08-09-23 - Structure and function of the cortex

Question 1

Learning outcomes

Answer 1

• Recall the main features of neurons and synaptic transmission
• Recall the main glial cells and their functions including myleinating cells and describe features of multiple sclerosis
• Describe main cell types and layering of the cell cortex and outline the connectivity of the layers with other cortical structures and subcortical ones
• Distinguish between primary and association areas (unimodal and multimodal)
• Recall examples of primary and association cortex for vision, audition, sensation.
• Outline the functions of the prefrontal area and explain features of language processing and cerebral dominance
• Be aware of the importance of white matter bundles and the use of diffusion tensor imaging

Question 2

What % of the brain is grey and white matter?

What are they each made up of?

What is their purpose?

Answer 2

• GREY MATTER (unmyelinated)
• Makes up about 40% of the brain
• Contains neuron cell bodies, axon terminals and dendrites
• Processes information
• WHITE MATTER (myelinated)
• Makes up about 60% of the brain
• Made up of bundles of axons which connect to grey matter areas
• Facilitates communication between different areas of grey matter in the brain and other parts of the body

Question 3

What are Glial (glioma) cells?

What are 5 roles of glial cells?

What are the 4 glial cell types of the CNS?

What are the 2 glial cell types of the PNS?

Answer 3

• Glioma or Glial cells are the “supporting cast” of the nervous system
• 5 roles of glial cells:
  1) Hold neurons in place
  2) To supply them with nutrients and oxygen
  3) To insulate
  4) To protect them against pathogens
  5) To clean up or “prune” any dead or useless cells/ pathways.
• 4 glial cell types of the CNS:
  1) Oligodendrocytes (myelination)
  2) Astrocytes
  3) Microglia
  4) Ependyma (lining cells of the CNS cavities)
• 2 glial cell types of the PNS:
  1) Schwann cells (myelination)
  2) Satellite cells (support cells in ganglia)

Question 4

What are 2 roles of Oligodendrocytes in the CNS?

Answer 4

• 2 roles of Oligodendrocytes in the CNS:

1) Provide structural support to neurons

2) Insulate neurons by wrapping a myelin sheath around them

Question 5

What are 4 roles of Microglial cells in the CNS?

Answer 5

• 4 roles of Microglial cells in the CNS:

1) The resident macrophages of the CNS

2) Phagocytose pathogens or dead cells

3) Antigen-presenting cells (present pathogens to other immune cells to trigger a larger immune response)

4) Involved in “synaptic pruning”
* During synaptic pruning, the brain eliminates extra synapses. Synapses are brain structures that allows the neurons to transmit an electrical or chemical signal to another neuron.
* Synaptic pruning is thought to be the brain’s way of removing connections in the brain that are no longer needed

Question 6

What are 2 roles of the Ependymal cells of the CNS?

Answer 6

• 2 roles of the Ependymal cells of the CNS:

1) Form the ependyma, an epithelial lining for the ventricles and the spinal cord

2) Secrete, circulates and maintain homeostasis of cerebrospinal fluid (CSF)

Question 7

What are 7 roles of the Astrocytes (“star-cells”) in the CNS?

Answer 7

• 7 roles of the Astrocytes (“star-cells”) in the CNS:

1) Function as metabolic and mechanical support for the CNS

2) Control water distribution

3) Maintain metabolic homeostasis

4) Reactive Oxygen Species Scavenging

5) Define architecture of the CNS

6) Regulate migration/ pruning/ synaptogenesis

7) Help maintain but do not make up the Blood Brain Barrier (more next slide)

Question 8

What is the blood brain barrier (BBB)?

What does the BBB consist of?

What is its structural integrity dependent on?

Answer 8

• The blood-brain barrier (BBB): A barrier composed of endothelial cells and their tight junctions
• Structural integrity highly dependent on astrocyte ‘end feet’

Question 9

What are Schwann cells similar to?

What are the 2 types of Schwann cells?

What are their roles?

