Lecture 4/5: Cytoarchitecture and Cytoarchitecture Maps

Question 1

Cytoarchitecture

Answer 1

• Cytoarchitecture is the structure and organization of the neurons in the cortex.
• Some of the characteristics we look at are size of cells, types of cells, density of cells and a couple of things related to the organization of cells (cellular collums, layers)
• we want to study cytoarchitecture because there is not much known and what is known is not very certain at the moment. → hardly any research done on the cytoarchitecture inside the sulci.

Question 2

How do we study cytoarchitecture?

Answer 2

1) Slice a part of brain
2) Stain the gray matter (ex: Nissl Stain → just stains cell bodies)
3) Look up close on microscope

Question 3

How can we see the cerebral microstructure?

Answer 3

In order to see the cerebral microstructure, we must stain the cell bodies.

Golgi stains: stains 10% of neurons, but stains them completely (the ones it does stain, stains them very well)

Nissl Stain: stains the cell bodies of all neurons (by staining the endoplasmic reticulum).

Weigert Stain: Stains the myelin of the axons (the white matter) → myeloarchitectonic

Question 4

What can you use stains for?

Answer 4

• Specific parts inside the cell bodies
• receptors
• neurotransmitters
• dendritic spines

Question 5

Types of cortex

Answer 5

1) Allocortex (old cortex): anywhere from 3-4 cortical layers (not your traditional 6 layers).
2) Neocortex (new cortex): 6 cortical layers
ex: Area 44 and 45

Question 6

Layers of Neocortex

Answer 6

Layer I (molecular layer): comprised of a few scattered neurons. Present troughout the cortex in the brain.
Layer II (external granular layer): dense layer of very small round pyramidal neurons which sometimes appear to be granular.
Layer III (external pyramidal layer): pyramidal neurons which get larger the deeper into the cortex they go.
Layer IV (internal granular layer): small round cells.
→ a lot of the input comes in (most noteable characteristic of neocortex).
Layer V (internal pyramidal layer): pyramidal neurons, often denser in the upper part than in lower part.
Layer VI (multiform layer): Spindle-shaped neurons/ modified cells, the lower part often blends with the white matter.

Layer III → main output layer from cortical to cortical areas.
Layer V → main output from cortical to subcortical areas.

Question 7

Types of Neocortex

Answer 7

Granular neocortex: Fully formed granular IV.
Ex: area 45 and 47/12
- Subset of granular neocortex called Hypergranular cortex (koniocortex): granular layer IV and the rest of the layers are granular in appearance.
Ex: area 3b (primary somatosensory cortex) - so many inputs coming into sensory areass so all the neurons are structured like granular cells to receive a bunch of inputs.
Area 17 (primary visual cortex)
Area 41 (primary auditory cortex)

Dysgranular cortex: Slightly granular layer IV interupted by pyramidal cells from III and V.
eg: area 44

Agranular cortex: no granular layer IV
eg: area 4 and area 6

Question 8

1. The best stain to use for cytoarchitectonic analysis of the cortex is?
2. When stimulating the exposed cortex of patients undergoing surgery, Dr. Wilder Penfield found that the precentral gyrus contains
3. Which of the following lack the typical six layers found in neocortex?
4. Which of the following was considered the main language pathway for many years?
5. Fill in the blanks: The globus pallidus lies ___ to the thalamus but ___ to the putamen

Answer 8

1) The Nissl stain
2) A map of the body corresponding to voluntary motor control
3) the pyriform cortex, the hippocampus, and the cortex of the cingulate gyrus
4) the arcuate fasciculus
5) lateral, medial

Question 9

Area 47/12

Answer 9

• Typical 6 layers
• Good granular layer IV
• Area involved active memory retrieval (with area 45)
• granular cells in layer IV are much smaller than pyramidal cells.

Question 10

Area 45

Answer 10

• Distinct granular layer IV
• Large pyramidal cells in the lower part of layer III called gamma (I) cells by Economo and Koskinas
• Active memory retrieval and processing area
• Some definitions of Broca’s area include area 45.

The differentiation of area 45 from area 47/12 is in the bottom of layer III (layer 3C) → there are dark spots: bigger + more darkly stained.

