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PROFESSOR: So we're going to try to arrange your brain
dissection within the next week.
And if we have to we'll just do it during class time,
though it's a little bit short for the section.
But we can do it.
It's better than not having it.
Unless there's some evening that everybody can do it, in
which case, we could have maybe an hour and a half
instead of an hour.
How many of you have done a sheep brain dissection?
One.
Two.
[INAUDIBLE]
You did--
in January.
AUDIENCE: I did one in January [INAUDIBLE]
PROFESSOR: If you've done one already, then you'll get even
more out of the next one that we do in this class.
So that's good.
They're not required, because there's a few people that are
squeamish about it, can't stand to do
dissections at all.
So you're not required to do it.
They can learn quite a bit about the sheep brain online
of course, including getting manuals for
dissection and so forth.
But I think it's very useful to put on gloves and look
directly at the brain.
OK.
We started talking about the amygdala.
We'll try to finish that today.
I pointed out that it's closely related to the
[? corpus ?] striatum.
Some people consider it, as Cajal did, for a [? big ?]
caudal part of the corpus striatum.
But the gene expression data indicate that it's probably
sufficiently different, because some people don't like
to call it striatum.
And actually, there are parts of it that are more striatal
and parts that are not.
So it's a bit complicated.
I take a functional approach and a connectionist approach.
When it comes to function and connections, it deserves to be
treated as a complex but still single structure that
functions like the rest of the corpus striatum, except a
different kind of function.
So here it is in the rabbit brain seen in ventral view.
There's the olfactory bulb up in the front.
And you'll see illustrated some of the connections.
The olfactory bulb, which includes some that go directly
to a portion of the amygdala, the portion nearest the
surface of the temporal lobe.
Here in this little box, you see different subdivisions,
which I tried to separate there with different marks.
I put in red the cortical and medial parts that get direct
olfactory projections.
And actually, many of those don't come from the main bulb
but come from this little caudomedial portion of the
bulb, the accessory olfactory bulb that gets its input from
the [? former ?] nasal organ in the roof of the mouth.
Many animals respond to pheromones important in their
mating behavior and other social behavior by input
through that organ.
OK.
Here is a dissection of the rat brain.
You see the multilayer neocortex up here.
There's the hippocampal formation with fibers coming
out of the hippocampus that are
heading towards the septum.
And they will form the fornix columns that project all the
way to mammillary bodies.
OK.
The amygdala sits here in the temporal lobe.
If we went a little further back, we would see the
hippocampus, which comes down behind the internal capsule,
the caudal edges.
It's an in-folded medial and caudal edge of the hemisphere.
And then, just anterior to the ventral end of
it, we have the amygdala.
And this is the cortical node.
You see these cells that come--
it looks like cortex really, except you don't find the
white matter down below that you find in the cortex.
And then, the medial nucleus.
The basal nucleus here.
Central nucleus, lateral nucleus out here.
And here, in the hypothalamus, you see that very clearly
outlined cell group, outlined partly because the cells are
dense in their staining, but also because there's fewer
cells in this shell around the nucleus.
And the projection from the amygdala here that follows a
loop around, just like the fornix, many of those axons
end in that shell.
We will show that here.
So the output--
let me blow that up a little bit--
this is the same picture.
The output fibers, major output, is called the stria
terminalis.
And those axons actually can be seen here.
Many of them are coming out of that central nucleus that the
arrow's pointing to.
And then they're going up and around the internal capsule.
These are internal capsule fibers, which we can put--
they're coming like this.
Here they're forming the cerebral peduncle.
Do any of you know what I put in the grey here?
What this is--
coming up the side of the diencephalon?
It's a tract.
It started out at the optic chiasm.
Now it's going up the side of the diencephalon, that's the
optic track.
OK.
What happened to the stria terminalis?
Well, it goes around the back of the internal capsule.
But we see it again here.
It's quite separate from the fornix fibers.
