Tools in Neuroscience

Question 1

Most Common Approaches When Designing An Experiment In Behavioural Neuroscience?

Answer 1

1) Induce a loss of function (eg. patients with strokes, using antagonists)
2) Induce a gain of function (eg. using antagonists)
3) Monitor behaviour and brain activity simultaneously (not a true experiment, correlational)

Question 2

Scales Used in Brain Imaging

Answer 2

• Spatial Resolution : The ability to observe the detailed structure of the brain
• Temporal Resolution : The ability of an imaging technique to track changes in the brain over time

Question 3

Recording the Brain’s Electrical Activity

Answer 3

• All processes in the brain are electrochemical by nature
• Single-cell recording:
• • Quite invasive
• • Intracellular…
• • Tells you which one specific cell
• • Population Coding : we have to use a lot of cells (rostral plots)
• Extracellular…
• • Much easier than intracellular
• • Use the polarization to see if inside or outside the neuron (positive means outside, negative means inside of the cell)
• • Action potential is flipped upside down because it’s outside the cell
• • Electrode is getting information from many cells (from neighbouring cells) as well which tends to be an advantage
• • Use multiple to help decode it all (you are measuring the difference)
• Electroencephalography (EEG)
• Event-related potentials (ERP)

Question 4

Describe Convergence and Divergence

Answer 4

• Generally the brain uses parallel processing, distributed representations and population coding… but,,,
• Study : Halle Berry Neuron
• • Some high convergence in the brain
• • Probably still involved in the brain
• • Participants had medial temporal lobe epilepsy
• • Epilepsy –> no brain is better than bad brain, so remove the tissue that is causing the seizures if meds are not working
• • Easiest way to discover which brain tissue is bad by using electrodes
• • In the study, a specific neuron was firing every time the participants saw Halle Berry. and didn’t fire for anything else

Question 5

What is EEG?

Answer 5

• Measuring from the scalp (limitations?)
• Waves have both a frequency and amplitude
• Frequency measured in Hz (cycles/second)
• Steps…
• • Electrodes are attached to the skull, corresponding to specific areas of the brain
• • Polygraph electrodes are connected magnets, which are connected to pens…
• • … that produce a paper record of electrical activity in the brain. This record indicates a relaxed person

Question 6

EEG : Brain States – Explain

Answer 6

• As you get deeper sleep, frequency decreases and amplitude increases
• Alpha (8-12Hz), beta (12-30Hz), gamma (26-100Hz), delta (0-3Hz), theta (4-7Hz)
• Directly related to your action potentials firing frequency
• Larger amplitude means that neurons are firing more in sync (stacking up on each other), smaller means opposite

Question 7

EEG : Gamma Waves – Explain

Answer 7

• “Information processing”, attention, maybe consciousness
• Meditation : highest amplitude gamma recorded (meditating monks)
• • Gamma changes with skill level
• Rhythm possibly mediated by fast-spiking, GABAergic interneurons
• • Play a key role in synchronizing neuroactivity

Question 8

What are ERPs?

Answer 8

• Averaged response to a stimulus → have participants do the same task over and over again
• Electrical activity can be converted into a colour representation showing the hot spot for the visual stimulus
• Subcomponents
• Assume difference in brain processes
• P1 (first positive amplitude), P2 (second), etc.
• N1 (negative amplitude) → related to memory (a deeper N1 is something you’ll remember more)

Question 9

What is Transcranial Magnetic Stimulation?

Answer 9

• Usually to make “virtual lesions”
• Potential therapeutic applications
• Can increase brain activity temporarily in a certain area
• Using a magnetic field to cause changes in the voltage of these neurons
• Non-invasive

Question 10

Examples of Studies Using Rats

Answer 10

• Morris water maze : milky white water (opaque), put rat in water and they try to get out because they don’t like it, artificial signals around the room (spatial cues), eventually stumble upon a hidden platform just under the water, the rat steps up on the platform to be dry → after a while, the rat will always go to the platform no matter where you put it requiring spatial navigation
• 5-choice serial reaction time task : continuous performance task, measure of impulsivity and visual spatial attention (?), if the rat pokes its nose in the hole that lit up, if the light is on for long it’s easy (otherwise hard), intertrial interval changes
• Conditioning (classical, operant) : Classical gives no control to animal, operant gives animals control
• T-maze
• we infer cognitions through changes in behaviour*

Question 11

What is the forced-swim test (FST)?

