5th OIBC
Spring Symposium
Mind and Brain
The Astonishing
Hypothesis 10 Years On
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9.15 |
Hugo Brunner (Lord Lieutenant of Oxfordshire): Welcome and Opening of
Symposium and 10th Oxford Conference |
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9.30 |
Peter Somogyi (Director,
Anatomical Neuropharmacology Unit, Dept of Pharmacology, Oxford U): Space and
time in neural networks. |
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11.00 |
Tim Bliss (Head of
Neurophysiology, NIMR, Mill Hill, London): How brains store memories |
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11.45 |
Barbara Sahakian (Dept of Psychiatry,
Cambridge U): Thought, emotion and stress. |
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13.30 |
Terence Ryan (Wound Healing
Institute, Dept of Dermatology, Oxford U): Creativity and dyslexia. |
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14.15 |
Alastair Compston (Head of Neurology,
Dept of Medicine, Cambridge U): Neurological disease in adults. |
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15.30 |
Paul Matthews (Director, Oxford Centre for Functional MRI of the Brain,
Dept of Clinical Neurology, Oxford U): Functional imaging |
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16.15 |
Summing up |
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16.30 |
Close of Symposium |
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18.30 |
Reception at Mansfield College |
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19.15 |
Conference Dinner at Mansfield College |
Space
and time in neuronal networks
Peter Somogyi
Medical Research Council, Anatomical Neuropharmacology Unit
Oxford University
How does the brain
achieve the fantastic processing power that enables animals to react to
external stimuli in a fraction of a second, and us to think and create art and
science, including the analysis of the brain itself? Nervous systems evolved in
order to assist the organism in its interactions with the external and internal
environment. A major organisational principle of the nervous system is the
subdivision of functions into centres, operations into circuits, processing
steps into distinct cells and communication sites into distinct plasma membrane
domains on the surface of nerve cells (1).
I will explore the
organisation of the cerebral cortex, the structure holding our knowledge,
conscious experience, culture, failings and much else. We learn about the world
with our cortex and act according to our previously learned and stored
knowledge. The challenge is to define the processing unit of the cortex (2),
the basic cortical circuit, from molecular composition through cell types to
the dynamic behaviour of neuronal networks in the living, intact brain. The
cortex receives information via the thalamus from the sensory organs, as well as
generating its own activity. The workhorses of the cortex are the pyramidal
cells, which connect the different cortical areas, as well as informing the
rest of the brain and spinal cord what is going on. Information is transmitted
via electrical signals - called action potentials -, which travel along the
processes of the neurons and evoke the release of chemical messengers, most
frequently the amino acids glutamate and GABA, at specialised sites called
synapses. In addition, cortical neurons also communicate with each other via
direct electrical connections without releasing chemical messengers. Each
pyramidal cell receives information on its dendrites from up to 30,000 other
nerve cells and sends information to 10,000-50,000 nerve cells. The incoming
information is not distributed randomly on the surface of the cells, but is
targeted to highly restricted locations; SPACE is subdivided even on the
surface of the single cell into functional domains. A large variety of cells
with short-range connections modulate the activity of pyramidal cells, and, as
a result, pyramidal cells can only fire propagated signals, the action
potentials, in certain time windows. When we investigate the time of signalling
originating from different cell types we find that they subdivide TIME,
depending on which part of the pyramidal cell they address (3). The cortical
network of cells generates regular rhythms of activity against which external
events are measured. This incredible time machine can achieve an accuracy of
signalling of one thousandth of a second.
In general, a
co-operative division of labour in time and space between distinct neurons
underlies the enormous processing power of the cortex, which is based on the
rhythmic activity patterns that emerge from its intrinsic design.
1.
Shepherd, G. M. (2004) Synaptic Organization of the Brain, Fifth
Edition, Oxford Univ. Press, Oxford
2.
Somogyi P, Tamas G, Lujan R, Buhl EH (1998) Salient features of
synaptic organisation in the cerebral cortex. Brain Res. Rev. 26:113-135.
3.
Klausberger T, Magill PJ, Márton LF, Roberts
JDB, Cobden PM, Buzsáki G, Somogyi P (2003) Brain state- and cell type-specific
firing of hippocampal interneurons in vivo. Nature, 421:844-848.
Functional imaging: A window on the mind
P.M. Matthews
Centre for Functional Magnetic Resonance Imaging of the Brain
University of Oxford
What does it mean to
feel? How do we make a decision to act? What is an emotion and how is it
generated? These fundamental questions about the things that make us human are
now the subject for academic study by cognitive neuroscientists. One of the
most powerful approaches has been to use the tools of functional brain imaging.
