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PROFESSOR: OK.
A little more about the normal striatum,
but then we'll spend the rest of time talking
about Parkinson's disease and treatment of Parkinson's and--
with methods that are to being explored
not just for Parkinson's but other diseases as well.
We ended on this rather difficult network diagram.
The one thing that I note that's missing here
besides the obvious things like I
didn't put in the neocortical connections
except the one from the thalamus because it
receives a striatal connection.
And actually the major output of the globus pallidus
is to ventral thalamus.
Where's does the VA of the thalamus project?
Does anybody know?
You know what the ventral posterior nucleus is.
It gets the spinalthalamic tract and the medial meniscus
pathway carrying some other sensory information.
But that's caudal part of the ventral nucleus.
The more anterior parts of the ventral nucleus
are related to motor areas of the cortex.
So the VL projects to the primary motor cortex.
That's in the middle.
And the VA projects the premotor cortex.
Both can be considered motor cortex.
The VA differs from the VL in that it's more concerned
with movement patterns, whereas the motor cortex itself, when
stimulated, moves individual muscle groups controlling
a single finger, for example.
A wrist or elbow or single joint.
But what's missing from this that I wish I had more on
was inputs to the subthalamic nucleus,
especially because that nucleus is providing
the major excitatory projections to the globus pallidus
and to the nigra.
Obviously very important.
If you're missing that the whole system becomes
unbalanced and you get some pretty striking movement
pathologies in humans.
The only thing I could find was there are projections coming
in there, excitatory projections from somatosensory
cortical areas and some more directly
from somatosensory pathways coming from below.
So what exactly that means, what I would like to see
is a good computer model of this entire system
because that's obviously pretty complex.
And I think it would help us a lot in understand
how this whole system works.
But anyway, the kind of connections
we have here with inhibitory pathways
that are then connected to structures
that inhibit further structures.
So you have inhibition of inhibitory pathways.
Obviously important in understanding
the kind of things that go wrong with basil ganglia disorders.
Parkinson's disease is the first example here.
That's where you get cell loss here in the substantia nigra.
And the cells that are being lost are in the Pars compacta
here that provides that dopamine input putamen and cuadate.
And it leads to-- that's one of the major things that happens
in Parkinson's.
And the striatum doesn't work well.
You get-- the most obvious symptom
is you get a tremor [? regressed ?].
And if they make an intentional movement,
they'll stop the tremor.
But if they're just sitting still,
they'll show this kind of tremor.
Very characteristic of Parkinson's disease.
But as the disease progresses, you get an akinsesia.
They move less and less.
They have a characteristic gate.
It's very recognizable.
And then in the late stages of the disease,
there are other things that happen too.
Cognitive deficiencies show up.
Other systems are clearly effected, not
just the dopamine pathways and the nigra.
But it is that nigral degeneration
that accounts for the things that we
see when Parkinson's disease is diagnosed.
And other diseases like-- you get
cell loss in the striatum in Huntington's disease, which
is a genetic disease where it doesn't appear until adulthood.
When people-- initially it looks like whenever
they intend to move a limb, they,
instead of moving the limb in a controlled way,
they make a ballistic type movement.
Have any of you ever seen people with these things?
Parkinson's disease in aged people is more common.
Whether that's really Parkinson's disease,
they have Parkinson's like symptoms
because they begin losing cells due to vascular
insufficiencies.
But anyway, in chorea, or especially in hemiballism--
in hemiballism they have a lesion
of the subthalamic nucleus on one side.
And when they make-- they intend to make a movement,
they make a ballistic movement, that is, a flinging movement.
The claim is that even these become involuntary.
To what extent that's really true I'm not sure.
But people say they didn't intend to doing that.
But on the other hand, we're constantly
making small movements.
Basically, their habits now cause them problems
because they can't-- they don't have normal control.
Huntington's chorea, the genetic disease,
they make writhing movements that
was named the chorea or dance-like movement.
But basically, they're involuntary movements.
When people first getting it, they
tend to hide it as if pretend they were doing something
intentionally.
