Neuropsychological assessment -Spatial and non- spatial working memory at different stages of Parkinson's disease

Brain damage often results in an impairment or disability in brain functioning, which can vary in severity. In order to understand the magnitude of the brain damage and exactly what functions have been effected, clinicians have designed a number of tests. These tests aim to measure which functions have been effected, for example motor functions, memory, intellect and language among others, as well as assessing how severe the damage is. This procedure is called Neuropsychological Assessment. The types of tests used usually follow one of two routes, either a fixed set of battery tests is provided, where the battery consists of a number of specific tests that are always used in conjunction with each other and make up the battery (eg, The Halstead–Reitan Battery contains a number of specific tests to access general intelligence). The second option is a flexible selection where the clinician carefully chooses which tests to give the individual, based on the individuals assessment. A paper written by Owen et al 1997 used a battery of tests to assess spatial, verbal and working memory. The tests were carried out on a group of patients with Parkinson's disease who were compared to a number of normal controls. END The findings were that medicated patients with Parkinson's with severe clinical symptoms were impaired on all three tests of working memory, in contrast medicated Parkinson's patients with mild clinical symptoms were impaired on the spatial working memory but not on the other two. Non medicated patients with mild clinical symptoms were not impaired on any of the tests. These findings suggest that the symptoms of Parkinson's emerge and subsequently progress. The results of the tests are important because they help us to learn more about specific disorders and how they effect normal brain functions.

Memory

           Memory is an umbrella term for functions such as encoding, retrieving, recalling and recognising information. It is commonly divided into two different types, long-term memory (LTM) and short-term memory (STM). STM allows recall for a period of several seconds to a minute without rehearsal, its capacity is very limited. LTM however has a much larger capacity, meaning one can remember a much larger quantity of information and recall can last for an unlimited period of time, sometimes an individuals lifetime. The hippocampus and the frontal lobes are both implicated in memory, another area is the diencephalon consisting of the thalamus and the hypothalamus. Damage to any of these areas can result in memory loss and result in a memory disorder such as Amnesia. Amnesia is a disorder which is characterised by a loss of memory. There are two sub types, Retrograde amnesia refers to individuals who suffer a loss of memory for events that occurred before the trauma (loss of LTM) where as Antrograde amnesia refers to a loss of ability to learn new information and an inability to make long lasting memories post trauma however, memories prior to the trauma are still intact (Loss of STM). END.
           There are a number of other specialised types of memory that can be used to store information, depending on the task. Declarative memory sometimes referred to as explicit memory is one of two types of long term memory and refers to memories that can be recalled such as facts and knowledge, this refers to material that is consciously learnt and retrieved. This type can further be divided into episodic memory which is used to store personal experiences such as a memory from your favourite holiday and semantic memory which stores factual information (such as naming the capital cities of the world). The other type of LTM is procedural memory, often referred to as implicit, because the memory process for learning and recalling such memories is unconscious. This includes memories that are used to perform skills, for example how to drive a car. These sorts of memories are concerned with the ability to perform motor functions in a certain order, these types of memories are called 'proceduralized'.
Working memory actively holds information in the mind in order to perform further processing. For example reading a sentence and then processing the words so you can understand it.
Lateralization of memory
Encoding and retrieval of episodic and semantic memory has been associated with activation in the pre frontal and medial temporal cortex. Activation may be left-sided if the episodic material is verbal, bilateral if non-verbal. Working memory selectively activates the pre frontal cortex.
A model called the HERA model has been proposed to account for the differences in activation seen during memory encoding and retrieval. HERA stands for hemispheric encoding-retrieval asymmetry. This model argues that the left hemisphere is more active during episodic encoding, whereas greater activation in the right frontal cortex is seen during episodic retrieval.

