Neuroscience Methods Flashcards
Methods of studying the nervous system
- Visualising and stimulating the brain
- Recording psychophysiological activity
- Invasive research methods
- Pharmacological research methods
- Genetic manipulations
X-ray techniques
The brain is mushy, with not much variability in its mushiness from one part to the other, or even between it and the fluid that surrounds it.
•Hence normal X-rays not very useful except to confirm location of foreign objects for medical purposes….
Contrast x-ray techniques
Use an injected substance known as a contrast agent
•Contrast agents provide image contrast between different bodily compartments.
•In the case of x-ray techniques it usually refers to contrast between the intravascular compartment (within blood vessels) and the extravascular compartment (everything else)
•e.g. cerebral angiography (see image)
Magnetic resonance imaging (MRI)
Put energy in via radiofrequency waves
•The energy is absorbed and then emitted in a way that gives information about the chemical properties of the tissues (mainly to do with hydrogen content)
•So MRI allow you to build up a detailed picture of brain structure that is sensitive to the differing tissue types (white matter, grey matter)
•Very high spatial resolution, but this is just brain ‘structure’
Functional magnetic resonance imaging (fMRI)
tune’ your scanner to be sensitive to something that disturbs the way the energy is absorbed and the emitted
•This something is blood, because blood contains haemoglobin, which contains iron
•The scanner can be made very sensitive to the effect of the iron in the blood on the way the energy given to tissue by the radiofrequency pulse is re-emitted
•When haemoglobin is carrying oxygen, it ‘hides’ the iron, so actually fMRI is really picking up on the oxygenation of blood in the tissue
Hence Blood Oxygen Level Dependent (BOLD) fMRI
•Activated brain cells can call up more (fresh, oxygenated) blood, so fMRI tells us about brain activity
Positron emission tomography (PET)
make a contrast agent that is specifically targeted to the biological process we want to image
•Get a chemical that binds to the target (e.g. oxygen, glucose, specific receptors)
•Attach a radioisotope (radiation emitting molecule) to that chemical (specifically a positron emitter)
•Inject this tracer (contrast agent) into the subject
•Detect the emitted radiation and use a computer to work our where it is coming from (tomography)
•Excellent for informing on specific biological processes (fMRI very limited in this respect)
•Spatial and temporal resolution poor compared to fMRI
•Uses radiation, so much more limited in research applications
EEG- electroencephalography
gives indication of regional brain activity underlying electrodes – good temporal resolution, poor spatial resolution – good for detecting signs of epilepsy
Helps to have subject in an electrically shielded environment to minimise electrical noise
•Analysis is complex and takes a lot of time!
•Signals are often separated into different frequency bands (slow wavesfast waves)
•Different frequency bands appear to relate to distinct neurophysiological processes
can be used to look at brain responses to a specific stimulus – and Event Related Potential (ERP)
MEG - Magnetoencephalography
Magnetoencephalography is the other side of the ‘electromagnetic coin’ to electroencephalography
•The electrical current of large numbers of cells and white matter tracts (bundles of axons, think wires) induces a magnetic field that can be detected with a very large and odd looking machine
•MEG signals are very small and hard to detect
•But, a little less interference by scalp & skull than electrical signals so can offer better spatial resolution than EEG
Stimulating the brain: TMS, TDCS
Induces electrical current in brain tissue which disrupts the ongoing activity
•Used in research to ‘turn off’ parts of the brain so that their role in a cognitive function can be assessed
•Hard to target precisely
•Some evidence of clinical potential (e.g. in treating depression)
Pass (mild) current through the brain, between the positively charged anode and the negatively charged cathode
•Can excite or inhibit underlying brain tissue, which may be useful experimentally
•Early evidence for cognitive enhancement effects and possible clinical benefits, but simplicity of device may risk mis/over-use
Other psychophysiological measures
Skin conductance (sweating)
•Heart Rate
•Blood Pressure
•Pupil Dilation
•Muscle Tension
•Body Language?
Invasive methods in animal models
Strictly regulated (by the Home Office in the UK)
•Requires a careful justification of how likely benefits of the research for either other animals or humans outweigh the costs
•Three guiding principles for all research involving animals (3Rs):
1.Replacement (can another method be used)
2.Refinement (can it be done in a better way that further maximises the cost:benefit equation)
3.Reduction (can it be done with a smaller number of animals)
Possibilities with invasive methods
1.Make direct measurements of the activity of brain cells.
2.Determine connectivity between structures, flow of information
3.Disrupt connectivity between structures to determine effects upon circuit function
4.Lesion specific structures to inform us about what function that structure performs
Make direct measurements of the activity of brain cells.
There are several different methods of recording activity of brain cells, some target single cells (intracellular recoding, also termed unicellular recording)
•Some record from larger numbers of cells (extracellular recording)
•The intra vs extra –cellular terminology just refers to whether the tip of the electrode is inside the cell itself (intra), where it is relatively insulated from the activity of surrounding cells
Determine connectivity between structures, flow of information
Stimulating electrodes can be inserted into one part of the brain (including into single cells) [A] and recording electrodes inserted into another region (or single cell) [B]
•The effect of stimulating the first region (or cell) [A] on the second [B] can then be determined
Alternately (or as well), we can inject tracers into a structure and map out their connection to other structures by examining post-mortem brain tissue
•Anterograde tracers……Tracer travels forward along axon towards next synapses in regions B and C
•Retrograde tracers….. Tracer travels backwards along axon towards cell body in region A
Retrograde tracers
Tracer travels backwards along axon towards cell body in region A