But in fact, it gets worse and worse
until it becomes very obvious that they
don't have any control.
So we think the double inhibition helps explain it
because when you lose a lot of inhibition,
cells tend to become hyperactive and produce
abnormally increased movement instead of lack of movement.
In Parkinson's disease, you get reduced movement except
for the tremor.
In these others, you get excessive movement.
So let's go back to a more inclusive view of the striatum.
Talk about-- integrate the limbic striatum with this.
We went through that a little bit in the last part.
The limbic structures are in here in the hemisphere.
And we're talking now, in limbic striatum,
the structures of the striatum, they
give the output of these limbic system structures shown
in the red stripes and you know are
concerned with motivation and emotion.
And so in-- this is the view we want.
If you look at the striatum in the hemisphere,
if the hemisphere's transparent, you
will see the striatum in these locations.
And the entire ventral striatum, I
would include amygdala as part of it.
We know that the amygdala is actually
a combination of pallial and striatal structures,
but a good part of it is striatal
and it functions in many ways like a striatal.
Like the dorsal striatum does with its connections
from neocortex, the ventral striatum and amygdala
do for the limbic system, including
the formation of learned habits.
But the habits, of course, are very
different for ventral striatum.
They're habits of feeling and emotion.
I don't think I'm going to go through this in detail because,
but it's Larry Swansons' more inclusive view of the striatum.
I will simply summarize it this way--
he, of course, has first the dorsal striatum and pallidum,
somatic system, caudate putamen with its outputs
to the pallidum, which are the globus palladis-- two segments.
I just want to point out if any of you deal with rodents
and you try to find that internal segment,
it's very difficult because they're basically
cells embedded in the peduncle.
It's called entopeduncular nucleus,
the nucleus enclosed by the peduncle.
But it is there, nevertheless, because
of these cells with the connections.
But in the larger animals the pallidum is quite separable.
But all these other structures you
could call part of the ventral striatum.
But he includes the septal nuclei
and he calls the medial striatum and pallidum.
And amygdala structures.
And he has the pallidal part as a bed nucleus of the stria
termanalis.
It's the way he-- some people really like to systematize this
and Swanson liked to do that.
In my-- I just take all of these structures
and call it the ventral striatum because there
are a lot of similarities in the way these structures function.
They're all getting outputs.
They're all getting out outputs from
the limbic cortical regions.
They're all involved in habit formation.
Pretty much parallel to the way the dorsal striatum
works for the non-olfactories and non-limbic systems.
All right.
Can anyone answer question eight for me?
Just contrast the neocortical projections
to the putamen versus the projections to the caudate.
How are they different?
Why is it when we treat Parkinson's
we're always dealing with putamen when actually
the caudate is also involved?
AUDIENCE: [INAUDIBLE].
PROFESSOR: Sorry?
AUDIENCE: [INAUDIBLE].
PROFESSOR: It's because-- exactly.
The inputs to the putamen are from the sensory motor
areas of the neocortex.
Somatosensory and motor areas.
Areas 3, 1, and 2.
Area 4, area 6 in Brodmann's terms.
Why, in question nine-- I'm trying to say here
why would you expect the corpus striatum to be involved
in almost all of the functions of neocortex?
The answer is very simple.
Almost all of the neocortex projects to the striatum.
You can say a similar thing for the cerebellum.
All of those structures, they get cerebellar input.
Input from neocortical-- so many neocortical areas
project to the pons, which then projects to the cerebellum.
So we know that the cerebellum then
has got to be involved in more than just simple coordination
of movement.
Because there's a coordination of a lot of things
involved with timing adjustments that the cerebellum
is so good at.
In this case, it's the striatum.
That means when you have corpus striatum pathologies
you can get many different problems
besides-- but the thing that people notice
the most, the most common complaint of the people
with damage to the corpus striatum,
or of course any of these diseases,
is the effects on movement.
This is just a picture shows the central cortex here.
And by central cortex, we always mean somatosensory, motor,
and premotor or supplementary motor areas.
There's a number of premotor areas or supplementary motor
areas.