Frontal Lobes

The frontal lobe is an area of the brain that can be seen in both humans and other mammals. It is positioned at the front of the cerebral hemispheres and is thought to be the most complex lobe of the brain. This is because it is responsible for a number of higher brain functions, including mediating abstract thought, as well a planning and organising behaviour and emotions. It is also involved in memory, creativity, intelligence and language among other functions.
Over the last 150 years there have been a large number of case studies of patients with damage to the frontal lobes. The most well known is an individual called Phineas Gage who suffered a severe accident, in which an iron rod was blown through his head during a construction accident. This caused severe damage to the frontal lobes and severely altered aspects of his personality. Later case studies showed that damage to the frontal cortex was associated with impaired cognitive and intellectual functioning. Although observable effects from brain damaged individuals have been a useful tool into mapping the frontal lobes, there are a number of tests that have been designed to measure frontal lobe function.
The most commonly used test to measure frontal lobe function is the Controlled Oral Word Association test which was formulated to measure verbal fluency and involves asking the patient to name as many words as possible beginning with the same letter. Those with frontal lobe damage often perform much poorly than controls. The Wisconsin card sorting test is another well known test used to analyse frontal lobe functioning. This involves the subject sorting cards in to piles, using different rules for example by shape colour or number, without warning the experimenter changes the sorting principle. It is commonly found that those with frontal lobe damage take much longer to adjust to the new principle ( this is called perseveraton), compared to normal controls.
The symptoms caused by brain injury to the frontal lobes can be quite vast but most commonly it reduces a persona ability to plan and organise, effecting both planning ahead and voluntary motor behaviour. An individuals perception of smell and taste can also be altered when the frontal lobes are damaged. t is also found that damage to the frontal lobes causes individuals to become lethargic and speak very little, often doing poorly on verbal tests.

Hemispheric Lateralisation

The human brain is split into two cerebral hemispheres, connected by the corpus callosum. Broad generalisations are often made about each hemisphere having characteristic labels. The left side is often thought to deal with language production and comprehension and generally be more rational and analytic. The right hemisphere on the other hand is often labelled as creative, emotional and intuitive. Underlying these labels is the idea that each hemisphere is thought to be qualitatively and quantitatively different, with one hemisphere being more dominant in a particular characteristic than the other hemisphere. This is supported by evidence from a number of different studies involving research on language, visuo spatial abilities, and split brain patients. Split brain patients are people who have under gone a particular type of surgery in order to try and rid epileptic seizures. The surgery involves severing the corpus callosum in order to destroy the path of the epileptic seizure. The result of this surgery is that the two hemispheres are unable to interact because all connections have been broken and therefore the two hemispheres act as two separate brains. This finding suggests that the two hemispheres are independent of one another.
The research on language has most commonly been tested by using neuroimaging techniques such as Functional Magnetic Resonance Imaging (fMRI) scans which measure the flow of blood within the brain, the faster the flow of blood, the more oxygen that is being used and therefore the more energy the brain is using. This scan helps us to see which areas of the brain are active when different tasks are completed and thus helps us to localise brain function. When studying language participants are given tasks such as recognising words or may be asked to speak or read a few sentences, therefore allowing us to see where these functions take place, in most patients language tasks are found to activate areas within the left hemisphere. Occasionally some people are found to have activation in the right hemisphere but this is much rarer .

Emotion

Emotions are often produced by stimuli that have high significance to the individual, and thus give rise to high bodily arousal, arousal meaning physiological response, often those related to fight or flight reactions.
There is controversy about whether it is the emotion (sadness) that elicits the physiological response
(eg crying), or the physiological response that elicits the emotion.


There have been a few different theories of emotion
Common Sense theory: Claims that the individual will first experience the stimulus (for example- See a bear), the perception will then occur (interpretation of stimulus -Danger), which will lead to an emotional state and this will cause the bodily arousal (pounding heart).
James Lang theory: Claims that it is the other way round and that the stimulus is followed by the perception of the stimulus, followed by bodily arousal and this leads to the emotional state (fear).
Cannon Bard theory: Claims that after the perception of stimulus, both the bodily arousal and the emotion will occur at the same time.
Schachter Cognition plus Feedback theory claims that the same physiological arousal accompanies all emotions but it is our own interpretation of the physiological arousal, that defines the emotion we feel. This is because emotions are subjective to the individual, happy sad angry all mean different things to each one of us but it is how we label our feelings which is important.
In order to understand how we process emotion it is important to look at the brain in more detail. It has been found that there are specific areas within the brain that have a role in emotion.
The amygdala is a collection of nuclei in the anterior temporal lobe and has been found to be heavily involved in emotion. In 1998 Le Doux called the amygdala the 'emotional brain'. There are several factors factors that provide evidence for the role of the amygdala in emotion. Firstly case studies with humans who have damage to the amygdala. It has been found that post  injury, humans have a reduced number of emotional behaviours and often exhibit a change in personality traits, such as being more aggressive and grumpy, suggesting an alteration in there emotional state. Secondly researchers have created experimental lesions in different species of animal and noted the behavioural changes both before and after surgery. Research with psychopaths has also found that damage to the amygdala has effected their ability to read facial expressions and thus there ability to understand emotion. This may account for their lack of empathy with there victims, since they do not understand what pain or fear look like. The amygdala has also been implicated in fear conditioning, it has been found that when pathways to the amygdala are damaged the animal subject can not learn fear conditioning, therefore reinforcing the role of the amygdala.
It has been found that the right hemisphere of the brain is more involved in emotional perception, particularly the orbito-frontal cortex. The majority of evidence again comes from human case studies of brain lesioned individuals. However both hemispheres have been found to be involved in emotional expression.

