Neuro: Introduction to Clinical Neuroscience

Question 1

What is white matter?

Answer 1

The axonal structures that connect different parts of the cortex together - connects cortical grey matter to the deep grey matter

Question 2

Describe the cellular structure of the Brain Network.

Answer 2

• Brain surrounded by Dura. Outside of this there is the skull protecting the brain.
• CSF space with arteries from cardiovascular system that deliver oxygen via penetrating arteries and arterioles that go all the way down to the deep grey matter structures.
• Within the cortex there is a mix of glial astrocyte cells
• There is also the neurones.

Question 3

What are the different parts of a neurone and their function?

Answer 3

Axons - Project down through the white matter. Enables connectivity between different parts of the deep grey matter and parts of the cerebral cortex as well as down into spine and peripheral nervous system.

Cell body - Processes signals from dendrites. Can cause signal being transmitted down the axon to other brain cells.

Dendrites - Receive signal from other neurones.

The dendrite structure grows and develops as you learn and build up memories. There is branching and pruning of dendrites. Enables the brain to have very high plasticity.

Question 4

How can the cellular structure of the brain become damaged?

Answer 4

• Diseases of the vascular system can lead to the blockage of arteries
• Alcohol and nicotine can cause blockage of blood flow to particular parts of the brain causing stroke.
• Disease of the cells themselves e.g. astrocytes can become cancerous and there is proliferation of cells resulting in brain tumours
• There can also be diseases of the axons e.g. Multiple Sclerosis (MS) which results in demyelination of the axons. This damages the transmission of the cellular signals.

Question 5

How is AI based on our brains?

Answer 5

The structure of having cell bodies that process signals from many cells and sending them out to other cells is what has been turned into 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 6

What do the cases of brain damage prove to us?

Answer 6

They show us how, when a certain area of the brain is affected/damaged, certain traits/functions are consequently affected. Proves that different brain areas were responsible for governing different functions e.g. damage to Broccas area affected speech of a patient.

Question 7

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

Answer 7

Haemmorrhagic stroke - a few blood vessels have haemorrhaged and bled into the brain. Stroke is often associated with localised regions of problems e.g. may lose ability to talk, weakness down one side etc. Its damage is localised.

Glioblastoma - Cancerous glial cells. Highly infiltrative disease. This makes the disease hard to treat because you can surgically remove the core of the tumour but there is diffuse migration of tumour cells from core along white matter tracks to distant parts of the brain cannot remove all of this without removing functioning parts of the brain.

Hippocampal sclerosis - This is a structural change in the hippocampus. It can cause seizures, and it found in Alzheimer’s and other dementias

Question 8

Briefly, describe how X-ray CT imaging works.

Answer 8

In X-ray computer tomography, X-rays go through the body and are picked up by detectors on the other side of the body. Beam and detector rotated around the whole of the body. Signal intensities are taken at different angles around the whole of the body.

Mathematical processing turns this into a cross sectional image that separates out the high intensity absorption of bone from the soft tissue.

Bone shows up very bright since it absorbs X-rays very heavily. Blood within the blood vessels also absorb X-rays strongly.

So modern CT in a 2D or 3D form can be used to show brain tumours, stroke, traumatic brain injury. Only takes a few minutes.

However there is not very good delineation of the grey and white matter structures within the brain. Use magnetic resonance imaging for more detail.

Question 9

Describe a T2 weighted image.

Answer 9

• The sequence weighting highlights differences in the T2 relaxation time of tissues in MRI.
• In a T2 weighed image, the more fluid in a tissue, then the brighter the signal intensity.

Question 10

Briefly, describe how MRI works.

Answer 10

• MRI is a soft tissue imaging technique
• A strong magnetic field creates magnetisation in all the tissues
• This magnetisation is from the protons of hydrogen in water and fat in the tissue
• The magnetisation direction can be manipulated by radiofrequency pulses to produce an MRI signal which is picked up by the scanner to create an image
• The intensity in the image depends on water content, tissue structure, blood flow, capillary perfusion, microscopic diffusion of water, paramagnetics, T1 and T2 (properties of the tissue - different between different tissue types and pathologies) etc

So rather than the single contrast in CT, you get a wide variety of contrasts.

