1. The study of the nervous system: a brief history
Topic 1
The study of the nervous system: a brief history
PS3002: Brain & Cognition
John Beech

2. Introduction: how knowledge of the structure of the nervous system developed
A central problem in behavioural neuroscience (and psychology), once we have recognised that the brain controls behaviour, is how the brain works.
Can we find out how the brain works by examining it in the minutest detail?
“...that a man should simply and profoundly say that he cannot understand how consciousness comes into existence - is perfectly natural. But that a man should glue his eye to a microscope and stare and stare and stare and stare - and still not be able to see how it happens - is ridiculous...” Kirkegaard 1846

3. Localisation of function
One of the starting problems is whether the brain works as a single unit or as a collection of specialised units. If it is a collection of specialised units, then damage to one of these units should result in specific changes in cognitive and perhaps emotional performance.
One neurological patient might have an isolated face recognition problem.
Another patient may have a problem not just with faces but extending to other objects. This suggests that this patient has a more general impairment in perception.

4. Localisation of function
But yet another case may have no problems with faces, but can’t see objects. E.g. fruit in the form of a face is seen as a face, but not as fruit.
Shows a double dissociation: on the one hand one can have a patient with problems recognising faces but not objects, but on the other patients with no problems recognising faces, but difficulty in recognising objects. This suggests that there is a specialised unit for dealing with faces, which may or may not be damaged.

5. Phrenology and pigeon fanciers
The issue of localised versus holistic processing is a very old question about the brain, with opinions swinging back and forth over time.
Gall and Spurzheim (1810s) fathers of phrenology. They declared that the brain was organised around 35 specific functions showing consistent localisation.
If a person used that faculty more, then that area of brain would grow, and could be detected by feeling bumps on the skull.
This was criticised by Michael Kreider ( ) on the grounds that phrenology had not been scientifically tested and until that time its current status was that it was not scientifically proven. In fact, he was critical of all quackery, and he included mesmerism (hypnosis) under this umbrella.
However, he thought that phrenology was useful in that it made doctors and scientists examine the brain with a view to examining regions that could be associated with functions of the brain and the body.
Gall

6. Phrenology and pigeon fanciers
Flourens (1824) perhaps influenced to an extent by Gall & Spurzheim - experimented with pigeons and rabbits. He showed that different parts of the brain were responsible for quite different functions. When the cerebral hemispheres were removed then all perceptions and judgements were lost.
By contrast, when the cerebellum was taken away the animal lost its balance and its motor coordination. When the brain stem (medulla oblongata) was removed, the animal died.
From this he concluded that the cerebral hemispheres were the area of higher cognitive functioning, the cerebellum controls and integrates movements and the medulla controls the body’s vital functions such as circulation, breathing and the body’s stability.

7. Phrenology and pigeon fanciers
But because he didn’t have the means for more specific testing, he believed that processes such as memory and cognition were distributed through the brain.
So, Flourens viewed the brain as an aggregate field – at least for the higher cognitive functions - all brain functions occupying the whole (c.f. modern concepts of distributed or holistic processing).
Flouren’s view prevailed for about the next 30 years, until the clinical findings in France and Germany – to do with the pathology of language gave some insight into higher cognitive functions. This later work showed that these functions actually had a specific location in the cortex. There were also to be advances due to experimentation using electrical stimulation of the surface of the cortex in primates and dogs in England and Germany, to provide further evidence for localisation of function.

8. Broca and Wernicke
In 1861, Pierre Paul Broca (French neurologist) described a patient who could not speak after a stroke, although he could still understand language. (Actually this patient uttered just one word: “tan” and so became known as “Tan”.)
After Tan died, at post-mortem, he was found to have a small contained area destroyed by neurosyphillis. This area came to be known as - Broca’s area. This areas controls speech – the motor expression of language.
In 1876 Carl Wernicke (German) – had a patient who had the complementary deficit: he could speak freely, but what he said could not be understood. This patient had great problems in language comprehension.
He had a more posterior lesion (in relation to Broca’s area), at the junction of the temporal and parietal lobes in the left brain.
These observations had a massive impact on thinking about the brain.
Wernicke

