Neuroscience Methods 1

What are neuroimaging methods important for?

What are neuroimaging methods important for?

• techniques important for research into causal mechanisms in the brain for cognition and behaviour

• advent of neuroimaging techniques gave rise to field called cognitive neuroscience

CT - computed tomography

• based on X-rays → high energy that can penetrate tissue

• measures tissue density (contrast medium)

• scans brain

• parts that are more dense in tissue will block more X-ray light

How does a CT machine work + what does it scan?

• CT scan has a big ring + bed where patient lies on

• machine includes X-ray source which sends X-rays to other side of the ring (taurus)

  • detectors located on either side → patient will partially block X-rays

• ring rotated around the body → body illuminated from all sides

• body can shift through taurus for 3D scan of the body

• raw data = tissue density as measured by an X-ray bundle that is rotated around the body

  • data collected from all angles → computer can calculate an image

• white and grey matter + cerebrospinal fluid + skull + skin = can be seen

What are the advantages and disadvantages of CT scans?

Advantages:

• not very expensive

• available everywhere

Disadvantages:

• high energy electromagnetic waves are damaging

  • X-rays can cause DNA mutations

what is the physics of MRI machines?

MRI targets hydrogen atoms. H is a proton. The proton has an electrical charge, and since it spins around its axis with a given frequency, this leads to a magnetic field, with a North and South pole

• all organic molecules in the body contain H atoms

• normally (outside scanner) H atoms are randomly oriented in tissue

• consequently there is no net magnetic vector

How do MRI machines work?

• MRI scanner has very strong fixed magnet

• H atoms in the body are forced to align their orientation to its field

• adapt their spinning frequency to the strength of the magnetic field its in

• scanner produces a pulse of electromagnetic (radio) wave → matches frequency of spinning atoms

• forces part of the atoms to flip their alignment to a high-energy state (in the opposite direction → resonance)

• radio wave input is switched off → high-energy atoms start to flip back

  • this process generates a radio wave of the exact same frequency as the input wave

• MRI machine can “listen” to this echo and determine when it occurs and how strong it is

• after a while we are back where we were and ready to send in new radio pulse

How do we localize in an MRI scanner?

• on top of the strong main magnetic field, we apply smaller magnetic gradients in 3 directions (x,y,z)

  • separates and determines the exact spinning frequency of the H atoms according to the location in 3D space

How can we use this to create an image?

• echo strength relates to amount of H atoms, which is different in different tissues

• timing of the “flipping” back process and this of the echo depends on the organic compound/tissue that the H atom is stimulated in

  • lipid: fast

  • water: slow

What are some of the different types of MRI images?

• PD: proton density (how many protons are present)

• T1: realignment with magnetic field

• T2: misalignment of phases due to spin - spin interactions (true T2)

MRI: the big magnet → why?

• 1 Tesla (1) = weak scanner → 10,000 Gauss

• Earths magnetic field → 0,5 Gauss

• Standard scanner = 3 Tesla

  • main magnetic is continuously on (can be very dangerous)

What are the advantages and disadvantages of MRI?

Advantages:

• not invasive/no damage

Disadvantages:

• metals are dangerous

• more expensive than CT

Functional imaging techniques

try to localize function of cognitive processes

Positron Emission Tomography (PET)

• based on injecting some compound in a subject

  • compound is radioactive

  • emit a positron (opposite of an electron)

  • decaying in your body → emits positron

• if positron meets electron → 2 photons generated

  • travel in opposite directions of the travel direction of the positron

• taurus (ring) with detectors → detect when photons hit the ring

What are the advantages and disadvantages of PET scans?

Advantages:

• wide variety of questions

• trace specific metabolites

• various timescales

Disadvantages:

• radiation exposure

• inconvenience

• limited resolution

• expensive

functional MRI

• neural activity requires energy (glucose)

• increased activity leads to increase in blood flow (blood response)

  • oxygen carried by haemoglobin in blood

  • deoxyhaemoglobin affects MRI T2*, which can be measured over time

    • deoxygenated state: gave its oxygen to local tissue (got rid of oxygen)

    • deoxyhaemoglobin = magnetic → locally affects MRI image

BOLD response

B = blood

O = oxygen

L = level

D = dependent

• blood necessary to supply energy (glucose)

• glucose consumption exceeds oxygen consumption, hence surplus in oxygen

• note time scale

Hemodynamic response function (HRF)

• note time scale of BOLD signal after brief activation → limits temporal resolution

• BOLD is largely associated with neuronal input (synaptic graded potentials), not output (action potentials)

Subtraction Principle in fMRI

1. absolute signal is meaningless → two or more cleverly chosen conditions must be compared

2. Signal levels in two or more conditions subtracted, use of some static

3. Any location in which difference passes a carefully determined threshold, is considered real (”activation”)

4. findings noted down, and published

Advantages and Disadvantages of fMRI

Advantages:

• easily accessible

• non-invasive

• good spatial resolution (mm) and moderate temporal resolution (s)

• data easy to interpret

Disadvantages:

• indirect measurement of neural activity (blood oxygenation)

• awkward environment

• low signal to noise ratio

Transcranial Magnetic Stimulation

• hold coil to the outside of a person’s head and produce a very strong electromagnetic pulse

  • create a brief electromagnetic field by having large electrical current through the coil

  • start and stop current = production of magnetic field (momentarily)

• induced strong field in a small part of the head

  • leads to ion currents in the brain → electrical and respond to magnetic field

• consequence of magnetic pulse → random

  • lot of Kerns mess things up locally

  • deduce what does function/functions differently after “messing up”

What is TMS?

• relatively new (1985) technique that induces current in the brain by using a magnetic field outside the skull

• can induce muscle twitch or phosphenes, or disrupt activity

• not an imaging technique, but allows inferences about the necessity of activity for a given task

• an experimental treatment for some psychiatric/psychological and neurological disorders

How TMS works:

1. large but short magnetic field transports electrical signal through the skull

2. short electromagnetic pulse creates large magnetic influx, and in turn induces current

3. current evokes neural activity

Practical considerations

• coil shape

  • target larger or smaller areas

• stimulation depth

TMS Mechanisms

• TMS causes synchronous activity of some subpopulations of neurons that are sensitive to the orientation of the coil

• two important effects:

  1. direct activation of motor/visual areas

  2. disruption of ongoing activity (virtual lesion)

Advantages and Disadvantages of TMS

Advantages:

• reversible lesions

• moderate spatial and high temporal resolution

• ability to show causality

• non-invasive, subjects are conscious, repeatable

Disadvantages:

• uncertainty

  • which neural elements most sensitive

  • exact location

  • exact extent

• long term effects rTMS (safety)

• only regions near the skull can be targeted