Question 11

What was used before MRI?

Answer 11

• Nuclear Magnetic Resonance (NMR)
• Chemical sample in solution sits within a strong magnetic field.
• A radio frequency pulse interacts with the protons in the chemical sample you are interested in.
• Second coil picks up a radio frequency output and this is detected and amplified and turned into an NMR spectrum.

Question 12

Describe a T1 weighted image.

Answer 12

• Related to the time it takes for the magnetisation to realign with the magnetic field.
• CSF shows up very dark because it takes a long time for the magnetisation to align whereas white matter shows up very bright and grey matter is in between.
• Absence of signal from the bone, grey signal from the bone marrow and also grey signal from the scalp.
• Gives very good delineation between white and grey matter so we can look at anatomical changes.

Question 13

What can we see as a result of increased specificity of MRIs?

Answer 13

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

Question 14

Describe the composition of white and grey matter.

Answer 14

Grey matter:

• Cell body
• Dendrites
• Intracellular and extracellular water

White matter:

• Long axonal pathways
• These are surrounded by myelin sheaths (very fatty tissue)
• Consists of CH3 and CH2

Question 15

What is diffusion MRI used for?

Answer 15

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.

Question 16

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

Answer 16

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

Question 17

What is the basis of the fMRI?

Answer 17

A very powerful technique for understanding active brain processes.

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

So in BOLD fMRI (Blood Oxygen Level Dependant functional MRI), the part of the brain that becomes active during a specific task (e.g. cognitive, motor task etc) will cause this part of the brain to have an increase in signal intensity in the fMRI sequence.

Question 18

Describe MR spectroscopy (MRS)

Answer 18

Multiparametric - variety of chemical signals that relate to metabolic and cell processes. Can see if there are changes that go on with different diseases e.g. stroke, brain tumours, epilepsy, schizophrenia etc.

• Biggest peak in the brain is from NAA (comes from neurones)
• Peaks from tCr (total creatine - creatine and phosphocreatine related to metabolic processes)
• Peak from tCho - cholines, phosphocholines, glycerophosphocolines (involved in membrane metabolism). This peak is increased in brain tumours.
• Can see that there is a peak from myo-inositol (ml). Found in glial cells.
• Some peaks from the neurotransmitters glutamate and glutamine cant be well distinguished as individual peaks
• In abnormal tissue you will get signals from lactate (present in stroke/ischaemia)
• Also in abnormal tissue you will get signals from lipids (often present in brain tumours where there is necrosis)

Question 19

Describe glutamate neurotransmission.

Answer 19

• Major excitatory neurotransmitter
• Pre-synaptic contains glutamate and is released by electrical signal to cross the synaptic gap and be picked up by receptors on the post synaptic neurone. The electrical signal will the continue.
• Glutamate that doesn’t travel across and get picked up by the receptors will get picked up by astrocytes, converted to glutamine which is then fed back to the presynaptic neurone.
• So glutamate and glutamine are very important in the functionality of the transmission of signals between neurones. Changes in these concentrations of glutamate and glutamine have been found in a wide variety of neurological disorders.

Question 20

Where has in vivo MRS demonstrated changes in Glu and Gln concentrations

Answer 20

• Aging, depression, mood disorders, epilepsy, genetic disorders, hepatic encephalopathy, brain tumors, tumefactive multiple sclerosis lesions, alcohol addiction, drug abuse, schizophrenia, traumatic brain injury and neurodegenerative disorders.
• Glutamatergic drugs being developed and assessed in some disorders to try and rebalance abnormalities in the amount of glutamate and glutamine which may be being caused by the disease.

Question 21

What is the basis of PET scanning?

Answer 21

Radionuclides are incorporated into pharmaceuticals that are specific for metabolic processes or cell receptors.

The radiopharmaceutical are injected and generate a localised gamma ray signal relating to metabolism of cellular function.