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Here I want to join my voice to that of
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the the speakers the fact This for this
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very gracious invitation join you for
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this very exciting. Um I plan to speak
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to you is my title indicates on
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biological base of individual all of
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the in the nature of age related memory
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disorders. Um since some of you to not
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spend twenty four hours a day thinking
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about the brand I thought it would put
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my discussion of learning and memory
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into a bit of a star for context for
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you too you can see how we develop that
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occur notion of how we learn and
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remember. Let me begin by introducing
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them MM to them as magical qualities of
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online learning is you know is the
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means whereby we acquire new knowledge
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in the world. And memories the process
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whereby retained that knowledge over
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time most of the knowledge we have
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about the world the most about skills
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are not don't and branded breath but or
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as a result of this knowledge built
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over a lifetime we are in good measure
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who we are because what we learned and
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what we remember fortunately we were so
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the capability of forgetting. So if you
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wanna forget this like you have my
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permission to do we yeah so a specific
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disorders of learning in disturbances
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memory want the developing infant as
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much as the mature might not meant to
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be tradition makes it affects the
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quality of life of young people love
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"'em" normal weakening of memory with
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age is used for and that is the
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stations of all times Z.'s Hartsfield
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memory is the glue that binds our meant
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to live together without the unifying
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force of memory our consciences will be
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broken up into as many fragments is
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zero seconds in day memory that life
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without them we would be empty
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meaningless imagine a life without
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memory. This is like wearing he
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suffered from her presence F like this.
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Was wiped out this medial temporal or
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including happy campers areas I mean he
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was waving about twenty back trendy
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image what have one night train to use
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one hundred three this what we remote
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just like that the difference we didn't
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need to to to in the sense is going to
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keep in touch which is not something we
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should is really isn't this recession
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like okay from the spell sense is a
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pain in the sense of any kind with you
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know the I don't remember sitting down
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on the chip for job was to use it as a
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was an to me I'm losing invasions of in
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those first posing the question when I
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heard that actual lessons accompaniment
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oh let me put this in a bit of a
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context for you it's convenient just
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divide the study memory to to plots the
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systems problem remembering. And the
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molecular problem remember the systems
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problem memory ask where the brains
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memory for the molecular problem and we
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we say what are the mechanisms whereby
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the storage occurs in each site. Let me
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begin with the systems problem greater
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in the brain is not restored this was
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starkly part of a larger question to
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any mental process be localised to
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specific regions of the brain or mental
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functions if you see distributed
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throughout the bright the in a tent to
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address this question it brought up
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some of the greatest intellectual
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accomplishments of brain science in the
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nineteenth century it all again with
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fancy ocean yeah well of course know
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intimately. I he told Indiana it around
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eighteen hundred needed to major
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insights in the relationship between
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mine neighbour bring he did away with
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cartesian dualism you argue that or
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mental functions of biological and the
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rice on the bright and second audio
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argue even more radical notion the
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different all the functions can be
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localised to different regions of the
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cerebral cortex ninety new is well with
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you and I do that there were four also
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the brain frontal temporal are
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unacceptable forty new from psych a
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logical studies that there were more
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than for psychological processes go on
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so he needed to have some way of
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localising these other functions in the
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brain. And annotated by subdivide in
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the brain into about forty different
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regions each one of which carried out a
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particular mental function he thought
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that the cognitive functions when the
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front of the brain comparison causality
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a sense of time sense of two the
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sentiments oh so the maybe federation
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one in the middle of the brain and
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instinctual functions courses this
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combat of nets if mister mac to draw
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parrot a lot back of the break now how
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can decide to localise these functions
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to these different regions of the brain
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is really very simple. He whatever out
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to the Leslie company. I examined the
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leadership I was impressed with that
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that they're very very prominent
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foreheads that were from a consulting
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company really large problem for high
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contrast other companies a sure I know
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for what we're so thought you know that
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the right all these people the front of
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the brain is the concerned with
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cognitive functions it launches ended
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questions I lost all about that. So you
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have for example people to make
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comparisons which is essential for
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leave a company that it becomes larger
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if you work at Nestle that pushes
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harder frontal bone and pushes it out
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and you also have things that affect
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the back of the brain for example that
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women they work for Nestle are
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extremely rude. I think women that just
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that the woman you meet industry And
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they have a problem back at the head
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the less romantic women that work for
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other companies have a very shallow
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that I find out of course no how this
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works them market misreads romantic of
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the the back of the brain you practise
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a lot of romantic love well on this
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made a fantastic impact this actually
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call for knowledge what that we're all
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imagination particularly united states
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if they woman again today a man
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seriously how father would ask him to
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for them and then you would probably
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discard to see what was suitable you
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want to come whatever they're always
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sceptics in a problem any french
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scientist by the name of the movie on
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PF Ron said what is the experimental
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evidence behind this yeah nothing. So
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he said he's gonna test this. He took
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experimental animals door. S cats rats
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chickens any cut out the back of the
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brain. And this is fact it in some
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cases the ability to move around but
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had no effect that all the ability to
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make a lot of you know so he came to be
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basic conclusion inset or perceptions
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all publishers occupy the same C
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deserving organs the faculty of CD of
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conceiving of really really different
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constitutive faculty which is
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essentially one well brain really
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carries out similar functions and or
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functions you distribute it freely
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throughout the brain mental functions
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ERP Anna localise in specific regions
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of the brain the thing started tell
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about the middle of the century when a
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major neurologist came along but the
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name of P apollo program Brock argue
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that there probably is localisation of
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function but not to the skull but to
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the brain itself different regions of
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the brain probably have specific
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functions and the way to study that is
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to encounter patience queer reasons for
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particular functions in the C where in
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the brain is that function localise and
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he can't get a very very interesting
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person who had difficulty with speech
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you could understand language perfectly
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well but I couldn't express itself for
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language read I keep the autopsy broken
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discovered that there was a lady should
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and the front of the bright but this is
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very interesting anyone to talk to
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people about you wanna give scientific
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lex's but so we needed to name it
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somehow. And destructive instructor
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instrument then a modestly name that
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they have to sell but we do that pretty
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soon discovered several other patients
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that had exactly the same lesion or on
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the same side on the left hemisphere
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any enunciated loophole Les mis people
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fish we speak without left hemisphere.