One of [INAUDIBLE].
And it shows the projections from there in the reddish brown
going to the putamen lateral to the cerebral peduncle.
This is lateral to the internal capsule, I should say.
And the internal capsule fits in here.
The caudate nucleus is mostly medial to it.
The anterior-most part is the largest [INAUDIBLE] caudate.
It's getting inputs from all of the other cortical areas,
including some of these areas [INAUDIBLE].
This is from a picture in [INAUDIBLE].
And we leave some of these white,
including the visual areas here.
But in fact, even in a hamster that I've studied
I've traced projections here from the visual area
as I see the projections of the caudate nucleus.
And it also includes prefrontal areas here.
All right.
And this is an updated view of the projections
from the cortex.
And they just show one section of the cortex here.
How it projects to the entire striatum,
both dorsal and ventral, and also
to the intalaminar and midline nuclei.
Because these nuclei, remember, have direct projections
to the striatum.
So that means this little area here,
the [? pair of them ?] [? trick ?] to the nucleus
around the midline nuclei.
It projects to this corner of the striatal structures,
including where this basalis is.
And this area of cortex projects to that same area.
So you'll see it's a highly organized system.
The parts most similar to dorsal--
what we've been calling dorsal striatum
involved getting the input from somatosensory and motor cortex.
They show in green here.
You can see here that that's going
to the dorsal lateral region of the striatum.
So the ventral striatum is really ventromedial here.
Dorsolateral then ventromedial according
to more recent studies of these projections.
And the input to the caudate is much more complex.
I went through some of the studies
and found this kind of system where you got projections
from orbital frontal cortex that form
these huge columns medially.
And they can be traced in that same position all around
to the very tail of the caudate.
This is internal capsule in here.
And here are other parts of the dorsolateral prefrontal cortex.
Posterior parietal, which is very far from the prefrontal.
See, it's all these different areas here
and here are projecting this complex pattern to the caudate.
But it's actually more complex than that
because if you look at the actual studies like here,
they trace projections here from prefrontal areas and here
from parietal cortex.
And then you look at a part of the striatum.
You see these-- it's not entirely blue here
and pink here, but in the middle here
there's a lot of interdigitization indicating
that there's a lot we don't understand
about how this is working.
That is, the striatum itself must
be doing some integration of these inputs
because the interdigitization of the projections of the anterior
and posterior association areas--
this area and this area.
Those two projections tend to be very
close to each other in the striatum.
Why is that?
To do that we have to understand a lot more about that cortex,
which we haven't talked so much about yet.
But in fact, this pattern is not well understood.
It's functions are not well understood.
This slide is just talking about-- in clinical neurology
they talk about these different functional circuits
involving the striatum.
All of that's to be expected when
you know that all of these different cortical areas
project there.
For example, frontal eye fields of the frontal lobe we know
are critical for intentional eye movements can
be affected by striatal lesions.
Well, that area projects to the striatum,
just like the motor cortex and the somatosensory cortex do.
Other parts of the prefrontal cortex
project there and, because of that,
other cognitive functions that are
so important in human functioning that
depend on prefrontal cortex, you'd
expect them to be damaged.
It's just not as common in these basal ganglia diseases.
Maybe it's because we don't know.
A lot of people go through life without actually exercising
higher cognitive functions that well.
I saw that with tongue in cheek, but I
think it's probably right.
So we don't notice when they suffer a pathology.
We just think he had too much to drink a little bit too often
or he's getting old or this or that.
Whereas in fact, it can be due to these striatal functions.
Similarly, the limbic areas affect movement and motion
because they project to striatal as well.
Striatal damage or any pathologies
to the striatum, that's a common area for interruption
in vascular supply to the fore brain.
Vessels that come in from the base of the brain
go up through the ventral striatum
and sometimes they reach the internal capsule as well.
So you'll get not just the movement disorders
from the interruption of those axons of the internal capsule.
You'll get changes in mood and emotion as well.
Another complication that I mentioned in the chapter
is the stria zones.
This is an interesting compartmentalization.