In fact, it's a complete separation right there.
It's not so obvious in the picture.
There's actually ventricle in between.
And then they appear again down here.
There's stria terminalis fibers actually terminating in
that shell around the ventromedial nucleus.
Well, if it terminates in a shell around the ventromedial
nucleus, why do I think it projects to the
ventromedial nucleus?
It's because these neurons-- you're just
seeing their cell body.
If we could see their dendrites, you would see the
dendrites poking out into that shell.
This shell here isn't empty.
It just doesn't have many cell bodies.
It's got the dendrites of these cells and the axons of
the stria terminalis terminated on those dendrites.
I can draw that into the picture that
was on the web later.
OK.
So what more can we say about the inputs to the amygdala.
Well, the old inputs, we think were the most ancient are--
one we already mentioned--
olfactory projections.
But there are also projections that come from the hindbrain
from the gustatory region, carrying taste and pain
information.
Actually the nucleus in the hindbrain, the parabrachial
nucleus, Nauta says it's in the
caudal end of the midbrain.
So it's a little bit arbitrary where you divide these
subdivisions.
But we know that both pain and taste
input reaches the amygdala.
More recently evolved inputs--
we think they're more evolved, but they're
pretty ancient too--
one of them carries auditory information, coming direct
from the medial geniculate body of the thalamus.
Another carries visual information.
But it doesn't come directly from visual cortex.
It doesn't come from the optic track, except maybe a very
small number of axons.
Most of it comes by way of the inferotemporal cortex.
So it's comparing information on complex configurations,
object information we think into the amygdala.
And here's that picture we saw a long time ago that shows
experiments on these three different species--
the opossum, the hedgehog, and the tree shrew, where they
labeled the neurons in the medial geniculate body.
I can say they labeled a bunch of cells here, in the medial
geniculate.
Then they traced the axons going forward and out to the
auditory cortex but also into the amigdala.
And they find that in all three species.
They're greater in the opossum.
And in fact, in the opossum, the amygdala projection is as
big as the neocortical projection.
So the amygdala is getting a lot of sensory input coming
from the brain stem and coming from the cortex.
Now this is a typical medical school textbook.
It'd be totally confusing, because there they show the
temporal lobe down here.
This is actually in the temporal lobe.
There you have the end of the hippocampus.
And it's in behind--
it's actually the right hemisphere on the other side
of the brain stem.
Very difficult, if you don't already know from dissections
or whatever where these things are placed.
The only thing that you can really make out from this is
that the inputs are coming from limbic system-- in fact,
the bulb, parahippocampal areas, septal area, so forth.
So let's stick with the stria terminalis for a little while.
It's a major output of the amygdala.
It has a route similar to fornix fibers coming out of
the hippocampal formation.
This is an important connection for the
amygdala-influenced motivational states of the
animal or the person.
The stria terminalis comes from this nucleus, which if
you look from below like this, it's hidden by the basal
nucleus and cortical nucleus there.
It's up above.
But in this picture, I'm just indicating it in the center of
the amygdala there.
And I'm showing stria terminalis fibers that go
around the internal capsule.
So they're both above and below the internal capsule.
And here it is forward, diving down through the septum and
terminating in a nucleus we call the bed nucleus, the
stria terminalis.
And on this, on a parasagaittal view, you see
how similar to hippocampal fibers it is.
Here's the amygdala in the temporal lobe.
Remember this is the hemisphere with the--
it's been separated from the brain stem.
There's that [? move ?] the brain stem down here,
including the upper brain stem,
hypothalamus, and thalamus.
So this is internal capsule.
And there go the fibers from the amygdala, stria terminalis
around the internal capsule.
And then in front of the thalamus, there's the bed
nucleus, the stria terminalis.
And then we can follow those fibers further, as shown by
the red arrow, into the hypothalamus.
And they actually go further into the
midbrain limbic areas.