Question 11

Area 44

Answer 11

• Dysgranular layer IV (interupted layer IV)
• Broca’s area proper
• Electrical stimulation to this area .can cause speech arrest

Question 12

Area 6VR

Answer 12

• Premotor area (premotor cortex)
• No layer IV (sometimess there is a space where layer IV could of been)
• Agranular cortex
• Difficult to distinguish layers.

Question 13

Area 4 (medial surface)

Answer 13

• Agranular area
• Largest neurons (feet neurons) in the brain are in layer V, called Betz cells
• Poor border with the white matter, even seen in anatomical MRI
• Thick cortical ribbon
• Primary motor area

Question 14

Betz cells

Answer 14

Following the homonculus, as you move down, the size of the cells changes because it doesn’t have to go as far.
Orofacial → quite small cells (smallest)
Hand → smaller
Foot → largest

Question 15

Area 3b

Answer 15

→ similar to area 17 and 41
* Hypergranular cortex (very small)
* Very distinct layer IV
* All other layers appear granular
* Thin cortical ribbon
* Primary somatosensory area

Question 16

Differences in cytoarchitectonic composition and organization (what we see structurally) leads to…

Answer 16

Differences in cytoarchitectonic composition and organization (what we see structurally) leads to differences in functions.

agranular areas = motor related areas
hypergranular areas = sensory areas
frontal granular area = processing area

Things develop out of the central sulcus

Question 17

Obstacles to the study of cytoarchitecture.

Answer 17

• Non-optimal sectioning (need to start with good sections.
• Not being able to analyse an entire brain.
• Cutting artifact (if you cut it more thick, it will show that there iss a lot of cells)
• Staining artifact
• Quantitative analysis are difficult
• Labour intensive
• Accesibility (Expense, Access to brain,Process it)

Question 18

Optimal vs Non-optimal angles of cut

Answer 18

Optimal Cutting: Cutting the cortical tissue perpendicularly to the direction of the sulci or gyri to obtain clear views of the cytoarchitectonic layers (cuting perpendicular to the sulci or gyri that you are intersted in).
* Some of what we do in the lab involves the optimal cutting around sulci of interest for cytoarchitectonic analysis.
* We use neuronavigation techniques to plan each part of the brain that will be processed based on sulci of interest.
→ Use MRI to help navigate
→ optimize the blocking using anatomical MRIs and neuronavigation techniquess (see what we have before going into the tissue)

Question 19

Brodmann’s Map

Answer 19

• The gold standard?
• one brain
• cytoarchitecture
• No stated criteria (never said why each area is different)
• No accounting for sulci
• No homologies between anumal species (did not do comparitive cytoarchitecture)

Why are we using the naming convention from a 100+ year old map?
* The study of neural cytoarchitecture began with the invention of the Nissl and Golgi stains at the end of the 19th century when allowed us to see neurons for the first time.
* By the early 1900s, scientists worked away and were able to come up with the first cytoarchitectonic maps

Question 20

Campbell (1905)

Answer 20

• In 1905, Campbell created the first complete cytoarchitectonic map of the human brain.
• He talks about the importance of optimal cutting
• In his map, there is some representation of different neurons

Brodmann followed with his map.

Question 21

Economo and Koskinas (1925)

Answer 21

• Economo and Koskinas published their extensive map and atlas in 1925.
• This work took around two decades to complete.
• Much of their nomenclature is still used today with regards to areas in the parietal and temporal lobes.
• They justified what they did → justified procedures and nomenclature.
• nomenclature = Fabcde…, Pabcde…, Tabcde…, Oabcde…

Question 22

Sarkisov (1949)

Answer 22

• used brodmann numbering system
• Similar to Economo and Koskinas map

By the 40s and 50s, the study of cytoarchitecture and cortical anatomy had slowed down considerably.
→ War was happening
→ Behaviourism: People were focused on behaviour and not the brain.
Nevertheless, the study of some structural/functional relationships was progressing.

Question 23

Penfield

Answer 23

• Founded MNI (montreal neuro institute)
• He was doing micro stimulation of the cortex when doing surgery.