It's a little different from that interdigitization
of the projections from the anterior and posterior
association areas of cortex.
This refers to the projections of acetylcholine axons
and the staining [? for ?] cholinesterase,
that you get in the striatum.
There are areas in the striatum where there's
almost no staining with cholinesterase and other areas
where there's heavy staining.
We call these p-zones where there's no staining.
We know they have to be functionally different.
It's been very difficult to work out the functional differences.
I mentioned some of the recent work in that area [INAUDIBLE].
I think we talked about the-- oh,
these are about the cell types.
There's huge numbers, but most of them are characterized.
These are just structural divisions
where you have these large interneurons of the striatum.
This is throughout the striatum you get these cell types.
Acetycholine-containing cells that-- they're short axon
interneurons using acetyocholine.
So we know that that's why there's cholinesterase
staining.
And yet, now we know there's these areas that don't get it.
We just don't know completely why that's true.
And there's many cells that use GABA.
There has to be because of all these inhibitory projections.
We know that the dorsal striatum projects directly
to the nigra with a GABA pathway.
It projects to globus pallidus, both segments,
with GABAergic pathways.
But those GABA cells, the GABAergic cells,
can be further characterized in terms
of peptides they contain like one type contains
not only GABA but substance P, and it
tends to project to the nigra and to the internal segment
of the globus pallidus.
GABA with [? encephalon, ?] those cells project
to the outer segment of the globus pallidus.
So they're using the same main neurotransmitter
but they're modulated by different peptides.
Again, not fully understood.
But clearly they have some functional difference.
This is where I mentioned the stria
zones and those acetylcholine internuerons.
I just want to say a little bit about these terms used
for humans.
The lentiform nucleus.
Did I talk about that before?
This shape right here is the lentiform nucleus,
the lens-shaped nucleus.
The outer part is putamen and the inner parts
are the two segments of the globus pallidus, the output
structures.
That's the lentiform nucleus.
There's the internal capsule, and medial to it
there's the caudate nucleus.
It looks small here, but this a big human
brain so it's actually not so small.
So you see the same thing on the two sides.
I think we saw this before when we talked about the output,
the [INAUDIBLE] [? to the ?] [? meticularus ?],
the pathway that goes from the globus pallidus here that loops
around the internal capsule and goes to the ventral anterior
thalamus.
OK, so you can see if you were doing a dissection how
you would get to it and go into the sylvian fissure here.
Here it is in the photograph.
You can just push it apart.
You'll expose this buried cortex.
What is the buried cortex called?
It's called the island.
The insula, the island cortex.
Sort of a-- I guess it looked like that
to anatomists going in through the fissure
and finding a cortex down there that's
covering the outer part of the striatum here, the putamen.
There's another little layer of cells
there between the putamen and the neocortex
called the colostrum.
It's very widespread inputs and I'm not
spending time on that in the class now.
But we talked about temporalization
and how that forms.
I just wanted to point out that in this picture
these are the axons that form the internal capsule coming
down through the striatum.
So this is left hemisphere.
The caudate nucleus is on the other side of it.
It would go all the way around.
But back here what does it do?
Well, the caudate goes all the way around.
So down here you see it below those axons.
So if you make a cross-section, you
can see the caudate there and there.
There's white matter in between the caudate
and the other parts of the putamen.
And here we see white matter here
between cuadate and putamen.
[? And ?] the whole length of [? that nucleus ?] in fact.
And remember that if we follow the caudate all the way around
right here it abuts the amygdala.
So this would be the position of the amygdala here.
So let's talk about Parkinson's disease now.
I'm sorry I didn't deal with-- I left a lot of things hanging
there, but it represents the way the field is
to tell you the truth.
There's a lot we don't know.
So I want to talk about one of the major treatments that
was developed in recent years.
It's interesting because it was based on neuroscientific study
that began with studies of rats and then moved
to a new treatment for Parkinson's disease
using tissue transplantation from fetal humans,
the product of abortions.
They're obtained in abortions.
