Topic 4- investigating the brain Flashcards

1
Q

How did da Vinci contribute to the study of the nervous system?

A

Although well-known as an artist, he made extensive study of human anatomy and produced intricate images. These images demonstrate:

Some of the early investigations – De Vinci carried out experiments as well as drew images

A consideration of health and disease as he tried to understand what was changing in disease.

Scientific investigation could challenge previously held beliefs, e.g. identifying the olfactory nerve as a cranial nerve, which da Vinci was one of the firsts to do.

Focus on structure to infer function in many cases. The drawings were intricate as structure was now looked at to determine function. However, we cannot fully infer function from structure. Broddman’s work showed that being able to categorise the brain in terms of the microstructure was really helpful but that sometimes something that looks structurally similar to another area of the brain performed a completely different function.

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2
Q

Explain phrenology.

A

Early attempts to map structure from function did not even look at brain structure – they looked at the surface of the skull. This was the study of phrenology.

They believed that the lumps and bumps on the skull could be used to infer things about the underlying brain and the personality of the individual.

In recent years, researchers have used data collected from modern imaging to disprove the idea that lumps and bumps on the skull can indicate brain function in an individual.

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3
Q

Explain how function was inferred from dysfunction and brain lesions.

A

An alternative approach to inferring function from structure was to examine cases where brain damage has arisen and look at the subsequent changes in behaviour. If you can identify the location of the damage and the changes you can infer the function of that area:

Phineas Gage is a very famous example of this having had an accident involving explosives.

He shot the rod straight through his skull, causing damage to the frontal lobe.
He survived but had various reported changes including to personality.

His case has been hugely exaggerated but also very influential e.g. contributing the use of lobotomies.

Brain lesions are usually unique to the individual as they are uncontrolled events so results cannot be generalised.

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4
Q

Explain the research of Wilder Penfield.

A

He was one of the pioneers of modern brain mapping. He was carrying out surgery for people with epilepsy. Before he did the surgery, he electrically stimulated the areas of the motor and sensory cortices which allowed him to map out different areas of the body onto the cortex.

He was then able to do it in a controlled condition on multiple patients with epilepsy. This is a massive step up from studying brain lesions.

A transcript from one of his surgeries shows that when Penfield stimulated ‘area 3’ which maps onto the patients thumb she experienced a tingling sensation in her thumb when that area of the cortex is activated, and when the stimulation was moved to another area of the cortex the patient reported hearing music. This points to mapping out the sensory cortex, and suggests tat the patient is awake. It is possible to do brain surgery with an awake patient due to the evolutionary reason that the brain itself has no sensory receptors as there is no survival advantage associated with having pain signals in the brain.

All of Penfield’s work was conducted on patients with epilepsy as they could not justify opening up the skull of a healthy person. The idea of looking at dysfunction to infer function can be compared to breaking a computer to understand it’s function. Function cannot be determined from the brain when not in a healthy state.

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5
Q

Explain using CT scanning as a way to measure brain structure.

A

Computerised tomography is an X-ray based approached to examining brain structure:

The patient is placed in an X-ray tube which also contains a detector. Ionising radiation is therefore used.

X-ray signals pass through the individuals brain and what is not absorbed is detected by the detector.

Different tissues are able to absorb different amounts of the signal, creating an image of the brain.

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6
Q

Explain using MRI scanning as a way to measure brain structure.

A

MRI makes use of strong magnetic fields and radio frequencies to create an image of the structure of the brain:

The person is moved into a strong magnetic field.

Certain atoms in the body (mainly hydrogen) react to this magnetic field by aligning with it.

When the magnetic field is removed the atoms fall back to their original position and emit a radio-frequency wave as they do so. This can be detected.

Through a series of applying a magnetic field and then removing it, it’s possible to create an image of the structure of the brain.

MRIs scans have slightly more detail that CT ones and are used more frequently because they are more available.

MRI is typically used for:

Diagnosis e.g. looking for a brain tumour

Staging a condition- looking for very subtle signs of progression of an illness such as Alzheimers disease

To guide brain surgery- having a very clear image of an individual’s brain prior to undertaking brain surgery can be very helpful

It’s often combined with other techniques

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7
Q

What are some disadvantages of using MRI scans?

