biol125-lectures/neuroanatomy2.md

## Neural Systems

* Circuits that do the same kinds of things are grouped into 'systems', e.g. sensory systems and motor systems
* Many neurons function between these systems, called associational systems. Associational systems are the most complex and least well characterized systems.

Note:

Last time we learned some of the basic cellular anatomy of the nervous system. Today we will put the system in nervous system–– because nervous systems really are greater than the sum of its parts… in other words our brain is not just a blob of cells but it is the interconnections between cells, groups of cells, and brain regions that allow our fantastic feats of emergent biological computation. So lets discuss the overall the structure of the nervous system. 

First of all it is a system of systems. In other words…

TODO: exchange pngs for jpgs in this document

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## Major components of the nervous system and their functional relationships

<div><figcaption class="big">central nervous system (CNS)</figcaption><video height=200px controls loop src="figs/cns_overview.m4v"></video><figcaption>[C. Krebs CC BY-NC-SA, Univ. British Columbia](http://www.neuroanatomy.ca/3D_files/3D_index.html?id=1)</figcaption></div> 

<div><img src="figs/Neuroscience5e-Fig-01.10-1R_cfe2e3e.png" height="400px"><figcaption>Neuroscience 5e Fig. 1.10</figcaption></div>

<div><img src="figs/Neuroscience5e-Fig-01.10-2R_b4b3e07.png" height="400px"><figcaption>Neuroscience 5e Fig. 1.10</figcaption></div> <!-- .element: class="fragment fade-in"-->

Note:

This illustrates the two top level systems of the nervous system, the CNS containing the brain and spinal cord and the PNS containing nerves and ganglia exiting the spinal cord.

This diagram outlines the functional hierarchy of different components or systems within the whole nervous system including relations between internal and external environment and sensory receptors in the PNS as well as skeletal muscle and smooth, cardiac muscles that the nervous system controls.



right vagus nerve primarily innervates the SA node, whereas the left vagus innervates the AV node

pns supplies smooth muscles, cardiac muscles, and glands. functions to maintain homeostasis, and is concerned with involunary functions. 


---

## Anatomy terms

* Nerves– bundles of axons, enveloped by glial cells that myelinate them
* White matter– areas of axon tracts
* Grey matter– areas of cell bodies 

<div><img src="figs/coronal7b_21f2276.jpg" height="300px"><figcaption>B. Crawford and K. McBurney, Univ. of Victoria</figcaption></div>


Note:

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## Common techniques to visualize brain structure

<div><figcaption class="big">Cell stain (e.g. Nissl/Cresyl violet, H&E)</figcaption><img src="figs/2240_cell_4aa2d7c.jpg" height="300px"><figcaption>[Brain Biodiversity Bank MSU, NSF](https://msu.edu/~brains/brains/human/coronal/montage.html)</figcaption></div>
<div><figcaption class="big">Fiber stain (e.g. , Heidenhahn, Luxol fast blue)</figcaption><img src="figs/2240_fiber_d16bc49.jpg" height="300px"><figcaption>[Brain Biodiversity Bank MSU, NSF](https://msu.edu/~brains/brains/human/coronal/montage.html)</figcaption></div>


Note:

- Cell stain is Nissl stain
- Fiber stain is Luxol Fast blue

Luxol fast blue stain  
: stain and observe myelin for light microscopy  
: a copper phthalocyanine dye  
: soluble in alcohol  
: binds bases found in lipoproteins of myelin sheath  

Hematoxylin and eosin stain  
: H&E stain  
: Hematoxylin is also called natural black 1, it is a chemical from the heartwood of the logwood tree  
: hemalum is formed from aluminum ions and hematein (an oxidation product of hematoxylin) and binds to DNA, staining nuclei dark blue  
: eosin stains hydrophilic cytoplasm, generally intra- or extra- cellular proteins staining tissue red  

Nissl stain  
: basic dyes (e.g. aniline, thionine, or cresyl violet)  
: stain negatively charged RNA blue  
: Nissl substance (rough endoplasmic reticulum)  

Thionine  
: thionine acetate or Lauth's violet  
: tetramethyl thionine is methylene blue  

aniline  
: aromatic amine  
: precursor to polyurethane and many industrial chemicals  
: indigo dye prepared from aniline  

Nissl substance  
: large granules of RER with rosettes of free ribosomes  
: sites of protein synthesis  
: found in neurons  
: named for Franz Nissl  

Heidenhahn  
: 1892  
: lithium carbonate  
: myelin stain  



--

## Magnetic resonance imaging (MRI)

<div><img src="figs/2240_cut_aaaa4be.jpg" height="200px"><figcaption>[Brain Biodiversity Bank MSU, NSF](https://msu.edu/~brains/brains/human/coronal/montage.html)</figcaption></div>

<div><video height=400px controls src="figs/Animation01-01MagneticResonanceImaging.mp4"></video><figcaption>Neuroscience 5e Animation 1.1</figcaption></div> 

Note:

MRI

* Uses rotating magnets to generate image
* Non-invasive
* Can view images from any angle
* Resolution under 1 mm
* Can be adapted to do functional MRI imaging

fMRI

* Oxy-hemoglobin and deoxy-hemoglobin have different magnetic resonance signals
* Brain areas activated by a specific task utilize O2, then a pulse of O2 comes back and creates an influx of oxy-hemoglobin
* Can repeat task many times over
* Spatial resolution– millimeters
* Temporal resolution– seconds


---

## Cell bodies that do similar things are grouped together

* PNS– Nerve cell bodies are located in ganglia (ganglia have neurons and glia in them). Dorsal root ganglia, cranial nerve ganglia
* CNS– Nuclei are compact accumulations of neurons having roughly similar connections
* Cortices (cortex)– sheets of cells of similar function

Note:

The term we use for cell bodies grouped together in the PNS is ganglia. In the CNS cell bodies are accumulated together as nuclei or if they are arranged in highly ordered sheets or lamina it is called cortex.