Movement Disorders

There are a number of disorders to the human motor system. These are most commony caused by either a lesion to the cortex or a degeneration of neaurons in subcortical structures within the brain.
The main area of the brain involved in production of  movement is the frontal lobe, most importantly the premotor cortex and the primary motor cortex. The premotor cortex is involved in preperation of movement and is used in complicated sequences of action such as playing the piano. It is divided into two parts the Lateral premotor cortex -external preperation of movement
Medial premotor cortex -preperation of internally generated movements
The primary motor cortex -involved in the movement of voluntary muscles

When looking at movement disorders it is important to understand that we have two subcortical loops with in our brain. The direct pathway and the indirect pathway.
The Direct pathway is excitatory and makes it more likely for a movement to happen
The Indirect pathway is inhibitory and makes it less likely that a movement will happen.

The subcortical structure most commonly involved in motor dysfunction is the Basal ganglia - a collection of  nuclei that act as a cohesive unit. Disorders caused by the basal ganglia often result in excessive or restricted motor activity, an example of such a disease is Parkinsons Disease.
The main symptoms that are used to classify Parkinsons are;
Akinesia which means a general loss of movement, movement becomes slower and harder to coordinate
Rigidity which is a stiffness of muscles
Tremors particularly when the body is at rest.
 The cause of this disorder is due to a depletion of dopamine-generating cells in the substantia nigra (a region of the midbrain). There are a number of modern treatments that are effective at managing the early motor symptoms, mainly thorugh the use of dopamine agonists such as LDopa, thease are compounds that activate dopamine receptors in the abscense of dopamine. The reason dopamine agonists are used is because we can not give dopamine directly, since it is unable to pass through the blood brian barrier, where as agonists can. Agonists helps to reduce the early symptoms but as the disease progresses, these drugs eventually become inaffective. Once this happens rehabillitation has been shown to help reduce the symptoms and there is also the option of surgery. Newer techniques such as stem cell transplants using fetal tissue and gene therapy are also being researched . 
Another motor disorder is Huntingtons Disease, which is caused by a degeneration of the caudate nucleous and Putamen (both involved in voluntary movement) -A loss a GABA neurons in the striatum reduces cell activity in the indirect loop. The resulting symptoms are;
Behaviour changes - Moodiness, Paranoia, Psychosis
Abnormal and Unusual Movements- Jerky movements/ slow uncontrolled movements
Dementia- A loss of judgement/ memory/disorientation. 
Currently there is no cure for Huntingtons disease, drugs can be given to reduce symtoms but they do not stop the progrssion of the illness, which eventually reuslts in death.
It is important to note that huntingtons disease is 100% genetic.
Another movement disorder is Tourettes Syndrome. 
This disorder is classified by multiple motor tics and atleast one vocal tic. Symptoms include head jerking, grimacing, mouth twitching and rapid eye blinking aswell as limb tics. Vocal tics include uttering wrds out of context and vocalising socially unacceptble words. The severity of the disorder varies greatly, some people  have tourettes very mildly where as others can be severely affected. Tourettes can be particularly limiting since vocal tics can include coprolalia - using obscene language and echolalia which involves repition of phrases that the sufferer hears others use. Sufferers of tourettes are often found to have other psychologicl disorders such as ADHD, COD and self harming.
As of yet there is no clear cause of the disorder but specialists believe that the drug dopamine is implicated, since at has been found that drugs that block dopaine D2 receptors are reduce the degree of coprolalia.
Early diagnosis and treatment of this disorder is essential. The diagnosis is confirmed by observing the pattern of symptoms and al though there is no set cure, most people are able to live a pretty normal life. For those patients whos symptoms get in the way of their daily routine they can be prescribed drugs to keep some of their symptoms under control. Psychotherapy or behavioural therapy can also be used, as can relaxation therapy.
Apraxia is another movement disorder but is different from the previous three because it is caused by brain damage. The most common causes are a tumour, dementia, stroke and traumatic brain injury. If you ask a patient with apraxia to do something they will be unable to perform the required task even though they understand exactly what they are needed to do. Depending on the type of apraxia they will either have trouble performing an action or speaking even though there muscles work fine and they understand what they are required to do. The problem is that the muscle movements are uncoordinated and therefore a completely different action or word is produced rather than the one that is required, it is important to note that the patient is often aware of there mistake. 
There are several different types of Apraxia;

