Introduction to NIBS: NIBS in a nutshell

hi welcome to this introduction to
non-invasive brain stimulation in this
brief lecture we'll be introducing the
three main brain stimulation techniques
we'll be talking about electrical brain
stimulation magnetic brain stimulation
and a more recent addition to the family
ultrasonic brain
stimulation we're going to give examples
for each of these techniques and we're
going to introduce them for example on a
question that you might ask we're
already taking a deep dive where you're
showing you the power of these
techniques well let's get started a
How do we learn
first question that many are interested
in is how we learn and how our brain is
plastic and adapts to our environment
and what we've seen here is that this
relies on a specific neurochemistry in
fact it's the neurotransmitter Gaba that
needs to be inhibited for learning to
take
place and we've measured and recorded in
the brain that this is accompanied by a
very specific pattern of brain waves we
see these high frequency waves that are
entrained in a much slower
fluctuation this is what we've observed
and measured but how important are all
these components to answer that question
we cannot simply measure from the brain
nor can we only theorize about how
everything is working we need to
intervene well luckily we have such
techniques in one of the studies they've
applied transcranial electric
stimulation and they did so in exactly
that alternating fashion that was also
recorded from the brain this is called
transcranial alternating current
stimulation and in in this
Interventional approach you're able to
induce the brain activity and modulate
it in the direction that you would like
it and that allows us to tell
if actually these brain waves are
causally important for the function
we've seen well here we were talking
about learning and there this is studied
in the context of a very simple learning
task it is to move your thumb as fast as
you can uh we've done this a million
times already but if you ask people to
practice it they still get faster they
get faster and faster and this is called
motor learning that is dependent on the
sensory motor cortex
and exactly over that piece of the brain
they've applied two electrodes you can
see them differently colored and they
ran a small current between them and in
the midle you can see the modeling of
the electric field that is induced and
applied on the brain on the right you
can see this shape over
time if we expect that this specific
high
frequency um brain waves are important
for
learning we should see that we can
actually modulate maybe even boost motor
learning and the beauty of this approach
is that we have very close control
conditions imagine for example placing
all those high frequency bursts but now
in the troughs of the slower wave this
is the specificity we can approach with
trans cranial electric stimulation let's
look at some of the results well
everybody learns and we see here on the
x-axis time on many times they've
practiced and they get faster and faster
the acceleration actually is higher and
higher right so people are learning
they're training in this simple task and
if we apply during their learning you
can see that block the transcranial
electric stimulation they not only get
they get faster at uh learning you can
see the blue line here higher up and
this is a control for stimulation versus
no stimulation what we call a sham
condition but I
the effect lasts and holds on the
learning um has really been modulated
also beyond the stimulation period
people have learned better we have a
beautiful control condition in this case
I've introduce the what if we place the
high frequency burst the fast waves not
in the troughs and here you can see that
this maybe in the beginning did boost
your learning A bit but it doesn't
retain right so it's very spefic
specific and we now know with Callo
evidence that it's this high frequency
burst in the peak that really Drive
learning here motor learning and it
shows you that we can modulate the brain
activity and really test very specific
hypothesis of how the brain works if
you're skeptical about this actually
rightly so it all sounds a little bit
magical and I in this case the author
thought so too so what they did is after
finding these clear and clean results
they said let's do it again again and
they pre-registered the study and they
found even stronger learning effects in
in a second and independent group so
here what we've seen uh we have a
hypothesis about a certain brain circuit
and in a brain function in this case
motor learning we would like to causally
test our hypothesis of which brain waves
are really driving this function we
apply electrodes we model where we
induce and the electric field in the
brain and we can see behavioral effects
in this case that are learning effects
that are very specific to one
intervention and not in the control
conditions this shows the power of
transcranial electric
stimulation let's move to a second
question that will also introduce an
second brain stimulation technique maybe
you're not interested in a basic
question of how the brain works but
Depression
you're really aiming for a therapeutic
effect and many of us are looking for
new and novel ways to treat depression
this is a disorder a brain disorder that
affects so many people around us and
currently our treatments are often not
effective enough what if we can give the
brain a little bit of a push in the
right direction and we know from
previous literature and research that
there are certain prefrontal circuits
involved in the control of uh the
emotional effects of depression
and it looks like that circuit is
particularly stuck as if it's difficult
to adapt to change to learn so even if
you do receive therapy maybe cognitive
behavioral therapy it is still very
difficult to move in a positive
direction what if we can give the brain
a little bit of a nudge open a window of
plasticity we call it inducing
plasticity specifically in these
circuits well this is what people is
what people are trying with repetitive
stimulation over one of those prefrontal
regions called the dorsal lateral
prefrontal cortex dlpfc and the
stimulation they're choosing here is an
a particularly powerful one called
transcranial magnetic
stimulation I'm going to introduce you
to one of the most novel therapies the
technique has already been around for
treatment of depression since the mid90s
but in recent years we're seeing that
people are becoming better and better at
targeting where exactly in the brain
they need to be in fact some are
