So we have an episode about spindle neurons,
sometimes called von -economo neurons. And these
are very relevant to the autistic phenotype.
So these are spindle, sometimes called von -economo
or V -E -N. Von Economo neurons. Von Economo
kind of discovered these in the 1920s. Before
that, though, in medical literature and medical
textbooks, there were some mentions of it around
the late 19th century, 1880s and so forth. I
think there were some mentions of it, how these
certain type of neuron shaped a little bit different.
We'll draw them out shortly. But these are called
spindle neurons because of the shape. More recently,
over the last 20 years, a researcher named John
Allman has studied these quite extensively. He
has a lot of good research on dispental neurons.
These are very fascinating because they are only
found in a few type of creatures, very socially
active type of creatures. So humans have them,
larger primates like orangutans, gorillas, bonobos.
A few seditions like whales and dolphins have
them. Elephants. So there's only like 10 or 12
different species that these are discovered in.
And humans have them in primarily two different
regions. Two regions that we've discussed quite
in detail. the anterior cingulate cortex or the
ACC and the insula, specifically the frontal
or the anterior insula. So these spinal neurons
are, they're provided to have rapid transmission
for social context is what they're doing. They're
very larger than normal neurons and they only
act mainly on the different types of monoamines,
especially dopamine and serotonin, and a specific
cell, a peptide, that we've never discussed,
I don't believe, and that's neuropeptide Y. So
very, it's not really discussed quite frankly.
And some of these things are, well this is a
peptide, so if you remember, oxytocin and vasopressin
episode. Peptides are just a collection of proteins,
amino acids. So oxytocin and vasopressin are
pretty easy because there's only nine and they
share the seven of the nine peptides. But neuropeptide
Y has 36 protein bonds or chains of proteins.
And these are, the neuropeptide Y is heavily
involved with fear buffering. So It kind of makes
sense if you're navigating a social world. And
whenever I'm talking about social world, it's
not just necessarily communication or hanging
out with others and so forth. It's not really
what this is about. This is more of a specific
type of social environment. This is just interacting
with anything from the environment. Humans are
very social creatures, so we're constantly being
entangled with many different types of things
in the environment. Other things with the neuropeptide
Y is regulating things like food intake and metabolism
and autonomic functions, things like breathing
and heart rate. So, you know, it's a peptide,
so they have a pretty diverse type of functioning
the peptides do, similar to the oxytocin and
vasopressin. So, These two brain regions right
here are very critical, and that's why I just
listed them out before we got started so we can
go over the roles of them. So the ACC, the anterior
cingulate cortex, which is here, it's part of
the medial prefrontal cortex. It's commonly just
highlighted as a medial prefrontal cortex nuclei
or subdivision. It has massive roles, and we've
covered these roles in several different episodes.
But conflict monitoring and error detection,
evaluating risk and reward. So potential choices
and outcomes is what this is kind of doing. We
talk a lot about internal calculators. ACC is
a huge internal calculator for these types of
things. Go -directed type of behaviors. So it's
in the medial part. Typically with things like
the prefrontal cortex and the dorsal striatum,
the more medial you are, the more in the middle
or inside, deep inside the brain, is more reflective
of goal type behaviors. And then the habits kind
of branch off laterally, okay, as we evolve as
species, different types of species. It's goal
directed on the inside. and then habit forming
will come later because that that requires a
lot of repetition so it grows outward is a good
way of thinking about that. In mice and rat studies
there are good go directive versus habit formation
and you can do things like outcome devaluation
to kind of disassociate the behavior because
you can't ask the rat or mouse they they can't
tell you. controlling autonomic functions as
well, and physiology. And we often say right
here, adaptive responses. When we're responding
well in the environment, that's called adaptive
responses. And with autism, you can think about
just an overarching way of describing it as a
lack of adaptive responses, because there's not
a lot of skill set. There's not a lot of social
databases and skills to pull from as we navigate
the world. Second is the insula. The insula is
a very fascinating region because it has privilege.
It's very privileged to having information coming
in about the brain, what's going on inside the
brain, the thoughts and the feelings and so forth,
the different brain waves, and the body. So it's
getting information from the physiology. My heart
rate's okay. I'm okay right now. My breathing,
the depth and rate, I'm okay right now. But what
if you're not what if you're I'm just sitting
here or you're just sitting around not doing
much physical activity and your heart rates jumping
and your breathing's kind of The rate in depth
is kind of off. You might register. Oh, something's
not right here Well, that's feeding up to the
insula to inform the rest of the brain. Something's
not right here and The insula is also getting
information from the environment. So three main
Data sources to pull from, the brain state, the
body state, and the environment. How is the living
organism incorporating all three of those? So
the insula is a very fascinating little region
here, and it's right here. This is the frontal
part, and then the posterior part kind of expands
this way. Now the insula is very lateral, okay,
especially in comparison to the ACC and all of
these other subcortical areas. that will go over.
It's very lateral. It's more likely that it came
on board later in the evolution. This is also
known as a gatekeeper in task switching. So one
thing that's fascinating about the cingulate
cortex is, and it doesn't matter if it's the
anterior, the posterior, the subgenual, whatever,
the cingulate Let's imagine these are white fiber
tracks, nerve tracks, nerve fibers, or so forth.
Okay. Remember, we've talked about things like
the fasciculi and things, um, these nerve fibers,
myelination and so forth. They, um, they connect
brain regions. This will bring brain regions.