Cortex  
: latin for bark  
: outermost (or superficial) layer of an organ  
: kidney cortex  


--

## Cell groupings: cortex vs nuclei

<figure><figcaption class="big">Cerebral cortex and thalamic nuclei</figcaption><img src="figs/2060_cell_abf6617.jpg" height="300px"><figcaption>[Brain Biodiversity Bank MSU, NSF](https://msu.edu/~brains/brains/human/coronal/2060_cell_labelled.html)</figcaption></figure>


Note:

Here is one of those cell body violet stained sections-- you can see the cortical sheet and different subcortical nuclei in the thalamus, etc. We will go over this in more detail later.


---

## Basic parts of the CNS

<div style="width:500px">
<div></div>

* cerebral hemispheres (cerebral cortex)
* diencephalon (thalamus, hypothalamus)
* cerebellum
* midbrain
* pons
* medulla
* spinal cord

</div>

<div style="margin:0 50px;"><img src="figs/Neuroscience5e-Fig-A02-0_crop_ce0acbb.png" height="500px"><figcaption>Neuroscience 5e Fig. A2</figcaption></div>

<!-- <div style="margin:0 50px;"><img src="figs/Neuroscience5e-Appendix-Opener_c87eac5.png" height="500px"><figcaption>Neuroscience 5e</figcaption></div> -->


Note:

These are the basic parts of the CNS

Forebrain 

Brain stem includes the midbrain, pons, medulla, and a portion of the spinal cord

Think about how the nerves represent incoming and outgoing info from a specific location on the body.

cervical enlargement

lumbar enlargement  
: nerves which supply the lower limbs  

cauda equina  
: nerves that innervate the pelvic organs and lower limbs. Includes motor innervation of the hips, knees, ankles, feet, internal anal sphincter and external anal sphincter.  

Spinal nerves: cervical, thoracic, lumbar, sacral, coccygeal

---

## Anatomical terminology for CNS locations

<div><img src="figs/Neuroscience5e-Fig-A01-1R_3e6816d.png" height="400px"><figcaption>Neuroscience 5e Fig. A1.1</figcaption></div>


Note:



---

## Anatomical terminology for the three axes of the brain

<div><img src="figs/Neuroscience5e-Fig-A01-2R_da3eff9.png" height="400px"><figcaption>Neuroscience 5e Fig. A1.2</figcaption></div>

Note:


---

## Spinal cord

* Extends from the base of the skull to the first lumbar vertebra
* Receives sensory info from skin, joints, and muscles of trunk and limbs and contains motor neurons responsible for both voluntary and reflexive movements
* Nerve fibers bundled in 31 pairs of spinal nerves. There is a sensory division (dorsal root ganglia) and a motor division (ventral root)
* Is thicker in regions that innervate the limbs

Note:

Lets start with the spinal cord which in human contains about 1 billion of your 100 billion neurons in your nervous system.


It extends…

It receives sensory…

So it carries both afferent and efferent information. 

Nerve fibers…

Is thicker…

Cervical enlargement, lumbar enlargement

---

## Spinal cord

<div><img src="figs/Neuroscience5e-Fig-A04-0_823983c.png" height="500px"><figcaption>Neuroscience 5e Fig. A4</figcaption></div>

Note:

This illustrates the overall structure of the spinal cord.

---

## Internal anatomy of the spinal cord

* Contains both white and grey matter
* Grey matter shaped like an 'H'. Dorsal horns and ventral horns
* Dorsal horns contain sensory relay neurons– receives input from periphery (afferent)
* Ventral horns contains motor neurons that innervate muscles– send output (efferent)
* Interneurons are in intermediate zone
* White matter contains longitudinal tracts of ascending and descending axons grouped together by function

Note:


- *Preganglionic visceral motor neurons (innervate glands) are found in the intermediate/lateral region*

---

## Internal anatomy of the spinal cord

<div><img src="figs/Neuroscience5e-Fig-A05-2R_crop_8491c98.png" height="500px"><figcaption>Neuroscience 5e Fig. A5</figcaption></div>


Note:

sympathetic chain ganglia  
: stress, flight or flight response, epinephrine  
: 20–30K cell bodies  

---

## Spinal cord tracts

<div style="width:500px;">
<div></div>

* Dorsal column– sensory signals travels up it to the brain
* Lateral columns– also called the cortico-spinal tracts. Carries signals from brain to interneurons and motor neurons in ventral horn
* Ventral columns (sometimes called anterolateral column)– carry pain signals up and motor signals down

</div>

<div style="margin:0 50px;"><figcaption class="big">Cell (top) and fiber stains (bottom)</figcaption><img src="figs/Neuroscience5e-Fig-A06-0_e4f9186.png" height="400px"><figcaption>Neuroscience 5e Fig. A6</figcaption></div>

Note:

Dorsal column-sensory info travels up to the brain.

