I would like to take a moment and mention a pressing
issue we are seeing in our modern world. And
that is tech use and tech light. The data are
impressive and concerning on isolated wavelengths
of light, especially shorter wavelengths, which
is blue light. For those that don't know, We
have chromophores, which are special proteins
that absorbs specific wavelengths of light. For
blue light, the light that is LED light and tech
light, that protein is called melanopsin. Melanopsin
is responsible for our circadian biology, physiology,
and cell functioning. hormone regulation, and
even a connection to an area huge for mood. A
consideration we should include is this protein
was not even discovered until 1998. It seems
important for us to understand how our biology
uses the different wavelengths of light. for
various aspects of our biology. This blue light
chromophore is our master controller, our master
clock. Remember circadian rhythm is a two -part
process, two independent parts, light and dark.
For a quick reference, see the 2017 Nobel Prize
in Physiology medicine. But for now, I have something
exciting. I want to introduce a product unlike
any other product available. A highlight is the
product from Daylight Computer Company created
their product based on these factors. The Daylight
Computer is completely blue light free. It has
no flicker. Short wavelength flicker. is extremely
harmful for our eyes and downstream biology.
Light flicker is constantly turning our central
nervous system on and off. Essentially it is
like going to a light switch and repeatedly turning
it on and off. The problem is blue light and
LED light does this and it is so rapid You cannot
even perceive this in real time. The daylight
computer is the lowest stimulation and foremost
for sensory sensitive users. It is no question
that the alternative product, especially when
used at night, do not address or consider this
in their product. It is so toxic to human biology.
Big tech corporations have patents on how their
short wavelength implicate the human nervous
system. And a bonus, despite daylight computer
not having backlight, it is very functional for
outdoor use. And of course, increased sunlight
is always preferred. I am happy to offer a discount
for the Daylight Computer. You can use the code
Autism for a $25 off coupon. Again, use the code
Autism and the discount code for $25 off. See
the link in the show notes to Daylight Computer
Company or just give it a quick search in your
internet browser. Use the code Autism. for $25
off. For today's episode, we will expand on the
so -called Neuralation Time. Today, we will get
into the process of brain development. We will
talk briefly about maternal factors and biomarkers.
My ask to you is this. To understand why autistics
have so many comorbid conditions, mostly related
in the medical conditions. Consider how and when
the brain and body are created and connected
in this time during embryogenesis. So some common
maternal factors, some biomarkers, if you will.
Tyrosine is a big one. Remember the risk of Hypothyroid.
Many times, the mother will be put on a levothyroxine,
maybe 50 to 200 micrograms daily dose. And this
is usually taken in the morning. What's curious
about this is you take this in the morning and
you can only have water, no food, or other types
of drink for 30 to 60 minutes. Now, if your metabolism
is good, you can get by with just 30 minutes
for the medicine to kick in. Essentially, what
we are doing here with prescribing this medication
is replacing the lack of sunlight we are getting
during the day. Remember, tyrosine is an aromatic
amino acid, and it absorbs strong, short wavelengths
of light. Also related to the hypothyroidism,
with the T3 and T4, iodine is often supplemented
to mitigate the risk of autism. Iodine is the
3 and 4 in the T3 and T4. Remember the Autism
in Parkinson's episode. We cover T3 in good detail
about its cellular roles, not just hormonal,
but for the vast roles on the cell. Also, and
similar to tyrosine, is tryptophan. Tryptophan
is a huge one because of its roles in embryogenesis.
We will get into that in more detail in a future
episode with tryptophan, microtubules, and mitosis.