A

The patient is required to lay very still and this may be difficult for some people such as children or people with a tremor. It is also quite claustrophobic.

It is very noisy in the scanner.

Some people with medical implants (e.g. cochlear implant) or other metal implants that cannot be removed may not be able to have a scan.

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8
Q

Explain using diffusion tensor imaging as a way to measure brain structure.

A

Diffusion Tensor Imaging is a special type of MRI so uses the same principles around magnetic fields and radio-frequency waves:

DTI allows the mapping out of white matter tracts (myelinated axons).

This method uses the fact that water molecules within the brain do not diffuse at random in the brain, rather than take the path of least resistance and this is along the axons rather than across them.

So if we can measure the direction of the diffusion of water (via hydrogen) then we can map out the likely pathways through the brain.

This is one of the only techniques we have to look at pathways of the brain rather than structures.

Note although generally considered a structural method, it is starting to be used in functional studies too.

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9
Q

How do we measure brain function?

A

There are two ways to do this; direct and indirect measures.

Direct measures of brain function must be measuring neural activity- the activity within neurons. This can be done in two ways:

Measuring electrical signals from neurons- the action potentials but also some of the postsynaptic potentials

Measuring the magnetic fields induced by the electrical signals- electrical and magnetic fields are set up at right angles from each other- so an electric field travelling left to right will have a magnetic field induced perpendicular to that. Wherever there is electrical activity in the brain there is a corresponding magnetic field and so any recording of that is a direct measure of brain activity.

The alternative to direct measure of brain activity are indirect measures. These measure a correlate of neural activity rather than actual neural activity.

The most commonly used correlate is metabolic activity:
When neural activity increases the neurons require greater amounts of oxygen and glucose and this is carried to them via blood.

So blood flow should increase when oxygen and glucose requirements are higher.

Therefore measuring blood flow reveals areas of increased neural activity.

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10
Q

Explain electroencephalography.

A

EEG is a direct measure of brain activity.

It measures the electrical signals from the brain through the skull, by the placement of large electrodes at set positions on the skull:

Electrical signals from within the brain seep through the sutures of the skull, as this is the path of least resistance, and can be detected by the electrodes.

This process is very quick, virtually in real time so the technique has excellent temporal resolution (good time accuracy). When an area of the brain is active, the EEG picks it up almost instantly.

Because the signals take the route of least resistance through the sutures, it can be hard to tell where they originally came from, even with complex calculations, so the method has very poor spatial resolution.

It is a cheap technique, which is portable and has minimum discomfort for the participant.

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11
Q

Explain the processing of the EEG signal.

A

The EEG signal provides a waveform for each electrode. This could be as few as 19 or as many as 256.

Each waveform can be categorised by frequency which can be associated with different functions. A waveform could have a high or low frequency; researchers use frequency bands to categorise these and different frequencies are associated with different brain functions.

It can also be used to look at stimulus evoked responses by time-locking the frequencies to a particular event:

Event-related potentials can be recorded by looking at the EEG signal immediately after a stimulus or event.

This can be used to examine the brains response and sometimes sequence activity to a complex stimulus.

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12
Q

Explain magnetoencephalography.

A

MEG is a direct measure of brain activity.

It measures the magnetic fields induced by neural activity using detectors containing SQUIDS (superconducting quantum unit interference devices):

The magnetic fields are induced simultaneously with the electrical activity, meaning there is no time difference between the two, and these are detected immediately, giving excellent temporal resolution, comparable to EEG.

Unlike the electrical signals the magnetic ones travel directly from the source so it is easier to know where they have come from.

However, the magnetic fields are quite weak and degrade quickly as they move through the brain so a signal from the very middle of the brain will be quite weak by the time it reaches the detectors and may not even be detectable. This means this technique has excellent spatial resolution for outer areas of the brain like the cortex but not below this as the signals have started to degrade.

The technique is very expensive because of the SQUIDS and not portable but for cortical studies it gives excellent resolution.

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13
Q

Explain the haemodynamic response.

