An Introduction to Neuroscience

Robert Cronshaw, a Medical student at Jesus College, Cambridge, introduces you to the fascinating subject of neuroscience.

Neuroscience is the study of the function of the brain and encompasses a wide range of topics including cell biology, electrophysiology, biochemistry, neuroanatomy and how cells cooperate to process information.

It can be used to explain phenomena including optical illusions, the automation of motor skills and even something as basic as learning. Of course neuroscience does not yet have the answers to everything and it is still a mystery how a very large number of communicating neurons can result in conscious experience. This brief introductory guide aims to give you an overview of the fascinating and still growing world of neuroscience.

Basic Neuroanatomy

The anatomy of the brain is a surprisingly complex topic and goes far beyond the simple labelling of areas of the brain as frontal, temporal, parietal and occipital. When viewed in a “coronal” section (a line running from left to right) the brain appears like this:

As may be seen in the figure, the brain has many white and gray areas. It is actually the gray areas of the brain which are very cell dense and the vast majority of processing in the brain is carried out in the outer gray layer, called the cortex. This suggests that the brain, especially the human brain, has a great number of folds in it in order to maximise the area of cortex, although this did originally mislead early anatomists into thinking that the brain was an organ designed to dissipate heat. One of the functions of the cortex is to receive sensory information from the rest of the body and process it, in an area called the somatosensory cortex:

This was mapped out by a surgeon called Penfield, who while operating on patients suffering from epilepsy, stimulated different parts of their brain. He found that he could reliably mimic sensations from a certain part of the body by stimulating the same part of the brain in epilepsy sufferers. He then used this information to create what is known as the “sensory homunculus”, a visual representation of what cortex and how much is devoted to sensation from a specific body part.

He also attempted to map out a motor homunculus, located on a strip of cortex adjacent to the somatosensory cortex, however this was less sucessful. This was because the motor cortex does not simply represent individual muscles in certain body parts, but represents complex actions, with many muscles acting in synergy to achieve a certain goal (eg hand, arm and mouth muscles acting together in feeding). This results in the same muscle being represented many times in the motor cortex and it is this which underpins recovery in stroke victims, as the representation of a muscle in one pathway could be used by another, damaged, pathway. What is essential for this is neuroplasticity, the brain’s ability to change itself.

Basic Nerve Physiology

In order to understand the mechanisms behind many neurological pathologies and  processes, including neuroplasticity, it is very important to have a basic understanding of how the nerves in the brain work. They are very similar to nerves in the rest of the body, except they recieve a large number of inputs and can also provide outputs of many different kinds depending on the stimulation they recieve. The basic principle of a nerve cell then is to process many inputs, decide whether or not to fire and then carry the signal to its target. A nerve cell carries its information to its target via an “action potential”. This is a single pulse of electrical activity down the nerve, with the nerve acting in a similar fashion to a piece of wire. However, unlike a wire, a nerve cell has relatively poor conductance and so the signal must be regenerated all the way down its length. This is achieved by having “voltage gated” ion channels. As the electrical signal spreads down the nerve these voltage gated channels are opened by electrical changes in order to allow more ions to pass into the cell and continue to generate the electrical signal. Once this signal reaches the end of the nerve it acts on different voltage gated channels which allow the signalling ion, calcium, into the nerve terminal. This then activates the release of a “neurotransmitter”, a chemical substance which either excites or inhibits nearby nerve cells, i.e. increases or decreases their chance of firing an action potential. These neurotransmitters work by opening more ion channels in the target cell, therefore allowing the electrical signal to continue to be propagated or inhibited, depending on the ion channels acted upon. A nerve cell in the brain will be recieving many of these excitatory and inhibitory signals at any given time and it will process these to decide whether it in turn will fire on not.

Neuroplasticity

Neuroplasticity is a very broad term and refers to two main concepts. The first is the ability for the brain to change plastically on a cellular level, altering the strength and type of connection between two adjacent nerve cells. The second is “cortical remapping”, the idea that if some of the cortex is damaged and no longer functions other parts of the cortex can take over this function or the opposite, that if a part of the cortex is functional but disused other functions can take over and spread into it. An example of cortical remapping is in musicians who play stringed instruments. As the fingers in their left hand are highly stimulated and crucial in playing their instrument, they are represented by a greater area in the cortex, compared to a normal person.