• Apraxia of speech: sounds and words may be distorted, repeated of left out, - difficulty putting words together i the correct order.   
• Buccofacial or orofacial apraxia: Cannot carry out movements of the face, such as licking the lips, sticking out the tongue, or whistling. 
• Ideational apraxia: Cannnot carry out learned complex tasks in the proper order, such as putting on socks before putting on shoes.
• Ideomotor apraxia: Cannot voluntarily perform a learned task when given the necessary objects. For instance, if given a screwdriver, the person may try to write with it as if it were a pen.
• Limb-kinetic apraxia: This condition involves difficulty making precise movements with an arm or leg.

Apraxia ia associaited with left, usually parietal, hemisphere lesions in right handers. The most common treatments is speech therepy for those with speech apraxia eg repeating the same words many times, and slowing down how a person talks.

Visual Perception 2

Hemispatial Neglect - Is a neurological disorder resulting from damage to one hemisphere of the brain, the result of this damage is a reduction in the ability to concentrate and a loss of vision in the opposing visual field. Most commonly it is due to damage on the right side of the cerebral hemisphere which causes visual neglect on the left side of the visual field. Neglect on the right side of the visual field is rare because processing for the right side is done by both the right and the left hemisphere.
This type of visual neglect can sometimes occur after a stroke, unfortunately there is no established treatment for this disorder and therefore it is important that research continues to be carried out, in order for us to understand the underlying mechanisms. So far researchers have identified a few different areas of the brain that they believe to be involved in this disorder, damage to the parietal lobe and lesions to the inferior frontal lobe have both been found to be related. The good news about this disorder is that two thirds of people diagnosed with Hemispatial neglect do recover with time. 
There are a number of tasks that are used to study people with this disorder. Firstly researchers can track eye movements, this shows exactly where the individual looks, when they are shown an image, patients with hemispatial neglect tend to only focus on the right side of an image. 

Another task often used is a copying or painting task. This involves asking the individual to either copy an image that is displayed to them on a screen, or paint something, such as a self portrait. Below there are two examples of drawings done by people who have hemispatial neglect. This clock is a particularly good example of how this disorder works, nearly the whole of the left side of the clock is not visible to the patient showing they are lacking severely in visual perception on the left side of their visual field. The flower drawing below is another example of a patient with a very limited visual field.

Patients can also be assessed by means of a cancellation task.. Patients would be given a piece of paper with lines, like the image to the right and asked to put a line through all of the lines they could see, very often only the lines to the right of the centre would receive a cross.

 There are three main defecits that people with hemispatial neglect can have, these factors can vary in quanity which help to explain why there can be such vast differences between individuals who suffer from the disorder
1. A reduced processing capacity
 2. An impairement in keeping track of there eye movements and remembering where they have looked before.
3. Inability to sustain attention on a given task.


 Blindsight- This is a phenomenom where people have been found to have blindness in a certain area of there visual field. Patients have no visual awareness of stimuli, however when they are asked to predict aspects of a certain stimuli such as location or movement of an object,  they are able to predict correctly, at levels significantly above chance. This is different from residual blindness because patients with residual blindness only have light perception- this is the ability to tell light from dark and judge the direction of a light source, they can not make predictions of the movement of locations of objects within the visual field.


Blindsight suggests a seperation between conscious perception and fast motor reactions, Milner and Goodale offer an explanation for this in there'two visual brains' theory. They suggest that there are TWO vision systems one for visual perception (conscious awareness) )and one for  visuomotor control (unconscious).

Visuomotor control happens in the Dorsal stream which provides automatic, unconscious vision for action, it processes spatial information and is responsible for abilities such as returning a football that is passed to us. It contains a map of the visual field and is also good at detectig and analysong movements. It is responsible for Online/unconscious decisions that are made in the here and now, it is the evolutionary 'older' cortical pathway and ends in the posterior parietal cortex.
However the Ventral Stream is in charge of the visual perception system and travels to the temporal lobe, it is involved in object identification and form representation.
 