If I take my pen here, I can show the fibers--
oops.
Here they come from the hippocampus
around the similar route.
Here they're coming out of the hippocampus.
Here they're going into the septal area.
We picked them up again here.
And they go to the mammillary bodies and others into the
hypothalamus.
So the two routes are very similar.
But only one of them was called the arch of
[? fornication, ?]
[INAUDIBLE]
fornix.
The other is just the stria terminalis.
All right.
When you look at a picture I like this, because I've done
anatomy so long, I don't just see the cells.
I see fiber pathways too.
But the fiber pathways--
what are those?
There are a lot of little cells in there--
what are they?
What are the little cells in the fiber bundles?
There they are in the optic track.
There they are among the fornix fibers.
Here they are in the white matter of the hemisphere.
We know that's mostly fibers.
Here they are in the corpus callosum.
What are all those little cells?
What cells surround axons in the CNS?
They're similar to the cells in our peripheral nerves, in
our arms and legs, and everywhere.
OK, the Schwann cells.
What are they in the CNS?
[INAUDIBLE]
The oligodendroglial cells, oligodendrocytes.
We call them oligodendroglia or oligodendrocytes.
And they wrap their membrane around axons
and form the myelia.
So that's what we're seeing.
So there comes the stria terminalis.
There, and there, and there.
And if we're dealing with the fornix, there are
these axons up here.
There are these axons here on their way to mammillary body.
And in both cases, there are terminations there all along
through the hypothalamus.
OK.
Now here is the human brain.
And, of course, it's got this enormous hemisphere.
This is in a section in front of the thalamus.
So here's the caudate, the internal capsule.
We can see its connection with the white matter of the
hemisphere.
Here's the putamen.
Here's the globus pallidus.
And then below the globus pallidus, OK, there's tissue
here we call the basal forebrain in front of the
hypothalamus.
There's the septal area up there.
Bed nucleus of the stria terminalis
would be right there.
And it's coming from the central
nucleus of the amygdala.
The stria terminalis is coming out here and would be found
again here if we went back a little bit.
We'd find it up next to the fornix fibers just as we did
for the rat.
Here in the blue, we marked the amygdala.
But actually we didn't mark all the--
this would also be amygdala, cortical
nuclues of the amygdala.
OK.
I decided this is--
I inspected it really carefully today, and I see
that Naute's actually removed it from this textbook.
And I don't want to use it in class anymore, because it's--
I think it's more confusing than it is helpful.
If I can get my pen back here.
OK.
So let's talk a little about how we know about functions in
the amygdala.
There have been a lot of lesion studies.
The ones on monkeys are pretty well known, because they were
part of a famous syndrome called the Kluver Bucy
syndrome, which was a syndrome produced in monkeys by
excisions of the whole temporal lobe.
And of course, if you take out the temporal lobe, you're
removing what?
Amygdala, and the pole.
You're removing much of the hippocampus.
And you're removing neocrotex of the temporal lobe too.
So they got symptoms of all of these lesions.
Different components.
And then the studies were--
this was in the '30s, Kluver and Bucy did it.
Then later, so that's like seven years ago.
And then they began making lesions separately in these
different structures.
And we now know the lesions of the amygdala alone make
monkeys seem very tame, because they lose their normal
defensiveness and aggressiveness in social
situations.
It's dangerous to play with them as if they're truly tame,
because it totally depends on the situation they're in.
The monkeys become--
if they're left in a social situation, they become
socially isolated.
They lose their sensitivity to social dominance
relationships.
So a subordinate monkey will walk right up to the alpha
male and slap him on the back.
You can imagine how the alpha male reacts to that.
He beats up the other monkey that does this.
And so the amygdala lesion animals end up pretty beat up
and socially isolated.
They lose their normal fear in response to visual inputs.
Monkeys are usually very afraid of snakes, for example.
These monkeys aren't.
Other things that monkeys would normally be afraid of,
they're not.