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This made a tremendous impact in the
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scientific community to German
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scientists fits and that's it begin to
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stimulate the surface of the cortex
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with electrodes and just see what
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happens is stimulated this and awards
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and they found that as a stimulated
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different areas they get movements in
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different parts of the body and the way
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that actually for the map face all lang
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systematic representation of the body
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surface and them more immaculate
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stimulate what area you almost gonna
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alike moves this is really quite
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remarkable and that led to the third
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rediscovery call veronica is soon is
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exactly for medical school. We made a
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remarkable discovery you found a region
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of the brain it which the person could
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express language perfectly well but
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couldn't make themselves understood
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this is very interesting this is
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located the back of the brain at the
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front of the brain. So he can you
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needed name it or distinctive people
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about it general modestly now we have
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the model okay named have to itself for
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Nicosia area but one of the interesting
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thing about vertigo which I find so
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fascinating use it often helps to come
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in second model that first the
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discovery because we come in second you
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see a broader perspective. And he was
00:10:46
able to say well what you you were the
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complex function like language. It's
00:10:51
not localised to a single area it
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involves a whole system it
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interconnected system and a let's make
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sense out of this there is the auditory
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cortex and which you hear language you
00:11:07
know that's necessary for understanding
00:11:09
language and you want or cortex is near
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the visual cortex also the back of the
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brain and both of these areas in terms
00:11:17
that feed into very because here we are
00:11:20
so if you read something well you hear
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something that feeds into your
00:11:24
comprehension of language and as you
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also knew there was a path we call be
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awkward physically lose the fed to
00:11:32
progress area more or broken area was
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right need gizmo to strip that I talked
00:11:37
about it but thankfully with neither
00:11:39
vocalisation area any connected to
00:11:41
work. So that was a whole system that
00:11:44
he discovered the first time a complex
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system at the sec it induced upon
00:11:48
bought moreover you could make a
00:11:51
prediction that someday somebody in
00:11:55
this room would be able to describe is
00:11:59
there talk of aphasia we did not
00:12:01
involve I verticals yeah we were broke
00:12:04
as you can anybody in the audience tell
00:12:06
me what sort of a leisurely decidedly
00:12:08
you must know that I but it's a first
00:12:13
time I found him speechless I've known
00:12:15
this guy I I for a guy you tell me this
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is that does that mean see like since I
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see I see this side. said very quietly
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an every gene mutation out of we have
00:12:37
in this connections in there if you cut
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the pathway. P it between verdict is
00:12:43
variable yeah the patient in the states
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absolutely everything you say you can
00:12:48
express himself clearly but there's no
00:12:51
connection between the two is like a
00:12:53
presidential press conference I think
00:12:57
we should go. and information comes out
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but there's no connection between I
00:13:04
think that maybe it twentieth century
00:13:06
men mental many mental processes been
00:13:08
localised to specific regions of the
00:13:09
brain. But that begs the question what
00:13:12
about memory a complex process like
00:13:14
maybe can it be stored in the brain not
00:13:17
many people like all actually professor
00:13:19
of psychology at all the big deal he
00:13:22
said it cannot be localised. It's a
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diffuse property of the bright. And is
00:13:27
it is because he use rats to run mazes
00:13:30
and he found that we need took out the
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visual cortex is still the the task
00:13:35
really took together your other court
00:13:37
is tolerant task. So in said memory
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must be distributed throughout the
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bright but didn't realise is that these
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animals and that is dumb missy thought
00:13:46
if you took out one area that that the
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visually area the and what would use
00:13:50
tactile sensation to work the males
00:13:53
feature got another yeah we would use
00:13:54
other kinds of sensitive information.
00:13:57
So it lay actually was wrong in the
00:13:59
person first pointed this out. So we
00:14:02
actually had a few like for ryan's
00:14:04
diffuse it distributed but the person
00:14:06
really solve the problem is well look
00:14:07
and feel while the pen field to the
00:14:11
right of what was it Olympia was the
00:14:13
night tenure at Columbia university
00:14:15
people you wanted to be chamber the pop
00:14:17
and he was not given that opportunity.
00:14:19
So long to Montreal oh the rock if only
00:14:22
game a lot of money to store them
00:14:23
Montreal neurological institute devoted
00:14:25
to understanding the human cerebral
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cortex. He like to deal with patients
00:14:31
that had scar tissue on their brain
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which course seizure activity. And he
00:14:36
developed a technique for operating on
00:14:38
them. And then on the best ties
00:14:41
condition you realise that the brainy
00:14:43
doesn't have any pain itself. is the
00:14:45
brain per citizen feel any pain So if
00:14:48
you infantry scale with a long like an
00:14:50
anaesthetic you can if you open up the
00:14:53
scale open up the brain the only skull
00:14:56
expose the brain and then you can
00:14:59
stimulate different areas to make sure
00:15:01
you don't take canary that's valuable I
00:15:03
woke as you know your verticals here.