Visual Perception 1 continued

-Why do we need to move our eyes across a scene?

1 Most notably, the high spatial resolution is confined to a small fraction of the retina, the fovea. This makes sense, as implementing the foveal resolution abilities across the whole retina would not only have been very difficult, but the resulting flood of information reaching the brain would have been impossible

to accommodate in a reasonably sized skull.

-Would it not be easier if we could see the whole scene in front of us at once?

2 No, evolution has created a retinal periphery that covers a large portion of the visual environment and can monitor it for high contrast, low spatial frequency, fast changing or otherwise salient events. Once such events have been identified, the organism can either reflexively or voluntarily foveate them for a detailed analysis. For this purpose, a dedicated motor system has been developed. But it is activated only when aworthwhile target for an eye movement has been identified.

-What does FEF mean? And what is its role in vision?

3. FEF stands for the frontal eye Field, it is an area in the frontal cortex involved in the

generation of motor commands for pointing the eyes, and therefore directing the foveas, toward desired target locations FEF plays a central role in directing spatial attention, this process is directly linked to the generation of eye movement commands.

Visual Perception disorders

Firstly it is important to understand how we gather visual information. 

Our eyes make Saccades- These are rapid eye movements, from left to right, they are quick simultaneous movements of both eyes in the same direction and happen 2 to 3 times every second. 

There are a number of different visual perception disorders.

The most well known being Agnosias, Visual Agnosias, Object Agnosia and Prosopagnosia.

There are two main functions that can be negatively effected by disorders, these are

Object perception- What is it? and Spatial Perception- Where is it?

Agnosias - is a loss of ability to recognize objects, persons, sounds, shapes, or smells. However the specific sense is not defective nor is there any significant memory loss, it is a fault within the connections of the brain.

Visual Agnosias Is the inabilty of the brain to make sense of the world, often characterised by the inability to recognise others faces and well known objects.

Object Agnosia  is the inability of the brain to make sense of or make use of some part of otherwise normal visual stimulus and is typified by the inability to recognize familiar objects, sufferers however have no problem recognising faces.

Prosopagnosias- Also known as faceblindness and facial agnosia: Patients cannot consciously recognize familiar faces, sometimes even including their own, they therefore tend to rely on peripheral cues such as an individuals hair colour or voice. They can however still recognise basic objects.

Akinetopsia -Also known as motion blindness, is an extremely rare neuropsychological disorder in which a patient cannot perceive motion in their visual field, despite being able to see stationary objects without issue.

Research from people who suffer from these visual perception disorders, suggests that objects and faces may be processed in separate perceptual mechanisms/ Brain areas.

Seperate areas of the brain have been identified using FMRI scans

- FFA has been shown to become more active during face viewing whereas another area 

- PPA becomes more active during object recognition.

Moore and Armstrong found that the FEF (Frontal eye field) plays a central role in directing spatial attention.

Studying Cognitive Neuropsychology

Neuropsychology has three main aims, firstly it attempts to localise function this means to identify specific areas of the brain and find out their functions, secondly assessment of deficit because it is important for neuropsychologists to be able to understand exactly what is wrong with a patient so they can treat them in the best way possible and lastly to build models using data from their patients to understand what is considered normal psychological processing. In order to fulfil these goals neuropsychologists use several different approaches.
The first technique is to look at case studies of brain damaged patients, by doing this they can understand the impaired and intact abilities of the individual which will lead to a better understanding of cognitive functioning and hopefully allow for rehabilitation. It also helps us to understand the link between the damaged area of the brain and the resulting change in behaviour, thus allowing for localised function.
One particularly famous case study was on a patient called  Henry Molaison (nicknamed HM) who was a young man who suffered from severe epileptic fits attributed to a sever bicycle accident at the age of 7. In order to remedy his epileptic fits HM was offered surgery which he accepted. Parts of HM's medial temporal lobe were removed from both sides of his brain including two thirds of his hippocampus, after the surgery his hippocampus appeared to be non functional and he suffered from severe antrograde amnesia, meaning he could not commit new events to his long term memory. Case studies such as this have helped neuropsychologists considerably in localising function, they are useful because we are not allowed to lesion parts of someone's brain in the name of science, therefore natural cases of brain damage are quite rare and therefore valuable to our understanding.



Another interesting fact is that we have touch receptors all over our bodies, and there are more receptors in some areas of our bodies compared to others. This means that there is more cerebral cortex used to process the feeling of touch in some areas of our body compared to others.
The image to the right of this page shows an image of a body in direct proportion to how much cerebral cortex is used to process touch for each body part.