Neuroplasticity at the cellular level can be summarised by the phrase “cells that fire together, wire together”. What this essentially means is that cells that happen to be stimulated simultaneously will strengthen the synapse (connection) between them, making it easier for one cell to stimulate the other next time it is excited. The mechanism behind this relies on having two different ion channels in the target nerve, both stimulated by the same neurotransmitter (glutamate). These receptors are called AMPA and NMDA. AMPA is a standard post-synaptic receptor, allowing excitatory ions to flow when glutamate is released. In contrast NMDA will only allow these ions to flow when the cell is already depolarised. What this means is that if a nerve cell is trying to stimulate another nerve cell with many NMDA receptors it will only succeed if that cell is already depolarised by another cell, this is the “firing together”. If this occurs the synapse will be strengthened by a signalling process due to ions flowing in through the NMDA receptors, ultimately leading to the inclusion of more AMPA receptors. This means that in future the stimulating cell will be better able to stimulate the target cell without it already being excited.

By this process the brain has essentially “learned” to closely associate these two neurons such that one is better able to stimulate the other. It is thought that this process could underpin learning in the human brain at a very basic level and certainly seems to be the basis of Hebb’s law that “cells that fire together, wire together”.

This might all seem a bit dry, but described here is a fundamental basis for learning and this is far more than theoretical, it has been applied in practice in a technology called BrainPort. In patients who have suffered damage to their senses, such as their balance systems, BrainPort can provide an alternative means of sensory input, via gentle electrical stimulation of the tongue. If the patient leans forward, the front of the tongue is stimulated, if they lean to the right, the right side is stimulated. In certain cases of sensory damage there may be some nerve input that has remained undamaged, however this is cancelled out by a great deal of noise from the damaged nerves. What BrainPort allows the brain to do is selectively choose the neurons providing useful information. How does it achieve this? By stimulating the correct balance neurons (via the tongue) at the same time as the useful nerves are stimulating them it increases the strength of the synapse between the two. Meanwhile the synapses providing noisy information are not enhanced so their impact is reduced. Ultimately this allows function to be restored even when not wearing the BrainPort device due to the plastic increase in sensitivity to the useful sensory information.

Motor Control

It could be argued that the entire brain is devoted to motor control, from the raw sensory information coming into the brain to the direct signals to specific muscles leaving via the spinal cord. Ultimately everything the brain does is designed to guide our movement, whether it is running a race or moving a chess piece. In the words of Nobel Prize winner Charles Sherrington “To move is all mankind can do, whether in whispering a syllable, or in felling a forest…”. Therefore the definition of motor control is limited to the primary motor cortex and the motor areas which act directly upon it, in order to prevent this area from covering everything the brain does. The two key areas acting on the primary motor cortex (the area of the brain which enacts movements) are the supplementary motor area (SMA) and the lateral premotor area (LPA). These have been studied in lesion studies in monkeys, a study where a part of the brain is deliberately damaged in a lab animal and the effect on their behaviour is monitored. The result of these studies is fascinating and really brings into focus how damage to one part of the brain can drastically change behaviour.

For example, before a lesion to the lateral pre-motor area monkeys were capable of reaching around a piece of obstructive glass to reach a treat. After a lesion to the lateral premotor cortex the same monkeys were now unable to process the sensory information that a piece of glass was blocking their direct reach and that there was a hole available that they could use to reach the treat by reaching through it and to the side. However, the monkey’s vision was still clearly intact and basic sensory integration was still intact, with the monkey still able to reach in the correct direction of the treat. This deficit is due to the lateral premotor area’s role in sensory directed movements and integrating this sensory information into the resultant motor output. Interesting the LPA is also the area where “mirror neurons” were first described. These are neurons which fire when making a movement, but also when watching someone else make a movement. They are currently the subject of much discussion; in addition to their usefulness in learning movements some academics have suggested that a mirror neuron deficit may be related to conditions such as autism, however this has proved very controversial and most academics instead accept the empathising-systemising (or extreme male brain) theory of autism.

