I would argue that a lot of us spend
most of our time learning from the very
early days of our lives we start by
learning to walk talk and with years of
painstaking effort we even become
amazing artists athletes who outperform
any possible imagination and scientists
and engineers with creative minds which
makes the world that we live in as
interesting as we have seen however when
brain disorder strikes we take an
absolutely devastating setback which
most of us never recover from it’s not a
matter of effort where no matter what
you do most of us can never get back to
all the light painstaking effort
achievements that we achieve throughout
the life world-class athletes can no
longer walk and the most beautiful mind
find themselves unable to conduct the
most daily basic daily routines of life
why is that why is it that still to this
day we remain in this really dark age
where we cannot do anything about these
neurological disease one possible
explanation for this is that we have
been completely ignoring one very
important fact about the brain which is
that it is a circuit in many of our
effort to attack neurological disease we
have ignored this fact putting us
possibly in this situation with amazing
developments in
over the past decades where for example
with the Human Genome Project we now
know a lot about all of the genes in our
body and with subsequent developments in
molecular and cellular biology that also
is now equipping us with a lot of
knowledge on how all of the cells in our
body works however in the context of the
brain one of the most important thing to
know is the status of your neural
circuit your main goal in maintaining
brain health is to keep the neural
circuit function in this normal range
there are many reasons why we might get
kicked out of this normal range where it
might be genetic predisposition or your
lifestyle or injury infection and even
just aging by itself and some of the
efforts to return back to the normal
range could include removing the cause
that took you out to the brain disorder
or elem to start with but actually
removing the cause may not necessarily
bring you back to your normal circuit
status there it’s also important to
remember that you might have to do
something else in order to take you back
to the normal range but importantly in
order to achieve this task of getting
your neural circuit function back to the
normal stage you need to know what that
is without having the knowledge of your
circuit function and your goal it’s very
difficult to achieve that task and so in
short if we can find what is wrong with
the brain circuit we can fix the brain
possibly like we readily fix electronic
circuits however if you currently go to
the clinic you will find something very
far from such systemic approach there is
very little that they can do to
measure your brain circuit status
largely due to technological limitations
the only place where you might find
brain circuit function measurement is in
an epilepsy clinic where they use aegs
which are electrodes that you place on
the skull
to measure the electrical activity of
the brain and while you do these
measurements in the state-of-the-art
clinic what the doctors would do is to
look at lines like this that show that
it slows the electrical activity and the
doctor would just sit there for hours
trying to detect abnormal events and
also possibly trying to imagine what
that might mean in the context of your
circuit dysfunction obviously this is a
very difficult task and there is very
limited information that comes out of
this interestingly despite the fact that
our ability to understand the circuit
status of the brain is so limited one of
the newest and most promising therapy
for brain disease includes
neurostimulation therapy
neurostimulation therapy is where you
place electrodes directly into the brain
and pulse currents in hopes that you can
normalize the circuit function it’s a
direct electrical intervention that
truly recognizes the fact that the brain
is in fact an electronic circuit one of
the most amazing accomplishments of
using a neuro stimulation therapy
includes the fact that one could arouse
patients that were in a minimally
conscious state for over six years by
using electrical stimulation the patient
could wake up from a minimally conscious
state just by pulsing the electrical
current which is an amazing
accomplishment however when you do
something without knowing exactly what
you’re doing there are many problems
it’s been difficult to replicate that
outcome and in other scenarios you also
find that the same kind of therapy you
apply to the disease sometimes makes the
patient better and sometimes even makes
the patient worse why is that imagine
trying to fix your electronic circuit
all of you who don’t necessarily know
how the circuit is working and trying to
zap it into life back again if you’re
lucky it might work and if you try hard
enough many times you might get lucky
but obviously this will be a very
difficult task the reason why so far we
have been doing this in a trial and
error map fashion has been largely due
to again technical limitations in my
laboratory we recently tried to solve
this problem by combining new technology
that allows us to individually control
different neuronal circuit elements
while also doing high spatial resolution
imaging to see what the consequences of
different manipulations are and in this
example we stimulated the central
thalamus the area that was simulated for
arousing the patients from the comatose
state and in one case when we stimulated
them at low frequency ten Hertz you
could see that the subject actually
loses consciousness while if you just
simply change the frequency of
stimulation to high-frequency hundred
Hertz the same subject now gained
consciousness it’s a remarkable
difference in an opposite polar spectrum