Answer 9

• Schwann cells in the PNS are similar to oligodendrocytes in the CNS
• They are the principal glial cells of the PNS
• 2 types of Schwann cells:

1) Myelinating Schwann Cells wrap around axons/ neurons to form a myelin sheath

2) Non-myelinating Schwann Cells enfold several axons together to form a Remak Bundle

Question 10

What are Satellite Glial Cells in the PNS similar to in the CNS?

Where are they found?

What is their role?

What are they central in the development of?

What should they not be confused with?

Answer 10

• Satellite Glial Cells are thought to be similar to astrocytes within the CNS as share many anatomical and physiological characteristics
• Satellite Glial Cells are Found in sensory, sympathetic and parasympathetic ganglia
• Satellite Glial Cells cover the surface of neuron cell bodies (somata) in ganglia of the peripheral nervous system
• Thought to be central to development of chronic pain
• Not to be confused with satellite cells which are muscle stem cells (totally different)

Question 11

What type of condition is Multiple Sclerosis (MS)?

Which sex does it affect most commonly?

What does MS attack?

How does it affect signalling in the CNS?

At what age do symptoms typically start?

How can symptoms vary?

Answer 11

Multiple Sclerosis (MS) is an autoimmune demyelinating disorder of the central nervous system

Affects females: males 3:1

MS attacks oligodendrocytes and their myelin

Demyelination causes signals in the CNS to be slowed, distorted or not get through at all

Symptoms typically start in 20s/30s

Symptoms vary and may affect:

1) Vision

2) Co-ordination and balance

3) Memory and cognition

4) Emotions

Question 12

Describe the 4 types of MS. Which is the most common? How do symptoms differ between each type?

Answer 12

• 4 types of MS:

1) Relapsing Remitting
* The most common type: 85% of cases
* Characterised by acute periods of relapse then recovery
* Symptoms do not worsen during recovery/ remitting phases, but patients may not return to original baseline after a relapse
* Can progress into secondary progressive MS

2) Secondary Progressive
* People with relapsing remitting MS can progress on to secondary progressive, where symptoms steadily worsen
* Thanks to newer therapies, less patients are progressing to secondary progressive

3) Primary Progressive
* The most severe type of MS
* Affects about 10-15% of patients
* Must never have had relapse/ remitting but have commenced with progressive symptoms from the beginning

4) Progressive Relapsing
* Steady progression of disease but with periods of acute relapse as well

Question 13

What is the main treatment for MS?

What treatments are used in acute relapse?

What treatments are used in severe disease?

What is used to treat spasticity?

What is used to help maintain mobility and independence?

What is needed for those with significant disability?

Answer 13

• The main treatment for MS is Disease Modifying Therapies (DMTs)
• Short courses of high-dose corticosteroids often used in acute relapse
• Haematopoietic stem cell transplantation sometimes used in severe disease
• Baclofen tablets or Botox injections used to treat spasticity (stiff or rigid muscles)
• Physiotherapy/ Occupational therapy to help maintain mobility and independence
• Consider social care in those with significant disability

Question 14

Describe the main cortical landmarks (in picture)

Answer 14

Question 15

Describe the basic divisions of the cortex (lobes, sulci – in picture)

Answer 15

Question 16

What are subcortical structures?

What are the 4 sub-cortical structures?

What is the most significant sub-cortical structure?

What is the thalamus?

Where is it located?

What is the role of the thalamus?

Answer 16

• Subcortical structures are a group of diverse formations deep within the brain
• 4 sub-cortical structures:

1) Diencephalon
* Thalamus
* Epithalamus
* Hypothalamus
* Subthalamus

2) Pituitary Gland

3) Limbic System
* Hippocampus

4) Basal Ganglia

• The most significant of these is the Thalamus
• The Thalamus is a large mass of grey matter located at the core of the diencephalon
• The thalamus has reciprocal connections with all parts of the brain and acts as a relay station between areas. It is also involved in sleep/wake cycles

Question 17

How is the cerebral cortex organised?