Well, there've been a few people with
amygdala lesions too.
Sometimes, they make these lesions on purpose, because of
disease tissue that's causing very bad epilepsy.
It's a very debilitating syndrome that tends to get
worse over time, because cells that have undergone seizure
activity frequently become more sensitive to additional
seizures and can basically ruin the
function of the person.
So they're pretty desperate for some kind of help.
And they try to remove just the diseased tissue.
But in some cases, they remove quite a bit.
And in other cases, it's due to actual
traumatic damage or tumors.
And people with amygdala lesions have shown a loss of
autonomic reactions that normally accompany fear and
anxiety states.
So they don't get the increased cortisol levels in
the blood for example.
They don't show the rapid heart rate that people tend to
show when they're afraid.
They may show other components of fear.
But they don't show these autonomic reactions.
And also, they've seen, even in the monkeys, altered
dietary preferences.
And in both humans--
and this was well-known from the monkey studies--
they show hypersexuality.
Now in people that's not all the time.
And it's not clear if it's just variations in the lesion
or why it's so selective.
If you stimulate the amygdala--
and this has been done in both monkeys and people, as well,
also, there's some cat studies-- if you stimulate the
cortical medial area, you get things related to oral,
orality, salivation, [UNINTELLIGIBLE]
chewing.
But you also can get elimination behavior,
inhibition of voluntary movements.
Things that happened during novelty exposure to extremely
novel situations.
Other parts of the amygdala, you'll get arousal,
unattentiveness.
You can actually get attack behavior in cats.
Fear and/or rage have been elicited.
And people also show anxiety and
other very strong emotions.
But they're not all these powerful emotions related to
fear and anxiety.
They also get deja vu experiences from stimulating
the amygdala.
And it's believed that when people experience deja vu,
it's probably due to abnormal amygdala activity.
It's more common in young people.
The whole Papez circuit is prone to seizure activity.
And you get transient seizure activity in people.
And again, it's more common in young people.
Most kids outgrow it by the time they're about your age.
How many of you know what deja vu experiences are?
Have you had them?
I had them fairly often until--
But once I got into--
I don't know-- mid-college years I think they were
disappearing.
All right.
What is deja vu?
Can somebody describe it?
It's when you're in a situation that's novel, you
know you've not been there before, but you
feel like you have.
You're sure you have.
I've been here before.
I have this strange feeling I've been here before.
I'm seeing it again.
And yet, all the evidence indicates that you have not
seen it before.
The experience--
the feeling of being there before is what's controlled by
this region of the brain.
OK.
Now in rats, most of the studies have focused on fear
behavior and learning of fear.
This is an experiment I took out of the physiological psych
textbook that I used to use.
At the left side there, you see a rat being exposed to a
novel sound.
And they're measuring his heart rate here in the time
the rat spent immobile, when he just froze when the
stimulus came on.
OK.
So he didn't spend very much time freezing.
But he did when it was novel.
Most animals, when there's a very new
stimulus, they will freeze.
And they will get a transient increase in blood pressure.
In people, it's the same with people.
OK.
But it doesn't last very long, once the stimulus is not
novel, you won't get those reactions.
But if you pair that sound, which is now not novel
anymore, with shock to the feet.
You get, of course, a very big rise in blood pressure.
And they freeze for a long period of time, even if the
shock is brief.
And you don't have to do that much, even one trial is enough
to induce fear conditioning.
Now when the sound comes on, the animal has
learned to be afraid.
So now you get the increase in blood pressure and the
freezing just in response to sound.
So that's what fear conditioning is.
And that's led to this popular notion that the amygdala is
critical in this circuitry of fear as this textbook put it.
It was based on the work of Ledoux back in the '90s.
And he's showing the centrality of the amygdala
with its various inputs, directly from the thalamus
from sensory areas like from inferotemporal cortex, similar
projections of other modalities.
And there's also input from the hippocampus.