00:15:05
He had been frame by showing any
00:15:09
century lather showed it all the time
00:15:12
work with my keys with cats imagine
00:15:14
I've gotta preparation at that stage
00:15:16
back to me if I stimulate that the pay
00:15:18
she's tell me what they sense
00:15:20
impatience some say oh I see visual
00:15:23
sensations he was stimulating the
00:15:24
visual cortex you would be able to get
00:15:27
speech by stimulating local vertical
00:15:30
stereo. But when you got the up areas
00:15:33
in the temporal lobe he was able to
00:15:34
elicit memory patient would say oh I
00:15:39
remember it was like to have my first
00:15:40
shot or a man with say a remember what
00:15:43
they play at a problem that I intended
00:15:46
but I graduate from high school so it
00:15:48
was really quite fascinating that you
00:15:50
would be able to local lies actual
00:15:52
memory by stimulating different parts
00:15:54
of brain them at let it friends in new
00:15:56
Orleans I should tell them members of
00:15:58
the new exactly institute one wild
00:16:01
about this I think you'd be hard to
00:16:02
play with the meeting no matter what
00:16:04
with the tape recorder because you
00:16:06
thought on Koch is mental processes
00:16:08
would be the linear in the brain and
00:16:11
you define these areas which really
00:16:14
stimulated gave them the best results
00:16:16
in terms of a listed in memory. And the
00:16:19
things that would and sell definitive
00:16:22
proof for the point of the hippocampus
00:16:25
and the media type remote being
00:16:26
involved in memories which came from a
00:16:28
certain about the remote immigrant when
00:16:30
you scroll field this is a tragic
00:16:32
example but it what signs a gradient
00:16:35
Scott will work a patient called H and
00:16:41
order very interesting history what he
00:16:43
was about twelve years old he was not
00:16:45
over by by sickle and left and punches
00:16:48
we came through came to he began to
00:16:53
have seizure activity. And then seizure
00:16:55
activity for the longest time was well
00:16:58
controlled. He was able to finish high
00:17:00
school was the beginnings of a job and
00:17:02
hold it down but then after a while
00:17:04
this is activity became worse and worse
00:17:06
and you couldn't be controlled and you
00:17:08
presented himself just although you had
00:17:10
a bilateral division of the temporal
00:17:13
scrollable removed the temple from both
00:17:17
sides the first time this sit everybody
00:17:18
down. And field never removed decisions
00:17:22
about cited didn't calculations on both
00:17:24
sides you remove villages of both sides
00:17:27
in fact if you be about CHM died about
00:17:31
three or four years ago and this
00:17:32
control with very modest always as a
00:17:36
the epileptic medication but despite
00:17:40
the fact that the epilepsy was like on
00:17:41
the control it left them with the most
00:17:43
profound women distribute you could
00:17:45
possibly manage so that was beside
00:17:49
himself he called up in Philly said
00:17:51
this is a tragedy can fill the green
00:17:53
said because only do want they try to
00:17:56
learn as much solicitations week and so
00:17:58
we can benefit of the people. So he
00:18:00
said I will send you Brenda Eleanor who
00:18:02
was my colleague she's been working
00:18:04
with me on all of these memory cases
00:18:06
and brand available study this patient
00:18:10
and learn a great deal from incision
00:18:14
began to study a German what press was
00:18:17
not that only the elementary defect.
00:18:19
But how much we totally certain aspects
00:18:22
of memory may for example you may then
00:18:27
the memories that had prior to the
00:18:29
surgery. So you maybe is lovely
00:18:31
variances in high school you remember
00:18:33
it the the English language is actually
00:18:36
didn't change in any way or the
00:18:37
intellectual functions before the
00:18:39
surgery will completely intact. So long
00:18:42
term memory some things that a god must
00:18:45
be stored elsewhere not and the
00:18:46
hippocampus perfectly good short term
00:18:50
memory if you gave me a telephone
00:18:51
number eighty four five four four seven
00:18:53
you remember that perfectly well so
00:18:55
short term memory which is that what he
00:18:58
was lacking was the ability to convert
00:19:00
new short term memory into new long
00:19:03
term memory short term memory of
00:19:07
graduation cannot be converted to
00:19:09
monitor memory that you would carry
00:19:11
forward for the longest time. So this
00:19:16
is a major major discovery this is the
00:19:18
first time we had strong biological
00:19:19
evidence that maybe could be localised
00:19:22
to specific area of the brain and then
00:19:25
but it doesn't made another fantastic
00:19:28
discovered. She found despite the fact
00:19:31
that you could not convert short term
00:19:32
memory to larger memory for many kinds
00:19:35
of learning process ease there a
00:19:37
certain things you could do very well
00:19:39
alert perfectly well you can learn
00:19:42
motor tasks. So if you okay okay a a
00:19:48
lot of a stall and ask him to fill in
00:19:51
the outlaw. And to do not by looking at
00:19:54
it and not looking at the pencil but
00:19:56
the nodded eventually like looking in
00:19:58
the mirror you would make a lot of
00:20:02
mistakes twenty first began and Monday
00:20:05
don't and trials the first day he would
00:20:07
get better and better to draw it to the
00:20:09
outline of the star Tuesday much better
00:20:12
for a Wednesday perfect. This is the
00:20:15
way you want I would perform at this is
00:20:17
what agent but yes agent how come you
00:20:21
did so much better on Wednesday than
00:20:23
you do them money would say what you
00:20:26
talking about a never done this before
00:20:28
in my life oh Uh planning is one of the
00:20:40
worst cases that you see I know if I
00:20:51
would do it now I'm not saying I'm a
00:20:55
difference renderings no sense to troll
00:20:58
by not taken after ugliness no software
00:21:01
and hardware or not now living in other
00:21:07
news down by it's going to be fine not
00:21:11
to just bring destroyed cheating isn't
00:21:14
the only possibility you see. V someone
00:21:20
you can use I don't know the names and
00:21:22
something are colours like yeah you see
00:21:28
I mean it's not me oh and or yes see in
00:21:36
tells you something also very good well
00:21:39
let me make one point first with this
00:21:41
made clear is that memory is not in
00:21:45
unitary faculty of mine. But comes in
00:21:47
at least two forms implicit also called
00:21:51
non tired of what expected declarative
00:21:54
implicit is more and perceptual skills
00:22:00