Describe the 4 layers of the cerebral cortex?

Answer 17

• The cerebral cortex is organised into different layers (lamination)
• 4 Layers of the cerebral cortex:

1) Cerebral cortex external grey matter
* Convoluted shaped gyri increase packing per volume

2) 6 layered neocortex (most of the cerebral cortex)
* There is a somatic sensory and primary motor cortex in the neocortex
* Recent evolution

3) 3 layered paleo cortex

4) 4 layered archio cortex

Question 18

What are the 2 main types of neurons of the neocortex?

What layers are they mostly found in?

What is each layer responsible for?

What direction are inputs/outputs processed?

Answer 18

• 2 main types of neurons of the neocortex:

1) Stellate interneurons
* Mostly in granular layers of neocortex (2 and 4)
* There are external granular and internal granular layers
* For inputs and local processing
* Inputs are processed from the thalamus to the external layers of the brain

2) Pyramidal neurons
* In pyramidal layers of neocortex (3 and 5)
* For outputs to local and distant targets
* There are External pyramidal and internal pyramidal layers
* Outputs are processed into the internal layers of the brain towards the brain stem and spinal cord

Question 19

How do layers of the cerebral cortex differ?

Answer 19

• Layers will vary in thickness/ cellular composition from region to region within the brain
• E.g Note in the diagram the internal pyramidal layer (V) of the primary motor cortex is thicker than in the sensory cortex for example

Question 20

Where 4 areas do Input (afferents) to the neocortex come from?

What happens to topographical and non-topographical information?

Answer 20

• 4 areas do Input (afferents) to the neocortex come from:

1) Ascending information from the thalamus
* Topographical thalamic information is routed to specific areas of the cortex for primary processing (e.g. somatosensory sensation, hearing)
* Non topographical information is routed to the appropriate areas in the cortex.

2) Ascending information from other sub-cortical structures
* These include the hypothalamus, basal parts of the forebrain and the brain stem (involved in sleep/arousal amongst other things)

3) Commissural fibres (from pyramidal neurons) which travel between hemispheres

4) Association fibres (from pyramidal neurons)

Question 21

What is the nature of output (efferents) from the neocortex?

Describe the projections of the cortex (5 lines).

What are ipsilateral hemispheric projections of differing lengths associated with?

Answer 21

• Output from the neocortex is always excitatory in nature and is always via pyramidal cells, i.e. uses excitatory neurotransmitters.
• Projections of the cortex:
• All parts of the cortex project to the thalamus
• Projections from the somatosensory and motor cortices provide most of the input to the basal ganglia
• Cortex projects to the brainstem nuclei (which deal with motor and sensory information)
• Cortex projects to spinal cord (onto motor neurons in the anterior horn)
• The cortex in one hemisphere can project to the contralateral hemisphere
• There are ipsilateral hemispheric projections of differing lengths (longer ones between association cortices and shorter ones for example between sensory and motor cortex)

Question 22

What are 3 ways we learned about the functions of the neocortex?

What are 4 different types of scans be used to learn about the functions of the neocortex?

Answer 22

• 3 ways we learned about the functions of the neocortex:

1) Histology
* Brodmann divided the brain into 52 regions based on cortical cell prevalence and distribution of the different cortical layers (histology) Note that most cortex is neocortex (relatively new evolutionarily, comprising 6 layers)

2) Measuring the effects of localised damage following trauma/stroke (association and disassociation) or during electrical stimulation of a particular area in an awake patient.

3) Scanning the activity of the brain during defined tasks
* EEG – poor spatial resolution
* CT (computerised tomography)
* MRI & fMRI
* PET

Question 23

What are the 3 different functional regions of the cortex?

What is the function of each area?

Answer 23

• 3 different functional regions of the cortex:

1) Primary areas - receive thalamic input with relatively little processing

2) Association areas - integrate and pass on information from all relevant areas of the CNS – largest portion of the cortex

3) Cerebellar cortex - integrates ascending proprioceptive information with descending movement intent, and feeds back to cerebral cortex to refine movement

Question 24

What is the role of the primary areas of the cortex?

