multiple individual difference images
  • epiphenomena: averages of averages may not represent individual differences
43
Q

what are the limitations of PET?

A
  • Expensive: ~$10,000 per scan due to the need for fresh radioactive molecules and cyclotron
  • Temporally slow: scans take 45 minutes, making it hard to capture fast, moment-to-moment activity
  • Poor spatial resolution: larger voxels than MRI, imprecise localization of radiation source, energy may be detected in multiple directions
44
Q

what are the strengths of PET?

A
  • Target specific systems or proteins: can create radio-labeled molecules to track specific systems (glutamate)
  • Useful for lifespan or condition changes: can track long-term changes (dopamine system aging)
  • can potentially be used for diagnosing Alzheimer’s by tracking protein aggregation
45
Q

what is diaschisis in PET imaging?

A
  • a phenomenon where damage to one area of the brain can affect other distant, connected regions
  • shown in PET images, as brain activity is altered in non-damaged areas due to the disruption of the connected region
46
Q

how does PET reveal dopamine activity in addiction?

A
  • PET scans show decreased dopamine activity in people recovering from addiction
  • even when not using drugs, recovery is associated with hypoactive dopamine systems
  • Dopamine D2 receptors are lower in recovering addicts
  • indicates “permanent” changes to the dopamine system, unlike other systems which recover during addiction recovery
47
Q

what is fMRI (functional magnetic resonance imaging)?

A
  • focuses on blood’s magnetic properties
    - deoxygenated vs. oxygenated blood
  • active brain areas use more ATP, requiring more oxygen, resulting in more oxygenated blood
  • lay an fMRI on top of a structural image
  • measures BOLD response - blood oxygen level dependent response
48
Q

what is the BOLD response?

A
  • BOLD (Blood Oxygen Level Dependent) response tracks the ratio of deoxygenated to oxygenated blood
  • active brain regions show more oxygenated blood
  • takes about 6 seconds for blood oxygen levels to increase after brain activity starts
  • researchers subtract 6 seconds from peak BOLD activity to find when activity started
  • usually rely on algorithms to decode BOLD responses
49
Q

how does neurotransmitter activity affect the BOLD response?

A
  • astrocytes help regulate oxygenated blood during BOLD response
  • axons signal to both dendrites and astrocytes
    1. neurotransmitters bind to dendrites and astrocytes at glutamate receptors
    2. calcium levels rise in astrocytes
    3. astrocytes signal blood vessels to dilate, bringing in more oxygenated blood
50
Q

what is paired image subtraction in fMRI?

A
  • compare two conditions with all elements the same except for the variable of interest
    - subtract common elements to isolate the effects of the variable being measured
  • quality of results depends on the quality of the control condition
51
Q

what is event-related fMRI? what are it’s limitations?

A
  • more common in fMRI studies
  • uses regression to measure the relationship between two changing variables
    - e.g., as money increases, where does BOLD activity increase?
    - don’t need to have control because we are doing regression
  • avoids the need for paired image subtraction

Limitations of event-related fMRI:
- requires repeating trials to reduce noise
- tasks need to be engaging to maintain participant focus

52
Q

what are eleven problems with interpreting fMRI?

A
  1. spatial averaging - we are averaging averages, results can be not representative of any of samples (epiphenomena)
  2. spatial resolution - voxels are 2-6mm cubed, averaging scans doubles the size and messes up resolution
  3. temporal resolution - takes scans of slices and puts them together, there is spaces in time (2-4 seconds) between the slices
  4. not necessarily necessity - neuroimaging is correlational
  5. focuses on increases in activity - we assume more activity = more cognition, but some places are more active at rest than during a task
    - found that bold responses were higher when a person wasn’t doing the task, vs. when they were doing the activity
  6. regional hemodynamics - some parts of the brain always get more blood flow, hemodynamics look different (hippocampus), need to be more nuanced with statistical procedure
  7. confounds: anxiety, boredom - **heads are sometimes locked into place, hard to stay engaged, easy to fall asleep
  8. confounds: drugs - make data more noisy, even caffeine and asthma steroids, nicotine
  9. anticipatory hemodynamics - if you make people do something repetitively, the brain starts activity before the trial actually happens
  10. reliability - test-retest to confirm, reliability is about 30% (not very good)
  11. statistics - must do a statistical test for every voxel (~60,000+), significance = p > 0.05, 1/20 is a false positive, which is a lot when you are doing a million analyses
53
Q

what is resting state functional connectivity MRI (default mode network)?

A
  • use BOLD and choose a part of the brain to be the seed region
    • compare activity in all parts of the brain to the seed region
  • look for areas that are firing and becoming quiet together, which ones are correlated (functional connectivity)
    • medial prefrontal cortex and posterior cingulate are highly correlated
  • default mode network - brain regions that are active when mind wanders
    • includes - medial prefrontal cortex, posterior parietal cortex, PCC, hippocampus, lateral temporal cortex
54
Q

what event made researchers more cautious of fMRI statistic limitations?

A
  • 1/20 is a false positive, which is a lot when you are doing a million analyses
    • found emotional activity in a dead salmon, shows false positives
  • correcting for multiple comparisons - use more conservative statistic (bonferroni)
    • if we don’t, we will get false positives
55
Q

what was the study on the heavy metal brain? what did it tell us?

A

studied resting-state functional connectivity of the default mode network (DMN) in heavy metal listeners compared to classical music listeners
- found significant differences in brain activity between heavy metal listeners and classical music listeners
- claimed that the groups had differences in tongue movement but this was not supported by actual behavioral measurements (whether they actually sing)
- no behavior was measured, so differences in brain activity cannot be directly linked to behavioral differences
- emphasizes that brain activity alone cannot be used to infer behavioral differences (need multi-methodological approach)
- study warns that comparing any two groups of people could reveal meaningful differences, but this doesn’t necessarily translate to meaningful behavioral differences