Tryptophan here is vast. But remember, tryptophan
is an aromatic amino acid as well. So it needs
the sunlight. And we will get into on that episode
about how indirect supplementation, maybe tryptophan
from food is an example, doesn't really play
into this. Also, the B9. We've covered B9 in
the folate. That is a big biomarker and maternal
risk factor. Remember this role with MTHFR. and
methionine for the DNA methylation. Omega -3
is a big supplemental factor to mitigate the
risk of autism. Remember what we've talked about
with DHA and how DHA is just vast for electrons,
moving electrons through the body. Vitamin D
is an easy one. And gestational diabetes. We
will get into that on a different episode even
about how the growth hormones and excessive maternal
insulin -like growth factors or the placenta
growth can signal over -stimulate cell division
in the embryo in this timeline that we are fitting
right now. So sticking with this theme, some
common environmental insults and toxins. but
remember autism predates these findings these
were not problems back in the canner kids and
asperger kids and all the way up through the
60s 70s 80s 90s and so forth these are all kind
of new there's pollution glyphosate aluminum
the bpa is a big one very concerning mercury
of course Just see the episodes from Nicole Rincon
and Christian Lyaw for a full review on some
of these environmental insults and toxins. So
during embryogenesis, and we are creating the
brain here, remember the four cell types, proencephalon,
mesencephalon, ROM encephalon, and then the fourth
one, the spinal cord. Okay. So this happens early
in embryonic development, specifically during
the process of neurolation, when the neural tube
forms and begins to differentiate into the primary
brain, vesicles. These three structures, the
proencephalon, mesencephalon, and rhombencephalon,
are the first major divisions for the brain.
And this appears around the third to fourth week
of the embryonic stage. approximately 21 to 28
days. So the proencephalon is responsible for
the forebrain. This begins to form around day
22 or 23 as the neural tube closes and expands
at the anterior, so the front end. And by the
end of the fourth week, the proencephalon differentiates.
So it further divides. It becomes a larger complex.
So it differentiates into two secondary vesicles.
And we are creating the brain here. The first
vesicle is the telencephalon, which will become
the cerebral hemispheres. So very vast for humans.
And the second vesicle is this diencephalon.
And this will form the thalamus, that sensory
relay station. We've talked about the thalamus
in great detail. If you want to understand sensory
perception processes, you must understand the
thalamus. It also forms the hypothalamus, the
little nuclei that is responsible for our hormone.
It combines the brain and body through the hormonal
system. The diencephalon are also responsible
for some eye development and the epithalamus.
The mesencephalon, a big region of interest for
us. This is a very curious region. We will get
into more detail on it towards the end of the
episode. But this also emerges at the same time
as the proencephalon around day 22 or 23. And
it's in the middle portion of the neural tube.
It makes sense that it's in the middle portion
because this will eventually be called the midbrain.
However, unlike the other two areas, the proencephalon
and rompencephalon, you know, the mesencephalon
does not subdivide into further vesicles. It
remains the mesencephalon. And this is very,
very curious to me. The rompencephalon, the hindbrain,
to no surprise, forms around day 22. and 23 as
well. This is the posterior end of the neural
tube. By the end of the fourth week, it divides
into two further areas of the brain. The first
one is the metencephalon, and this develops the
pons and cerebellum. The cerebellum is a very
underrated region of interest for essentially
all humans. but especially autism. This is a
big part of motor coordination, motor control.
And if you look at the brain stem or any part
of the brain, you can just see this just looking
at the full brain from the lateral position.
The pons is a little football -shaped region
on the anterior part of the brain stem. And lastly,
the myencephalon. The myencephalon is responsible
for the medulla. This part of the inferior brainstem
is responsible for several automatic responses.
Physiology and just reflexes, all of these things
that we don't have to necessarily think about
doing. We just do them, like breathing. So, all
three areas. The proncephalon, mesencephalon,
and rhombencephalon occur around day 22 and 23
when the neural tube forms and begins to differentiate
into a larger, more complex organ called the
brain. Then around day 28, these other primary
vesicles start subdividing except for that mesencephalon.
And what we're doing here is just developing
the brain, the large complex brain. And a big
region of interest here, from the previous episode,
the subdivision and signaling, the molecules
used the sonic hedgehog to undergo this task.