suggesting we should do an a brain scan
in the uh Mr to really see where
specific brain regions are more strongly
or weaker connected and you might see if
we're simply placing or stimulation in
this case a big magnetic coil called a
transcranial magnetic
stimulator um over the head measured
from the outside we might not be at the
right place according to somebody's
individual brain connectivity and this
here in the left panel is indicated by
the blue spot where the connectivity is
the strongest in the circuit where we
want to be so we are moving or Target
and stimulating and individualizing
where we are delivering transcranial
magnetic
stimulation we're doing so not just a
single pulse but repetitively to really
Drive that circuit into a plastic State
and one of the approaches people have
taken here is they say well we need
quite a fair bit of energy they say to
really make a change we need a higher
dose and if we have a high dose we know
that we have all patients included
because you can see in the dose response
line here if we're just in the middle
maybe half of the patient would be
responding but what if we drive it to an
extreme we really want an effective
therapy after all so what they're
suggesting is to give three times the
standard number of pulses for in one run
uh and then 10 runs per day and that's
all those rows and then five days in a
row these are thousands of stimulation
pulses in a single week that really
pushes that system and it opens a window
of plasticity and we're already seeing
that over those five days the depression
symptoms are reduced right every day
people feel a little bit less depressed
and after that week of a very intensive
therapy the depression scores stay
relatively low for a longer period in
time well depression is is not an easy
disease and it cannot be easily cured so
often people are envisioning that you
might need multiple of these
intervention weeks when a depressive
episode would come
back but here we've learned that it is
possible to use brain
stimulation for therapy to start
treating symptoms of brain disorders
that it might be really important to
think about where exactly you're
targeting and maybe we need neuroimaging
to guide it we've also learned that we
need to think about the dose and for a
therapeutic dose it might make sense to
really go to the strongest possible dose
and we've seen that these might induce
longer lasting effects what we call
delayed effects really clinical effects
Deep brain stimulation
let's now move to a third example of the
third technique and we're moving back to
basic science imagine that you're
interested in a function of the brain in
something that well hopefully all of us
do every day decision making something
that humans are particularly good at you
would hope well we know that this relies
again on these
prefrontal um brain regions but but here
also how they interact with subcortical
regions it's not as if brain region one
brain region all alone makes all of the
decisions it's really about the
interplay between different brain
regions in a
circuit and if we want to change that
inter Play We Now not only need to be at
the surface of the brain but also want
to go deep to the subcortical structures
so we might be interested in the circuit
between well a brain region is subgenual
anterior singular cortex a deep cortical
region or even the amydala that's a deep
subcortical region that's particularly
important in learning and emotion but
how do we reach those you've heard about
transcranial electric stimulation and
then I've talked about transcranial
magnetic stimulation they both look
fantastic but they're limited to the
surface of the
brain they cannot reach deep without
stimulating everything in between that
might be a little bit dangerous so we're
moving to our third technology and
that's a relatively recent one it's
called transcranial ultrasound
stimulation and here we're using
ultrasonic waves that we can focus
safely from outside of the skull to a
deep and very precise Target in the
brain I'm showing you some early work
that was done in makak monkeys these are
non-human primates very closely related
to us humans and we can Target and focus
these waves on the left you see for the
end interior singular cortex or even
coming from both sides on the Deep
subcortical structure the
Amala we're looking here for an effect
that might last a little bit longer that
has a stimulation that has delayed
effects and we were basing our work on
previous research that showed that if we
deliver these pulses repetitively for 40
seconds and then 10 times a second that
the effects the modulation might last a
little bit longer even a bit longer than
an hour and that means that we after
stimulation we can put the monkeys or
even humans back into the scanner and we
can measure their brain activity and see
how this is modulated by the ultasonic
stimulation and what we observed is that
resting state brain connectivity was
specifically biased and modulated at the
focus of the ultrasound site right you
can see there were able using MRI to
measure across the whole brain but only
at the focus we see the strongest
effects now if I'm diving a bit deeper
in one of those examples and I'm using
here the Amala let's look at the signals
that we're measuring we are looking at a
monkey brain from the front and on the
left you can see the star where the AA
the subcortical structure is and
colorcoded is which brain regions really
Co activate with the Amala so across the
whole brain we're measuring brain
activity and it fluctuates up and down
but some brain regions are working
together they're strongly coupled and
these are colorcoded in hot colors and
you can see the frontal pole and the
orbital frontal cortex all brain regions
that we know are strongly connected with
the
Amala but on the right you see what
happens after only 40 seconds of
ultrasound these connections they're
disrupted the coupling is less strong
and this is an effect that lasts for
about an hour or even a little bit
longer now by combining brain
stimulation with neuroimaging we're able
to have proof of Target engagement we're
also able to see where or effect happens
does it happen everywhere is it specific
to one site are we changing one brain
region or whole circuit the comination
of brain stimulation tools together with
neuroimaging is particularly
powerful so so we've looked at three
different brain stimulation techniques
transc crano electric trans cranio
magnetic and transc crano ultrasonic
stimulation and the upcoming lectures
will dive deeper in each of of those
three thank you very
much