Neuropsychologists also use behavioural studies to help there research. These studies can take many different forms but one example would be to put some one in front of a blank computer screen and ask them to press the space bar when they see a black dot appear, from this you can measure a persons accuracy and latency in response, which will test there cognitive functioning.

More recently Neuroimaging techniques are used to study the living brain. Neuroimaging falls into two broad categories, structural imaging scans which look at the structure of the brain and are used to diagnose large intracranial diseases/injury's (such as tumours) and functional imaging, used to identify metabolic diseases such as Alzheimer's. The main ones used by neuropsychologists are the 
Electroencephalogram (EEG) : measures and records the electrical activity of your brain by attaching electrodes to the patients scalp, these electrodes are hooked up to a computer and record the electrical impulses (event-related potentials) from the brain. The positives are that it is a non invasive technique which gives high temporal resolution, and is relatively  easy and cheap to run however it is weak at localising function and not very effective at dealing with mass neural activity.
Positron Emission Tomography (PET): Measures emissions from a radioactive isotope that is injected into the blood stream. The isotope gives off positrons that collide with electrons and create gamma rays which are detected by the PET scanner and can build up a detailed image of the brains functioning. The benefits are that it gives high spatial resolution, a 3D representation of activity, and that by injecting different compounds you can measure different things such as blood flow, oxygen consumption and glucose metabolism. However it is invasive and has poor temporal resolution, as well as being very expensive.
Magnetic Resonance Imaging (MRI): A technique that uses magnetic fields and radio waves to produce high quality two- or three-dimensional images of brain structures. Advantages of this technique is that it gives good spatial resolution and is non invasive and non toxic, as well as providing both 2D and 3D images. However the machine used is quite claustrophobic and noisy and radio frequencies must be shielded.
Functional Magnetic Resonance Imaging (fMRI): Measures Blood Oxygen Level Dependent (BOLD) responses. Activity of neural funtion is measured by an increase in blood flow. The advantages are that it is non invasive and non toxic, with high temporal resolution and excellent spatial resolution. However analysis of the scans is complex and expensive to run, also not good for people who are claustrophobic and very noisy.
Transcranial Magnetic Stimulation (TMS): Causes depolarisation or hyperpolarisation in the neurons of the brain by using electromagnetic induction to induce weak electrical currents using a magnetic field. Thus can induce activity in specific or general parts of the brain with, minimal discomfort, allowing us to study the functions or interconnections of the brain in detail.


It has been found that there is a cross over in the visual pathway. The diagram below shows what happens when we see something in our visual field.

 

.

The History Of Neuropsychology

Neuropsychology is concerned with the effect the brain and the nervous system have on an organisms behaviour. It is a science which attempts to study the components of the brain in order to understand how the brain functions. The study of the nervous system dates back to 1700 B.C. At this time the majority of people believed that illness and brain abnormalities were caused by the supernatural. The most common treatment at this time was trephining, it was the first surgical treatment to be used and involved drilling a hole in to the patients head to release the evil spirits, it was thought that it would cure problems such as migraines, epileptic seizures and mental disorders. However at this time scientific knowledge was very limited and this treatment often resulted in death from loss of blood, it had little scientific basis. The next important marker in the history of neuropsychology came from the ancient Egyptians. The first writings of medical treatments were found on papyrus and detail the first attempt to localise brain function. Unfortunately scientific advancements were limited in the following years since the Ancient Greeks had a strong aversion to dissections meaning that the approach was less scientific and thus less accurate . Hippocrates is one of the most well known figures in medicine and he is best known for his theory of the four humours. He believed that all illness was a result of an imbalance of four fluids within the body; blood, phlegm , black bile and yellow bile. This belief lasted for a long time and influenced other physicians such as Galen.. However In the 16th Century Vesalius made a breakthrough, he was the first person to make accurate observations of the human brain. He is often thought of as representing the period of time when empirical research and careful observations triumphed over long standing beliefs of Galen and Aristotle.  In the 19th Century Wernicke showed that the cerebral cortex is linked to understanding speech, and Broca found an area of the brain which was involved in speech production. Since these findings there have been a number of new techniques that have been used to map the brain and there functions, such as scanning techniques and stereotoxic equipment and surgery. Technology has played a vital role in assisting advancements in neurobiology and without it our knowledge would be very limited.