History, levels of analysis, methods
2025-08-26
“If understanding everything we need to know about the brain is a mile, how far have we walked?”
“About three inches.”
National Geographic (2014)
Trephining (trepanning)
- Deliberate creation of openings in the skull
- Earliest evidence +7,000 yrs old
- Q: Why did they do this?
- A: Treat head injury, epilepsy, mental disorders, release evil spirits
Egyptians (1,500-3,000 BCE)
- First written (hieroglyphic) record of the term “brain”
Beer-making (~2-5,000 BCE)
- Speculate: What might beer-making have to do with the neurological bases of human behavior?
Greek and Roman era
- Hippocrates
- “Father of Medicine”; Hippocratic Oath
- Brain seat of intelligence (Chudler, n.d.-a)
- Epilepsy a disease of the brain (Chudler, n.d.-a)
Aristotle
- Aristotle (~335 BCE)
- mind and body not distinct
- brain “cools” the body, heart is the mental organ
Galen (~177 CE)
- Physician in Roman Empire, of Greek descent
- Anatomical reports based on dissection of monkeys, pigs
- Influenced by Hippocrates’ notion that human temperaments (~personalities) linked to “humors”: blood, black bile, yellow bile, phlegm
Galen (~177 CE)
- Observed that gladiators’ head injuries impaired thinking, movement
- Speculated that fluid filling the brain cavities called ventricles, circulates through nerves, body
- “Ventricular” theory of nervous system function
Leonardo da Vinci (~1508)
- Wax casts of ventricles
- Ventricles not spherical!
- Better “measure” \(\rightarrow\) more precise evidence
Andreas Vesalius (1543)
- De Humani Corporis Fabrica Libri Septem (On the fabric of the human body in seven books) (Wikipedia contributors, 2025a)
- 1st detailed drawings of brain and body anatomy
René Descartes – mid 1600’s
- Reflexes “reflect” sensory events in the world
- Reflexes ≠ voluntary functions
- Reflexes and animal “minds” are physical, machine-like
René Descartes – mid 1600’s
- Human mind is not machine-like
- “Dual” influences on behavior
- Physical + spiritual
- Philosophical dualism
René Descartes – mid 1600’s
- Soul controls body via pineal gland
- Fluid from ventricles cause muscles to “inflate”
- One of the earliest “mechanistic” accounts of behavior
Spatial resolution
Churchland
Spatial and Temporal Resolution
Sejnowski, Churchland, & Movshon (2014)
- Within an individual
- molecular
- genetic
- receptor
- chemical
- neurotransmitters & hormones
- cellular
- neuronal firing
- molecular
- Internal to individuals
- network
- lateral inhibition
- area
- Visual cortex (V1) varies by ~2x between people
- region
- Wiring/connectivity differences
- system
- network
- External to individuals
- Social
- Friends, family, teachers, others
- Non-social
- Neighborhood, school, state/region, country
- Physical environment
- Social
- Within one lifetime
- Microseconds
- detection position from acoustic stimulation
- Milliseconds
- action potential
- Seconds
- changes in EEG power
- short-term memory
- Microseconds
- Within one lifetime
- Minutes
- synaptic plasticity
- Hours
- memory consolidation
- Hormone (melatonin, cortisol) levels
- Days
- Minutes
- Within one lifetime
- Weeks
- Months
- Years
- education & training
- disease processes
- cultural change
- Across lifetimes
- Centuries
- cultural changes
- Millenia
- Natural & sexual selection
- Centuries
Sejnowski et al. (2014)
Golgi stain
- Camillo Golgi
- Complete nerve cells, but only 1-5% of total
Do neurons connect like pipes?
Santiago Ramon Y Cajal
- Argued for neuron doctrine: there are gaps between neurons
- Neurons pass info like relay runners
- Shared 1906 Nobel Prize with Golgi
Nissl stain
- Franz Nissl
- Only cell bodies
- Cellular distribution, concentration, microanatomy
- Density of staining ~ cell density/number
Histochemical tracers
- Neuron information flow polarized–flows in one direction
- ≠ electronic wires, but like pipes
- Tracers are substances that flow one direction down the neuron, allow starting/ending points to be traced
Histochemical tracers
- Retrograde (“backward” from axon terminal to cell body)
- Anterograde (“forward” from cell body to axon terminal)
You can help map the connectome
Computed axial tomography (CAT)
- Computed tomography CT
- X-ray based
How tomography works
MRI
- Some common substances (e.g., H) & complex molecules have magnetic dipole
- Axes align with strong magnetic field
MRI
- When alignment perturbed by radio frequency (RF) pulse, speed of realignment varies by tissue
- Realignment emits RF signals
MRI
- Types
- Structural
- Functional (fMRI)
- Reveals tissue density/type differences
- Gray matter (neurons & dendrites & axons & glia) vs. white matter (mostly axons)
Diffusion tensor imaging (DTI)
- Type of structural MRI
- Measures patterns of movement/diffusion of \(H_{2}O\)
- Reveals integrity/density of axon fibers
- Measure of connectivity
- Colors used to visualize orientation of fibers
MR Spectroscopy
- Some complex molecules generate distinctive signals that MR detects
Voxel-based morphometry (VBM)
- 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.?