Tissue that would normally be thrown out,
but they were legally able to get that tissue and use some.
You will see about how old they had to be,
but they were always from tissue that
would have simply died if it wasn't used.
But then we'll talk about new neurons for the adult brain.
Not just implanted, but neurons that are either from stem cells
or normally generated in the brain of adult animals
and mammals, including humans.
We walked about that once before when
we talked about the olfactory bulb.
I talked about new neurons being generated
in the lateral ventricles even in adulthood
and how they migrate forward into the granular layer
of the olfactory bulb where there's cell turnover.
Constantly those cells in the olfactory bulb
are being replaced.
The same thing happens in the hippocampus
so we'll talk about that.
So let's talk first about the fetal nigral
transplantations, a therapy for Parkinson's disease.
[? High ?] brain imaging is used to assess
the success of those transplants.
Before any functional effects are seen,
they can find out if the cells are surviving.
And then we'll talk about the new cells.
Does everybody understand what Parkinson's disease is?
Why is it that-- we know the cells of the nigra that produce
dopamine are gradually lost in Parkinson's disease.
Why is it they don't see any symptoms of Parkinson's disease
until 80% of those cells are gone?
Any suggestions?
You remember what I said in the book?
Why don't you see symptoms until 80% of them are gone?
In fact, as we will see, the treatments for it
would be more successful if they could catch it earlier.
But they don't.
The reason seems to be collateral sprouting.
When you remove a small proportion
of the dopamine-containing cells,
the axons die going to striatum, the dopamine axons.
But the remaining ones simply sprout collaterals,
take over the space.
There's a lot of evidence for that
because it happens in many systems,
not just in baby animals but in adult animals.
You get collateral sprouting into denevated areas.
So for example, if I cut-- remember
I gave this example a long time ago, Chapter 13.
You lose axons in your hand due to an arm injury
or maybe pressure too long on your arm transects some axons.
They will regrow, before they regrow, you can lose function.
You can lose your ability to extend your hand, for example.
I mentioned that that happened to me once.
And then what happens?
You don't have to wait for the regeneration
to occur before you get return of function.
Why is that?
Collateral sprouting, because you
haven't killed all the axons, the remaining ones
will sprout over a period of about two weeks.
That will happen and you start getting most of your function
back.
You have to have adequate innervation
or you feel extremely weak.
You have to have a lot of innervation
to get those muscles to discharge properly.
But the same things happening in the corpus striatum.
Collateral sprouting.
And because it's ongoing, it's probably the reason
why making lesions gradually, as the skin a slow-growing tumor.
It's also a lot harder to detect because you're
getting connections being replaced.
It's when you make the lesion all at once
that you see the maximum effects of the lesion.
Anyway, the most dramatic discovery of a treatment
concerns this use of tissue from fetal nigra.
And this is what I mainly what I want
to talk about here, fetal nigra transplantation.
They're basically taking nigral tissue just removed
from a fetus.
It's little chunks of tissue but in a solution.
They suck them into a pipette and inject them.
That's basically what they're doing.
Why do you think it might be true
that the topographic organization of connections
isn't a critical factor in the functioning
of the nigral striatal connections?
You're not causing a regeneration of nigra
to striatum.
You're just putting the nigral tissue directly
into the striatum.
So normally the striatum doesn't contain dopamine cells.
But if they put the dopamine cells into the midbrain,
do you think the axons are ever going to reach the striatum?
It's a big distance in an adult human.
It wouldn't work.
Yes?
AUDIENCE: [INAUDIBLE].
PROFESSOR: Right.
That's part of the research that was done.
AUDIENCE: [INAUDIBLE].
PROFESSOR: No.
No, but they were interested in working out
the best ages of the human tissue
because you don't want to go doing that procedure on humans
when the fetal tissue is not in plentiful supply,
especially because then putamen-- they're putting it
all in the putamen because they're
trying to treat these bad motor symptoms, you see.
So they're not focused on caudate nucleus.
They're focused on the putamen.
And the putamen is very large in adult humans.
And those fetuses are very tiny.