and that's localised to be make the
00:22:01
like the cerebellum and the simplest
00:22:03
case is which I will also show you in
00:22:05
reflex pathways themselves and is
00:22:07
characterised by the cell that it
00:22:09
happens almost automatically
00:22:11
unconsciously cool. So when you learn
00:22:16
how to ride a bicycle you first tell
00:22:18
yourself which you left for for would
00:22:19
you write for for what what have you
00:22:20
learned if you talk to yourself you
00:22:22
fall off the bicycle. So you don't do
00:22:24
that anymore this is in contrast
00:22:26
explicit memory you think back to what
00:22:28
you have to get the last time you think
00:22:30
you know on your last birthday that rim
00:22:33
a conscious effort of recall fact of
00:22:37
events and that's stored in the media
00:22:39
temporal open at the campus. So
00:22:41
apparently it was studying was only one
00:22:43
major component of memory the expos
00:22:45
memory which requires conscious or
00:22:48
recall but what you also notice it
00:22:51
class wearing is that I have to master
00:22:53
certain pieces on the piano. They move
00:22:56
from explicit or implicit you can do
00:22:58
them automatically. So even though we
00:22:59
didn't have a temporal or you could buy
00:23:01
perfectly well would be ask them
00:23:03
afterwards you you enjoy playing that
00:23:04
is that what that we're talking about
00:23:06
applet out of for the last twenty five
00:23:08
years. So let me move on to the second
00:23:11
component that is the Michael a problem
00:23:13
or memory what are the mechanisms
00:23:15
whereby memories storage science it
00:23:18
turns out that implicit explicit memory
00:23:21
these two forms despite the fact the
00:23:23
radically different have features in
00:23:24
common. And I'm gonna size the
00:23:27
similarities what was difference there
00:23:29
is stages in memory storage in each
00:23:31
case is a short memory the last minutes
00:23:33
long term every the last days to weeks
00:23:35
to what always that invariably but
00:23:40
always occurs to convert short term to
00:23:43
monitor memory is reputation practise
00:23:46
makes perfect and won't remember
00:23:49
requires you protein since this is in
00:23:51
gene expression says actual alteration
00:23:54
of gene expression in your brain is
00:23:56
result of learning. This makes people
00:23:59
very unhappy sometimes you know maybe
00:24:03
sitting in the audience say oh my god
00:24:06
gene expression is gonna be all the to
00:24:08
me I'm gonna go home tonight I'm going
00:24:10
to sleep with my husband and I love
00:24:12
that we planning at the baby and that
00:24:14
for baby has to remember all the drivel
00:24:17
that I heard today because the genes
00:24:20
are expressed well to get that might
00:24:23
date is gonna have those jeans not to
00:24:25
worry these are not the genes in over
00:24:27
for this or these are localised pieces
00:24:30
of the campus are there is a great. So
00:24:32
you have my permission to do whatever
00:24:33
you not on use two different animal
00:24:38
models to exploit implicit explicit
00:24:40
memory I'm gonna use this nail applies
00:24:43
here to study implicit memory storage
00:24:46
which does not require conscious
00:24:47
attention I'm going to use the mouse
00:24:49
I'll also say something about people
00:24:51
the study exposition of memory storage
00:24:53
which requires conscious attention let
00:24:55
me begin with implicit memory storage
00:25:00
in the planes here using is example
00:25:03
blurred fear sensitisation nice you can
00:25:06
tell at a glance is up fancy is he not
00:25:09
only beautiful animal there's a highly
00:25:10
intelligent animal this is exactly the
00:25:14
sort of animal anyone of you would
00:25:16
select for the study of running but
00:25:18
this animals not only a very attractive
00:25:22
and very intelligent but it's very
00:25:23
accomplished messages argument would
00:25:29
knew that is this mantra of any
00:25:31
investigative digit of got the Nobel
00:25:33
prize what is attractive about a place
00:25:36
here your brain of mind has a hundred
00:25:39
billion neurons at its peak the
00:25:42
dialogue act the applause he has twenty
00:25:44
thousand or is it the twenty thousand
00:25:48
neurons are distributed in a nervous
00:25:50
system made up of ten ganglia each band
00:25:53
in has two thousand nerve theirselves
00:25:56
mull over is two thousand nerve cells
00:25:58
and a focus not on one behaviour but a
00:26:01
number of different behaviours. So the
00:26:03
number of cells committed to a single
00:26:05
be able I can be quite small a hundred
00:26:07
no cells even less in addition for
00:26:10
reasons we don't understand. a place
00:26:13
yes the largest theirselves in the
00:26:15
animal kingdom They're millimetre in
00:26:18
diameter when I was before I became
00:26:21
presently out the I could see them with
00:26:23
my naked I not only be lost but a very
00:26:27
distinctive imposition. So you can give
00:26:29
the names harry Richard Tom plot five
00:26:33
all kinds of then we're not that
00:26:35
imaginative simply column are two or
00:26:37
one depending upon which side again
00:26:39
going the all the rights on that side
00:26:40
but anyway is a large you a uniquely
00:26:44
identifiable nerve cells and with this
00:26:48
simple animal with the simple nervous
00:26:50
system we've selected a very simple
00:26:52
behaviour it yeah withdrawal reflex the
00:26:54
animal had at least to organ quality of
00:26:57
it is external to the body covered by
00:26:59
she skated protective sheet cake skin
00:27:02
the mantel shelf which consider she's
00:27:04
not well the syphon if you now apply a
00:27:07
tactile stimulus to the side and you
00:27:09
get a press withdrawn a big gel like
00:27:11
withdrawal by hand from a touch. This
00:27:14
simple behaviour can be modified by
00:27:16
four types of learning sensitisation
00:27:18
capitulation classical conditioning up
00:27:21
confusion harmonica to focus and
00:27:22
sensitisation of form where three if
00:27:26
you scare the hell out of the animal by
00:27:27
giving a shock to the table you now
00:27:30
applied tactile stimulus deciphering
00:27:33
you get it more powerful withdraw and
00:27:36
the we the animal will remember that
00:27:38
insult and give you more powerful draw
00:27:40
depending upon the number of
00:27:41
repetitions if you give a single
00:27:43
shocked at the tail remembers it for
00:27:46
minutes if you give repeat attractive
00:27:48
remembers it for days or weeks the
00:27:51
neural circuit of this turns out to be
00:27:53
remarkably simple they're a sensory
00:27:55
nerves twenty for them that make the
00:27:57
right connections to the motor neurons.