10. Broca’s aphasia
Damage to Broca’s area may produce a condition called Broca's aphasia* (sometimes known as expressive aphasia, motor aphasia, or nonfluent aphasia). They are unable to understand or create grammatically complex sentences: speech will contain almost nothing but content words.
In the following passage, a Broca's aphasic patient is trying to explain how he came to the hospital for dental surgery:
"Yes... ah... Monday... er... Dad and Peter H... (his own name), and Dad.... er... hospital... and ah... Wednesday... Wednesday, nine o'clock... and oh... Thursday... ten o'clock, ah doctors... two... an' doctors... and er... teeth... yah.”
(*Aphasia is a difficulty in producing or comprehending language because of brain damage. 80,000 get this each year in the USA – usually from middle age to late years.)

11. Hughlings Jackson – a British Neurologist
Hughlings Jackson, later in the 19th century, argued in favour of localisation of function.
He proposed that epilepsy was due to rhythmic discharges of groups of neurons.
Noted that in epileptic seizures there was often an anatomical progression of the parts of the body involved; suggested a map of the body in the brain.
Also noted that lesions on the right side of the brain were more likely to affect visuo-spatial activity than those on the left.

12. Hughlings Jackson (cont.)
However, he did not assume a one-to-one correspondence between localisation and function.
After a stroke, functions were not entirely lost, and sometimes showed some recovery:
Speech: could still usually say a few words.
Motor action: those who could not move their hands voluntarily to places on the body still might scratch those areas as an automatic response
These observations suggested to him that such functions could be supported by healthy brain areas which remained.

13. Hughlings Jackson (cont.)
Hughlings Jackson was one of the neurologists who later confirmed Broca’s work. He also made some important theoretical contributions. He suggested that higher cognitive functions such as memory and thought were not so influenced by lesions compared with “lower” functions, such as those controlling breathing and circulation.

14. Technical developments
Techniques were limited to the external observation of site of injury, or post-mortem study of the brain to localise damage.
From this interest a more experimental approach grew.
Fritsch and Hitzig, two German physiologists helped our knowledge about the localisation of function when they electrically stimulated small regions of the exposed brain of an anaesthetised dog.

15. Technical developments
This showed that certain locations consistently resulted in movements of parts of the body. The stimulation of some areas produced contractions of the front or the hindlegs. This was important work as it was the first research to show that there is a more detailed localization of function. It was also important for starting a new paradigm for brain mapping.
Following this, German neuroanatomists, in particular, using technical developments in microscope design, began a minute study of the brain.
They aimed to identify different functional areas, using cellular stains such as the Nissl stain* for cell bodies.
(* = stains to show extranuclear RNA – Nissl’s substance – in nerve cells.)

16. Brodmann and the development of localisation
In this way Korbinian Brodmann (German born) identified 52 distinct areas of the cortical surface, based on microscopic appearance.
Many of these areas have now been shown to have distinct roles, using modern techniques, eg 17 vs 18 for vision; 44, 45 for Broca’s; 1,2,3 somato-sensory cortex.

17. Brodmann-original map coloured

18. Brodmann – outline with functions

19. Feodore Krause took the Fritsch and Hitzig work (on the dog) further and stimulated the cortices of anaesthetised patients undergoing brain surgery to remove tumours. His mappings proved to be quite accurate and these were the background to later investigations by researchers such as Wilder Penfield in the 40s and 50s.

20. Sir David Ferrier, a British neurologist and anatomist also extended this work by his experimental work on dogs and monkeys working between
He electrically stimulated the cortical gyri (the ridges on the cortex) of these animals and determined 15 distinct areas that precisely controlled movement.
Later he removed these same areas surgically and demonstrated that the corresponding motor function had ceased.
A drawing of Ferrier’s stimulation points on a monkey cortex.
Sir David Ferrier

21. Sir David Ferrier
Ferrier believed that these same points were replicated in the human brain. Fortunately he was successful.
As an example he was correct in predicting the precise area in a cortical lesion that was associated with the paralysis in a patient’s fingers and forearm. Subsequently Macewen, a surgeon, took out the tumour with considerable accuracy.
So this meant that using these techniques neurological analysis became much more accurate.