So to get-- the problem is you put it
in the putamen, the axons from those new cells
that they're putting in there don't grow very far.
They grow very slowly and they don't grow very far.
We'll review that quickly here.
So you need a number of fetuses to get
a really adequate implant for one patient.
And that means it's hard to get enough fetuses.
AUDIENCE: [INAUDIBLE].
PROFESSOR: Because there's a lot of people with Parkinson's.
AUDIENCE: [INAUDIBLE].
PROFESSOR: Yeah.
Even if they could do that-- and I don't know of any research
that really tried that.
But in other systems they have tried,
and generally it fails because once systems contain
a lot of myelin, the myelin inhibits the growth of axons
because of [? the nodal ?] protein.
It's very difficult to get it to grow.
[? If ?] maybe a prior knowledge of how to get it to happen
were a little more advanced, we could create pathways
where it would go.
You see, the problem is you're putting the dopamine cells
directly into the putamen.
That means the normal circuitry, the normal stimulus
for nigral cells is missing.
But what they were counting on is--
and this worked in rat research.
They got a lot of function back in spite of all that.
OK.
So if you don't think the topography is very important
because we're just dealing with a-- as I point out here,
the actual dopamine release doesn't
require high information content.
It's a neuromodulator.
It's simply changing the way those cells are
working in the putamen.
So that's why we think.
It really doesn't matter the topography [? for it. ?]
AUDIENCE: [INAUDIBLE].
PROFESSOR: Yeah, well, that's another issue, isn't it?
Stria zones versus non-stria zones
could drastically affect how it's
working, at least subtle aspects of movement
and the way people learn habits and so forth.
Maybe they can't learn much.
You'd like to look to see how much do they really study
these patients that do get some recovery.
But the question you're asking is a major one.
You need to find those things out.
We know that the donor age is critical.
And why would we expect that?
Well, studies of the development in,
ontogeny of human dopamine producing cells,
indicate that they first appear five and a half
to six and a half weeks post-conception.
And little processes grow out from those cells beginning
at eight weeks post-conception.
And the axons first reach the striatum at nine weeks.
Well, once they've already grown all the way to the striatum,
we already know from various studies of animals
that when you damage cells that have already grown
a lot of processes, that they become much more vulnerable.
They're going to die if you damage them very much.
Because then you're damaging a lot of processes.
So it was predicted that you would
have to go in this early period before most
of those process, the dendrites and axons, have even grown.
And that's what they found.
And to do that research, as you mentioned they're actually
taking the human tissue and putting it in rats
striatum when they found out that they
could do that successfully.
They wanted to find out which ages to use.
So here they took-- you see a lot of surviving cells.
The black indicates the dopamine.
Actually it's tyrosine hydroxylase, the enzyme
that you always find in dopamine processes themselves.
They took it from a fetus 41 days post-conception
and it survived very well in the rat striatum.
If they took from 72 day post-conception, that's
after the axons have normally already started
reaching the striatum, then they didn't get good survival.
So they knew they had what-- that's
how they found out the age range they had to use.
Now how can they use imaging of the living brain
to assess transplant success?
By using fluorodopa, which allows
you to use positron emission tomography and find evidence
for living dopamine cells.
And of course if the patient dies,
they can use nueroanatomical methods.
Basically [? indianal ?] staining
for tyrosine hydroxylase.
And they can assess then post-mortum.
OK.
You can read about fluorodopa online and how it's [? the-- ?]
and this just mentions histological procedure
on the autopsy material to find out
where those dopamine cells are.
And this is just some of the results.
The dark staining here is dopamine.
And you don't get tyrosine hydroxylase
unless it's in live cells.
And you see, if you look in higher magnifications,
the whole feltwork of processes dopamine
has-- this is all from a graft because when they do these--
this is from a human brain with surviving
graft of fetal tissue.
There's a lot of dopamine axons in parts of the putamen.
If they get a long ways from where they put the implants in,
this is what it looks like.
Almost nothing.
On the right.
Because they don't [? grow ?] very far.
Here's where they're putting in rat
and you see very good survival here.