Question 24

Homunculi

Answer 24

• Developed by Penfield → he came up with the homunculus

At this time they wanted to create a common space for neurosurgeons so that they could talk and discuss about the brain areas and their patients/cases.

Question 25

Talairach and Tournoux (1988)

Answer 25

• 3D atlas of the brain, first standard space for surgeons to work with.
  → example: use the coordinate system and areas as a standardized procedure.
• Help people find common areas, figure out what is going on at specific locations.
• Created a common coordinate space which allowed neurosurgeons to compare their findings and better localize areas of interest.

Issues:
- Projected Brodmann’s 2D map onto a 3D grid-space.
- Only used one brain as an example.

Question 26

Revolution in neuroscience

Answer 26

• PET (Positron Emission Tomography) allowed us to see a functioning brain in 3D (see it live).
• MRI (magnetic resonance imaging) allowed us to see cortical anatomy in a living human, and allowed us to see if its functioning through the BOLD Signal (blood-oxygen dependent signal) in fMRI.
• PET is more invasive. MRI is non-Invasive

Question 27

PET Scan

Answer 27

• Does not show the anatomy (not the tissue)
• Good to study behaviour, thinking, people

Question 28

Anatomical vs Functional MRI

Answer 28

Anatomical → to see anatomy
Functional → blobs to see brain activity.

Question 29

Why do we still use Brodmann’s map?

Answer 29

• Due to the explosion of functional and anatomical research that was now possible, researchers needed a common space to work in and used the one that was available: the Talairach and Tournoux atlas, which wass based upon the Brodmann map.
• This is one of the main reasons why the brodmann map and its nomenclature is important to this day.

Question 30

Economo and Koskina’s work

Answer 30

Looks like Brodmann’s Map but:
* Multiple brains
* Blocked at least one brain optimally
* Clear criteria for named areas
* Large photomicrographic plates showing the areas described.
* Accounted for Sulci
* Did not look within sulci (very hard to look within)

Question 31

Criteria for cytoarchitectonic map

Answer 31

Ideally a cytoarchitecture map should provide:
* Verifiable and repeatable criteria for area parcellations (say what is found in specific areas)
* Relationship between cytoarchitectonic areas and morphological features
* Homologies with animals should be determined when possible.

The cytoarchitecture should be analyzed from the most optimal angle as possible to allow for appropriate descriptions and analysess to be made.

Question 32

Bailey and Von Bonin (1951)
Is this map valid?

Answer 32

• After they made proper cytoarchitectonic maps, they decided they did not like it.
• So, they made a map based on granularity (like campbell’s map)

Is this map valid?
Yes, but not very useful.
→ Bailey and Von Bonin had clear cytoarchitectonic criteria. Although it did not lead to many parcellated areas, it is still accurate, verifiable and repeatable.

Question 33

Resting State Connectivity Parcellations (Gordon 2014/2016)

Answer 33

• Watch the brain as it was resting to see your brains activation and coactivations.
• It is not a cytoarchitectonic map, nor is it anatomical. It is functional.
• It is a functional map based on tthe BLOOD Signal.

Question 34

MNI space

Answer 34

• Last 20 years.
• Instead of Talairach and Tournoux Atlas.
• 152 brains put together and averaged
• More realistic common space from which to work from.
• Tried tto average out sulci as to have more clear view.

Notes:
- commonly used 3D grid spaces have not necessarily been created based upon cytoarchitecture.
- Do not assume two types of maps or data will overlap perfectly, unless significant evidence is provided.

Question 35

Problem with Neuroanatomical Maps

Answer 35

1) The criteria for creating the maps can be different.
-cytoarchitecture
-myeloarchitecture
2) The criteroa for delineating areas can be different
- Bonin and Bailey focused only on granularity
- Economo and Koskinas had a more detailed approach
3) The methodological approaches used for creation of a map can be different.
- Qualitative analysis: Brodmann, Economo and Koskinas
- Quantitavive (numberss to support) analysis: Ziles, Mackey, Economo and Koskinas
- Projection (2D map drawing slop it over to 3D grid): Talairach and Tournoux
4) The relationship between areas and morphological landmarks are not always considered (Zilles, Talairach and Tournoux most 3D representations of average brainss)
5) Nomenclature is a nightmare ex: BA 17 or V1
→ Function is overlapping with cytoarchitecture
→ Different ways of reffering to areas. Refer in a functional way (V1 → Visual) or a cytoarchitectonic way (BA 17).
6) Evolutionary relationships are not usually properly controled.