A

When a neuron or a set of neurons fire, it takes about seven seconds before blood flow to the area increases. The increase in blood flow brings the increase in oxygen and glucose. When the neurons stop firing, the levels of oxygen and glucose fall to even lower than they were originally and so for a very brief period of time the area that was active is operating at a deficit- this is about 15 seconds after the neurons have fired. Then everything returns to normal.

For imaging techniques using metabolic correlates of neural activity there is a way of dividing the brain up into little cubes. Within each small cube there will be thousands of neurons.

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14
Q

Explain functional magnetic resonance imaging.

A

The haemodynamic response is about different levels of oxygenated and deoxygenated blood in brain regions.

These two types of blood have different magnetic properties, meaning they respond differently to the magnetic field:

This difference creates the Blood Oxygen Level Dependent or BOLD signal, which is what an fMRI measures. As the amount of blood flowing to an area changes based on neural activity, we see a change in the BOLD signal.

This signal is derived from slow changes within the brain (the haemodynamic response) and therefore it has poor temporal resolution relative to direct methods.

However, it is based on MRI and there signal is consistent across the brain so it has excellent spatial resolution.

It has all the same issues as MRI e.g. noisy, claustrophobic etc.

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15
Q

Explain positron emission tomography (PET).

A

In PET, the individual receives a radioactive substance (usually oxygen or glucose) by injection or inhalation prior to the scan.

This substance travels in the blood. When blood flow to an active area increases as part of the the haemodynamic response, the radioactive signal from this area will also increase:

The process of the haemodynamic response combined with radioactive decay means very poor temporal resolution.

This signal does not decay on the spot where activity happens. A positron is released as part of the decay process. This moves through the surrounding tissue and at some point will bump into an electron and the process of annihilation will occur. Annihilation produces a gamma ray, which is detected by the scanner. This means that the signal does not derive from the exact location of the tracer but rather from the nearby region, and so spatial resolution is limited.

The scanning is very expensive because of the radioactive substances. It also carries risk.

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16
Q

Explain using PET to examine specific neurotransmitters.

A

It is possible to target specific neurotransmitter systems with a PET scanner.

It is possible to use a tracer which will bind to specific receptors. It will bind to these receptors effectively but not as effectively as the natural neurotransmitter would, and so when the transmitter is actually present it will displace the tracer and we will see a change in the level of radioactivity.

PET is the only of the methods that can show neurotransmitter specific changes.

17
Q

Explain the spatial (mm) and temporal (ms) resolutions for the different techniques.

A

Smaller numbers in resolution are better.

EEG- 20mm, 1ms
MEG- 15mm, 1ms
fMRI- 5mm, 1000ms
PET- 8mm, 50,000 ms

18
Q

Explain experimental lesions.

only for animals

A

Accidental lesions cannot be carefully controlled and before and after testing is normally not possible. Experimental lesions can be produced very precisely and a range of techniques are available:

Irreversible lesions include radio frequency or electrical lesions, excitotoxic lesions and aspiration.

Reversible lesions include local anaesthetics.

The type of lesion will depend on the study requirements and some are more selective to neurons in a certain area than others.

19
Q

Explain non-selective lesions. (only for animals)

A

RF or electrical lesion removes all tissue (neurons and fibres passing through) around tip of electrode. Often used to mark recording site.

Excitotoxic lesion removes cell bodies but not fibres passing through. These work by binding to glutamate receptors and essentially exciting the cell to death.

Aspiration removes all tissue in area. Often used for cortical regions as effectively sucked away.

Local anaesthetic suppresses activity in area including fibres passing through. It can be hard to judge extent of suppression because it is not always obvious how effectively the local anaesthetic has diffused through the tissue.

20
Q

Explain selective lesions.

only for animals

A

Selective Toxins provide lesions that target certain types of cells and therefore certain neurotransmitters.

You might want to remove a particular neurotransmitter you believe to be particularly important to a function and measure the function before and after removal.

E.g. dopamine has several different dopamine pathways with different functions. If you wan to remove just one pathway you can put a slective lesion into that pathway using 6 Hydroxydopamine (6OHDA). You can inject this into the pathway or the area where the pathway ends. It will be taken up and travel back to the cell body and result in the death of the dopaminergic neurons. We can look at the effect of these neurons being present and then absent to understand the role that they might play.