The sonic hedgehog is a big region of interest
for this process to happen. Okay, before we get
into the different nuclei in specialized roles
of the mesencephalon. Let's just kind of zoom
out here and understand the mesencephalon from
an evolutionarily perspective here. So the mesencephalon
is a very ancient part of the brain. If you think
about it, it's at the bottom. So it's conserved
across many different species and across evolution.
In simpler organisms, the midbrain Especially
that optic tectum area that we covered in the
Autism in Eye Movements episode when we first
kind of introduced the mesencephalon. This is
a machine -like, first responding type of structure
and it's dominant for sensory input and integrating
sensory, especially the vision. And with humans,
the forebrain takes over many of those higher
functioning. included in vision remember the
brain is roughly 40 to 45 percent dedicated to
vision but the midbrain retains this critical
unified roles for processing this sensory input
this is kind of the first stop even so functionally
the mesencephalon develops into the midbrain
which we will cover And that includes structures
like the tectum. So the superior and inferior
coeliculi. The inferior is auditory reflexes.
And the tegmentum area. So a region of interest
here covered in many, many episodes. The substantia
nigra. And also, we'll introduce the red nucleus.
And this is involved in movement and reward.
These functions also integrate sensory reflexes
and motor coordination. The subdivision might
disrupt the midbrain's role as a relay and integration
hub between the forebrain and the hindbrain.
So it kind of connects the different areas of
the brain. Now one thing to consider, because
as brains evolve, they grow in size, they grow
laterally, and posteriorly, okay? They just move
out and up. The midbrain here is kind of squished.
It's kind of a tight fit between the ROM encephalon,
the lower areas, and then this huge pro -encephalon
area, the human cortex and so forth. Evolutionarily,
Functionally, this mesencephalon is very limited
on its capacity to expand. However, it seems
like the living organism and the roles here that
we will get into with the mesencephalon, it cannot
allow for more description, more roles and functions.
Relatively speaking, the mesencephalon is very
small. So just to recap and a kind of a summary,
for the mature brain, once developed, the proencephalon,
including the telencephalon and diencephalon,
this is the biggest expansion. This has the biggest
role as far as brain size, real estate. And this
is for complex cognition and the sensory processing.
The mesencephalon, or just the midbrain, we've
covered that. The ROM encephalon evolves into
the MET encephalon and my encephalon. And this
is kind of specialized for control of movement
and automatic functions. Those reflexes, like
breathing and heart rate and so forth. We don't
have to think about that stuff. We often don't
have to think about movements either. Have you
ever just paid attention to how much a human
moves? even whenever it's not really goal -directed,
there's not a task at hand. It's very fascinating.
So some factors of the subdivisions here. The
subdivisions process, this is orchestrated by
kind of intricate patterns along the anterior
to posterior and the dorsal to ventral axis of
the neural tube. And some key drivers here include
morphogen gradients. Things like fibroblast growth
factors and WNT proteins and sonic hedgehog.
Now with autism research the WNT proteins is
highly researched. It's a region of interest
as well. There are transcription factors and
gene expressions. So a couple of different examples
here if you want to kind of go into the rabbit
hole if you will. These include OTX2 and GBX2,
Pax6, PAX6, and EMX2, and HOX genes, H -O -X.
You can look up those if you wish. And there
are signaling centers, like the anterior neural
ridge, A -N -R. This is kind of helps regulate
the WNT. And from earlier, with that midbrain,
the mesencephalon, being kind of compact, it's
kind of tightly squeezed into this region, there's
a midbrain -hindbrain boundary, it's called.
And this kind of stabilizes the midbrain as a
single unit while allowing the cerebellum to
kind of evolve. Cellular proliferation and migration.
We will have future episodes diving deep. deep
into this kind of dense and hot topic for the
autistic brain. So proliferation and migration.
This is a very hot topic for the autistic brain.