Question 36

Difference between T&T and MNI

Answer 36

• T&T’s atlas represents a SINGLE brain (Broadmann’s map), whereas MNI space
  represents the AVERAGE of numerous brains
• Therefore, MNI space more accurately represents what is happening in the population
• However, they are both 3D representations

Question 37

Problem with people using maps

Answer 37

*They do not usually acknowledge the issues mentioned above
* Like some of the maps, they do not generally consider the relationship certain areas may have with the local morphology
* They implicitly trust the map’s accuracy
* They may wrongly report information about an area by misidentifying the area of interest (because people don’t know how to find out where they are).
* Brains are often averaged together, blurring data

Question 38

Criteria for maping the cortex

Answer 38

*In order to parcellate the cortex, you need to have proper criteria, cytoarchitectonic or otherwise
* The criteria should be consistent within and between species
* Sulcal and gyral patterns should be taken into account
* The cortex should be analyzed from optimally cut tissue to maximize repeatability (so that u get good data)
* Quantitative approaches can be undertaken, but the exact cytoarchitectonic differences being measured need to be known

Question 39

What are we trying to accomplish?

Answer 39

• Consistent cytoarchitectonic criteria to better define and compare areas
• The relationship between cytoarchitectonic areas and gross
  morphological features such as sulci and gyri
• Evolutionary relationships of various cortical areas through comparative
  cytoarchitecture, which is only possible with meaningful
  cytoarchitectonic criteria
• How to more effectively parcellate the cortex quantitatively
• Relate functional findings (fMRI, electrophysiology) to anatomical areas

Question 40

Comparitive Cytoarchitecture

Answer 40

Comparison between human and maquake monkey.
→ They used the broadmann area and nimbered random areas in frontal libe of monkey.

Question 41

Pros and Cons Of Economo and Koskinas work?

Answer 41

Pros
* Optimally cut tissue
* Clear photomicrographs of identified areas
* Clearly defined criteria
* Verifiable reults
* Can be applied across speciess

Cons
* Not much is know about transitionss between areas
* Not much is known about what happens within the sulci
* How the cytorachitectonic borders may change when there is a variation in the sulcal pater ns is known.

Question 42

Example of bad comparative cytoarchitecture

Answer 42

*A rat has prefrontal cortex
* A human has prefrontal cortex

Conclusion?
Rats and humans have the same cortex in the prefrontal area.

This is wrong because…
Rats do not have a central or a precentral sulcus, so calling it prefrontal cortex is already not accurate
* Even if you concede that a part more “in front” of the rat brain is technically prefrontal, that does not necessarily mean that the cytoarchitecture is comparative in any way
* Rats do not have neocortex: all of their cortex is different forms of old cortex and they do not have any areas with a distinct layer IV
* Human prefrontal cortex is all granular
* These two regions in the two species can not be equivocated

This highlights the need for appropiate criteria when cpmparing the anatomy or cyoarchiecture of different species.
→ you need to understand what you are comparing or equivocating
→ do not assume tow areas are the same just necause they have the same name.

Question 43

Reminders

Answer 43

• Cytoarchitectonic maps are useful tools for locating regions in the brain
• They can help us interpret functional data, but the relationship is not
  one-to-one
• None are perfect, so it is important you use them with a critical mind
• There is still so much we do not know about the areas in the brain,
  especially within the sulci
• Be careful when presented with a map with Brodmann areas labelled if it
  was created using functional information, or a different kind of stain

Question 44

Why are good marps important tools?

Answer 44

• They help us know where we are and where we want to go
• They help us avoid misidentifying areas
• They help us integrate multifaceted types of data: different anatomical
  features, functional data, connectivity data, etc.
• They help us understand the similarities as well as the differences all
  brains share
• They help us better understand when abnormalities have occurred