22. Camillo Golgi
Meanwhile (turn of the century), in Southern Europe, Camillo Golgi, an Italian neuroanatomist, developed a remarkable silver stain which stained whole neurons, but was only taken up by 1 % of them; we still don’t know why this is so.
This stain revealed a complex, detailed and beautiful architecture, in various brain areas.

23. Camillo Golgi

24. Santiago Ramón y Cajal
Different architectures were seen in different brain areas, varying for example between cortical areas, subcortical areas and peripheral ganglia.
Golgi interpreted his images to mean that nerve cells were connected in a continuous network.

25. Santiago Ramón y Cajal
However, Ramón y Cajal, in Spain, observing similar preparations, stained in the same way, drew the conclusion that neurons were distinct entities which carried information. These neurons could pass information from one to another, in one direction only, at contact zones.
Cajal’s response to seeing the stain – translated by Sherrington, the neuroscientist who invented the term “synapse” – is shown next.

26. The art of neuroscience ?
“Against a clear background stood black threadlets, some slender and smooth, some thick and thorny, in a pattern punctuated by small dense spots, stellate or fusiform. All was as sharp as a sketch with Chinese ink on transparent Japanese paper.”
“And to think that that was the same tissue which, stained with carmine or logwood, left the eye in a tangled thicket, where sight may stare and grope forever fruitlessly, baffled in its attempt to unravel confusion, and lost forever in twilit doubt.”
“Here on the contrary, all was as clear and plain as a diagram. A look was enough. Dumbfounded, I could not take my eye from the microscope.”
(The above quotes are from Santiago Ramón y Cajal ( ), when  in 1887 he looked through a microscope at a section of neural tissue stained with a silver preparation.)

27. The fine structure of the nervous system
Considerable progress was made in delineating the fine structure of individual cell types ( e.g. Purkinje cell).
Purkinje cells are like big oak trees having more branches than any other cell type. It carries every piece of information output from the cerebellum. Such cells control to a great extent the refinement of motor activities.
Helmholtz suggested the use of cells from other species as models; squid giant axon was initial source of our information on axonal conduction in all nerve cells.
The observation of the fine structure of the brain did not elucidate further the issue of localisation of function.
The fine structure of the nervous system

28. The fine structure of the nervous system
However, it was a major step forward, and led on to the dominant neuron doctrine; essentially that it might be possible to understand brain function by analysing the patterns of interactions of individual neurons.
Some facts:
However it also pointed up the enormity of this task, since it is estimated that there are 1011 (100 thousand million or “100 billion” USA) nerve cells in the human brain (or, 100,000,000,000 cells). The brain’s % of body weight is 2%. Its weight is 1,300 – 1,400g. (Sperm whale is 7,800g). There are 186 million more neurons in the left hemisphere than in the right. It takes 8-10 sec to lose consciousness after loss of blood supply. Rate of neuron growth in early pregnancy = 250,000 neurons a minute!
The octopus has 300 million neurons in its brain.

29. The impossible task
In fact of course we can’t measure any more than a small number of them individually, and even if we could, we could not handle or understand the information, especially given its dynamic nature.
We progress by integrating information at all levels of organisation, from the molecular, to the cell, to the neuronal assembly, to the broad brain region, through to behaviour.
The number of possible interactions is impossibly large, so we have to constrain the models we make by the functional results (i.e. behaviour), and correlate observations across different levels of detail.
The extent to which that can be done is really the basic theme of this section of the module.

30. To return to the localisation of function issue…..
Many scientists, however resisted the concept of one brain area, one function. Even in Broca’s time, Marie, a contemporary of his, was pointing out that only half of the patients with lesions localised to the third frontal convolution (Broca’s area) displayed speech impediments.
Broca’s aphasia was also sometimes found in patients with lesions in neighbouring areas, rather than those confined to the third frontal convolution.
[We now understand that this occurs because the precise localisation of a specialised area can be decided during development, i.e. for some functions there are predispositions, but a degree of plasticity]

31. Lower and higher functions; local and distributed processing
Removal of quite large areas in the brains of dogs or rats resulted in little behavioural change (c.f. pigeons), again suggesting these areas had global functions.
Neurologists were sometimes amazed at the extent of lesions revealed at post-mortem on their patients, in view of the minor behavioural effects observed during life.
Even the most ardent holists, however, conceded that there was a difference between removal of the occipital cortex, and of the motor cortex, i.e. that there was some localisation of function.
However it was argued that “higher” functions, such as thinking and memory could not be localised. Moreover, the effects of lesions can be misinterpreted ….

