NEURO: Introduction to Clincial Neuroscience

Question 1

What is the function of the CSF?

Answer 1

The CSF acts as a conduit for cleaning out toxins, and it acts as a cushion for the brain

Question 2

What are the different parts of a neuron, and what do they do?

Answer 2

A neuron is made up of 3 main parts: the dendrites, the cell body and the axon.
The dendrites receive signals from other neurons; these get processed in the cell body, and the signal is transmitted down the axon to other cells.

Question 3

How is AI based on our brains?

Answer 3

This structure of having cell bodies that process signals from many cells and sending them out to other cells is what has been turned into what we call the artificial neural network.
Artificial intelligence and deep learning are based on structures like this, where there is a computer version of the brain. You can have a signal into the node, and that node may or may not send out signals to other nodes. All the nodes are interconnected.

Question 4

What do the cases of brain damage prove to us?

Answer 4

They show us how, when a certain area of the brain is affected/damaged, certain traits/functions are consequently affected.
This proves that different brain areas were responsible for governing different functions.

Question 5

List some different brain diseases and how they affect the brain.

Answer 5

Post-mortem pathology:

• Glioblastoma: It’s a highly infiltrative, malignant brain tumour. It’s not easy to remove the tumour because of how infiltrative it is; we would have to remove a large part of the brain as well.
• Haemmorrhagic stroke: It occurs when blood vessels to the brain are blocked, killing off the part of the brain supplied by those vessels. Its damage is quite localised.
• Hippocampal sclerosis: This is a structural change in the hippocampus. It can cause seizures, and it found in Alzheimer’s and other dementias.

Question 6

What are the 2 aspects of the brain’s regions for functional localisation?

Answer 6

• Sensory homunculus: A sensory homunculus represents a map of brain areas dedicated to sensory processing for different anatomical divisions of the body. The primary sensory cortex is located in the postcentral gyrus, and handles signals coming from the thalamus.
• Motor homunculus: A motor homunculus represents a map of brain areas dedicated to motor processing for different anatomical divisions of the body. The primary motor cortex is located in the precentral gyrus, and handles signals coming from the premotor area of the frontal lobes.

Question 7

When are X-rays useful for the brain?

Answer 7

The brain is completely surrounded by the skull which absorbs the X-rays, thus it is not possible to see the anatomical structure of the soft tissue in the brain in any great detail.

Planar X-rays are useful for viewing traumatic brain injuries such viewing bullets or nails.

Question 8

Briefly, describe how X-ray Computer Tomography (CT) imaging works.

Answer 8

X-rays (the X-ray tube rotates around the body) are beamed through the patient, these X-rays are picked up by an array of detectors on the other side of the body.

Thus, the brain is measured at different angles.

With complex mathematics, those separate lines can be turned into a 2D cross sectional image.

Modern CT shows a great more detail showing 2D, 3D and blood flow. It can be used to show brain tumours, stroke, traumatic brain injuries. It is fairly quick and used routinely for clinical diagnosis.

Question 9

Briefly, describe how Magnetic Resonance Imaging (MRI) works.

Answer 9

It is a soft tissue imaging technique. Our brain is 75% H2O - hydrogen atoms have protons and are charged.

• a strong magnetic field creates magnetisation in all the tissue
• this magnetism is from the protons of hydrogen in water and fat in the tissue.
• the magnetism direction can be manipulated by radiofrequency pulses to produce an MRI signal to create an image.
• the intensity in the image depends on water content, tissue structure, blood flow, perfusion, diffusion, paramagnetics etc.

A radio frequency pulse is sent into the brain that interacts with all the positive protons of hydrogen molecules. These protons generate a signal from within the tissue that is picked up by frequency coils.

After some computer processing, it’s turned into the 2D image that we see.

Question 10

What is T2 in MRIs, and how does it change based on brain damage?

Answer 10

T2 weighted image (T2WI) is one of the basic pulse sequences in MRI. The sequence weighting highlights differences in the T2 relaxation time of tissues.

T2w MRI - signal intensity increases with increased water water content.

Increased tissue water and loss of cellular structure all lead to increased T2.

Question 11

What can we see as a result of increased specificity of MRIs (3D T1w)?

Answer 11

A 3D T1w image is related to the time it takes for the magnetisation to align with the magnetic field.