00:27:59
So they pick up from the syphon the
00:28:01
make the right connections to the motor
00:28:03
neurons and the more endurance
00:28:05
connectivity LS you know or you should
00:28:08
know neurons speak to one another
00:28:11
through a specialised structure call
00:28:13
the syntax that has two components the
00:28:16
sending orange component and the
00:28:17
receiving ignorance component what
00:28:20
happens when you start shock detail
00:28:22
when you shot detail you activate
00:28:24
modulator turnarounds these assert
00:28:26
interject easy them like the modulator
00:28:28
neurons of the basically bring the
00:28:30
colour that you could document energy
00:28:32
search allergic cells. It's these like
00:28:35
the teachers the act in a sense reader
00:28:37
and the or not and the egg to
00:28:39
strengthen the connections between the
00:28:41
censoring or an animal dinner. And that
00:28:43
is the key to learn or alteration in
00:28:45
the strength of preexisting connections
00:28:48
to give a single. KL shock you course a
00:28:54
functional changing a connection
00:28:55
mediated by second messages a system
00:28:58
call the sector gay P depended protein
00:29:00
try nice really picky that strengthens
00:29:04
preexisting connections is no
00:29:06
anatomical change whatever short
00:29:08
remember. But if you have five the
00:29:10
other sharks you activate changes I
00:29:13
told you before and that gives rise to
00:29:15
protein synthesis because right so the
00:29:17
growth of new synaptic connections. So
00:29:20
if you remember anything about this
00:29:21
lecture and I don't hurt design you
00:29:23
you're gonna walk out of this with the
00:29:25
different brain you walk into the
00:29:26
structure is it really quite powerful
00:29:29
changes. So in a plus here to see
00:29:32
doubling of number of selection of
00:29:34
synaptic connections with want to
00:29:35
remember this is a control censoring
00:29:37
their own control mode underarm after
00:29:40
long term sensitisation or use see
00:29:43
tremendous of incense ignorance remote
00:29:46
controls let me just show you what this
00:29:49
looks like you stimulate the tail you
00:29:52
activate deserted reject neurons these
00:29:55
are gonna receptor that increases
00:29:58
psychic AP the cells activates a kind a
00:30:01
score the cyclic AB the printer in plan
00:30:03
is the taxes that we said that the
00:30:04
terminal to enhance communication
00:30:07
between the sense you know dynamo
00:30:08
remember it does it by increasing
00:30:10
transmitter release transmitter is
00:30:12
carried in these small circular what
00:30:16
emails court synaptic testicles each of
00:30:19
them contains several thousand
00:30:20
molecules of transmit what happens with
00:30:23
the repeated tail shocks rupee tail
00:30:26
shocks this I can't be depended protein
00:30:28
cuttings moves into the nucleus in so
00:30:31
doing it activates another kind it's
00:30:33
map kind a to to have a double action
00:30:36
the map kindest removes it inhibitory
00:30:38
constraint call crap too and the second
00:30:41
again P depended protein content acts
00:30:43
and inactivated transcription quote
00:30:45
prep one that accent downstream jeans
00:30:48
I'm not gonna tell you about all of
00:30:49
them Christina told you a little bit
00:30:52
and hard talk about this and that gives
00:30:54
rise to the growth of new synaptic
00:30:55
connections and that's this table self
00:30:57
contained form and storage now you can
00:31:01
also show this this happens in the
00:31:04
human brain for example even in the
00:31:06
motor sphere the connection is an a
00:31:08
fixed. And you can see this for example
00:31:11
in violinists this we sleep in the
00:31:12
study of the quarter of representation
00:31:14
of the figures there people play the
00:31:17
violin. So in playing the violin the
00:31:20
right hand there's nothing you just
00:31:22
hold on to this board it was a back and
00:31:24
forth but the left handers this
00:31:25
delicate finger. And if you look at
00:31:27
people who play the violin they had a
00:31:30
larger representation of the fingers
00:31:32
into people don't play the violin. And
00:31:35
if you do what your mother told you
00:31:37
started an early age you will get
00:31:40
further growth in UB board extras that
00:31:42
people start later by some this is your
00:31:45
mother start early in life. What about
00:31:48
explicit memory storage memory for
00:31:50
instance. This involves the campus and
00:31:54
this is really quite fascinating. I
00:31:56
don't know what it's like here in in
00:31:59
Germany but but in but if you try to
00:32:02
get a cab and US you gotta taken from a
00:32:04
hundred street to harden twenty astray
00:32:07
design is not the foggiest notion what
00:32:10
you talk about you have to tell element
00:32:11
to go in london. You've gotta pass
00:32:14
request has want to qualify surprise
00:32:17
you really have to there well the
00:32:19
streets of of London just ask any camp
00:32:24
Java how to get from one spot another
00:32:26
he will immediately notice if you now
00:32:29
look at the hippocampus of a cab driver
00:32:31
it increases progress. inside along
00:32:34
with the driver okay And I say this to
00:32:37
the gentleman the front as soon every
00:32:39
tire that became fisheries that is what
00:32:44
we are I mean I'm gonna ask that the
00:32:49
contract unless they be changed to all
00:32:53
the CD people stay on as long as the
00:32:55
couple to do it which is another forty
00:32:57
fifty you can say this in the mouse the
00:33:01
mouse is a perfectly good examples and
00:33:04
they can do a variety of spatial okay
00:33:06
cast for example if you put a mouse on
00:33:09
a platform that has forty holes only
00:33:14
one of which lease an escape hatch and
00:33:16
shine online and play music mice online
00:33:19
people give lectures door like light
00:33:21
starlight music they want to get away
00:33:23
from all that noise and the only way
00:33:25
they can do that is the fine this
00:33:27
escape route and do would have the
00:33:29
world about recognising a particular