What are the 5 different primary areas of the cortex?

Where are they each located?

Answer 24

• Primary areas of the cortex receive thalamic input with relatively little processing
• 5 different primary areas of the cortex:

1) Primary somatosensory area is post central gyrus of the parietal lobe

2) Primary motor area is just anterior of the central sulcus

3) Primary auditory area is located in the medial temporal lobe

4) Primary visual cortex is located in the occipital lobe

5) Primary olfactory cortex is located in the anterior temporal lobe (piriform cortex)

Question 25

What is the role of the association areas of the cortex? What are the 2 types of association areas of the cortex? Where are Broca’s and Wernicke’s area found? What is their role? Are they unimodal or multimodal?

Answer 25

* Association areas of the cortex integrate and pass on information from all relevant areas of the CNS – largest portion of the cortex * 2 types of association areas of the cortex: 1) Unimodal (one type of modality input i.e. vision) 2) Multimodal (multiple modal input i.e. vision and hearing) * Broca’s area (language production) is usually found in the left hemisphere, in the posterior inferior frontal gyrus * Wernicke’s area (language comprehension) is usually located in the left hemisphere, in the superior temporal gyrus * Both Broca’s and Wernicke’s areas are multimodal association areas

Question 26

What is the role of the cerebellar cortex?

Answer 26

* The Cerebellar cortex integrates ascending proprioceptive information with descending movement intent, and feeds back to cerebral cortex to refine movement

Question 27

What studies are used to divide the cortex up?

Answer 27

* Brodmann’s regions along with functional areas regions delineated by the gyri and sulci of the cortex are commonly used to divide the cortex up

Question 28

What is the role of the primary motor cortex (part of neocortex)? Where is the primary motor cortex located? What 3 motor activities controlled by the primary motor cortex?

Answer 28

* The role of the primary motor cortex (part of neocortex) is the execution of movement * It has more direct control of motor activity than other motor areas * The primary motor cortex is located in the precentral gyrus * 3 motor activities controlled by the primary motor cortex: 1) Force of muscle contraction 2) Direction of muscle contraction 3) Speed of muscle contraction

Question 29

Primary somatosensory cortex. How is the somatosensory information relayed to the sensory cortex? What does stimulation of the sensory cortex produce? What do proportionally enlarged areas of the sensory cortex provide? What areas are enlarged on the sensory homunculus?

Answer 29

* Primary somatosensory cortex * Somatosensory information is relayed to the sensory cortex via the thalamus. * Stimulation of the sensory cortex produces sensations in the body which can be topographically mapped over the surface of the sensory cortex. * Proportionally enlarged areas provide cortical amplification * On the sensory homunculus, the oral cavity (lips and tongue), hands, and genitals are all enlarged as the more of the sensory cortex is devoted to these areas

Question 30

Primary visual cortex. How is the optic chiasm formed? What is the lateral geniculate nucleus (thalamus)?

Answer 30

* Primary visual cortex * The optic chiasm is formed when the optic nerves come together in order to allow for the crossing of fibres from the nasal retina to the optic tract on the other side * The lateral geniculate nucleus (thalamus) is a multilayered structure that receives input from both eyes to build a representation of the contralateral visual hemifield

Question 31

Primary auditory cortex. How do auditory signals enter the brain?

Answer 31

* Primary auditory cortex * Auditory signals enter the brain through the midbrain, enter into the medial geniculate nucleus (thalamus), and go towards the auditory cortex in the temporal lobe

Question 32

What does a majority/minority of the neocortex consist of? What is the role of association cortex? What does association cortex represent?

Answer 32

* The vast majority of neocortex is association cortex (higher order cortex) * The minority is primary sensory and primary motor areas * Association cortex functions to integrate information from other brain regions (interconnected by association fibres and tracts). * Association cortex represents the seat of our cognitive ability and so processing in these areas is where cognition occurs (this is not the same as consciousness)

Question 33

What is the role of Broca’s and Wernicke’s area? What can damage to these areas cause? What is expressive dysphagia and expressive aphasia? What is receptive aphasia?

