6. Methods

• Spatial resolution


  Ability to differentiate two points from each other. Imaging method with high this can detect two very close signals as distinct, instead of as one
• Temporal resolution


  Ability to distinguish two moments in time in imaging; high this means detecting two signals at the same place microseconds apart
• Scientists use humans as subjects for studies because they are the only way to develop actual treatments, do what you say much more easily, and are cheaper than raising a colony of rats or monkeys
• Model organisms


  Non-human scientific test subjects with the eventual goal of the research being done on them getting applied to humans
• Animal test subjects don't have very strict ethical guidelines meaning a broader range of possibilities, they perform things that humans don't (like flying or slithering) and are completely controlled their entire lives, eliminating personal experience bias
• WEIRD


  Acronym for people who are western, educated, and from rich democratic industrialized countries
• Phrenology


  Pseudoscience popularized by Franz Gall in the 1860s describing how we can predict a person's personality by the shape of their skull
• Paul Broca


  1860s neurologist who noticed a connection between a person's language deficits and an extremely localized brain injury
• Localization of function


  Idea that certain parts of the brain are necessary for specific function
• CT scan


  3D X-ray that revolves around a person as they move through a scanner then is compiled with a computer into a 3D model of the brain that can be assessed from any angle
• CT scans have a spatial resolution of 0.5 mm and and don't really care about temporal resolution because the structures being examined are generally for diagnostic changes over the course of days (like assessing healing or tumors)
• CT scans identify tissue density easily so is good for detecting meningitis, tumors, and hydrocephalus
• CT scan:

  • noninvasive, quick --> rapid diagnosis and easy observation
  • X-rays = mutagenic --> might lead to cancer if done too much, so only if info from scan is more important than a few extra months of background radiation
• X-rays


  High-energy beams of electromagnetic radiation that are capable of passing through many physical objects, disc. 1895
• X-ray scanning tech uses radiographic film that darkens when it by the rays, so air turns black, bones stay white, and tissue is shades of grey
• Diffusion tensor imaging


  DTI
• Computerized tomography scan


  CT scan
• Isotropic diffusion


  When a single molecule in a cup of water can move in any direction
• Anisotropic diffusion


  Type of water molecule movement observed in white matter tracts that are detected in DTI scans
• DTI

  • can give good spatial resolution and doesn't need temporal resolution
  • Cannot give us info on directionality of axonal projections
• DTI


  Uses MRI technology to detect and quantify the movement of water molecules to differentiate white matter from gray matter
• CLARITY


  Revolutionary 2013 technique by Karl Deisseroth that creates a perfect anatomical mold of the brain by flushing the entire thing with a gel matrix then dissolving all the lipids so that the light isn't refracted wrong
• CLARITY cannot be used on a living brain because it basically destroys the entire thing to get a mold with no functionality, but it's extremely useful for learning anatomy
• Patient tan


  Paul Broca's patient with severe damage in a specific part of the brain that let him only be able to say the word tan
• In vivo


  Experimenting on living organisms, which is good for realistic results but there are more ethical guidelines and a bunch of other unknown or uncontrollable bio factors at play
• In vitro preparation


  Experiment run on cultures of cells or isolated biomolecules in glass dishes with basically no ethical limitations but are less reliably able to be applied in therapies
• Ex vivo preparation


  Experiments run on dead organisms or parts of dead organisms
• Electroencephalography


  EEG
• EEG


  Attaching electrodes to patients head to see if any large wide-spread action potentials on the surface of the brain can be detected. Temporal resolution of 10000 hz, but only spatial resolution up to 7 cm3, at the full 128 electrodes. It is relatively cheap and can be fit into a backpack
• EEG: gel is applied to small patches of scalp, which is basically NaCl gel to be a conductor for the electrodes to get better signals. 20 - 128 electrodes can be placed, each one able to detect deflections as small as 10 microvolts. They feed into a computer, which then tells you which parts of the cortex were active and when
• The brain can have very large electrical charge changes, like when millions of neurons reach action potential at once. These currents produced on the cortex (surface) can be so large that they are detectable from the surface of the head, which is where EEG scans are used
• Positron emission tomography


  PET scan
• Tracer


  Radioactive compound where an atom is substituted with a radioactive isotope used in PET scans. FDG is a glucose analog, and because tumors take more energy, FDG concentrates at the tumor, which is how it's detected
• PET scan downsides:

  • exposure to radiation
  • bad spatial and temporal resolution (impossible to get more precise than a cm)
  • Difficult to tell differences in tissue even when drastic, so they're usually overlayed with a CT scan
• PET scan tracers emit positrons, and when they interact with nearby electrons two gamma particles are emitted in opposite directions, so then the scanner can trace where they came from
• fMRI advantages:

  • can operate while a person is engaged in a task so can measure what parts of the brain activate for stimuli
  • works on super strong magnets so no radiation
• fMRI


  When particles are under magnetic field align ether towards or directly against it --> when it by radio waves they lose their alignment and high energy state --> some are more affected by others based on blood concentration so we measure that
• Functional magnetic resonance imaging


  fMRI
• Blood oxygenation level-dependant signal (BOLD) shows changes in blood flow, which is related to the activity of neurons, and so helps us see which parts of the brain are getting activated in an fMRI scan in real time
• Diamagnetic


  Sensitive to a magnetic field