00:33:30
mocking in the world they a
00:33:32
capabilities in relationship to that
00:33:34
and be define it how is that me that is
00:33:38
mediated by the the campus is ultra in
00:33:40
a moment. And that is mediated fine
00:33:43
alteration in synaptic strength very
00:33:45
analogous to what you see in the
00:33:47
position. This is discovered by normal
00:33:49
one person anderson. And it has a early
00:33:52
face which correlates with short term
00:33:55
memory and a late phase which requires
00:33:57
protein sense this is a gene expression
00:33:59
which correlates with four trains
00:34:02
repeated simulation. So there is a
00:34:04
synaptic plasticity camping this. And
00:34:08
if you look at the mechanism on the
00:34:09
line that you secretly really phase is
00:34:12
different than in the place yeah it
00:34:14
involves a second messages signalling
00:34:16
but is a different can messenger it's
00:34:18
calcium curmudgeon pen importing kind
00:34:20
but the effect is the same a functional
00:34:22
strengthening of synaptic connections
00:34:24
the details differ. But want to
00:34:27
remember is amazingly similar there's a
00:34:29
market it or transmitter in this case
00:34:31
don't but mean that activates act again
00:34:33
P activate script is also equivalent of
00:34:36
prep to turns charging expression gives
00:34:38
rise to the ground three synaptic
00:34:40
connections. So even though this is a
00:34:42
wonderful thing about molecular biology
00:34:44
it will brain science it to the rest of
00:34:46
biology because it began to show how
00:34:48
maltese between widely different
00:34:50
processes well what intuitively not
00:34:52
expected the molecular mechanisms in
00:34:54
place and expose it to share component
00:34:56
but now we see that despite the fact
00:34:58
that differences be important
00:35:00
similarities. Now nice you could do
00:35:02
very nice genetic experiments you can
00:35:04
act out the cycle again P depend
00:35:06
protein kindness and see what you facts
00:35:08
that the plasticity the early phase not
00:35:11
all affected piece at two different
00:35:12
lines it which the second KP
00:35:14
dependability can is not that the light
00:35:17
face white yeah we can out of this
00:35:20
behaviour we can do the same task
00:35:23
before this is a normal mouse this is a
00:35:26
mouse and which P is in there but
00:35:27
tremendous compromises. So despite the
00:35:32
fact that in place an explicit maybe a
00:35:34
dramatically different they share
00:35:36
certain features in common people
00:35:38
involved mandatory transmitters for the
00:35:41
long term process. So only in one case
00:35:44
top mean for the the activation of the
00:35:46
psychic can't be the printed protein
00:35:48
kind it's for the late phase activation
00:35:50
of crap and both of these synaptic
00:35:52
connections this brings me to my last
00:35:57
topic which is memory in the ageing
00:35:59
brain. So I got interested in the
00:36:01
recently not a moment too soon but let
00:36:05
me take a look to do something
00:36:08
fascinating about this when I was in
00:36:13
medical school. We practically never
00:36:15
spoke about about summonses for cocaine
00:36:19
basically about what's up is is is a no
00:36:22
yeah that means and what didn't speak
00:36:27
what once hamas diseases because we saw
00:36:29
operations that were born around
00:36:30
nineteen hundred they didn't develop
00:36:32
times disease. I stand nineteen hundred
00:36:36
with fifty years. Now do cases genetic
00:36:39
meditation early onset alzheimer's
00:36:41
disease that we heard about but we
00:36:43
didn't bother discussing you "'cause"
00:36:44
you never saw that the light was and
00:36:47
Simon disease which is you know this
00:36:49
frightening disease it is becoming an
00:36:50
epidemic that occurs later in life. And
00:36:53
now. P men the weakest six left to be
00:36:58
seventy six women live to be eighty one
00:37:00
and longer well sinus disease comes out
00:37:05
of the late sixties so in the seventies
00:37:07
three percent of people have it in the
00:37:10
nineties half the population has is
00:37:12
really each is you heard before
00:37:14
epidemic proportions nice people lived
00:37:17
longer they also live better and you
00:37:20
heard in the last lecture. But also saw
00:37:23
something that looked more like the
00:37:26
energy that occurs as the rest of the
00:37:28
bottom you know there's a weakening of
00:37:29
you muscles as weakening of your ball
00:37:30
mass. And distance call euphemistically
00:37:34
but nine so that's and forgetfulness it
00:37:37
can only of normal ageing. But it
00:37:39
wasn't clear but that this was a
00:37:41
separate process whether this is really
00:37:44
the early stages of what's on this is
00:37:47
and so this became of interest in a
00:37:50
number of people including my
00:37:52
colleagues and myself beginning to
00:37:54
explore this is is a separate process
00:37:56
was an early stage of also necessary.
00:37:58
So my colleagues and I actually a paper
00:38:02
explore three features the age of onset
00:38:04
and progression anatomical localisation
00:38:06
and molecular defect let me begin with
00:38:09
the age of onset and progression my
00:38:13
still not show also on this disease.
00:38:15
You could implanted all time a gene
00:38:17
into them and people that a craze I
00:38:19
want so much straight but on their own
00:38:21
they don't show we'll turn this
00:38:23
disease. So I was interested in going
00:38:25
to the show insulated memory loss
00:38:28
building on their own show weakening of
00:38:29
memory with age will have to be to we
00:38:32
do a user old but it made like twelve
00:38:35
months they show as is thought to occur
00:38:38
with age related memory loss any
00:38:41
serious decline in memory moreover we
00:38:47
know what's on this disease begins in
00:38:50
the undermine the cortex Scott small
00:38:52
town tart imaging experiments and found
00:38:55
that what seem to be age related memory
00:38:57
loss was located then page arcs every
00:39:00
two quite distinct from a drop cortex.
