Methods

Interference methods: Interference is a method sometimes used to study the brain and behaviour. Part of the brain is removed (or badly damaged) and the effects this has on the behaviour of the person or animal involved are recorded. In humans the most commonly studied interference method involves naturally occurring lesions for reasons such as strokes or tumours. In animals however, lesions can be made artificially by methods such as ablation, electrolytic damage of certain areas of the brain, cooling of specific areas, by exitotoxic methods or by pharmacologically damaging specific brain areas. The brain is also studied by looking at the effect of stimulation on areas of the brain. This may be carried out on human subjects if they are undergoing brain surgery but is also carried out on animals. A single neuron may be stimulated either chemically or electrically, a section of the brain can be stimulated electrically when the top of the scull is removed, or by a strong magnet with the scull intact (TMS).

Correlation methods: Correlation methods are another method used to study the brain without invading it directly (as in interference methods). When using this method, the brain is looked at while the person is asked to perform specific tasks. The areas of the brain involved in this tasked can then be monitored using fMRI scans, which can look at different cross sections of the active brain. The main advantage this method holds over interference methods is that it can be carried out relatively easily and without any long-term damage to the patient.

Histology: Histology is the method by which neural tissue is prepared for examination. It involves 4 stages:
1. Perfusion; the blood is replaced with a clear liquid such as saline.
2. Fixation; a fixative is infused into the brain to prevent decay caused by bacteria, enzymes etc.
3. Slicing; slices of different widths and from different sections of the brain ore taken. The width of the slice depends on the method that is going to be employed to examine it.
4. Staining; different types of stains (e.g. golgi stain) are applied to the slice to show up different features (e.g. fatty tissue, cell bodies).

Immunocytochemistry: This method of investigation involves labelling antibodies designed to target specific structures in the cell (e.g. receptor molecules, proteins, organelles etc). Proteins themselves can also be labelled (radioactively or florescently) and their location within a cell can be seen. This is useful when you want to examine the pathways of things like proteins.

Autoradiography: When using this method, components such as those above are radioactively labelled. The tissue they are part of is then put onto photographic film so the radiation exposes the film. This can them be developed and examined. This method allows us to examine active parts of the brain (e.g. pathways).

Neurophysiology: Neurophysiology is the study of neurons, their interconnections and the pathways and systems they make up. Single neurons can be studied using methods such as patch clamping or voltage fixing and wider populations of neurons can be studied by recording their electric signals inside the brain (field potentials) or outside the brain (EEG, ERP and MEG).

Experimental lesion studies: Lesion studies are useful for dividing cognitive functions within the brain. Naturally occurring lesion, such as those caused by strokes are not always the best way of examining the brain, as they are often 'messy' and destroy large and non specific areas of the brain. Experimental lesion studies can be a lot more controlled in this respect and so can tell us a lot more about the functional structure of the brain. There are 4 main types of experimental lesion studies:

• 1. Ablation: A specific part of the brain is removed. However, this usually also involves the removal of all associated fibres and cells, so it is still difficult to say for certain that the part of the brain which was removed was directly responsible for the function under investigation.

• 2. Electrolytic: In this method, an electrode is inserted into a targeted area and is heated up. The heat then kills the surrounding cells. This allows us to study the effect of damage in very small areas of the brain. However, like ablation it still causes permanent damage to other cells and fibres in the immediate vicinity.

• 3. Cooling: This is effectively the opposite of the electrolytic method. A small implement is inserted into the brain and cooled. This deactivates the cells it is in contact with, but does not permanently damage them. However, as with the previous two methods, it is still somewhat broad in its target.

• 4. Exitotoxic: This method involves over stimulating neurons targeted with a specific pharmacological agent (e.g. kinic acid targets glutamate). This excessive over stimulation kills the neurons but leaves other cells in the area alive. This specificity is the main advantage exitotoxic methods have over ablation, electrolytic, cooling methods.

Stimulation studies: Stimulation studies can take the form of single neuron stimulation or whole brain area stimulation. Single neurons can be stimulated chemically or pharmacologically so the physiological effects can be seen. An exposed brain can be electrically stimulated in certain areas so a functional map of the brain can be made. The same type of thing is possible without exposing the brain if transcranial magnetic stimulation (TMS) is used.

Transcranial magnetic stimulation (TMS): TMS involves using a very powerful electrical coil to generate a voltage, which is used to stimulate areas of the brain so their behavioural function can be studied. The way in which function is discovered is because the TMS interferes with the normal functioning of the brain and disrupts the subjects' normal behaviour.

Electrode: An electrode is a devise which is used to inject a small voltage into a cell or to measure any voltage changes which may occur in the cell (e. a neuron) or on a larger scale. They are used in techniques such as voltage clamping studies, and are very useful as they can be very small.

Single-units: This is the measurement of any voltage change that occurs outside a cell. A tiny electrode is used to record the change. Single-units can be pooled to give a picture of the average activity of a section of the brain.

Electroencephalogram (EEG): An EEG is the recording from a large electrode placed on the scalp which picks up the electrical activity of cortical cells. An EEG is the measure of activity of the cortex.

Event-related potential (ERP): An event related potential is as action potential that fires in response to a specific 'event'. This could be an auditory stimulus, a visual stimulus or a mental event (i.e. recognising a specific target stimulus).

Brain imaging studies: Brain imaging studies are methods by which the living brain can be examined. Examples of brain imaging studies include computerised (X-ray) tomography (CT), positron emission tomography (PET) and magnetic resonance imaging (MRI). The brain can be looked at while the subject is carrying out certain tasks so functional location can be assessed.

2-DG: 2-DG studies are a type of brain imaging studies. In this case, a radioactively labelled ligand antibody is introduced into the brain. The positron-electron emits photons which are measured by detectors and form an image. This is similar to positron emission tomography (PET).

fMRI: Functional magnetic resonance imaging (fMRI) is another brain imaging method which, like PET shows an increase in blood flow to active areas of the brain. fMRI picks up an increase in oxygen levels and shows this as a colour change on a screen. The main disadvantage this method is that it is delayed and slow in that it takes a few seconds to show any change in oxygen level and blood flow. The spatial resolution of these two methods is also limited.