Functional magnetic resonance imaging allows a scientist to measure small blood
flow changes in the brain that accompany activity of nerve cells. If images are
taken while someone performs a task, the dynamic changes in activity of the
brain can be followed over time. The way in which we learn or recover from
illness can be mapped. The technique of functional magnetic resonance imaging
is safe and widely available. It is finding an ever greater range of
applications in understanding basic brain functions, monitoring disease and
assessing the value of treatments. This talk will review new approaches in this
exciting field.
How
Brains Store Memories
Tim Bliss
Division of Neurophysiology, National Institute for Medical
Research, Mill Hill, London
Our ability to store
memories implies that the nerve cells of the brain can change their properties
as a result of experience. It has been assumed for a century or more that the
changes in question involve a long-lasting increase or decrease in the strength
of the connections (synapses) linking the particular neurons that are active at
the time the memory is laid down. The psychologist Donald Hebb had proposed in
1949 that when two connected neurons fired together, the strength of the
connection between them would be strengthened. In 1973, synapses with just this
'Hebbian' property were discovered in the hippocampus, a region of the brain
essential for the formation of new memories, and one of the first areas to be
affected in Alzheimer's disease. In the hippocampus of rodents, a persistent
increase in synaptic strength lasting for days can be induced by brief episodes
of strong synaptic stimulation lasting seconds or less. The synapses 'remember'
this transient episode of intense activity. The elegant molecular machinery
that allows them to do this, and the relationship between synaptic plasticity
and memory will be the subject of my talk.
Thought, stress and emotion
TW Robbins
Dept. of Expt. Psychology, University of Cambridge
Professor of Expt. Psychology and Cognitive Neuroscience and
Director of the MRC Centre in Behavioural and Clinical Neuroscience
Thinking is now a
much-studied aspect of cognitive neuroscience, alongside basic processes of
perception, attention, memory and learning. Much is known about two types of
thinking that can be labelled as exemplifying 'hot' and 'cold' cognition. An
example of the latter is a test of visuospatial planning (not dissimilar to the
problems posed by positions in chess requiring equivalent 'working memory'
capacity), the so-called "Tower of London" test of planning. Accurate
performance on this test is known from the evidence of brain-damaged patients
and functional brain imaging methodology to be mediated by neural networks
including specific regions of the cerebral cortex such as the parietal cortex,
and the dorsolateral prefrontal cortex (within the frontal lobes). The
additional involvement of the caudate nucleus within the sub-cortical basal
ganglia explains its particular sensitivity to Parkinson's and Huntington's
diseases, in which the functioning of the basal ganglia is substantially
compromised,
'Hot' cognition is
exemplified by the decision-making processes involved in gambling, when risky
choices are made under conditions often of high emotional arousal. A different
part of the prefrontal cortex, the orbitofrontal cortex, is implicated in such
risky decision-making, again from evidence not only deriving from functional
neuroimaging in normal people, but also the impaired behaviour, particularly in
real-life situations, of patients with damage to this region. The orbitofrontal
cortex is probably at the head of a neural network especially implicated in the
emotions. The sub-cortical neurotransmitter systems such as dopamine and
serotonin serve to modulate the activity of this network and have been
implicated in the actions of both anti-depressant and addictive drugs.
Enhanced activity of
these subcortical neurotransmitter systems, usually experienced as greater
levels of stress, while often helping to optimise the functioning of some of
these neural networks and potentially enhancing certain forms of behaviour, often
causes a deterioration of cognitive functions which underpin thinking, such as
working memory. We will consider evidence from both experimental studies and
clinical investigations for how these sub-cortical systems interact with 'hot'
and cold' thinking, and thus enable the emotions to influence cognitive
function.
Creativity
and Dyslexia
Terence J Ryan
Oxford University and Oxford Brookes University
Trustee of The Arts Dyslexia Trust
The Dyslexic is someone
who has difficulty with reading and writing. There are many artists who are
dyslexic, Leonado Da Vinci being the best known. There are families of creative
people both in the Arts and in Science. Three generations of dyslexic Noble
Prize winners suggest that even such achievements have a genetic basis. Other
Dyslexics such as the speaker giving this talk who went to 16 schools, have
simply been badly educated. The Trust for whom he speaks helps artists to deal
with the bureaucracy of filling up forms to get grants or for exhibiting and
gives advice to worried parents of creative but dyslexic children..
2004 is a wonderful year
to examine one aspect of creativity which is linked to dyslexia and that is
spatial awareness. At the National Gallery there is the splendid exhibition of
El Greco and his spatial distortions and elongations. At the Tate Modern the
sun and mirrors are depicting a wonderful space, while the Exhibition of Donald
Judd gives an extraordinary exploration of space.
One feature of spatial
awareness is that sequencing, as well as remembering complex names or telephone
numbers, may be defective. This is a fundamental problem of the teaching of a
Developed World curriculum to Developing World rural illiterate people-the
Australian Aboriginal or various Tribal groups that are especially good
Artists. They tend to draw with an obvious disregard for sequencing or perspective
but they are very aware of space and never get lost. They cannot cope well with
"school".