and what you can see by directly
observing what the brain is doing you’ll
see that this is indeed due to the fact
that the brain network responds in a
completely different way in the case of
a ten Hertz stimulation you can see that
large areas of the brain is inhibited
denoted by the blue colors and in the
opposite case where it’s stimulated at
high frequency large areas of the brains
are recruited
as you can see with the let red color
video and because of the fact that
high-frequency stimulation recruited
really large brains of the areas of the
brain this functioned as a boot-up
circuit bringing you back into an
aroused state while in the other case
your sensory areas were inhibited where
you’re losing consciousness and as you
can see by directly observing what
circuit intervention does and what the
underlying mechanism is you can now
understand how the circuit can be
intervened to obtain desired outcome and
further taking these technology and
adding computational modeling approaches
what we’ve been able to do is to
understand what the circuits algorithm
is underlying different units of
behavior in this case we are
manipulating a very important circuit a
very important cell type implicated in
Parkinson’s disease and by selectively
modulating this cell type you can see
that there is increased movement in the
roading here with a clockwise rotation
and that particular behavior we can
pinpoint to an algorithm you see where
different parts of the brain engage
functionally where they talk to each
other to generate these movement where
now we can start to build building
blocks of how different behavioral units
are controlled by the brain we talked a
lot about the complexity of the brain
the brain consists of a hundred billion
neurons it’s such an impossible task we
still need to learn more and more about
it to do anything about the problems we
face we may need to up being able to
construct all the different
connectivities of the brain counting
every neuron and being able to record
from them and learning about their
activity those are all very helpful
information that will help us get closer
to getting a complete understanding of
the brain however now by having
these different building blocks of how
different behavioral units relate to an
algorithm we can start to make sense of
the circuitry without even having a
complete map when we build skyscrapers
we don’t necessarily solve all
differential equations for every single
element in the in the building we do
that by understanding specific
organizational principles now we have
this level of understanding where we can
start to build on it and to take these
principle into the clinic we have
started to build platforms where we can
now take a circuit informations from
individual patients in this case you can
see familiar lines that you saw in
earlier EEG diagrams now we can take
these eg make automatic detection of
various events and then from these
significant events that you’re
interested in you can build maps of how
the circuit functions you can directly
visualize the dynamic changes throughout
the brain network and also construct
diagrams of how they are interacting
with each other and we can now do this
in live patients for every individual
and by being able to understand the
individual patient’s brain network we
can start to customize and address them
in a way that we might fix electronic
circuits and so now by having this level
of understanding we can start to imagine
a future where we can take data from the
clinic provide individual level
diagnosis of what might be going wrong
in each one of your brains and based on
these circuit knowledge we can also
optimize therapy from whatever is
currently available even though we don’t
have a cure for any of the neurological
disease there are many different
therapeutic options that are currently
available that we also have trouble of
to patients because of the fact that
they’re mostly done in a trial-and-error
fashion but now with the information on
the neural circuits you can start to
give accurate predictions on how the
patients will respond and optimize it
for the individual patients some of
these therapy are very invasive
there’s surgical options and currently
patients are told that you have run out
of non-invasive options and so it’s up
to you to try whatever is available
that’s a very brutal choice for patients
now by being able to provide systematic
informations on your circuit whether a
certain therapy is indeed restoring your
dysfunctional circuit you can make
accurate predictions furthermore by
building individual brain profiles of
each and every one of the patients we
can for the first time have a clearer
understanding on how different parts of
the circuits are malfunctioning in the
case of neurological disease and once
you have this we can think of a
completely different approach to
developing therapy for brain disease now
only cellular molecular mechanisms are
targeted and when you design things like
nerve stimulation therapy they’re being
tried on a trial and error basis we
don’t have to do that anymore
by having an approach that’s systematic
that corresponds to something like
fixing electronic circuit taking a new
stance we can completely change the
landscape we watching friends and family
who suffer through neurological disease
is one of the most heartbreaking and
devastating experience one can have the
fact that you can not do anything is
something that makes us all despair
however we’re now starting to see light
we have now learned how to make building
blocks of solutions and we have a clear
direction
once we have some of these building
blocks in place we can imagine building
skyscrapers and so we will work hard to
achieve this goal and to be able to take
us to a new era of directly fixing
neurological disease soon thank you very
much [Applause]