Lateral columns-also called the cortico-spinal tracts.  Take info from brain and sends it to the muscles.

Ventral columns (sometimes called anterolateral column)- carry pain info up and motor info down.

*Cervical enlargement: Gray matter expanded to incorporate more sensory input from limbs and more cell bodies for motor control of limbs*

*Rexed's laminae are cytoarchitectonic divisions of spinal cord gray matter, see Table A1*

---

## Brain stem

* Target or source for all cranial nerves that deal with sensory and motor function in the head and neck
* Nuclei within brainstem are the targets and sources of these nerves
* Also is a throughway which all info going up and down must pass
* Because of its small area and restricted blood supply– it is very susceptible to damage

Note:

Now let’s talk about the brain stem, which is located more rostrally to the spinal cords locations we just discussed.

The brain stem is a target or source…

And all information from higher order or more rostral brain structures that goes to or from the spinal cord must pass through the brain stem.


---

## Subdivisions of the brain stem

<div style="width:500px;">
<div></div>

* Medulla– regulates blood pressure and respiration.
* Ventral pons– pontine nuclei, relay signals from cortex to the cerebellum
* Dorsal pons– respiration taste and sleep
* Midbrain– auditory and visual systems, substantia nigra pars compacta (dopaminergic neurons). Deteriorates in Parkinson’s disease.

</div>

<div style="margin:0 50px;"><img src="figs/Neuroscience5e-Fig-A07-2R_debbe82.png" height="300px"><figcaption>Neuroscience 5e Fig. A7</figcaption></div>

Note:


---

## Brain stem cranial nerves

<figure><img src="figs/Neuroscience5e-Fig-A07-1R_1b511b4.png" height="500px"><figcaption>Neuroscience 5e Fig. A7</figcaption></figure>

<!-- <div><img src="figs/cranial-nerves-facial-optic-oculomotor-trochlear-trigeminal-abducens-facial-vestibulocochlear-glossopharyngeal-vagus-accessory-hypoglossal2_7ba3227.jpg" height="300px"><figcaption></figcaption></div> -->

<!-- Cranial nerve nuclei of the brainstem
<div><img src="figs/Neuroscience5e-Fig-A08-1R_0aed220.jpg" height="300px"><figcaption>Neuroscience 5e Fig. A8</figcaption></div>
<div><img src="figs/Neuroscience5e-Fig-A09-0_f8f954b.jpg" height="300px"><figcaption>Neuroscience 5e Fig. A9</figcaption></div> -->


Note:

From the brain stem there emerges 12 left-right pairs of cranial nerves that carry afferent or efferent information mostly concerned with sensory and motor functions of the head. The exception is the the vagus nerve arising from the medulla which carries critical autonomic signals for your visceral organs and heart without which you cannot live.

--

## Cranial nerves

<div style="font-size:0.6em">
<div></div>

number | name | function
--- | --- | ---
I   | Olfactory Nerve | Smell
II  | Optic Nerve   | Vision
III | Oculomotor Nerve  | Eye movement; pupil constriction
IV  | Trochlear Nerve   | Eye movement
V   | Trigeminal Nerve |    Somatosensory information (touch, pain) from the face and head; muscles for chewing
VI |    Abducens Nerve  | Eye movement
VII | Facial Nerve  | Taste (anterior 2/3 of tongue); somatosensory information from ear; controls muscles used in facial expression
VIII |  Vestibulocochlear Nerve | Hearing; balance
IX |    Glossopharyngeal Nerve  | Taste (posterior 1/3 of tongue); Somatosensory information from tongue, tonsil, pharynx; controls some muscles used in swallowing
X   | Vagus Nerve | Sensory, motor and autonomic functions of viscera (glands, digestion, heart rate)
XI  | Spinal Accessory | Nerve  Controls muscles used in head movement
XII | Hypoglossal Nerve | Controls muscles of tongue

</div>

Note:

This lists these 12 cranial nerves and their relevant sensory and/or motor function they carry. Notice that many of the nerves carry mixtures of sensory and motor information, which you could see with the color coding on the previous slide. Also notice that 4 of the 12 nerves concern sensory and motor information from the eyes. In fact the cranial nerve containing the most fibers is the optic nerve which contains 1.2 million axons that carries all the information necessary to perceive the visual world around you (compare with 130 million photoreceptors and 0.7 to 1.5 million RGCs)

---

## Midbrain

<figure><img src="figs/mri_midbrain_170-labels_3f3d983.png" height="400px"><figcaption>[C. Krebs CC BY-NC-SA, Univ. British Columbia](http://www.neuroanatomy.ca/MRIs/mri_sagittal.html?id=1)</figcaption></figure>


Note:

The tectum of the midbrain, which is latin for ‘roof’ contains the superior and inferior colliculi and is important for processing visual and auditory information as well as shaping motor commands for orienting the head and body. 