00:39:03
So we thought we would take advantage
00:39:04
of this anatomical separation to
00:39:06
actually begin to explore some of the
00:39:08
market underpinnings of this. So we
00:39:10
want to explore the anatomical
00:39:13
distinction be between east it we
00:39:15
recently use ultimately changes the
00:39:18
line look at twenty three thousand
00:39:20
genes and what we did we use what patsy
00:39:22
specimens of people who did not have
00:39:24
all sums disease between the ages of
00:39:27
thirty eighty nine we can a blank page
00:39:30
are as to the enter model cortex to see
00:39:33
whether we can see she that wanted in
00:39:36
the became dangerously or every week or
00:39:38
with specific age related minimalist
00:39:41
and whether they wear jeans that
00:39:42
specifically period in a systematic way
00:39:45
is a function of age either that or up
00:39:47
in this way rate that defied nineteen
00:39:50
candidate it very this systematic way
00:39:53
halfway down the other half an no
00:39:55
refocus itself or on only one candidate
00:39:58
or BAB forty eight for reasons the big
00:40:00
completely moment it very in a very
00:40:02
systematic we're going down. So that
00:40:06
the lifespan of the individual. So this
00:40:09
simply shows you the level of the
00:40:10
messenger on it and the level of the
00:40:12
protein in the tent age iris for a TV
00:40:16
forty million and to run cortex also
00:40:18
like that other basis a brain no change
00:40:20
at all was very specific no one is or
00:40:24
maybe forty turns out. It's an
00:40:27
important component of the car complex.
00:40:29
So I showed you before. PJ fast for
00:40:32
it's crap for recruits speaker binding
00:40:35
protein and approved by me protein
00:40:37
weekly which obviously forty eight
00:40:39
which in stillness that lies that opens
00:40:41
up committed allows transcription to
00:40:44
occur. So it's the critical factor the
00:40:46
trick is gene regulation. So it's
00:40:49
clearly an interesting point. So in
00:40:52
humans you can do cover. relations you
00:40:55
can't do positive experiments very
00:40:56
easily So we turn to the mouse and we
00:40:59
danced ourselves. And the mouse ages
00:41:03
you see in the mouse is defined in a
00:41:05
albeit before that like you see in
00:41:07
people. And the fact is you do. This is
00:41:10
the page I was a million males but H
00:41:13
Ross you see a nice decline you don't
00:41:14
see this in other regions. So that we
00:41:17
can to we're nice expire I showed you
00:41:19
before we do an object recognition task
00:41:22
yeah mouse as well on this page passes
00:41:27
badly on this you know taking young
00:41:30
mouse. And you and hit a BAB forty
00:41:34
again mouse tremendous defect in object
00:41:38
recognition if you know take and all
00:41:42
that that has a defect. And you give it
00:41:44
a maybe forty eight you restore the age
00:41:47
related memory. So this is really quite
00:41:49
encouraging so we also interested in
00:41:53
seeing we had no to imaging experiments
00:41:56
in people and and and the mouse that
00:41:59
obviate be forty eight is I that I'm
00:42:03
sorry but had H jars it's a region
00:42:05
that's involved what happens if we had
00:42:08
it all be forty eight we repeat that
00:42:11
the defect in imaging that we it
00:42:14
detected in the intact animal both in
00:42:16
people under my son the answer is yes
00:42:18
you see a clear decrease in the imaging
00:42:21
of a candy jars with the inhibition of
00:42:26
martinis before. So this allows me my
00:42:29
first summary which is the age related
00:42:32
memory loss and what sounds disease
00:42:33
seem to be quite twisting. And age
00:42:36
related memory roast begins early yeah
00:42:38
it has a different anatomic location
00:42:41
and involve different likely defects
00:42:44
we've so far I described one it's very
00:42:47
like the others also something. So this
00:42:51
brings me to a final one which I think
00:42:52
has some relationship to nutrition we
00:42:55
wanted all the hormonal factors that
00:42:57
contributed cable dysfunction did you
00:42:59
have the time TVG in my exercise help
00:43:03
overcome these but one deficiency and
00:43:07
this is where get back I came out of a
00:43:09
collaboration with your okay think you
00:43:11
carried out or nothing really work his
00:43:13
work sure very beautifully that phone
00:43:15
is and and you can work on the phone
00:43:18
releases a hormone called ask your
00:43:20
calcium. And also tell select some
00:43:22
muscle lights and the pancreas it nice
00:43:25
in the test these lights on the Lever
00:43:27
and also acts on the bottom intending
00:43:31
to the brain it does a lot of things in
00:43:33
preventing cited depression if a
00:43:36
spatial every learning. So we were
00:43:39
interested knowing is it also fair it's
00:43:41
related memory loss. And sure enough
00:43:44
you inject asked accounts an advantage
00:43:46
are as you increase. PK dislike again
00:43:50
pita bread approaching chinese and fast
00:43:52
program and a PAB forty eight you're
00:43:57
not out also thousand you decrease fast
00:44:02
for Pratt and obviously forty so what
00:44:06
is being behavioural affect Sebastian
00:44:08
thousand administration. And his young
00:44:11
mouse. And using a mouse and a
00:44:14
particular behavioural task he's an
00:44:18
aged mouse if we give it a stochastic
00:44:21
we can correct the age related member
00:44:23
deficit it also enhances the memory not
00:44:28
only of all minus it enhances the
00:44:31
memory of all months yeah mice as well
00:44:34
as all at once and that gives you some
00:44:37
clothes so this is involved in memory
00:44:39
enhancement and what happens with a
00:44:41
vegetable mass but mess decreases. So
00:44:46
there is a progressive decrease in mass
00:44:48
and associated with that is the
00:44:50
decrease Askew calcium in the server
00:44:53
now if you know what you were told to
00:44:56
do only a if you exercise you increase
00:44:59
the level of a Alice and it's so you
00:45:02
can really see how exercise can lead to
00:45:05
the release of Austria thousand rumble
00:45:07
by be simple math and can help to
00:45:10
reverse age related memory loss. So let
00:45:13
me give you my second final summary
00:45:15
that stick out of the least my only
00:45:17
immediate age related memory was
00:45:20
through from one and all maybe forty
00:45:22
eight because it uses saucy would
00:45:24
decrease palm as this decrease plastic
00:45:27
also contribute stage related memory
00:45:29
loss conversely this might explain the
00:45:31
beneficial effects on cognition in be
00:45:33
aged a vigorous exercise which builds
00:45:35
bone mass the versatility of age
00:45:38
related memory loss strengthens the
00:45:41
idea that age related maybe lots of all
00:45:42
time is a distinct diseases. So we
00:45:45
sound but health insurance sound mine
00:45:49
but you know this than asleep before
00:45:50
you now know what for sure let me just
00:45:52
tell you my howling. Thank you very

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Conference Program