32. Effects of lesions
Hughlings Jackson pointed out the difference between localisation of symptoms, and localisation of function. A lesion might produce a particular (bizarre) symptom, but it did not follow that that area was specialised for the control of that function.
To use Richard Gregory’s analogy, if you remove a valve (transistor) from a TV set and wavy lines appear across the picture, it does not follow that that valve was “the wavy line suppressor”.
These considerations are still crucial when interpreting modern brain imaging data.

33. Effects of lesions II
The Gestaltists’ idea was that the brain functioned as a whole and that the whole was more than a sum of the parts. If one part is removed, the rest is a new configuration interacting in a new way. It isn’t that an element of behaviour is removed (Henry Head, 1918)
Lashley’s experiments with rats running mazes appear to confirm that the disability was proportional to the size of the lesion.
But there are many ways in which rats can run mazes, resulting in many opportunities for compensation, if there are deficits in particular modalities.

34. Maps in the brain
In the 30s, Woolsey, Bard and other neurophysiologists began to discover more extensive motor and sensory maps in the brain; each modality had more than one map.
The most elaborate is the primate visual system - more than 30 maps of information - extensive specialisation within the cortex - middle temporal area and visual motion information.
Kosslyn summary: Complex processes such as those described by the phrenologists are not individually carried out by single areas, but by interactions between many specialised processes. However, these “simple” processes which are recruited to exercise such abilities are localised.
As mentioned before, the precise localisation and organisation is laid down during the whole of development, rather than being committed in irrevocable detail in its earliest stages.

35. The psychological perspective
Physiologists and neurologists studied the structure and the disorders of the brain, but it was philosophers who had considered the problem of knowledge and the mind.
School of Hobbs Locke Hume + J.S. Mill ; all emphasised empiricism; all knowledge comes from sensory experience.
This, together with the idea that cognition was not amenable to study led to the behaviorist school in psychology - Thorndike, Skinner, Watson, in the first half of this century.
They believed in the analysis of behaviour by external means; brain as a black box; all behaviour learned as the result of chains of S-S links, or S-R links.
Any behaviour could be trained by appropriate methods.

36. The counter-revolution
The counter idea to this was that sensory experience provides data upon which pre-existing brain structures (and programs) act. Percepts are best understood in relation to the emergent properties of a stimulus - Gestalt psychologists.
Re-dawn of cognition as an appropriate area to study in the 1950s.
Developments in artificial intelligence.
Use of signal detection theory, and information processing concepts, in the analysis of cognition.
“Thinking” is based on representations and mental maps.

37. Neurolinguistics
Theoretical insights from Chomsky’s work on syntactic theories.
That is, for an important area of cognition, the complexity was built into the brain, and ran on rules and principles which were universally shared by humans.
Attempts have been made to simulate linguistic structures, and Hebb’s theory of cell assemblies. These suggested that a general purpose array of neurons can subserve any of a wide variety of functions. (c.f. general purpose computer).

38. Cognitive neuroscience
Cognitive neuroscience development - Hubel and Weisel - intricate demonstration of how cells interacted in the analysis of visual signals.
David Marr modelling of these processes - major attempt to bridge the gap between brain mechanisms and perception.
Fodor - philosopher - distinction between description at functional level - roles and purposes of events, and at the physical level - electrical and chemical characteristics of those events.

39. Neural networks
Marr’s hierarchy of levels - What is computed, How it is computed (algorithms used) and Implementation.
Initial models of networks need to be constrained by biology, and by:
1) the real properties of different types of neurons and communication processes within the brain, and
2) the real properties of behaviour (functional output)

40. Conclusion
The human brain is a lump of pinky-grey goo, weighing about 1.5 kilogrammes.
Over a period of some 200 years, our view of the brain has changed from merely that, to one of a fantastically detailed and complicated structure.
In fact it is often described as the most complex structure in the known universe.
Much information is now available on brain functional anatomy, and on the detailed cellular circuitry.
Next, we will be looking at modern methods available to cognitive neuroscientists, which can be put together to study the brain and behaviour in an integrated manner.