Answer 11

• The Forced Swim Test (FST) : place mouse in water where it can’t escape, see how long the animal swims until it can’t anymore (supposed to measure depression - animals that give up quickly were the animals that were not clinging to life), then researchers take it out
• FST used to measure depression in the rodent, as well as antidepressant medication efficacy
• Difficulties in interpretations → rodent will learn that if you stop swimming you’ll be taken out so they stop swimming right away (within-subjects), also lacks validity

Question 12

What is the Drug “Challenge” (amphetamine)?

Answer 12

• Intramuscular (IM) : injecting into muscle
• Intravenous (IV) : injecting into a vein
• Subcutaneous (SC) : injecting under the skin –> absorbs very slowly
• Intraperitoneal (IP) : –> perhaps most common
• Intraventricular : Injecting into the ventricles of the brain –> overcomes problems w drugs passing the blood-brain barrier
• Multiple doses is best (eg. saline only, then low, med, high) –> within subjects design

Question 13

What is the only part that tends to be very different between rats and humans?

Answer 13

Prefrontal cortex

Question 14

What are Four Invasive Electrical Recording Methods?

Answer 14

Electrophysiological Recording Methods…

1) Intracellular unit recording
2) Extracellular unit recording
3) Multiple-unit recording
4) Invasive EEG recording

Question 15

What is Stereotaxic Surgery?

Answer 15

• For lesions, optogenetics, electrodes, more
• Employ stereotaxic atlas and instrument
• Allows accurate placement of lesions, probes, electrodes, etc.
• Reference point used is bregma

Question 16

What are the Three Lesion Methods?

Answer 16

1) Chemical Excitotoxic Lesions : Causes really high glutamate neuron activity (letting too much calcium into the cell), can do w electricity but rarely used
2) Selective Chemical Lesions : Damaging specific system, ex. 6-OHDA - only affects dopamine (mimics Parkinson’s disease), 5,7-DHT - only affects serotonin (very upsetting to rats)
3) Reversible Lesions (aka. Inactivations) :
- - Temporarily shut off part of the brain
- - Either give them vehicle only (control), or give them a tiny amount of a drug that will temporarily shut off that part of the brain
- - Give them GABA agonists (a and b) –> e.g. baclofen + muscimol
- - Benefit - within-subjects design!

Question 17

Explain the difficulties of lesion studies

Answer 17

• A bunch of tissue on the way in get damaged as well so it might be screwing up your data
• Rats are super resilient meaning if you’re doing a legion, you can’t wait long because rats recover quickly
• Can’t start too early for pain medication

Question 18

What are Unilateral vs. Bilateral Lesions?

Answer 18

Unilateral have much milder effects and changes in behaviour, often need bilateral to get what you need

Question 19

What is Optogenetics?

Answer 19

• Introducing: light-sensitive ion channels (when photons hit them they induce a change in the shape of them and light goes through them - “photoreceptors”)
• Allows sodium to go through —> causing EPSP
• Pluck out that protein and put it in someone’s brain and when you shine light you’ll activate their brain —> induce gain of function
• Use system-specific transcription factors (things in front of the gene and that predicts how the gene will be transcribed —> predicts what parts of the brain the protein will be expressed in)
• Can be used for both recording/mapping and manipulation

Question 20

Structural Vs. Function Neuroimaging

Answer 20

• Static (Structural) : Single image…
• • Computerized axial tomography (CAT/CT)
• • Magnetic resonance imaging (MRI)
• • Diffusion tensor imaging (DTI)
• Dynamic (Functional) : Recording brain activity over time (or proxy for brain activity)…
• • Positron emission tomography (PET)
• • Functional MRI (fMRI)
• • Resting-state functional connectivity MRI (rsfcMRI)

Question 21

What is a Cerebral Angiography (aka. an angiogram)?