The drawing of a 3D cube may present some people with a problem and some will
never see the possibility of switching its front to back. Other aspects of
symmetry and balance as well as their role in the perception of beauty may also
cause difficulties.
One corollary of spatial
awareness is what happens when one is blind.Do touch and taste or hearing also
have a range of talent depending on sequencing or spatial discrimination?
Scientists are examining
the skills for recognising molecular shape depicted by the five senses of the
animal kingdom, the evolution of colour discrimination and the role of physical
forces such as gravity in determining special awareness
The Wellcome Trust and
the Novartis Foundation are awarding "Arts projects that are informed by
biomedical science".www.visions-of-science.co.uk
There is a problem. Science training is dominated by sequencing and the
defining world of words. Does such domination stifle Creativity?
Neurological disease in adults
Alastair Compston
Department of Clinical Neurosciences, University of Cambridge
The fundamental unit of
activity in the brain and spinal cord consists of neurones and their axonal and
dendritic processes embedded in a network of glia providing additional
structure and function, and organised into functional systems - motor, sensory,
visual, cognitive and autonomic, amongst others. Activity depends on conduction
of the nerve impulse down anatomical pathways; a transient shift in
neurotransmission at nerve endings leading to the activation of receptors; the
opening of ion channels which propagate continuation of the facilitatory or
inhibitory nerve impulse; and simultaneous orchestration of many inter-related
circuits. A price is paid for having a nervous system that provides such a
remarkable set of physical and mental attributes from running and catching,
learning and remembering, to planning and evaluating the behaviours that
achieve the main aims of the nervous system - sensing and responding to the
internal and external environment. Like any sophisticated machinery, everything
can go badly wrong. And in evolutionary terms, it makes more sense to jettison
the odd member of the species with a defective nervous system than to risk
losing grip of the complex systems established during development by building
in the capacity for extensive recovery and repair. It follows that diseases of
the adult nervous system are common and tend not to recover spontaneously. Thus
many of the illnesses that afflict individual members of society are chronic
and progressive over time. This is true of the degenerations that occur in
chemically defined systems in Parkinson's and Alzheimer's diseases, of the
static but usually irreversible physical injuries of the brain and spinal cord,
and of damage to specific regions from disturbances of the circulation -
stroke. But this rather gloomy formulation is not the whole story. Some
neurological diseases are characterized naturally by phases of damage followed
by spontaneous recovery. This is typical of multiple sclerosis, the commonest
potentially disabling neurological disease of young adults. In that disease,
the phases of symptom onset, recovery, persistence and progression are
functional impairment with intact structure due to inflammation related mechanisms;
demyelination and axonal injury with recovery from plasticity and
remyelination; and chronic axonal loss due to failure of enduring
remyelination.
Although long considered
incapable of regeneration, the adult mammalian central nervous system can undergo
stem cell dependent neurogenesis and gliogenesis, thereby (in principle)
re-establishing axon-glial interactions needed for remyelination and safe
conduction of the nerve impulse. An essential feature of stem cells is
proliferation and self-perpetuation. The relationship between injury and repair
of the central nervous system is complex. In health, glia and neurons mutually
exert survival effects on other constituents of the developing and mature
central nervous system. Activated glia mediate cell injury but the inflammatory
process also delivers growth promoting and neuroprotective molecules to sites
of tissue injury. Bystander damage is limited whilst degenerate material is
neatly excised. Thus, the nervous system is no longer regarded as an immutable
organ constrained by its fixed but nonetheless complex neural networks. Rather,
the picture emerges of an organ that knows how to sacrifice injured parts but
with the potential for restoring structure and function through a variety of
restorative physiological and biological mechanisms.
Extreme Emotions: Risk and Choice
Barbara Sahakian
Department of Psychiatry, University of Cambridge
Human emotions span a
wide range, with extremes such as manic elation and depressed sadness at either
end. This lecture describes how emotions can influence those parts of the brain
that are responsible for our decisions and actions, sometimes making us behave
in risky or bizarre ways.
This lecture also
highlights the distinction between "cold" and "hot"
processing. Cold, or emotion-independent, processing is thought to utilise
neural networks, including the dorsolateral prefrontal cortex. Examples of cold
processing include working memory tasks, such as the Tower of London task or
rehearsing a series of digits. Hot, or emotion-dependent, processing, in
contrast, is thought to utilise neural networks including orbitofrontal,
anterior cingulate and ventromedial prefrontal cortices. Examples of hot
processing are tasks that make use of affective material or produce an
emotional response, such as conflict situations. Of course, hot and cold
cognitive tasks are not completely distinct; most cognitive tests will have
elements of both hot and cold processing to different degrees, depending on the
particular task. For example, task feedback may provide both an informational
and emotional component. However, there is good evidence for the dichotomy
between hot and cold processing and the roles of these two types of processing
will be discussed.