• 1mm spatial resolution
• grey and white matter
• volumetry

We can see degenerative changes, developmental abnormalities and disease-specific changes.

Question 12

How does MRI show white/grey matter contrast?

Answer 12

T1w images give grey and white matter contrast.

In grey matter (cell body, dendrites and water - both intra- and extracellular compartments) has relatively free motion.
In white matter (long axon pathways), approximately 50% of the tissue volume is accounted for by myelin structures, meaning the T1 relaxation of hydrogen in lipid structures is very short.

Hence, the average T1 of WM < GM.

Question 13

Describe what you can see through mapping the early cortical folding process in the
preterm newborn brain.

Answer 13

Through mapping the early cortical folding process in the
preterm newborn brain. You can see the various stages of development of the brain in babies. A tw1 weighted image can show the curvature of the cortex (smooth in
preterm newborn babies). Children with low stimulation have reduced cortical development (thickness and complexity) opposed to those with greater stimulation.

• Genes are key early factors in development
• environment, education, emotional, nutrition, toxins are all major affectors in development
• Synaptic pruning and myelination changes: sensory & motor systems complete first (pre and early school),
• higher order functions still developing up to early adulthood.

Question 14

What is diffusion MRI used for?

Answer 14

Diffusion MRI used to highlight white matter pathways and how they’re connected.

It uses the diffusion of water molecules to generate contrast in MR images. MRI can measure how freely water can diffuse.
The colour in the scan can change due to anisotropy.

Anisotropy: a term used to describe a medium whose characteristic properties vary with direction of travel through the medium

Question 15

What pathological/structural changes in brain tissue cause lesions to appear bright on T2-weighted images?

(Question from lecture)

Answer 15

Bright regions on T2w images suggest increased free water content or loss of tissue structure, so
oedema, cellular damage, reduced cell density, necrosis, inflammation, demyelination, can all be
causes of bright T2w lesions

Question 16

Describe two physical/structural properties of neurones that enable uniquely different types of MR image
to be acquired.

(Question from lecture)

Answer 16

• The myelination of the axon of neurones leads to a lower water T1 relaxation time in white matter
  compared to the T1 of grey matter, hence in T1-weighted images GM and WM can be distinguished for
  assessing anatomical changes

-The tubular structure of axons leads to the diffusivity of water within them to be very directional.
Measuring the direction of maximum water diffusion allows us to determine the orientation and
connectivity of white matter pathways

Question 17

Why do you think the Stroop test is so hard? What does it tell us about how we process information?

(Question from lecture)

Answer 17

Stroop test: a neuropsychological test extensively used to assess the ability to inhibit cognitive interference that occurs when the processing of a specific stimulus feature impedes the simultaneous processing of a second stimulus attribute. - ‘the colour test with wrong labels’.

We are primed/trained to read, hence recognition and interpretation of words has priority and is a
subconscious process that is hard to override. For example, I xpct y hvae liltte diicultffy n rdaeing tihs dpseite
teh mdduled ltteers. Hence the word-reading program is well ahead in its processing pathway compared to the
conscious process you are being asked to perform to recognise the colours. Our world is interpreted with a
balance between subconscious bias and forced attentionality

Question 18

Give an advantage and a disadvantage of performing histopathological studies on post-mortem brain.

(Question from lecture)

Answer 18

Advantage: detailed microscopic histopathological analysis to understand disease effects and processes (e.g.
can stain for structures such as blood vessels, particular cell-types such as neurones, chemical types such as
amyloid) and this info could be related to clinical aspects of the disease when the patient was alive.

Disadvantage: Post-mortem studies don’t provide prognosis/diagnosis for an actual patient. There could be changes in the brain that don’t relate to any clinical symptoms, so need to be careful
how we interpret post-mortem observations.

Question 19

How do we get a 3D MR angiogram of the brain?

Answer 19

Very short TRs (repetition times) of about 10 nm are used. The inflowing blood provides a high signal against a darker background tissue signal.

Question 20

What is the basis of the functional Magnetic Resonance Imaging (fMRI)?

Answer 20

Blood flowing in the arterial side of the brain is oxygenated and blood in the venous blood is deoxygenated. Deoxyhaemoglobin is paramagnetic, its presence causes variation in the magnetic field. This causes a decrease in the MRI signal.