Most of that comes into the lateral nucleus.
But there are other parts that would make the [INAUDIBLE]
inputs too.
And then circuitry of the amygdala partly by
intra-amygdala connections reaches the central nucleus,
which then projects to its output pathways and affects
hormonal responses, autonomic nervous system activity, which
would change heart rate, and blood pressure for example,
and alter the emotions.
Produce emotional behavior if you're studying rats.
People, of course, would report the feelings that
accompany that.
OK.
I wanted to go through--
I drew this in because I didn't have a picture of it.
It's from an old experiment, way back in 1962.
A fellow named Downer was able to get the amygdala symptoms
in monkeys when they looked with one eye and not when they
looked with the other eye.
So if he patched one eye, he got the symptoms.
Let's say he patched the right eye.
They were normal monkeys.
He patched the left eye, and they were amygdala monkeys.
So what did he do?
What I've shown here is the optic chiasm, which I moved
out just so we can see it.
Otherwise, this is a top view of the brain.
And I've showed where the amygdala is there in the
temporal lobe.
So there's the frontal lobe, temporal lobe,
occipital areas here.
And then I've shown corpus callosum.
OK.
So he did an amygdalectomy in just one hemisphere.
Now if you do that in just one hemisphere and that's all you
do, the monkey is pretty normal, even if he's only
looking with one eye.
But if you split the optic chiasm and also the corpus
callosum, then--
and usually they include the anterior commisure in that--
then what happens is the input coming in from the left eye
here can only go to the left side of the brain.
So it reaches the visual cortex here.
And through transcortical routes reaches the amygdala.
And not shown in any of these pictures are what we now know
is a more direct pathway in the lateral nucleus to the
thalamus going right to the amygdala.
But because of the split chiasm here, it's only
reaching the left hemisphere.
Whereas, the input from this side is
doing something similar.
But now, it doesn't get to the left hemisphere at all.
And there's no amygdala on that side.
So the monkey has a totally different personality
depending on whether his left eye is patched or his right
eye is patched.
Very dramatic illustration of the importance of connections
controlling behavior, including emotional behavior
and feelings, which is why I like to go
through it in class.
OK.
The amygdala has been tied to a number of clinical problems
in humans, including excess aggression.
So I'm going to say a little bit about aggression, which is
mostly in male animals.
That's true for people too statistically.
Learned fear, as we already discussed, stress, and anxiety
states, and social insensitivity
as in autism states.
Here's from a study, where they looked at the effects of
androgens on aggressive behavior.
They're putting rats in pairs and recording the number of
biting attacks.
Rats are being aggressive towards each other.
And here, here's the normal biting attacks in a male rat.
And then the rat is castrated.
So testosterone levels go way down.
So does the aggressive behavior.
Here in females, low levels of aggression both before and
after removal of the ovaries.
Here with castrated males, low levels of aggression.
But then you start giving testosterone injections.
You give 150 micrograms per day, and you get a steady
increase in aggressiveness.
But only up to a certain point.
You reduce the testosterone to half that dose, it stays
pretty high.
You reduce it much more to 30 micrograms per day, and it
starts dropping.
It drops almost to the level of no hormones.
So once you're above a certain threshold of testosterone, you
get [? a new ?] aggressiveness.
Now where's the testosterone acting?
It actually acts directly on the brain.
There are receptors for these sex hormones in the brain.
And the amygdala is one of the places you find them.
You also find them in the hypothalamus and other areas.
A lot of that work on hormone binding in the brain was
started here at MIT in Joe Altman's lab.
Altman was the guy who discovered proliferation of
new neurons in the forebrain of mammals.
And he had a student, Donald Pfaff, who--
after he got his PhD and did postdoctoral work-- he became
a professor at Rockefeller University, where, I believe,
he's still working there.
He's only--
I think he's a year or two older than I am.