most of our time learning from the very
early days of our lives we start by
learning to walk talk and with years of
painstaking effort we even become
amazing artists athletes who outperform
any possible imagination and scientists
and engineers with creative minds which
makes the world that we live in as
interesting as we have seen however when
brain disorder strikes we take an
absolutely devastating setback which
most of us never recover from it’s not a
matter of effort where no matter what
you do most of us can never get back to
all the light painstaking effort
achievements that we achieve throughout
the life world-class athletes can no
longer walk and the most beautiful mind
find themselves unable to conduct the
most daily basic daily routines of life
why is that why is it that still to this
day we remain in this really dark age
where we cannot do anything about these
neurological disease one possible
explanation for this is that we have
been completely ignoring one very
important fact about the brain which is
that it is a circuit in many of our
effort to attack neurological disease we
have ignored this fact putting us
possibly in this situation with amazing
developments in
over the past decades where for example
with the Human Genome Project we now
know a lot about all of the genes in our
body and with subsequent developments in
molecular and cellular biology that also
is now equipping us with a lot of
knowledge on how all of the cells in our
body works however in the context of the
brain one of the most important thing to
know is the status of your neural
circuit your main goal in maintaining
brain health is to keep the neural
circuit function in this normal range
there are many reasons why we might get
kicked out of this normal range where it
might be genetic predisposition or your
lifestyle or injury infection and even
just aging by itself and some of the
efforts to return back to the normal
range could include removing the cause
that took you out to the brain disorder
or elem to start with but actually
removing the cause may not necessarily
bring you back to your normal circuit
status there it’s also important to
remember that you might have to do
something else in order to take you back
to the normal range but importantly in
order to achieve this task of getting
your neural circuit function back to the
normal stage you need to know what that
is without having the knowledge of your
circuit function and your goal it’s very
difficult to achieve that task and so in
short if we can find what is wrong with
the brain circuit we can fix the brain
possibly like we readily fix electronic
circuits however if you currently go to
the clinic you will find something very
far from such systemic approach there is
very little that they can do to
measure your brain circuit status
largely due to technological limitations
the only place where you might find
brain circuit function measurement is in
an epilepsy clinic where they use aegs
which are electrodes that you place on
the skull
to measure the electrical activity of
the brain and while you do these
measurements in the state-of-the-art
clinic what the doctors would do is to
look at lines like this that show that
it slows the electrical activity and the
doctor would just sit there for hours
trying to detect abnormal events and
also possibly trying to imagine what
that might mean in the context of your
circuit dysfunction obviously this is a
very difficult task and there is very
limited information that comes out of
this interestingly despite the fact that
our ability to understand the circuit
status of the brain is so limited one of
the newest and most promising therapy
for brain disease includes
neurostimulation therapy
neurostimulation therapy is where you
place electrodes directly into the brain
and pulse currents in hopes that you can
normalize the circuit function it’s a
direct electrical intervention that
truly recognizes the fact that the brain
is in fact an electronic circuit one of
the most amazing accomplishments of
using a neuro stimulation therapy
includes the fact that one could arouse
patients that were in a minimally
conscious state for over six years by
using electrical stimulation the patient
could wake up from a minimally conscious
state just by pulsing the electrical
current which is an amazing
accomplishment however when you do
something without knowing exactly what
you’re doing there are many problems
it’s been difficult to replicate that
outcome and in other scenarios you also
find that the same kind of therapy you
apply to the disease sometimes makes the
patient better and sometimes even makes
the patient worse why is that imagine
trying to fix your electronic circuit
all of you who don’t necessarily know
how the circuit is working and trying to
zap it into life back again if you’re
lucky it might work and if you try hard
enough many times you might get lucky
but obviously this will be a very
difficult task the reason why so far we
have been doing this in a trial and
error map fashion has been largely due
to again technical limitations in my
laboratory we recently tried to solve
this problem by combining new technology
that allows us to individually control
different neuronal circuit elements
while also doing high spatial resolution
imaging to see what the consequences of
different manipulations are and in this
example we stimulated the central
thalamus the area that was simulated for
arousing the patients from the comatose
state and in one case when we stimulated
them at low frequency ten Hertz you
could see that the subject actually
loses consciousness while if you just
simply change the frequency of
stimulation to high-frequency hundred
Hertz the same subject now gained
consciousness it’s a remarkable
difference in an opposite polar spectrum
and what you can see by directly