We'll go over the many columns as well, because
spindle neurons are heavy and layer five B, but
the cingulate And I learned this from Nolan Williams,
MD, PhD, just passed away. Very, very brilliant
researcher. Huge with investigating depression
and things like that. So hopefully his soul is
resting in peace. But the cingulate wraps. Wraps
around. white matter tracks like like like this
Okay So it's just wrapping around white matter
tracks and that gives the cingulate a lot of
access a lot of fast -acting access as well So
the insula and cingulate cortex, it makes sense
why it's really involved in these kind of fast
-acting rapid transmission type of social bonding
type of neuron. Okay, so if you remember, we've
covered a network, the so -called salience network.
These two regions are essentially the main regions,
the hubs of the salience network. So this is
a big thing. The salience network allows us to
divide our attention. What are we going to pay
attention to? What is most important to the living
organism? Okay, so you have the ACC and interior
insula and then you have all of these subcortical
areas. Things like the ventral striatum, which
is a Mostly the nucleus accumbens. The nucleus
accumbens is a very large region, to be frank.
The thalamus, of course, the hippocampus, the
substantia nigra compacta. Remember the episode
with Parkinson's and the basal ganglia? The substantia
nigra compacta is dopamine. The reticulata, which
is kind of, it's like a Nike check almost. And
the check part, the part that comes up. is the
reticulata. And then also the VTA, the ventral
tegmental area. This is dopamine. So these two
are dopamine areas. And then the amygdala and
the hypothalamus here. So the salience network,
these are mostly the hubs and these subcortical
areas are kind of nodes, what's called nodes.
So collectively these are kind of all working
together to help the living organism send our
spotlight of attention to whatever we find most
salient, salience network. And then also the
spindle neuron, there's, in 2008, there's small
clusters of the spindle neurons found in the
dorsolateral prefrontal cortex, just like clusters
of two. So they're very, very sparse, rare. with
the anterior cingulate cortex and the insula.
So we have approximately 100 ,000 to 200 ,000
spindle neurons in the central nervous system.
These are just neurons, okay? Now, overall the
human body has roughly 85, 88 billion neurons
in the central nervous system. So there's not
a whole lot of these spindle neurons in comparison
to overall neuron. What I want to really say
about, here let's just go ahead and erase this.
because I've talked a little bit about several
different times the paper from 2024 about the
salience network with six week old human beings
human infants and the salience network this was
done at UCLA UCLA sang at all and Lucinda Uden
is on this paper. U -D -D -I -N. Lucinda Uden
kind of really captured the role of the insula
in about 2008, 2010, and so forth was a really
high year for the insula or years. Still is,
it still is. But on six weeks, this study on
six weeks though, they used fMRI during Not non
-activity, so it's almost like a sleep state
on humans though they found that children that
would Had a high likelihood of having autism
so they had autism as their siblings already
had autism so they would hook fMRI up to these
human babies and just check their check their
connections essentially and The high likelihood
found that the salience network had a strong
connection to this area right here. The sensory
motor area, which is right here. A lot of our
adaptive, not adaptive responses, but a lot of
our automatic responses will live here versus
here. We'd like to send a lot more reflexive
things. Habitual things up to here and then it
can just feed down into the dorsal striatum and
then Kind of start the basal ganglia for movements
and actions so they found six weeks old a stronger
connection to the sensory motor area and if you
think about autism and kind of the rigid thinking
this and lack of cognitive flexibility right
here versus the the typical likelihood the other
children six weeks old they had a stronger connection
with areas here it's a big finding but nobody
does anything with it it's just kind of lost
in the academic literature nobody does anything
with this stuff and what's fascinating here is
you know it's UCLA it's like an ivory tower they
followed these kids up that um because they were
only six weeks old they followed them up to like
years two and three and they could confirm like
the ones that had a stronger connection to here
definitely indeed autistic phenotype nobody does
anything with this stuff though so let's draw
out the spindle neurons versus um things like
the pyramidal neurons okay so you know pyramidal
neurons they have this pyramid okay and then
you have the things like um these dendrites and
axons falling off of it and like so you get the
good idea here it's more like a like a typical
neuron especially the spindle or the the pyramidal
the spindle neuron the cell body is like that
it's more of like this that's why it's a spindle
neuron and it's bipolar So it looks a lot like
this. So here's a big thing too. It's it's much
larger and This allows for that rapid transmission
so The ones in the ACC are actually found to
be a little bit larger even the ones in the ACC
They can extend down quite a bit so it looks
more like that now if you remember the layers
of the many columns we had all of these type
of cells here and then layer four has the select
cells So forth and then down here we have more
of these And here's where you can find some of
these spindle neurons so they they can be like
much larger and so forth but they're very they're
very rare but they're predominantly in layer
five right here now not covered in the mini columns
little video is this layer down here directly
below these mini columns remember this is would
be considered a mini mini column and then we
would have very many different many columns and
it would eventually become a micro column and
so forth. This layer right below layer 6a and
6b is white matter. This is where a lot of distal
connections will happen. So these spindle neurons
remember inputs come here to layer four from
the thalamus and then it goes to two and three
because this is where the subjective experiences
of the living organisms essentially live is layer
three. It's a glare, all right? And then it will
shoot down to five. This larger spindle neuron
will allow this information to be received and
transmitted down to these white matter tracks
faster. And that way we can respond faster to
the environment. This is... Not so much a social
thing like I'm gonna go hang out with friends.
This is a survival thing. This is an ability
to Get information from the environment fast
so you can make decisions this is Space -time
again we're always talking about space -time
and these different spiral neurons are very rare
and they're regarding socialness and autistics
have kind of a complicated number with the spindle
neurons. At first, in the first four years of
life, it's kind of off and then later on in life
as well. It's just post -mortem studies. We'll
hit this. So there's a lack of kind of these
types of cells. And, you know, if you think about
the comment about the adaptive responses from
earlier, it's just, it makes socialness, the
outside world, I should say, complicated. And
because of this region right here, the insula,
the outside world, and the salience network,
our attention is going to be inward. to the self.