Ventral to the cerebral aqueduct through which cerebral spinal fluid circulates, you will find the tegmentum of the midbrain which contains the —>

--

## Parkinson’s- loss of dopamine making neurons in the midbrain's substantia nigra

<!-- <div><img src="figs/image5_72addde.png" height="300px"><figcaption></figcaption></div> -->

<div><img src="figs/coronal7b_21f2276.svg" height="300px"><figcaption>B. Crawford and K. McBurney, Univ. of Victoria</figcaption></div>

Note:

substantia nigra pars compacta, a nucleus containing neurons making the neurotransmitter dopamine that are important for regulating motor movements via their connections with the basal ganglia and which are devastated in parkinson’s disease.

*dark appearance due to high levels of dark pigment neuromelanin in dopaminergic neurons*  
*Neuromelanin is directly biosynthesized from L-DOPA, precursor to dopamine, by tyrosine hydroxylase (TH)*  

Now you’ve all heard the phrase ‘running around like a chicken with its head cut off’ —>

---

## The brainstem is all you need to live

<div><iframe src="https://www.youtube.com/embed/ATz3AdbjyRI" width="420" height="315"></iframe><figcaption>Mike the headless chicken</figcaption></div>

Note:

Well here is a grotesque way of convincing you that all you need to live is your brainstem…

* survived an axe beheading by Colorado farmer in 1945, 
* lived for 18 months with only a brain stem
* Fed corn dropped directly into his gullet 
* Mike choked to death during a sideshow tour in 1947, when the farmer was unable to clear Mike's esophagus

---

## Cerebellum

* Two hemispheres, several lobes divided by fissures
* Neurons in sheets, called cortex
* Receives sensory input from spinal cord, motor info from cerebral cortex, balance info from inner ear and vestibular organs
* Primarily used motor control, particularly in making postural adjustments and in fine-tuning movements
* Essential for the coordination, planning of movements, learning motor tasks and storing this information

<figure><img src="figs/ackman_mri-cerebellum_5dc7035.png" height="200px"><figcaption></figcaption></figure>


Note:

Cerebellum is latin for 'little brain.'

The cerebellum is located dorsal to the brainstem.

It has two…

Neurons are form cortical sheets.

Receives…

---

## Cerebellum

<!-- <div><img src="figs/image8_024acb9.png" height="200px"><figcaption></figcaption></div> -->
<!-- <div><img src="figs/image9_57ce87f.png" height="200px"><figcaption></figcaption></div> -->
<!-- <div><img src="figs/image10_cac162f.png" height="200px"><figcaption></figcaption></div> -->
<!-- <div><img src="figs/image11_ee714ea.png" height="200px"><figcaption></figcaption></div> -->

<div><img src="figs/2800_cell_cfb18b0.jpg" height="200px"><figcaption>[Brain Biodiversity Bank MSU, NSF](https://msu.edu/~brains/brains/human/coronal/montage.html)</figcaption></div>
<div><img src="figs/2800_fiber_6135263.jpg" height="200px"><figcaption>[Brain Biodiversity Bank MSU, NSF](https://msu.edu/~brains/brains/human/coronal/montage.html)</figcaption></div>
<div><img src="figs/golgi_purkinje-neuron-fig4-nobel-lecture_b18b837.png" height="200px"><figcaption>C. Golgi Fig. 4 Nobel lecture</figcaption></div>



Note:

Cerebellum is latin for ‘little brain’, and it does have a striking organization with lobes and fissures similar to the folding of the cerebral cortex to increase surface area and packing density of neuronal interconnections. You can see here its main cell body layer, obvious in this purple nissl stain for cell bodies here. It’s in this layer where you will find the beautiful purkinje neurons that we saw images of in lecture 01.


---

## Forebrain

<figure><img src="figs/Neuroscience5e-Fig-A02-0_crop_8d72d73.png" height="500px"><figcaption>Neuroscience 5e Fig. A2</figcaption></figure>

Note:

Now we're gonna use our forebrains to learn about the forebrain.

Cerebrum  
: the principal and most anterior part of the brain in vertebrates, located in the front area of the skull and consisting of two hemispheres, left and right, separated by a fissure  
: cerebral hemispheres– cerebral cortex, hippocampus, basal ganglia, olfactory bulb  
: develops from embryonic structure the telencephalon  


---

## Diencephalon

* Contains the thalamus and hypothalamus
* Thalamus– 'relay station to the cerebral cortex'– an essential link in the transfer of most sensory information from periphery to cerebral cortex. Also plays a role in filtering information from the periphery
* Hypothalamus– lies ventral to thalamus. Controls a variety of functions, growth, eating, drinking, maternal behavior by regulating hormonal secretions of the pituitary gland  Connects to virtually every part of brain. Important in initiating and maintaining behaviors that the organism finds rewarding

Note:

The diencephalon contains the…

The thalamus can be generally thought of as the relay station to the cortex. 

The hypothalamus lies ventral to the thalamus and controls an array of important physiological functions such as feeding, fluid balance, and hormonal secretions of the endocrine system.

---

## Thalamus 

* Pair of ovoid structures
* Incoming sensory information relays in the thalamus before entering the cerebral cortex. Many sensory, motor, and cognitive functions
* Highly organized connections with cortex
* Connections are mostly reciprocal

Note:

Thalamus is essentially the relay nuclei that routes sensory information into the cortex. This routing of information is highly organized with different subdivisions sending information in parallel pathways to different visual, auditory, and somatosensory regions of the cerebral cortex. But the connections are highly reciprocal with cortical areas, such that the thalamus is integral to many sensory, motor, and cognitive functions as well as the generation of different electrical rhythms that underly different sleep states.