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Shapiro launched Chroma to restore the natural
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Every design decision Chroma makes serves a purpose
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mesencephalon here, the midbrain. Let's understand
its roles, some of the nuclei involved, and what
it's trying to accomplish. Overall, it's very
important for various functions as motor control
and sensory processing and the autonomic regulation.
These things are vast for the central nervous
system, which is what we are creating here the
goal of the central nervous system is to move
the living organism and in large part the brain
is conserving and allocating and recruiting different
regions how is the living organism going to move
while sustaining its species by remaining safe
by staying alive so a big part here and key nuclei
is the Substantia Nigra. We've covered this in
the Autism in Parkinson's episode and in all
of the Autism in Basal Ganglia episodes. There's
probably four to six episodes on that features
the Substantia Nigra. This is a very interesting
little nuclei. Remember, just a quick recap here.
It's divided into two parts. the substantia nigra
pars compacta which produces the dopamine d1
dopamine so excitatory dopamine which are receptors
dr1 and 5 and d2 dopamine which is inhibitory
so receptors dr2 3 and 4 this is involved in
the motor control motor coordination the basal
ganglia our go no -go area right next to that
is the red nucleus now this is an introduction
to the red nucleus it plays a role in motor coordination
as well more specifically voluntary movements
and it is part of a so -called extra pyramidal
motor system So the extrapyramidal motor system
is essentially a network of some neural pathways
in the central nervous system that regulates
involuntary and automatic movements. And it's
responsible for some posture and muscle tone
as well. You might have heard of the pyramidal
system, but the extrapyramidal is a little bit
different. Some key components of the extrapyramidal
system include the basal ganglia. I don't have
to go into more detail about that. We've covered
that. The cerebellum. So it helps control fine
motor control and balance and timing. The brainstem
nuclei. The red nucleus and substantia nigra.
The reticular formation. We briefly mentioned
the reticular formation before. This is scattered
throughout the brainstem and regulates posture,
gait, and reflexive movements. Also involved
in the extra -paramental system is the thalamus.
We've covered the thalamus. However, if you think
about this extra -paramental roles and autism,
let's specifically mention its roles with autism.
So with the substantia nigra and the dopamine
dysregulation, you know that In the autistic
phenotype, there are some implications here,
some signaling processes that are abnormal, and
it's linked to repetitive behaviors and motor
stereotypies. This is where that is occurring
here. It's a very easy thing in autism to evaluate
and observe. The red nucleus and motor coordination.
So in autism, it contributes to that motor clumsiness,
which is very common, and motor delays. Those
delays in certain milestones like crawling, walking,
grip strength, and being able to just function
and coordinate movements. The basal ganglia circuits,
of course, because of the substantia nigra. There
are structural and functional MRI studies that
show the basal ganglia It's abnormal in the autistic
phenotype and both brain volume and connectivity.
Remember Dr. Hannah Stevens. She has wonderful
work on the dorsal striatum and it's kind of
enlargement. It's very dense here with dendrites
and axons. Remember the dorsal striatum is the
input area of the basal ganglia. It coordinates,
recruits different areas. for the related outcome
of the movement. So back to the nuclei within
the mesencephalon, there's an ocular motor nucleus,
which is the third cranial nerve. And this is
controlling eye movements. So if you think about
autism, we ought to go here. We ought to go to
the eye movements. It's not difficult to see
this is involved. An additional oculomotor nucleus
role is mediating pupillary constriction. So,
with the sympathetic versus parasympathetic fibers
here. It has a problem and its main goal here
is mediating the pupillary constriction for the
parasympathetic arm of the autonomic nervous
system. There's an accessory to the oculomotor
nucleus. It's proper nouns. Edinger Westfall
Neculus. This is also related to the parasympathetic
nucleus for the pupillary constriction. Then
the trochlear nucleus. Cranial nerve IV. And
this kind of intervates the muscles of the eye.
