Research Methods

  1. What is MRI
    • Magnetic Resonance Imaging 
    • Uses magnetic fields, and thew reflection of radio waves to produce a picture of internal workings
    • Maps out the diffusion of molecules, mainly water
  2. What is VBM?
    • Voxel-based morphometry
    • The brain is scanned and its volume is mapped
    • This is then compared to a template which 'smooths out differences'
    • This is then used to create an image using voxels, which represent the average volume of that cell and its neighbours 
    • Used by Woollett & Maguire (2011) who found that the back part of the posterior hippocampus was on average larger in the taxi drivers compared to control subjects while the anterior hippocampus was smaller
  3. What is DTI?
    • Diffusion tensor imaging
    • Like MRI but measures the restricted movement of molecules in tissues
    • Use multiple scans to create voxels that differ on movement, speed and how much stuff moves
  4. What are the pros and cons of VBM and DTI?
    • Automated means of revealing the relationship between variations in regional brain size /white matter pathways and cognition/behaviour
    • BUT doesn't shed any light into the link between brain and behaviour, or why any increases that are observed are happening (e.g, are there more neural connections now?)
  5. What is tract tracing?
    • Inject a solution (depending on what type of tracing you're doing) into an axon, or area around 
    • Follow the solution, to see how the diffusion and connectivity in that area use 
    • For instance, in autoradiographic tract tracing you follow the radioactive signature
  6. What is Immunohistochemistry?
    • Antibodies are extracted by infecting rabbits, or by culturing cells extracted from the immune system of mice
    • These are specific to neurochemicals being produced in the brain 
    • Bath slices of the brain these antibodies are specific to, and see where they bind 
    • Use fluorescent markers to tell where the binding has occurred, and thus where the neurochemicals are being produced
    • Mostly used on animals, but some donors now donate to a 'brain bank' allowing human testing
  7. Why is it harder to see white matter than grey matter?
    • It is surrounded by myelin fat, which is opaque 
    • Up until recently we had to cut this away to see structures
  8. Why do we no longer have to slice brains up to see them?
    • We can now make myelin transparent!
    • A mesh of monomers is created to replace the opaque phospholipid bilayer 
    • A positive electrical field is generated around the cells, pulling negatively charged tissue molecules out, through active transport
    • Chung et al, 2013
  9. What is the Allen brain atlas?
    Project aimed at creating gene expression maps for the brain of mice and humans
  10. What are the advantages of tract tracing and immunohistochemistry?
    • Tract tracing allows specification of which cells which connect brain regions
    • Immunohistochemistry allows different types of nerve cells to be distinguished, even if they look the same
    • Combined tract tracing and immunohistochemistry allows circuit descriptions of the brain
    • Immunohistochemistry can also be used to identify whether cells are healthy, or not
  11. What are the disadvantages of tract tracing and immunohistochemistry?
    • Both tract tracing and immunohistochemistry require fixation of the brain, so cannot be done in live animals or humans
    • Not all neurochemicals can be studied – it depends if you can raise antibodies
    • Allows only a single snapshot of the brain, so it is difficult to study dynamical processes such as memory or perception
  12. How does human neuropsychology usually work?
    • Compare a patient with brain damage (case study), or group of patients (group study), to healthy or control brain damaged patients, on psychological tests
    • Use the results to determine if damage to a particular region is needed for a that task
    • Make inferences about the role of structures or pathways
  13. What are the advantages of neuropsychology?
    • Helps identify which brain regions are necessary
    • Allows insight into the human brain – functions like language and be studied
    • Helps understand what might be the pathology in diseases processes such as Alzhiemers or mental health problems
    • Not constrained by the lab or apparatus used–(e.g. you can study whole body motion)
  14. What are the types of genetic modification?
    • Deletions: lead to large scale neural changes and sometimes compensation, often fatal
    • Knock-downs: gene expression is reduced
    • Knock-outs: gene only silenced by particular chemicals, so only certain circuits are affected
    • Knock-ins: new genes introduced
  15. What are the disadvantages of neuropsychology?
    • Lesions are never selective
    • Compensation can occur over time. The dynamics of recovery can be complex.
    • You cannot study Brain dynamics, Global brain involvement, Interactions between regions (not easily at least) or processes such as memory encoding
  16. What is optogenetics?
    • Control of nervous activity with light.
    • Rhodopsin is light-sensitive, so uses this to trigger action potentials and cellular activity.
  17. What are animal lesions, and what are there advantages?
    • Precisely cut out parts of the brain thought to be associated with specific functioning. Watch what happens and make inferences from behaviour and activation
    • Use of animals allows repeatable controlled experiments
    • Allows precise lesions of particular areas, even particular types of nerve cells,
    • Allows reversible lesions, at specified time points
    • Helps identify which brain regions are necessary
  18. What are the disadvantages of animal lesions?
    • Compensation may occur, even for transient lesions
    • It is difficult to determine whether nerve cells contribute directly to perceptions, or are instead connected to those that do
    • You cannot ask an animal what is seeing, feeling or thinking
  19. What does tCDS do?
    • Low current delivered to area by small electrodes on skull.
    • Alleged to improve normal cognitive ability, though meta-analyses find no net effect in any direction.
  20. What does fMRI do, and what are its benefits?
    • MRI that measures concentration of deoxyhaemoglobin; so can see regions of brain that are  active during certain tasks (using a lot of oxygen)
    • Radiowaves are transmitted into the person in a magnetic field, and the re-emissions are measured
    • No radiation, and  non-invasive.
    • Good spatial resolution which remains consistent
  21. What is Magnetoencephalography?
    Detects the net electromagnetic activity (caused by ion currents) of neurons to can see which brain areas become excited.
  22. What is Electroencephalography?
    Measures electrical activity through the scalp (conduction of Action potentials)
  23. What are the advantages and disadvantages of brain imaging methods?
    • Brain imaging allows you to examine the dynamics of the whole brain – not just small regions
    • Understand how many different brain regions interact
    • Examine processes impossible with lesion approach – e.g. memory encoding
    • Understand the brain regions and networks involved in processes such as language
    • BUT Can not tell you if a region is necessary
    • Limited in the ability to understand how individual cells, or small networks of cells contribute to cognition/behaviour
    • Limited by the immobility of the equipment–e.g. can’t examine brain activity in running
  24. What is calcium imaging?
    • Fluorescent recorder picks up Ca2+ as it moves around neurons
    • Links structure to function - can deduce synaptic pathways.
  25. What is single unit recording?
    • Looks at firing rates of single neurons, using electrodes to see what neuron is firing in response to stimuli.
    • E.g. useful in epilepsy as can insert electrodes to find foci of the epilepsy/seizures.
  26. What are Multiple-unit recordings?
    • Uses spiky electrode plate.
    • Can look at 50-100 neurons at a time. Then analyses them individually or together.
  27. What is Microdialysis?
    • First, drill a small hole in skull.
    • Insert probe. Pump fluid into brain. Substances in ECF diffuse through tubing. Fluid is collected and analysed.
    • Allows assessment of neurotransmitter concentration, for example, or changes in neurotransmitter concentration during certain tasks/stimuli.
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Research Methods