---

## Thalamus– gateway to the cerebral cortex

<div><figcaption class="big">Thalamus (brown), ventricles (blue)</figcaption><video height=300px controls loop src="figs/thalamus.m4v"></video><figcaption>[C. Krebs CC BY-NC-SA, Univ. British Columbia](http://www.neuroanatomy.ca/3D_files/3D_index.html?id=1)</figcaption></div> 

<div><figcaption class="big">Fiber stain</figcaption><img src="figs/2060_fiber-thalamus_207b466.png" height="300px"><figcaption>[Brain Biodiversity Bank MSU, NSF](https://msu.edu/~brains/brains/human/coronal/montage.html)</figcaption></div>

Note:

The thalamus is located in the middle of the brain…

*red nucleus is part of midbrain, without a corticospinal tract it controls gait. Baby crawling controlled by red nucleus. Arm swinging while walking*

---

## Thalamus subdivisions

<div><img src="figs/5892_Fig_a64022f.png" height="400px"><figcaption>Neuroscience 3/4e (5e Box A)</figcaption></div>

Note:

…and is the gateway for routing information into the cerebral cortex. It contains a number of different nuclei and subdivision that take information from other brain regions including the brain stem and sends to appropriate primary sensory or higher order regions of the cerebral cortex.

---

## Hypothalamus

<div><figcaption class="big">hypothalamus, sagittal mri</figcaption><img src="figs/ackman_mri-hypothalamus_7abb29b.png" height="300px"><figcaption></figcaption></div>
<div><figcaption class="big">hypothalamus, coronal section</figcaption><img src="figs/coronal5b-hypothalamus_32b4364.png" height="300px"><figcaption>B. Crawford and K. McBurney, Univ. of Victoria</figcaption></div>

Note:

- mediates endocrine, autonomic and behavioral functions

Controls a variety of functions, growth, eating, drinking, maternal behavior by regulating hormonal secretions of the pituitary gland.  Connects to virtually every part of brain. Important in initiating and maintaining behaviors that the organism finds rewarding

---

## Cerebral hemispheres

* Largest portion of the human brain
* Cerebral cortex– cognitive functioning
* Hippocampus– memory
* Basal ganglia– control of fine movement
* Amygdala– social behavior and expression of emotion

Note:

Now let’s finally talk about highest order parts of the central nervous system the cerebral hemispheres.

The two cerebral hemispheres sit atop and surround the diencephalon and much of the brain stem.  

Seat of cognition, but it doesn't work alone!

Limbic system includes the amygdala, as well as the part of the basal ganglia, part of the thalamus, prefrontal cortex, and the hippocampus. It is the integrative center for emotions, emotional behavior, and motivation

---

## Cerebral Cortex

* Highly convoluted shape-grooves (sulci) and elevated regions (gyri). If sulci are especially deep called fissures.
* About 2 to 4 mm thick, 100K neurons/mm<sup>2</sub>
* Segregated into left and right hemispheres connected to each other at the corpus callosum
* Anatomically divided into four lobes
* Functionally distinct regions
* Organized into layers
* Greatly expanded in humans

[http://brainmuseum.org](http://brainmuseum.org)

Note:



---

## Lobes of the cerebral cortex

* frontal– planning responses to stimuli, contains: motor cortex (precentral gyrus)
* parietal– somatic sensory cortex (postcentral gyrus)
* temporal– audition and insular cortex (taste)
* occipital– vision

<div><img src="figs/Neuroscience5e-Fig-A03-1R_3474298.png" height="250px"><figcaption>Neuroscience 5e Fig. A3</figcaption></div>
<div><img src="figs/Neuroscience5e-Fig-A03-2R_c3b128c.png" height="250px"><figcaption>Neuroscience 5e Fig. A3</figcaption></div>


Note:


---

## Cortico-cortical connection pathways

<div style="width: 400px; font-size:0.7em; margin-bottom:50px">
<div></div>

* within hemisphere
    * short vs. long (fasciculi)
* between hemisphere
    * mostly homologous connections
    * commissures
    * corpus callosum

</div>

<div style="margin-bottom:50px"><figcaption class="big">Fiber stain</figcaption><img src="figs/2240_fiber_d16bc49.jpg" height="200px"><figcaption>[Brain Biodiversity Bank MSU, NSF](https://msu.edu/~brains/brains/human/coronal/montage.html)</figcaption></div>

<div><figcaption class="big">Dorsal view</figcaption><img src="figs/Neuroscience5e-Fig-A11-1R_a8973d9_copy_9c648a7.jpg" height="200px"><figcaption>Neuroscience 5e Fig. A11</figcaption></div>

<div><figcaption class="big">Dorsal view cut away</figcaption><img src="figs/Neuroscience5e-Fig-A11-3R_17d31f5_copy_406b96a.jpg" height="200px"><figcaption>Neuroscience 5e Fig. A11</figcaption></div> <!-- .element: class="fragment fade-in"-->