And for many years, he's collected all kinds of
information on various kinds of behavior related to the
limbic system.
This just shows you how textbooks have stressed--
their anatomy is totally inadequate, but it's simply
pointing out the importance of the amygdala here in fear
conditioning and also post-traumatic stress
behavior, an abnormal type of fear conditioning.
And people that show this, it can very debilitating.
They can get for associations of--
they don't even know what's causing them.
They suddenly get changes in their behavior, including
freezing, inability to move, various things.
So people that have suffered severe stress often seek some
kind of treatment for this.
And that's made work on the pharmacology of the amygdala
and neurons related to amygdala outputs to be
particularly important.
This is just a little more on post-traumatic stress
disorder, where they give the list of brain regions involved
just to show it's not only the amygdala but many other places
in the brain.
But of course centers on hypothalamus, autonomic
nervous system, nucleus of accumbens--
that's part of the basal forebrain, a major part.
It gets major input the amygdala for example.
And of course, cortex and hippocampus is involved in
almost everything.
And this is just an example of how people--
what's been of particular interest
for the drug companies.
What kind of receptors do we have in the amygdala?
What are the neurotransmitters there?
One of the things they find is
corticotropin-releasing hormone.
It acts as a transmitter right in the amygdala.
There are CRH-containing neurons in the central nucleus
of the amygdala.
And that region also receives axons that contain
corticotropin-releasing hormone.
These cells in the amygdala project to the hypothalamus,
to a region called the median eminence, which is an area
that has axons contacting the blood vessels that run to the
anterior pituitary.
So the CRH then can directly reach the pituitary and cause
the release of adrenocorticotropin.
It brings the release of ACTH, which then raises the cortisol
levels in the blood stream, which is one of the large
changes that occur when you're under stress or in that severe
anxiety state.
So this is the kind of knowledge that drug companies
need to target areas to get drugs to work on these
conditions.
We've mention now basal forebrain.
Here we saw the nucleus accumbens, which is part of
the basal forebrain.
Let's go back to these pictures and point out which
of these structures here-- the basal forebrain is here.
Here's the septum.
Some people would include in basal forebrain.
I normally just include these structures below it.
And if we look at these sections--
here's the hypothalamus.
And here is basal forebrain structures just pouring a
little bit there.
One of the cell groups--
I've drawn these bunch of large acetylcholine-containing
cells right there.
That's basal nucleus of meynert, uses acetylcholine as
a transmitter.
And those are the cells that have widespread projections,
especially to the hemisphere, to the neocortex.
[INAUDIBLE]
distribute throughout the hemispheres.
OK.
And then the structure at the base here labeled with a T, is
the olfactory tubercle.
It's really the superficial part of the corpus striatum,
the ventral part of the corpus striatum.
It comes right to the surface.
And that's olfactory tubercle.
So the striatum gets direct olfactory input as I pointed
out early in the class.
That's true even modern mammals.
And then the deep part of the tubercle is just part of the
ventral striatum.
And portions of the ventral striatum have
formed distinct subgroups.
One of them is nucleus accumbens, which is a fairly
good sized cell group right in here.
And right next to it is the bed nucleus of the stria
terminalis.
These areas get a lot of input from both amygdala and
hippocampus.
OK, one more thing.
We'll make it today through the class.
I want to point out something that's been interesting for
studies of psychosis in humans.
When I was doing early brain lesion work, I worked out--
just for the visual system, and then later, with students
for the olfactory system--
the kinds of things that happen after early brain
lesions when axons can change their connections.
And I read a study--
I actually heard this study at a meeting in Germany when I
was, I think, an assistant professor here at MIT--
and the fellow gave a report, where he talked about people
who had been--
he was a neurologist.
And he had worked with a neurosurgeon in England.
They had done removals of the amygdala or
parts of the amygdala.
They were making temporal lobe lesions, because they had the
evidence that seizures of the Papez structures were starting
in abnormalities in that region.