Amount of deoxy-Hb relates to the amount of extracted O2. which is determined by tissue metabolism.

Increased glucose and O2 extraction lead to increased blood flow, which leads to reduced haemoglobin and so an MRI signal increase.

Question 21

Describe MR spectroscopy.

Answer 21

MR spectroscopy is multiparametric. This is done via using a standard clinical scanner.

MR spectroscopy compares the chemical composition of normal brain tissue with abnormal tumor tissue. This test can also be used to detect tissue changes in stroke, brain tumours, schizophrenia and epilepsy. The test is performed using an MRI scanner.

Question 22

MRS be used to identify glutamate.
What are some effects of glutamate/gluatmine?

Don’t memorise them all.

Answer 22

Glutamate is a major excitatory
neurotransmitter.

In vivo MRS has demonstrated changes in Glutamate and Glutamine concentrations in:
- aging
- depression 
- mood disorders
- epilepsy
- genetic disorders
- hepatic
encephalopathy
- brain tumors
- tumefactive multiple sclerosis lesions
- alcohol addiction
- drug abuse
- schizophrenia
- traumatic
brain injury
- neurodegenerative
disorders

Question 23

What is the basis of PET scanning?

Answer 23

Radionuclides are incorporated into pharmaceuticals that are specific for metabolic processes or cell receptors. The injected radiopharmaceutical generates a localised gamma ray signal relating to metabolism of cellular function.

PET scanners work by detecting the radiation given off by a substance injected into your arm called a radiotracer as it collects in different parts of your body.

Can be used to view strokes, alzheimer’s disease, parkinson’s disease etc.

Question 24

List 4 tracers used in PET scans.

Answer 24

• O-15 CO – cerebral blood volume (CBV)
• O-15 water – cerebral blood flow (CBF)
• O-15 oxygen – metabolic rate of oxygen (MRO) and oxygen extraction fraction (OEF)
• FDG – metabolic rate of glucose utilization (MRG).

Question 25

Give three properties/aspects of blood that are used to provide unique types of diagnostic imaging

(Question from lecture)

Answer 25

• Blood flow gives different MRI properties of the water in blood to the water in static tissue. A T1w image shows tissue as dark, but the flowing blood shows up as bright.
• The deoxyhemoglobin in blood is paramagnetic and its presence reduces the MRI signal in a T2w
  image. Changes in blood deoxygenation are used to detect changes in blood flow that occurs in
  functional activation of the brain in fMRI.
• Blood can act as a transporter of radiopharmaceuticals into the brain that undergo metabolic
  processes or bind to specific receptors for PET imaging

Question 26

Give one advantage and one disadvantage of 1H (proton) MRS as a diagnostic too

(Question from lecture)

Answer 26

• MRS provides signals from a variety of chemicals (NAA, choline, creatine…) in the brain that may
  change with disease (cancer, schizophrenia, stroke….)
• Single voxel MRS needs a volume of about 15mm cube to generate a strong enough signal – so doesn’t
  provide whole brain coverage and there is a need to know which single part of the brain the spectrum
  needs to be acquired from.

Question 27

Glossary

Answer 27

CT – computer tomography. Method of 2D and 3D imaging be measuring X-ray attenuation through tissue

MRI – magnetic resonance imaging. 2D and 3D imaging by detecting the signal from the protons in water and fat molecules. A wide variety of imaging methods are possible including T1, T2, diffusion, perfusion, and functional.

T2-weighted MRI. An MRI method which produces images with the signal intensity related to the tissue T2 relaxation time. T2 increases with increased water content

T1-weighted MRI. An MRI method which produces images with the signal intensity related to the tissue T1 relaxation time. T1 is different between grey and white due to their different cellular structure.

Diffusion-weighted MRI. An MRI method that allows the microscopic diffusion of water molecules to be measured in a specific direction.

PET – positron emission tomography. 2D imaging by detecting the gamma rays produced from an injected radiopharmaceutical

Radiopharmaceutical – a molecule that can be given intravenously or orally that has a radioisotope attached and that has diagnostic or therapeutic use. The molecule may have properties that allow it to target specific cell receptors, organs, or undergo specific metabolic processes in the body.