<div><figcaption class="big">MRI-DTI dorsal projection</figcaption><img src="figs/Neuroscience5e-Ch01-Opener_497d461_copy_b20f743.jpg" height="200px"><figcaption>Neuroscience 5e</figcaption></div> <!-- .element: class="fragment fade-in"-->

Note:


corpus callosum 
: connections the cerebral hemispheres
: only in placental mammals (the eutherians)
: absent in monotremes and marsupials and other vertebrates (e.g. birds, reptiles, amphibians and fish)

anterior commisure
: connects temporal lobes
: connects both amygdala
: crossed projects from olfactory tracts

---

## Primary versus non-primary cortex

<div style="font-size:0.7em;">
<div></div>

* Primary cortex
    * Cortical areas that are the primary projection fields targeted by the sensory input pathways
    * Cortical areas that are the principal fields which have neurons that project down into the spinal cord for effecting control 
    * Primary visual (calcarine sulcus)
    * Primary auditory
    * Primary somatosensory (post-central gyrus)
    * Primary motor (pre-central gyrus)

</div>

<div style="width: 400px; font-size:0.7em;">
<div></div>

* Non-primary cortex 
    * everything in between
    * referred to collectively as association cortex

</div>

<div style="padding:0 50px;"><img src="figs/Neuroscience5e-Fig-26.01-0_copy_c5817b1.jpg" height="200px"><figcaption>Neuroscience 5e Fig. 26.1</figcaption></div>

Note:

---

## Brain organization summary

<div><img src="figs/Neuroscience5e-Fig-A12-1R_copy_020ed62.jpg" height="315px"><figcaption>Neuroscience 5e Fig. A12</figcaption></div>

<div><iframe src="https://www.youtube.com/embed/snO68aJTOpM" width="420" height="315"></iframe><figcaption>Pinky and the Brain</figcaption></div>


Note:


---

## Laminar organization of neocortex

* Cortex itself has a thickness of only about 2-4mm.  
* 6 layers (neocortex)
    * Layer IV is the primary input layer
    * Layers II and III are cortico-cortical output layers
    * Layers V and VI descending output layers to connect with subcortical regions (basal ganglia, thalamus, brain stem, spinal cord)



Note:

---

## Cortical neurons are organized into layers

* The cerebral cortex is a layered structure
* Layers can be seen when the brain is stained with dyes that highlight cell bodies or fibers

<div><figcaption>Cells</figcaption><img src="figs/image17_f4be687.png" height="300px"><figcaption></figcaption></div>

<div><figcaption>Cells & fibers</figcaption><img src="figs/The_Cerebral_Neocortex_Jones-fig3-Meynert-1884_copy_fed3654.jpg" height="300px"><figcaption>Meynert 1884</figcaption></div>

<div><figcaption>Golgi stain</figcaption><img src="figs/The_Cerebral_Neocortex_Eccles-fig4-Jones-1981_f8dc197.png" height="300px"><figcaption>Jones 1981</figcaption></div>


<!-- <div><img src="figs/image1_83b0cd1.jpeg" height="300px"><figcaption></figcaption></div> -->

Note:

- *Meynert 1884, frontal lobe and cortex of calcarine fissure. First to describe cortical layering (bats, but also human and other animals). Sections fixed in potassium dichromate, stained with carmine, and cleared in oil of cloves.*



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## Defects in cortical development
<div style="width:500px">
<div></div>

* lissencephaly: smooth brain
* do not have characteristic gyri patterns
* leads to death, severe epilepsies and mental retardation
* cause is defects in neural migration during development

</div>

<div style="padding:0 50px;"><img src="figs/Walsh-curr-opin-gen-dev-2002-fig2_798163d_copy_878c80b.jpg" height="500px"><figcaption>Olson and Walsh, 2002 Fig. 2</figcaption></div>


Note:



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## Which of the following is true?

1. Do specific regions of the brain control specific functions?
2. Does each part of the brain do all functions?
3. Does a specific function come from many parts of the brain?

Note:

Now lets expand on how functions are organized in the brain. Which of the following is true

it’s a bit of a trick question because both of these answers are partially right depending on how you define a part of the brain or what kind of function you’re talking about, but it is not the case that

<!-- 
## Early 1800’s Franz Joseph Gall

* all behavior emanates from the brain
* particular regions of the cerebral cortex controlled specific functions, i.e. the brain does not act as a single organ.
* each function grew with use such as a muscle with exercise
* this growing causes the skull to budge creating a pattern of bumps “phrenology”

## Franz Joseph Gall– phrenology

Standing at his lectern, the priest stared steadily upon one man in the congregation: Franz Joseph Gall. With his angry voice echoing off the church's hallowed walls, he pronounced,"There are those amongst us, who have lost their way from our Lord's divine path. With pomposity, they state the mind is situated in an organ as mushy and insubstantial as the brain. What ludicrousness is this, when all intelligent men know that God has imbued our thinking into our very soul, whereupon no one can put his finger precisely on the spot!"

http://thevictoriantimes.blogspot.com/2011/10/galls-phrenology.html

<div><img src="figs/image21_cc3a4ac.png" height="300px"><figcaption></figcaption></div>

## Phrenology

<div><img src="figs/image22_f181430.png" height="300px"><figcaption></figcaption></div>

## Pierre Flourens (French)

* Tested Gall’s ideas by removing different parts of the brain (dogs and rabbits) and asked if specific functions were compromised. 
* Showed medulla important for respiration, cerebellum important for movements. 
* Lesions in cortex affected either zero or many behaviors. Concluded that the cortex was one organ and not regionalized.