So they targeted their electrodes right at that--
no, sorry.
They used the electrodes to find the diseased area.
But then they went in and actually excised the tissue.
Because they thought they could do a cleaner job and not
leave the seizure-causing tissue at all.
And that gave a unique opportunity, because they
could take that tissue and look at it histologically.
And they found that there were two different kinds of lesions
in these people.
And they did cure their temporal lobe epilepsy.
Temple lobe epilepsy can be very
debilitating as I mentioned.
So that's what they were treating.
These were all people with temporal lobe epilepsy that
had seizures starting there in the amygdala.
And they found two kinds of lesions.
Some of them were from--
they recognized as the kind of lesions you get from the
febrile convulsions, which occur usually right around the
time of birth and shortly after birth
from very high fevers.
And when the fevers are prolonged-- when the fever is
severe, it can cause these seizures, which if they're
prolonged can cause damage.
But the other kind was from what's called a hamartoma,
which is an abnormality of the temporal lobe.
It's like a tumor.
Although it's not a rapidly growing cancer.
So the person can live with it.
But it can cause problems as these were.
So they cured both of these people.
OK, now they did--
they looked at the data on those two groups of people.
And they calculated how many of them had been, at some time
before the surgery, had been hospitalized for any reason.
And they found that a lot of them have been hospitalized in
mental hospitals for schizophrenic-like symptoms.
The ones that had been hospitalized the most-- and
the difference was like 5% or 30%.
It is a huge difference.
It was the hamartomas, the ones with the much earlier
lesion of the temporal lobe.
So he had no idea why.
So my explanation was this.
Here's the amygdala.
And I'm showing some of the key
connections in the amygdala.
Here are projections of the amygdala to prefrontal cortex
and to the basal forebrain region,
including the septal nuclei.
And here, this could represent dopamine neurons or
neurogenergic neurons with a very widespread projection.
So the question is now what happens if you do that--
you wipe out the amygdala very early?
What does it do?
Well, you lose all these projections to prefrontal
cortex and septum.
You also prune these axons by eliminating their endings here
in the temporal lobe.
Then leading their endings elsewhere.
The prediction is that you will get sprouting of these
axons as I've shown in red here.
Here's the degenerated connections,
here, here, and here.
And here's the sprouting that you would predict.
It would lead to an increase in dopamine axons, because
dopamine axons project to both these areas.
It would also lead to changes in norepinephrine and probably
other widespread axon systems, including
acetylcholine and seratonin.
OK.
So first of all, is there evidence that other
schizophrenics, not just these people with the hamartomas get
schizophrenia?
And one of the signs of early lesions is enlarged ventricles
of the brain.
And you look at size of ventricles you see in--
here's the schizophrenics, here's the controls.
Ventricles are larger in the
schizophrenics, especially males.
For females it was not as great a difference.
And it was mainly when they're younger.
So there is evidence of early damage in at least some
schizophrenic.
And I wouldn't want to propose this as a general model of all
schizophrenia, because it's a whole family of diseases.
But the ones with the most enlarged ventricles, the most
evidence for early brain damage--
also evidence for [? paranatal ?]
complications and so forth--
are the ones that are the most difficult to treat.
OK.
These are all the widespread projecting systems.
And if you look at anti-psychotic drugs, look at
what they're binding to.
Here's the drug up here.
These are all anti-psychotic drugs.
Here are what they're binding to.
High affinity binding to the receptors is up here.
Low affinity down here.
And look at how consistent binding to the two dopamine
receptors in the blue there.
But it's also high for serotonin for
some of these drugs.
It's highly for adrenergic receptors
for a number of them.
The green and that yellow orange color, see
they're also high.
So basically, the very kinds--
these widespread axon systems that I think are critical in
controlling brain states, the overall state of the brain,
are the ones that are abnormal.
And there's a lot of interest in this now.
And it's going to be much more complicated
than I've shown here.