• History of neuroscience
• Levels of analysis
• Methods to the madness

• A. The brain has more parts than any other physical entity we know about.
• B. Physicists have largely ignored biology.
• C. Nervous systems are influenced by multiple factors we can’t (yet) measure effectively.
• D. Physicists only study “toy” problems.

• A. The brain has more parts than any other physical entity we know about.
• B. Physicists have largely ignored biology.
• C. Nervous systems are influenced by multiple factors we can’t (yet) measure effectively.
• D. Physicists only study “toy” problems.

• A. Boundaries
• B. Components
• C. Interactions among components
• D. Inputs and outputs
• E. Readily predictable behavior

• A. Boundaries
• B. Components
• C. Interactions among components
• D. Inputs and outputs
• E. Readily predictable behavior

• What can observation tell us about brain and behavior?
• Vital role of tools/methods/techniques in discovery
• “If I have seen further, it is by standing on the shoulders of giants.” – Isaac Newton, 1676

• Mental functions controlled by organs in the head, i.e., the brain
• Mental functions can be influenced by substances we consume
• Head injury can impair behavior and thinking
• Something flows from brain to body via nerves

• A. Limited technology.
• B. Limited cultural support for systematic observation & description. = SCIENCE
• C. Lack of ability to use knowledge even if it were acquired.

• Reflexes “reflect” events in the world
• Not the same as voluntary functions

• Reflexes and animal “minds” are physical, machine-like
• Human mind is not
  • “Dual” influences on behavior
  • Physical + spiritual
• Soul controls body via pineal gland
  • Causes muscles to “inflate”

• A. Yes, human minds are fundamentally different from animal minds. The human mind is influenced by both physical and extraphysical processes.
• B. No, human minds are similar to animal minds. The human mind arises solely from physical processes.

• Neuroscience shaped by new methods, tools
• Neuroscience shaped by great debates
  • Mind == brain debate
  • Are functions local or distributed?
  • Do neurons connect like pipes or pass info like relay runners?
• Forms at multiple levels of analysis contribute to function

• What’s a micro (spatially small) influence on/aspect of behavior?
• What’s a macro (spatially large)…
• What’s a micro (temporally short)…
• What’s a macro (temporally long)…

• Different methods, different levels of analysis
• Challenge of linking phenomena across levels
  • How does the micro affect macro or vice versa?
• Challenge of interpretation

• Tools in the neuroscientist’s toolkit
• What they tell us, and what they don’t

• What question does method X answer?
• What are we measuring?
  • Structure
  • Activity
• Strengths & Weaknesses
  • Cost (time/$)
  • Invasiveness
  • Spatial/temporal resolution

• Structural
  • What are the parts?
  • How do they connect?
• Functional (next time)
  • What do the parts do?

• Cell/axon stains
  • Golgi stain – whole cells
    • Camillo Golgi
  • Nissl stain – cell bodies only
    • Franz Nissl
  • Cellular distribution, concentration, microanatomy

• Soak tissue in Potassium Dichromate (\(K_2Cr_2O_7\)) then apply Silver Nitrate (\(AgNO_3\))
• Complete nerve cells, but only 1-5% of total
• Santiago Ramon y Cajal argued for neuron doctrine, shared 1906 Nobel Prize with Golgi

• Only cell bodies
• Density of staining ~ cell density/number

• Neuron information flow polarized–flows in one direction
  • ≠ electronic wires, but like pipes
• Retrograde (from axon terminal to cell body)
• Anterograde (from cell body to axon terminal)

“If understanding everything we need to know about the brain is a mile, how far have we walked?” – J. Lichtman

(National Geographic, 2014)

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• Pros:
  • High spatial resolution
• Cons:
  • Poor temporal resolution
  • Invasive

• Computed tomography CT
• X-ray based

• Magnetic resonance
• Some common isotopes (e.g., H) & complex molecules have a magnetic dipole
• Axes align with strong magnetic field
• When alignment perturbed by radio frequency (RF) pulse, speed of realignment varies by tissue
• Realignment emits RF signals
• How MRI works

• Structural
• Functional

• Reveals tissue density/type differences
• Gray matter (neurons & dendrites & axons & glia) vs. white matter (mostly axons)

• Type of structural MRI
• Measures patterns of movement/diffusion of \(H_{2}O\)
• Reveals integrity/density of axon fibers
• Measure of connectivity

• Voxels (volume-based elements)
  • like pixels in an image, but volumes of tissue
• Morphometry, measure (“metry”) form/morphology
• How does brain size or thickness vary by age, disease status, etc.?

• Spatial vs. temporal resolution
• Structural methods (parts, sizes, connectivity)

• Functional neuroscience methods