 -->

---

## Korbinian Brodmann (1909)

* Used subtle anatomical differences in the brain to divide it into discrete areas or regions
* Based on distinctive nerve structures and characteristic arrangements of layers
* 52 discrete areas– many still used today

<div><img src="figs/image23_910808c.png" height="300px"><figcaption></figcaption></div>

Note:

So first lets discuss how we came to define different parts of the brain, specifically cerebral cortical areas

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## Cortical regions have slightly different laminar organization

<div><figcaption class="big">cell body stain</figcaption><img src="figs/5892_Fig3_3d13523.png" height="300px"><figcaption></figcaption></div>


Note:

He used cell body staining like the Nissl stain to examine differences in general patterning/layering across the cerebral cortex.


---

## Brodmann areas

<div><img src="figs/5892_Fig4_3c30913_copy_40d8d23.jpg" height="300px"><figcaption>Brodmann 1909</figcaption></div>
<div><img src="figs/brodmann-color-crop_81018e1.png" height="300px"><figcaption>Brodmann 1909 color</figcaption></div>


Note:

Note areas 4 (primary motor cortex), 1,2,3 (primary somatosensory cortex), area 17 (primary visual cortex), area 18 (secondary visual cortex), area 41,42 (primary auditory cortex, also part of 22)

*Comparative localization teachings of the cerebral cortex in their principles, illustrated on the basis of Zellenbaues. Leipzig, Johann Ambrosius Barth Verlag, 1909 . 2nd edition, 1925. English translation by Laurence J. Garey: Localisation in the Cerebral Cortex by Korbinian Brodmann. Smith-Gordon, 1994; new impression: Imperial College Press., 1999*

*area 44,45 Broca's areas*  
*area 39,40,22 wernicke's areas*  
*area 43 gustatory cortex*  
*area 22 superior temporal gyrus*  


---

## Paul Broca (1861)

* Believed that functions could be localized in the brain
* Studied patients with aphasia– language disorders found in patients who have had a stroke
* Had a patient that could understand language but could not speak, problems with the organizational aspects of language. Found lesion in posterior frontal lobe (Brodmann areas 44/45)
* This kind of aphasia is called a motor or expressive aphasia
* Eight patients with similar problems all had similar lesions, always on the left side
* "Nous parlons avec l’hemisphere gauche!"  "We speak with the left hemisphere!"

Note:

We also define regions of the brain based on studies of brain lesions in patients. Recall the guy with the railroad spike from last lecture. Well the French physician Paul Broca in the 19th c. 

--

## Broca and a patient’s brain

<div><img src="figs/image25_2d10fa8.png" height="300px"><figcaption></figcaption></div>

Note:


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## Carl Wernicke (1874)

* Had a patient that could speak but not understand language. Called receptive aphasia
* Damage was to a different area– left side, posterior part of the left temporal lobe (Brodmann areas 22/39/40)
* Argued that simple perceptual and motor activities were localized to a specific area and that most functions result from interconnections between areas. Idea of "distributive processing"

Note:


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## Major brain areas involved in the comprehension and production of language

<div><img src="figs/Neuroscience5e-Fig-27.01-0_eaf66c7_copy_1841ced.jpg" height="400px"><figcaption>Neuroscience 5e Fig. 27.1</figcaption></div>



Note:

*Arcuate fasciculus: major association fiber tract in CNS that connects Broca’s and Wernicke’s areas*


---

## Characteristics of Broca's and Wernicke's aphasias

<div><img src="figs/Neuroscience5e-Tab-27.01-0_859de7f_copy_4abca30.jpg" height="300px"><figcaption>Neuroscience 5e Table 27.1</figcaption></div>


Note:

*Broca's aphasia patients have limited writing. Loss of the ability to produce language (spoken or written)*  

Apraxia
: verbal apraxia is difficulty starting and making voluntary movements (motor plans) needed for speech (with no paralysis or weakness of speech muscles)

dysarthria
: inability to move the muscles of the tongue and mouth to produce speech

agraphia
: inability to write

Agnosia 
: inability to process sensory information
: affects a single modality


syntax  
:the arrangement of words and phrases to create well-formed sentences in a language

Grammar  
:in linguistics it is set of structural rules governing the composition of clauses, phrases, and words in any given natural language. The term refers also to the study of such rules, and this field includes morphology, syntax, and phonology, often complemented by phonetics, semantics, and pragmatics

<!-- ## Conduction aphasia

* Inability to produce appropriate responses to heard communication, even though the communication is understood.
* Can speak fluently but bad at making the connection from what has been heard to how to reply.
* Often associated with damage in the Arcuate fasiculus –an axon tract that connects wernike and broca areas.