Answer 21

X-ray, inject some kind of contrast agent into the blood (a die of some sort like iodine), useful when someone has had a stroke

Question 22

What is Computed Tomography (CT)?

Answer 22

Many different x-rays at different angles (3D image)

Question 23

What is Magnetic Resonance Imaging (MRI)?

Answer 23

• When our atoms are put into a very strong magnetic field, they will align
• Knock them off their alignment, and then they return to the original alignment and when they relax and return they release energy that is recorded
• Benefits : Very detailed, high resolution, can distinguish between white and grey matter

Question 24

What is Diffusion Tensor Imaging (DTI)?

Answer 24

• Variant of MRI, relies on how water molecules move in the brain
• Which way is water randomly moving? A lot of the time it goes along the length of an axon and give you a map of white matter (all the myelinated axons)

Question 25

What is Positron Emission Tomography (PET)?

Answer 25

- Injecting a mildly radioactive tracer in the body (often glucose), and then it travels around giving you a heat map (hotter places have more glucose), the places that have more glucose are more active (bad temporal resolution) - Positrons from the radioactivity are released; they collide with electrons in the brain, and photons are produced - Useful for targeting specific systems (eg. dopamine system) - Subtraction method → you take all difference images and get the mean difference image

Question 26

What is the Functional MRI (fMRI) and the BOLD response?

Answer 26

- Oxygenated and deoxygenated blood have slightly different relaxation rate → changes response to MRI - This is called our blood oxygen dependent response (BOLD) - About 6 seconds after a part of your brain is very active, a lot of oxygenated blood rushes there - Uses paired image subtraction method (subtracting 6 seconds) --> quality of your results depends on the quality of your controls! - The BOLD response is cause by astrocytes - - Axon releases glutamate onto dendrite, astrocyte is around the edges (tripartite synapse) - - Astrocytes also have glutamate receptors - - When glutamate binds to the receptors on astrocytes, it causes the astrocytes to dilate the blood vessels and bring more oxygenated blood to the area

Question 27

What are problems with interpreting fMRI studies?

Answer 27

1) Spatial Averaging : Epiphenomena (results that aren’t real, or don’t reflect what actually happened - average isn’t representative) 2) Spatial resolution 3) Temporal resolution : Measured in seconds, up to 500 action potentials happen per second, can’t show moment to moment changes 4) Not necessarily necessity : In many fMRI studies, you get a lot of brain activity (even with controls) 5) Focus on increases in activity —> People's brains are much less active while in the fMRI doing the task, mind-wandering - - Resting State Functional Connectivity MRI, participant goes in MRI and does nothing, take seed region (region of interest), when it’s more active what other regions are also more activity (how about when it goes down?) - - The default mode network is the most commonly found active network during mind wandering —> Medial prefrontal cortex, posterior cingulate, lateral parietal cortex - - fMRI for Cognition (large overlapping maps in terms of different tasks) 6) Regional hemodynamics : Different regions of the brain have different hemodynamics - - Ventromedial Prefrontal Cortex is very hard to study because it’s close to a big sinus in your head and the big pockets of air mess with the info 7) Confounds : anxiety (not comfortable), boredom (hundreds of trials) 8) Drugs : caffeine, antidepressants, puffers, etc. 9) Anticipatory hemodynamics : when you do a task a lot of times, your brain predicts or knows in advance that a certain brain region will be activated meaning your brain will send blood and it will be activated earlier 10) Reliability : test retest, or within different studies, low reliability (30% voxels repeat) 11) Statistics : statistical test on every single voxel in the brain, .05 is the threshold so there’s a lot of false positives and false negatives on the t-tests

Question 28

What's wrong with the heavy metal brain study?

Answer 28

- Wanted to know how the brains of heavy metal music lovers are different from others - Control group was classical music lovers —> weird - Only performed resting state connectivity MRI —> didn’t do any psychology or tasks, only brain stuff