The other cortical area which directly acts on the primary motor cortex is the supplementary motor area. While the LPA is involved in motor action in response to external stimuli, the SMA is involved in internally generated movemens, such as playing the piano, where the position of the keys are already well memorised (internal stimulus). What is interesting about the SMA is it is not only active when performing internally generated movements, but also when mentally rehearsing them. Not only this, but improvements in accuracy in tasks such as the piano can really improve simply by activation of the SMA during mental rehearsal. It is thought that this basic ability to plan future movements in a very rudimentary way may have been a precursor to the much more “executive” functions of the frontal cortex, which is involved in choosing long term goals to base current movements on.

The Cerebellum

The word cerebellum literally translates to “little brain” and it owes its name to it’s physical appearance in the human brain. It sits at the back of the brain, as shown in the animation.

The cerebellum resembles a smaller version of the cerebrum. Early evidence about the cerebellum’s function came during the First World War, from a British neurologist Gordon Holmes. As the British soldiers wore hats which did not cover the back of their head they were much more susceptible to shrapnel injury in the part of their head where the cerebellum was located. He observed many symptoms in these patients, but the crucial observation was that after the cerebellum was damaged patients performed movements “as if each movement is being performed for the first time”. Therefore the cerebellum clearly has some kind of “memory” of how to perform well used movements that have been done many times.

To understand this phenomenon we must first look at the principles of control systems in the body, the feedforward and feedback  systems. Many systems in the body are actually controlled by a feedback system. This is a system which relies on taking sensory information, comparing it to a desired level and then making an adjustment based on the deviation of the sensory information from the desired outcome.

The problem with this system is an effect which can be noticed in everyday life, when setting the heating in a room or taking a shower. If we are too cold, we turn the heat up, which can then result in us feeling too hot and turning the heat back down, to the extent where we feel too cold again. There are two factors contributing to this problem. The first is latency: the delay between sensing the discrepancy and the effector systems being able to correct it. In the shower analogy this is due to the time delay from turning the dial on the shower to the new temperature water coming through the pipes. If we were to keep moving the dial until we were at the correct temperature we would have to be constantly changing to compensate for the delay. The other potential issue is sensitivity (or gain): the sensitivity determines the strength of the response to a stimulus and if it is too high it can cause wild oscillations either side of the desired variable, even with a small latency. Feedback control is inappropriate in motor systems because of the relatively high latency. While the feedback system would stop telling the muscle to move when the body part was in the correct position the delay in the feedback system would mean that body part would continue to move, such that it would end up in the incorrect position. While this system is not useful for the motor system, it is used in many other neurological functions such as control of blood pressure and thermoregulation.

For motor control we instead rely on the feedforward system of control. This is where the cerebellum and its role in learning come into play. A feedforward system relies on being able to anticipate corrections which need to be made and provide an appropriate response at precisely the correct moment to prevent deviation from the desired outcome. When a motor signal is sent to the muscles to attempt to achieve a goal an “efference copy” (a copy of the motor commands) is sent to the cerebellum. Amazingly, what happens in the cerebellum is that this motor signal copy is fed into a model system of motor actions contained within the cerebellum, which the cerebellum uses to make a prediction about the outcome of the action and correct any deviations as they happen. This prediction is based on both the motor command and current sensory information (important for making an accurate model of the external world).

Of course this is not an innate ability, no one is born with these model systems hardwired into the brain and they are actually learned as we learn to perform certain actions. The exact cellular basis behind this is reasonably well understood, but beyond the scope of this article. The basic principle is that the cerebellum compares the “efference signal” (the desired output) and the actual output. If these differ the cerebellum refines its model to eliminate the discrepancy in future. This makes sense of the difficulties encountered by the injured soldiers, the motor actions they had learned well during the course of their life would now be lost and it would be as if they had never learned them, as the centre in which this experience was stored was wiped out.

Conclusion

Neuroscience is an incredibly broad field with many different types of science coming together to answer one of the greatest questions in science: how does the human brain let us think? It is an area of very active research and as it begins to answer some questions it asks many others.