* Difficulty repeating words
* Fluent, but with many incorrect word substitutions
* Good comprehension

<div><img src="figs/image26_0d58d77.png" height="300px"><figcaption></figcaption></div>

## Arcuate fasciculus: major association fiber tract in CNS that connects Broca’s and Wernicke’s areas

<div><img src="figs/image27_5c764df.png" height="300px"><figcaption></figcaption></div>
<div><img src="figs/ArcuatefasciculusiinCortex_1c69f77.png" height="300px"><figcaption></figcaption></div>
 -->

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## Other evidence of brain regionalization

* Fritsch and Hitzig (1870)– discrete limb movements in dogs can be produced by electrical stimulation of the contra-lateral motor cortex. Thus the right hand is controlled by the left hemisphere. 'Dominant' hemisphere
* Wilder Penfield (1950)– neurosurgeon, localized motor functions by stimulating specific areas of the brain
* Roger Sperry (1960s)– split brain patient studies 

Note:

And there is lots of other evidence for localization of brain function, especially for sensory and motor information for limbs and body. In fact Fritsch…

And the Canadian physician Wilder Penfield performed classical mapping of motor function in the cerebral cortex by localized electrical stimulation.

And then there is the fascinating split brain studies of Sperry and Gazzaniga in the 1960s


---

## Penfield stimulation studies

<div><iframe src="https://www.youtube.com/embed/l1SAC1HcAzc" width="420" height="315"></iframe><figcaption>Stimululation based brain mapping</figcaption></div>

Note:

Epileptic patient. mapping the cortical tissue before resecting the site of tissue where the seizures are being generated.

*Start about minute 3*

---

## Split brain studies: Nobel prize 1981

<div style="font-size:0.9em; width:100%">
<div></div>

* The corpus callosum and anterior commissure are the two axon tracts that connect the two sides of the brain. They are sometimes cut to prevent the spread of severe epilepsies
* Each side of the brain works independently from the other
* Roger Sperry showed that the left hemisphere dominates speech, writing, right hand stereognosis, analysis of right visual field
* Right hemisphere dominates, emotional coloring of language, spatial abilities, left hand stereognosis, analysis of left visual field

</div>

<div><img src="figs/sperry_postcard_cf69954.jpg" height="200px"><figcaption>R. Sperry</figcaption></div>

<div style="font-size:0.7em; width:500px">
<div></div>

>"for his discoveries concerning the functional specialization of the cerebral hemispheres"

</div>





Note:

The classic split brain studies which Roger Sperry got the Nobel for in 1981 showed the lateralized localization of language that Broca and Wernicke anticipated as well as  several other higher functions. They took advance of the fact that in patients with severe epilepsies, sometimes the commissures connecting the two hemispheres are cut to prevent the spread of seizures.

And since each side of the brain to some degree can work independently of the other

* Humans are 90% right handed as a population and the degree of lateralization among individuals is strong, regardless of left or right-handedness
* 96% of right handers having left hemisphere speech, compared with 70% of left handers
* Twin studies have demonstrated some genetic influence on handedness, but 75% of the variance is nongenetic and individually specific, with only 25% explained by genes [#Bishop:2013]. Even the segregation of of handedness and language laterality suggests a complex polygenic set of factors, with 96% of right handers having left hemisphere speech, compared with 70% of left handers [#Bishop:2013].

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## Confirmation of hemispheric specialization for language

<div><img src="figs/Neuroscience5e-Fig-27_split-brain_copy_8719b7e.jpg" height="500px"><figcaption>Neuroscience 5e Fig. 27.3</figcaption></div>


Note:

Here is an illustration of the experiment performed by by Sperry and his colleagues for these split brain studies. 

After the corpus callosum connecting the two hemisphere was cut to alleviate epileptic seizures, the patients were asked to fixate on a point and name objects presented in each visual field. 

Now you haven’t learned about the visual system yet, but just as sensory information from your left hand goes to your right hemisphere, visual information from the lateral part of your left visual field goes to your right visual cortex. 

Split brain patients could not correctly name objects presented in their left visual field, presumably because that info could not reach the left hemispheres because the callosal connections were severed. But split brain patients could correctly name an object when presented in their right visual field, because that information was received by the left visual cortex and could be passed onto the language centers.

In all Sperry and his colleagues showed that language, mathematical, and logical reasoning is dominant in the left hemisphere and that shape recognition, spatial attention, emotional processing, and creativity in more dominant in the right hemisphere.

*right hemisphere: 'coloring' language with emotive tonal variation, 'prosody'. Adds additional meaning to verbal communication. Mandarin chinese. Monotone professor lecture*. Evidence suggest similar areas of the right hemisphere associate with this emotive coloring of language. 

Similar areas used in sign language thus this constellation of brain regions specializes in symbolic representation and communication, rather than just spoken language.


PET:
: positron emission tomography
: detects pairs of gamma rays emitted indirectly by a radioactive tracer injected into bloodstream (positron-emitting radionuclide)

CT:
: computerized tomography
: a series of X-ray images from different angles
: computer processing to create cross-sectional images


Babbling sounds from a baby shows that there is a pattern of sounds produced sequentially that are related to the phones necessary for producing spoken language. Language imitation follows other imitations (mirror neurons?) during developmental learning and behavioral acquistion. Brain is continuously simulating the future based on past experienced training patterns.




--


## Mapping brain activity with fMRI

<figure><img src="figs/Neuroscience5e-Fig-27.06-0_2687612_copy_718a9bc.jpg" height="400px"><figcaption>Neuroscience 5e Fig. 27.6</figcaption></figure>


Note:

- functional magnetic resonance imaging
- different patterns of brain activity localization depending on what the task is
- Actually sitting inside a small space magnet

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