21
Q

Explain electrophysiology.

only for animals

A

It is possible to record electrical activity using microelectrodes in animals. This can be done using a range of methods which broadly fall into:

Intracellular: The electrode is placed inside an individual neurons and the current recorded.

Extracellular: A slightly larger electrode is placed outside neurons in the extracellular space and the current recorded. However, it might be close to other neurons and so pick up signals from neighbouring neurons as well.

This can record spikes of electrical activities or post-synaptic potentials. This gives us a sense of both incoming and outgoing information of the neuron.

22
Q

Explain recording chemical signals.

only for animals

A

It is possible to measure chemicals present using methods such as microdialysis:

A probe is placed in the brain with reasonable precision and can continuously monitor the extracellular fluid.

At the end of the probe is a semi-permeable membrane which means that chemicals can cross the membrane. Typically, chemicals from within the brain cross into the membrane and are replaced by an artificial version crossing out of the probe and into the brain. This way we can collect some of the chemicals from the brain and take them out of the probe to analyse. This helps us understand when chemicals are low or higher than expected in certain health conditions or following certain behaviours.

Although this allows us to continuously monitor the brain because the probe can stay in place, the temporal and spatial resolution is poor. Although the probe is small, it is not tiny and so it is not always possible to know where the chemicals have come from, and because you have to pump the fluid very slowly so as to not damage the brain, the temporal resolution is poor.

Other techniques exist such as voltammetry which measures electrical changes and can infer the chemicals present from this as each neurotransmitter has a particularly electrical change associated with it e.g. a dopamine signature.

Being able to look at chemicals in the brain can be useful to understand basic functions and look at the effects of drug treatments for some conditions.

23
Q

Explain the anatomical approach of using basic stains to study the brain post-mortem.

A

This can be used post-mortem on a human brain.

This involves taking the brain tissue and processing it in a way that allows us to apply a stain to it. The stains can be used to identify different features:

Identify neurons and glia by staining the cell and looking at distinctive shapes.

Staining processes of cells e.g. axons and dendrites including spines using methods such as the golgi stain.

Trace specific pathways using anterograde or retrograde tracers. This wouldn’t be done on humans as they would have to be alive when it’s injected.

Anterograde tracers are injected into the cell body region and move towards the axon terminal indicating the path. The retrograde tracers are injected in the terminal region and move backwards to the cell body, telling you where the path starts. This helps mapping out pathways and how they might change in particular health conditions.

24
Q

Explain using immunohistochemistry to study the brain.

A

Immunohistochemistry is a technique that uses the process of selectively identifying antigens (proteins) in cells of a tissue and then tagging these with stain that can be detected:

These can be general markers e.g. cell activity.

They can also be very specific e.g. to an enzyme or reuptake channel protein which allows the stain to identify specific types of neurons.

25
Q

What are some considerations to take into account when interpreting animal behaviour?

A

We may look at specific behaviours in healthy animals and see what happens if the animal is lesioned or record from individual neurons during a specific behaviour.

  • lab animals live in a high controlled environment.
  • to make an animal do a particular behaviour requires a lot of training
  • a motivation must be induced; an animal will work for food or water. They may be given a normal amount of food but only given it after the task or they may be given slightly less food overall.
  • animals vary from one another and have key individual differences
  • animals can be nervous around people they don’t know or when placed in a new environment and so it is important that animals are habituated to the test environment and the individuals handling them.
26
Q

Explain using behavioural tasks in humans.

A

Animal studies can be useful to inform on human behaviour. Animals don’t engage in the same behaviours as humans however there are some very simple tasks that seem to inform about human behaviour.

For example, a morris water maze. This is a bit like a rat paddling pool and has milky coloured water. If you put a rat in there and it swims until it finds the hidden platform, it will very quickly go back to the hidden platform when put in the water maze again. This can help us learn about spatial memory and has taught us a lot about human memory. It can be used to study how some drugs can impact memory.

A T maze is a maze shaped like a T. A rat is placed in one arm and is allowed to wander down any of the other arms. To test impulsivity, one arm has a larger treat but requires the rat to wait 30 seconds before being allowed to eat it while the other arm has a smaller treat and no wait time. This is helpful investigating things like ADHD.