And here you see them surviving, how
they use to predict when they would
to be successful in humans.
So-- and I mentioned this.
It makes a big difference on where
you put it because of the size.
The striatum is so big.
This is about the rate of growth.
I used six here to calculate that they
would grow about a millimeter in seven days
at six microns an hour.
And we know that they never seem to grow more than
about two and a half millimeters.
Because remember, this is adult tissue
and there's a lot of inhibitory factors.
It's surprising to some people that they grow even that far.
OK, so we know the locus is important
because of the functions of the striatum.
They occur in different parts and they're
interested in the motor symptoms so they put it in the putamen.
So why do you think it's so slow?
It takes many months, even longer
than the axons are grown out, according
to [INAUDIBLE] results.
So we know that there's probably other aspects of maturation
of the neurons require a lot of time.
So it took a lot of patience in doing this.
And I mentioned other issues that are involved.
Lack of normal inputs, the fact that Parkinson's disease
involves other cell groups than just the dopamine cells.
It involved norepinephrine cells, for example.
We know less of about the function
of those groups in the striatum.
Then I mentioned collateral sprouting in addition.
The point is if the dopamine axons are showing collateral
sprouting, well, what about other axons?
When there's denervation, other axons
can show collateral sprouting, too.
So then the dopamine axons have to compete with those.
And the competition can take a very long time.
And it might not always be successful.
It's not easy to predict which axon [? is moving ?] out.
Usually the normal axon is [? moving ?] out.
But now they're not from the same person.
They came from elsewhere.
Does that mean they can compete just
as well as the person's own dopamine cells would?
We don't know.
So I'm asking about alternatives for that treatment.
I think I won't take time to go through this.
We're going to read about it.
The stem cells are the most interesting.
Scientific studies indicate that for advanced Parkinson's
patients there doesn't appear to be
much use of using this procedure.
It just doesn't work.
It worked well, though, for people that are less severe.
That is, the Parkinson's hasn't progressed as far.
So for them, it did work.
But of course, they're really concerned
with those people with the more advanced symptoms.
And they decided that the transplant procedure just
wasn't good enough, so that led to other types of treatments.
The thing used in the clinic-- there's
two methods used in the clinic.
One is called deep brain stimulation.
If you go online and just type in deep brain stimulation,
you'll find all kinds of articles
because residents-- medical residents in hospitals
love to do research and get their names on papers,
so you'll find paper after paper after paper
on their use of deep brain stimulation.
And yes, it works very well.
You stimulate the globus pallidus.
You stimulate the subthalamic nucleus.
You can get effects.
Often you can benefit the patients.
Which remember, they're missing a lot of the normal input
from those pathways that affect the system.
So if you stimulate it artificially,
you can improve their symptoms and that's what they
[? found. ?]
They also have gone in and just ablated structures.
And if they do that right-- the problem here is predicting.
Well, how do you know?
You only get one chance.
Ablated, you're not going to get a second change.
But they have found specific lesions
that-- they base it on animal work first.
And they do get some benefits, reducing movement problems.
And I just mentioned examples of lesion.
I'll talk a little more about the neurogenesis things,
but make sure you read that here and I'll answer any questions
you have about it.
There's a few very interesting issues
here about using-- both in using stem cells, which-- if you just
look now, do a search on stem cell treatment for Parkinson's,
you'll see there's a lot of recent things.
Some of it's by patented cell lines,
which I think is a horrible idea that the government has allowed
it.
And so now that creates all the problems that patents caused
and a lot of competition between groups and so forth.
But they are getting stem cells to work,
but it's not an easy thing.
There's many issues in getting those cells
to do what you want.
And the-- but I want to say a little bit
about the normal stem cells we have, creating new neurons.
In the hippocampal formation, not just in the olfactory
bulbs.
So we'll say a little bit about that
because we've talked about hippocampus before.
And then the main topic for next time will be neocortex.
First chapter on neocortex, Chapter 32.
And I posted questions on that chapter.
I've written questions for the next one too.
I'll get those posted probably later today.