It's responsible for downward and inward eye
movements. There's a mesencephalic... nucleus
of the trigeminal nerve cranial nerve 5 this
is part of the para -aqueductal gray we will
introduce momentarily this has involvements with
pro -proceptive input from the muscles in addition
the superior colliculus which we've covered and
the inferior colliculus which we've covered so
I will skip those but We are to the para -aqueductal
gray, the PAG. This is a very good region of
interest here because it contains nuclei involved
in pain modulation. Think about autistics and
that pain regulation. Sometimes our pain perception
is off and oftentimes with temperature as well.
In the late 80s and 90s that pain regulation
or that kind of perception, it was common for
it to be nicknamed retard strength. And today,
today's society probably wouldn't allow that.
They wouldn't like that, I should say. But retard
strength was very much a thing back in my childhood.
The PHE also is involved in autonomic regulation.
So with the heart rate and breathing, and it's
also involved in defensive behaviors. This is
a very cool area of the PAG. And just today on
311, a study showing that the ACC to the PAG
transforms signals tied to empathy to certain
behavioral responses. Remember the ACC? We've
talked about the ACC in quite detail. It's a
part of the medial prefrontal cortex. The ACC
is the anterior cingulate cortex. It's involved
in that internal calculation. It's a big region
of interest here. But when freezing, if you've
heard of the freeze, fight, flight, when freezing,
the PAG is involved here. And it shuts down the
body by sending signals down the spinal cord.
This is a very cool feature of the PAG. So the
next time you find yourself frozen, you're freezing,
as they say. Just think about how the PAG in
the mesencephalon, the top of the brain stem
there, is just shutting it off, shutting down
the downstream signals to the spinal cord. And
your extremities are not moving. It's very fascinating.
So let's look at the broader mesencephalon impact.
with autism. The superior colliculus we've covered,
it's a very fascinating little region here. And
the whole reason I got into the mesencephalon,
because the superior colliculus and the inferior
colliculus, its primary role is biasing the attention
of the living organism. Just imagine what this
has functionally with learning. learning the
environment. This is so easy to connect here
with the autistic phenotype. This is ought to
be one of the most significant regions of interest
here for understanding the brain development
during neural relation even and creating this
autistic phenotype. What makes autistics autistic?
This is so fascinating and underrated and overlooked.
So the PAG with autism, so for that autonomic
and emotional regulation. Autistic individuals,
through the work of these, this biology and neuroplasticity
with the experience and being forced into social
norms, we have a heightened rates of anxiety
and that atypical pain perception. This is a
very fascinating how the, this is the pain perception
in autism is very abnormal. The eye movements
as mentioned earlier with oculomotor, nuclei
that eye saccades. Remember the episode on eye
tracking as a biomarker. This is a very useful
tool to diagnosing autism at an earlier rate.
earlier stages in life. This is huge for kind
of interventions, kind of suppressing the harms
via the neuroplasticity, the changes in the brain
from experience. This is a big region here. And
proprioception. This is huge in autism. with
that motor planning the deficits in motor control
and oral motor difficulties so the speech articulation
that we've covered and autism and speech and
language which it should be language and speech
because language comes first and then the speech
but with the acuit fasciculus connecting verneki
and broca and then the midbrain down here. It's
huge, huge for autism. So I can't undervalue
here the mesencephalon and autism because of
its critical relay. It's the hub for integrating
all of these sensories and biasing the attention
of the living organism and all of the autonomic
responses. Sensory motor integration It's vast
here. Probably the top reason that the mesencephalon
is overlooked. And then the connectivity. We've
covered some connectivity with the Autism in
Eye Movements episode with the diffusion tensor
imaging DTI and the white matter tracks and the
timing of the neurodevelopmental. This is what
the whole episode and the last week's episode
is about, forming the central nervous system,
the brain and spine. Think about what we've covered
here today with the mesencephalon's role and
access to the spinal cord for motor movements
even. This is huge here. If you're listening
to the podcast or listening to the episode, please
feel free to leave a review or rating. In podcasting,
reviews, ratings, and downloads are huge and
I very much appreciate your feedback. You can
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Podcast.