PSYC 304: Midterm 3

transcranial magnetic stimulation

transcranial magnetic stimulation

briefly turns off part of brain using magnetic field coil to study what happens when there are deficits - makes “virtual lesions”

• disrupting voltage firing of local cells - magnetic pulses stimulates the nerve cells

• influences brain activity

transcranial magnetic stimulation positives and negatives

positives: improves symptoms of MDD, OCD, migraines and smoking addictions, noninvasive

negatives: expensive, not a lot facilities, minor uncomfortable neuro side effects (headaches, spasms, dizziness)

morris water maze

rat is put into a pool with opaque water and a hidden platform. time for rat to find the platform in the pool is measured many times - time to find the platform gradually decreases

• assesses spatial learning and the hippocampus (memory)

morris water maze positives and negatives

• positives: reliable, requires less training, no special motivation required

• negatives: can be stressful, may not be specific to spatial learning or memory, rodents may just float there

5-choice serial reaction time task

rat identifies which one of the 5 holes lights up - if they stick their nose in the right hole, they get a reward

• assesses attention, accuracy, motor impulsivity

• measures what happens when light flash shortens and impulsivity when rats are punished for picking a hole before light flashes

• conditioning (rats get faster)

5-choice serial reaction time task positives and negatives

• positives: tests multiple abilities, flexible

• negatives: time-intensive training, individual variation, difficult to isolate one motor function

forced-swim test

rodent is placed into a pool where they can’t escape - measures how fast they give up swimming

• measures depression, antidepressant medication efficacy

forced swim test positives and negatives

• advantages: easy to perform, sensitive to antidepressants

• negatives: learn that if they give up, they will be taken out of the pool so the giving up does not really measure poor mood; stressful for the animal

why use animal models?

• they truly model human behaviours

• mammalian brain similarity - have same divisions, similar organization (frontal cortex is smaller, cerebral hemisphere is a lot smaller)

• cognition is sophisticated - able to do many things

types of animal models

• morris water maze

• 5-choice serial reaction time task

• forced-swim test

• conditioning

• T-maze

potential routes to administer drugs to animals

• intramuscular

• intravenous

• subcutaneous

• intraperitoneal

• intraventricular

intramuscular

injections in muscles, like the shoulder (enters the bloodstream quickly)

• can leave a lot of soreness in small animals

• commonly used for medication administration

intravenous

injections into veins through catheters

• used for drug self-administration studies, replacing fluids, replenishing blood volume

subcutaneous

insertion of medications beneath the skin (cutis, below dermis and epidermis) by injection or infusion

• intended for slow, sustained rates of absorption (faster than intradermal injections), medication that can’t be taken orally

• ex. insulin, live vaccines

intraperitoneal

injection of a substance into body cavity (peritoneum)

• most often for animals, preferred when large amounts of blood replacement fluids are needed or problems prevent use of intravenous injection

• chemo for some cancers, infant peritoneal dialysis

intraventricular

injections into ventricles

• bypasses blood-brain barrier to central nervous system

• in animals, used to study effects of drugs, plasmid DNA, viral vectors in central nervous system

• in humans, treats spinal muscular atrophy, chemo in gliomas, drugs for long-term pain

best ways to test drugs on animals?

• multiple doses - saline → low → medium → high

• within-subjects design - test all conditions with one animal

• placebo = vehicle (saline)

invasive electrophysiological recording methods

• intracellular unit recording

• extracellular unit recording

• multiple-unit recording

• invasive EEG recording

stereotaxic surgery

procedure that uses 3D coordinate equipment to precisely locate and treat targets inside the body

• used for creating lesions, optogenetics, electrodes - allows accurate placement

• employs stereotaxic atlas (brain structure records for a specific animal) and instruments (helps to precisely locate brain sections)

• bregma = reference point

stereotaxic surgery positives and negatives

• positives: fewer risks because there are no surgical incisions, minimizes damage in hard-to-reach places

• negatives: small errors can be more impactful, shape of cerebellum can make surgery difficult in medulla and upper spinal cord

lesion types

• chemical - excitotoxic lesions

• selective chemical lesions

• reversible lesions

chemical - excitotoxic lesions

neurons damaged by over-activation of glutamate receptors

• spreads out evenly over a specific area, too much excitation can destroy neurons

• used to test drug treatments, neurotrophic factors, fetal neuronal grafts

Selective neurochemical lesions

Target specific cells in the brain, not entire areas

• 6-hydroxydopamine, 5, 7-dihydroxytriptamine (targets serotonin and its receptors)

• study brain function - indicates neuronal and axonal loss or dysfunction

Reversible Lesions

temporary inactivations of certain brain regions

• place a cannulae in brain to directly inject drug to specific brain region

• within-subjects: each rat can be case and control

• ex. baclofen + muscimol (GABA agonist, temporarily inhibit)

optogenetics

uses light to control activity of cells, tissues, organs with high temporal and spatial resolution

• light-gated ion channels (channelrhodopsins) - open with light, triggers APs

• use system-specific transcription factors (proteins expressed in only one area)

• can be used for recording/mapping and manipulation

positives and negatives of optogenetics

• positives: spatial and temporal resolution, can manipulate specific genes, noninvasive

• negatives: expression patterns are limited, can stimulate tegmental area, can cause widespread changes, inefficient

golgi stain

silver staining technique that is used to visualize nervous tissue under light microscopy