Introduction to the 12th Nestlé International Nutrition Symposium
Thomas Beck, NRC Director
22 Oct. 2015 · 8:57 a.m.
418 views
Introduction to Session I - Cognitive & Brain Development
Susan Gasser, Friedrich Miescher Institute, Basel, Switzerland
22 Oct. 2015 · 9:04 a.m.
The development of a healthy brain
Michael Gazzaniga, University of California, Santa Barbara, USA
22 Oct. 2015 · 9:16 a.m.
221 views
Q&A - The development of a healthy brain
Michael Gazzaniga, University of California, Santa Barbara, USA
22 Oct. 2015 · 9:56 a.m.
Early influences on brain development and epigenetics
Stephen G. Matthews, University of Toronto, Canada
22 Oct. 2015 · 10:49 a.m.
Q&A - Early influences on brain development and epigenetics
Stephen G. Matthews, University of Toronto, Canada
22 Oct. 2015 · 11:29 a.m.
Building the physiology of thought
Rebecca Saxe, Massachusetts Institute of Technology, Cambridge, USA
22 Oct. 2015 · 11:38 a.m.
154 views
Q&A - Building the physiology of thought
Rebecca Saxe, Massachusetts Institute of Technology, Cambridge, USA
22 Oct. 2015 · 12:10 p.m.
Introduction to Session II - Cognitive Decline
Kathinka Evers
22 Oct. 2015 · 2:02 p.m.
Brain health & brain diseases - future perspectives
Richard Frackowiak, CHUV University Hospital, Lausanne, Switzerland
22 Oct. 2015 · 2:11 p.m.
Alzheimer's disease: genome-wide clues for novel therapies
Rudolph E. Tanzi, Massachusetts General Hospital, Charlestown, USA
22 Oct. 2015 · 3:15 p.m.
Q&A - Alzheimer's disease: genome-wide clues for novel therapies
Rudolph E. Tanzi, Massachusetts General Hospital, Charlestown, USA
22 Oct. 2015 · 3:59 p.m.
Immunometabolic regulators of age-related inflammation
Vishwa D. Dixit, Yale School of Medicine, New Haven, USA
22 Oct. 2015 · 4:21 p.m.
Q&A - Immunometabolic regulators of age-related inflammation
Vishwa D. Dixit, Yale School of Medicine, New Haven, USA
22 Oct. 2015 · 4:59 p.m.
Introduction to Session III - Nutrition & Cognitive Development
Pierre Magistretti, KAUST, Thuwal, Saudi Arabia and EPFL, Lausanne, Switzerland
23 Oct. 2015 · 9 a.m.
Energy metabolism in long-term memory formation and enhancement
Cristina M. Alberini, The Center for Neural Science, New York University, USA
23 Oct. 2015 · 9:16 a.m.
129 views
Q&A - Energy metabolism in long-term memory formation and enhancement
Cristina M. Alberini, The Center for Neural Science, New York University, USA
23 Oct. 2015 · 9:53 a.m.
Building the costly human brain: implications for the evolution of slow childhood growth and the origins of diabetes
Christopher Kuzawa, Northwestern University, Evanston, USA
23 Oct. 2015 · 10:29 a.m.
Q&A - Building the costly human brain: implications for the evolution of slow childhood growth and the origins of diabetes
Christopher Kuzawa, Northwestern University, Evanston, USA
23 Oct. 2015 · 10:57 a.m.
Nutrition, growth and the developing brain
Prof. Maureen Black, University of Maryland, School of Medicine, Baltimore, USA
23 Oct. 2015 · 11:09 a.m.
Q&A - Nutrition, growth and the developing brain
Prof. Maureen Black, University of Maryland, School of Medicine, Baltimore, USA
23 Oct. 2015 · 11:49 a.m.
Introduction to Session IV - Decline & Nutritional Intervention
Tamas Bartfai, The Scripps Research Institute, La Jolla, USA
23 Oct. 2015 · 12:48 p.m.
On multi-domain approaches for prevention trials
Miia Kivipelto, Karolinska Institutet, Stockholm, Sweden
23 Oct. 2015 · 1:04 p.m.
Q&A - On multi-domain approaches for prevention trials
Miia Kivipelto, MD, PhD, Karolinska Institutet
23 Oct. 2015 · 1:39 p.m.
Methodological challenges in Alzheimer clinical development
Lon S. Schneider, Keck School of Medicine of USC, Los Angeles, USA
23 Oct. 2015 · 1:49 p.m.
Q&A - Methodological challenges in Alzheimer clinical development
Lon S. Schneider, Keck School of Medicine of USC, Los Angeles, USA
23 Oct. 2015 · 2:32 p.m.
We are what we remember: memory and age related memory disorders
Eric R. Kandel, Columbia University, New York, USA
23 Oct. 2015 · 3:03 p.m.
138 views
Concluding Remarks
Stefan Catsicas, Chief Technology Officer, Nestlé SA
23 Oct. 2015 · 3:50 p.m.

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