Transcript Components of memory - University of Leicester

Topic 1
The study of the nervous system: a brief
history
PS3002: Brain & Cognition
John Beech
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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
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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.
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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.
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Phrenology and pigeon fanciers
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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 (1803-1855) 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
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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.
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Phrenology and pigeon fanciers
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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.
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Broca and Wernicke
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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
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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.)
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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 visuospatial activity than those on the left.
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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.
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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.
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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.
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Technical developments
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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.)
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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.
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Brodmann-original map coloured
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Brodmann – outline with functions
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• 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.
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• Sir David Ferrier, a British
neurologist and anatomist also
extended this work by his
experimental work on dogs and
monkeys working between 18701875.
• 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
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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.
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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.
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Camillo Golgi
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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.
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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.
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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 (1852-1934),
when in 1887 he looked through a microscope at a section of
neural tissue stained with a silver preparation.)
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• 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
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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.
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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.
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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] 30
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 ….
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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.
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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.
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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.
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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.
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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.
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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).
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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.
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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)
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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.
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