observing what the brain is doing you’ll
see that this is indeed due to the fact
that the brain network responds in a
completely different way in the case of
a ten Hertz stimulation you can see that
large areas of the brain is inhibited
denoted by the blue colors and in the
opposite case where it’s stimulated at
high frequency large areas of the brains
are recruited
as you can see with the let red color
video and because of the fact that
high-frequency stimulation recruited
really large brains of the areas of the
brain this functioned as a boot-up
circuit bringing you back into an
aroused state while in the other case
your sensory areas were inhibited where
you’re losing consciousness and as you
can see by directly observing what
circuit intervention does and what the
underlying mechanism is you can now
understand how the circuit can be
intervened to obtain desired outcome and
further taking these technology and
adding computational modeling approaches
what we’ve been able to do is to
understand what the circuits algorithm
is underlying different units of
behavior in this case we are
manipulating a very important circuit a
very important cell type implicated in
Parkinson’s disease and by selectively
modulating this cell type you can see
that there is increased movement in the
roading here with a clockwise rotation
and that particular behavior we can
pinpoint to an algorithm you see where
different parts of the brain engage
functionally where they talk to each
other to generate these movement where
now we can start to build building
blocks of how different behavioral units
are controlled by the brain we talked a
lot about the complexity of the brain
the brain consists of a hundred billion
neurons it’s such an impossible task we
still need to learn more and more about
it to do anything about the problems we
face we may need to up being able to
construct all the different
connectivities of the brain counting
every neuron and being able to record
from them and learning about their
activity those are all very helpful
information that will help us get closer
to getting a complete understanding of
the brain however now by having
these different building blocks of how
different behavioral units relate to an
algorithm we can start to make sense of
the circuitry without even having a
complete map when we build skyscrapers
we don’t necessarily solve all
differential equations for every single
element in the in the building we do
that by understanding specific
organizational principles now we have
this level of understanding where we can
start to build on it and to take these
principle into the clinic we have
started to build platforms where we can
now take a circuit informations from
individual patients in this case you can
see familiar lines that you saw in
earlier EEG diagrams now we can take
these eg make automatic detection of
various events and then from these
significant events that you’re
interested in you can build maps of how
the circuit functions you can directly
visualize the dynamic changes throughout
the brain network and also construct
diagrams of how they are interacting
with each other and we can now do this
in live patients for every individual
and by being able to understand the
individual patient’s brain network we
can start to customize and address them
in a way that we might fix electronic
circuits and so now by having this level
of understanding we can start to imagine
a future where we can take data from the
clinic provide individual level
diagnosis of what might be going wrong
in each one of your brains and based on
these circuit knowledge we can also
optimize therapy from whatever is
currently available even though we don’t
have a cure for any of the neurological
disease there are many different
therapeutic options that are currently
available that we also have trouble of
to patients because of the fact that
they’re mostly done in a trial-and-error
fashion but now with the information on
the neural circuits you can start to
give accurate predictions on how the
patients will respond and optimize it
for the individual patients some of
these therapy are very invasive
there’s surgical options and currently
patients are told that you have run out
of non-invasive options and so it’s up
to you to try whatever is available
that’s a very brutal choice for patients
now by being able to provide systematic
informations on your circuit whether a
certain therapy is indeed restoring your
dysfunctional circuit you can make
accurate predictions furthermore by
building individual brain profiles of
each and every one of the patients we
can for the first time have a clearer
understanding on how different parts of
the circuits are malfunctioning in the
case of neurological disease and once
you have this we can think of a
completely different approach to
developing therapy for brain disease now
only cellular molecular mechanisms are
targeted and when you design things like
nerve stimulation therapy they’re being
tried on a trial and error basis we
don’t have to do that anymore
by having an approach that’s systematic
that corresponds to something like
fixing electronic circuit taking a new
stance we can completely change the
landscape we watching friends and family
who suffer through neurological disease
is one of the most heartbreaking and
devastating experience one can have the
fact that you can not do anything is
something that makes us all despair
however we’re now starting to see light
we have now learned how to make building
blocks of solutions and we have a clear
direction
once we have some of these building
blocks in place we can imagine building
skyscrapers and so we will work hard to
achieve this goal and to be able to take
us to a new era of directly fixing
neurological disease soon thank you very
much [Applause]
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