Answer 33

* Language is processed in Wernicke’s and Broca’s areas Broca’s area produces language * Damage to this area will result in expressive dysphasia, expressive aphasia, and patients can also struggle with written language * Expressive dysphagia is difficulty finding correct word or forming grammatical sentences * Expressive aphasia (complete loss of speech production). * Wernicke’s Area Interprets language * Damage to this area results in receptive aphasia * Receptive aphasia is Impaired comprehension of written and spoken language. * Patients’ speech is fluent but lacks meaning or context. * They cannot understand what other people are saying

Question 34

Clinical aspects to neocortical lesions. How can lesions In primary and association cortices differ? What is agnosia? What are 3 different types of visual agnosias? What are 2 types of auditory agnosias?

Answer 34

* Lesions in the primary cortex produce obvious deficits which can occasionally be mitigated by neuronal plasticity * Lesions in association cortices produce a wide variety of symptoms and are less stereotypical in nature. * Agnosia is loss of a particular sense * 3 different types of visual agnosias: 1) Optic ataxia – patients struggle to locate objects in space – struggle to grasp objects 2) What - Where pathway disorientation – the two streams of visual processing 3) Prosopagnosia (or face blindness) * 2 types of auditory agnosias: 1) Wernicke’s (receptive) and Broca’s (expressive) aphasias 2) Amusia – difficulty detecting pitch or recognising/ recalling music

Question 35

What is the primary function of the cerebellum?

Answer 35

* The cerebellum primarily functions to modify movement by comparing sensory information with pre-motor information and affecting change

Question 36

What are the 3 layers of the cerebellar cortex? What types of neurons are Purkinje cells? How can Purkinje cells be damaged? In what conditions has the loss of Purkinje cells been observed? What is cerebellar hypoplasia?

Answer 36

* 3 layers of the cerebellar cortex: 1) Molecular layer 2) Purkinje cell layer (most important) 3) Granule cell layer * Purkinje cells are unique to the cerebellum and act as inhibitory neurons * They are among the largest neurons in the CNS * Purkinje cells can be permanently damaged by toxic substances such as alcohol and lithium * Loss of purkinje cells has also been observed in some children with autistic spectrum disorder * Cerebellar hypoplasia is a neurological condition in which the cerebellum is smaller than usual or not completely developed.

Question 37

What 6 activities is the prefrontal lobes involved in? What are 4 features of frontal lobe damage?

Answer 37

* 6 activities the prefrontal lobes are involved in: 1) Attention 2) Morality 3) Planning 4) Working memory 5) Conscious decision making 6) Social behaviour regulation * 4 features of frontal lobe damage: 1) Personality changes 2) Deficits in planning and initiative 3) Perseveration (repetition of word, gesture or phrase) 4) Primitive reflexes (sucking reflexes)

Question 38

What is white matter composed of? What is the purpose of this? What are the 3 different types of bundles that white matter is composed of? What is the largest commissural bundle of fibres? What regions do they allow to communicate? What is Diffusion tensor imaging?

Answer 38

* White matter is composed of bundles, which connect various grey matter areas (the locations of nerve cell bodies) of the brain to each other, and carry nerve impulses between neurons. * 3 different types of bundles that white matter is composed of: 1) Commisural – cortex to cortex cross over the midline communication * The largest commissural bundle of fibres if the corpus callosum 2) Association – cortex to cortex ‘stay’ on the same side 3) Projection – communicate with other structures inside and outside the brain * Projection fibres located in the internal capsule and corona radiata * Diffusion tensor imaging is an MRI technique used to map white matter tractography in the brain

Question 39

Association fibres and MRI diffusion tensor imaging

Answer 39

Question 40

Projection fibres and MRI diffusion tensor imaging

Answer 40