• see neurons in clear detail

• characterize structure of different types of neurons

• takes a long time and is very inconsistent

nissl/cresyl violet stain

stains nissl, or the rough ER of a cell - gives cytoplasm a mottled appearance

• useful for distinguishing neurons and glia from one another, study arrangement of neurons

• detail of the neurons is not captured

fibre stains

Luxol-fast blue (LFB) and Toluidine blue

• observe myelin and white matter, stains tissue rich in DNA and RNA

green fluorescent protein

protein found in jellyfish and inserted into mammal brains to track gene expression and protein targeting - can track cells fate

• very stable and can be visualized in live cells, so dynamic behaviour can be observed

types of stains

• golgi stain

• nissl/cresyl violet stain

• fibre stains

• green fluorescent protein

neuroimaging

captures brain structure and function - can’t definitively determine causality

• non-invasive

static neuroimaging

stationary representation of the brain, measures brain’s intrinsic functional architecture - doesn’t measure activity

• X-Ray

• CT

• MRI

• DTI (form of MRI)

• doesn’t capture fundamental differences in brains (Younger vs. older brains, high vs. low SES)

x-rays

use invisible electromagnetic energy beams to produce images of internal tissues, bones, organs

• help diagnose tumours, bone injuries

• fast, cost-effective, visualize bones, noninvasive

• radiation exposure, can’t really visualize soft tissues, don’t know what is actually going on

CAT/CT scan

computerized axial tomography scan, noninvasive imaging using X-rays creating detailed pictures of inside of the body

• type of X-ray

• scanner takes multiple images of the brain from different angles, which are then set to a computer - analyzes radiation absorption patterns

• used for: assessing for brain tumours/other lesions, detect clots in the brain, guide biopsies of brain tissue

• can’t easily resolve white vs. grey matter, easy to implement but not useful for research

MRI scan

uses a large magnet and pulses of radio waves to scan 3D images of the brain (measured in voxels), producing images of brain structures - noninvasive

• detailed images

• electric current passed through coiled wires to create a magnetic field - sends and receives radio waves

• more accurate than CT scans - examines macrostructure and microstructure, detects abnormalities

how does an MRI scan work?

1. each hydrogen atom’s proton rotates about its axis with its own north-south dipole - normally protons are randomly diffused

2. when placed in a magnetic field, protons align in parallel

3. radio frequency pulse applied to tissue pushes protons to their sides, causing them to wobble about their axes

4. this motion is caused precession, which produces measurable vertical and horizontal fields

DTI scan

type of MRI that measures the movement of water molecules in tissue to create detailed images of brain and spinal cord

• difference in how water moves parallel to and perpendicular to nerve fibres (diffusion anisotropy)

• detailed images of brain’s white matter, direction of diffusion flow (identifies injuries and abnormalities)

• Diagnoses stroke, brain tumours, MS, TBIs, concussions

• More detailed than standard MRI - shows actual nerve tract

• helpful for white matter disorders - schizophrenia, psychopathy

dynamic/functional neuroimaging

captures ongoing neuro processes like blood flow through imaging technique that captures sequential images

• PET

• fMRI

• rsfcMRI

Positron Emission Tomography (PET)

nuclear imaging technique that uses radioactive tracers to visualize/measure metabolic activity of cells in tissues and organs

• uses a very tiny amount of radio-labelled cocaine, parts of the brain with the most dopamine light up the most

• need multiple sessions to subtract baseline from experimental condition

PET advantages and disadvantages

• advantages: useful for targeting specific systems (ex. DA)

• disadvantages: very expensive, temporally slow, poor spatial resolution

fMRI

non-invasive brain imaging technique that measures brain activity by detecting changes in blood flow

• oxygenated blood vs. deoxygenated blood - more oxygenated blood should be going to more active areas (BOLD response)

• see a curve in brain activity called hemodynamic response - after 6 seconds, there is a peak in oxygenated blood

fMRI BOLD response

blood-oxygen-level-dependent signal, reflects changes in brain blood flow and blood oxygenation

• astrocytes are causing differences in blood - causes an increase in calcium and dilates the blood vessels = increase in blood flow

paired-image subtraction

technique that involves subtracting one image from another to highlight differences between them (position, colour, brightness, shape)

• determine what is actually operating, not just baseline activity

• quality of results depends on quality of your controls

• as control gets more specific, activity in brain decreases

• utilized with fMRI

event-related fMRI

do not need a specific control condition, just need many iterations of the same variables to measure one area of the brain - avoid paired image subtraction

problems with interpreting fMRI studies?

• spatial averaging: averages do not represent any individuals

• spatial resolution: getting a millions neurons in one Voxel

• temporal resolution not as fast as other methods

• focuses on increases in activity and some regions are more active at rest

• incorrect interpretations due to bold responses

• anxiety and boredom confounds

• psychoactive drugs (nicotine, caffeine) hard to control for

• anticipatory hemodynamics shifting response earlier

• low reliability

• false positives

the heavy metal brain (Sun et al., 2017)

studying functional connectivity networks of heavy metal vs. classical music lovers - found significant differences, but if any study has significant sample size, differences will be significant

• made poor assumptions about why brains were different, data not fitted to make assumptions about behaviour