177 | Unlocking the Neuroimmune Connection: Exploring Immunoception, Brain Lateralization, and the Insular Cortex with Experts Drs. Peter Scire and Rob Melillo - Inflammation Nation: Science Informed Wellness

Episode Transcript
Available transcripts are automatically generated. Complete accuracy is not guaranteed.
Speaker 1 (00:03):
Hey everyone, welcome to the Funkbed Nation podcast.
I'm your host, dr Steve Noswery.
The views and opinionsexpressed by my guests in this
podcast are not necessarilyconsistent with my own views and
opinions.
However, I do my best to berespectful of their views and
opinions as they express them,even if they differ from my own.

(00:24):
Now let's get to the podcast,okay, so let's go ahead and dive
into this.
Honestly, I've been waiting forthis conversation with bated
breath ever since we saidgoodbye on the last call and,
just to give anybody listening alittle bit of grounding, we've
already posted two prettylengthy interviews that I've

(00:46):
done with Peter and Rob, and myhope today, guys, is to have
more of a clinical conversation.
I have posted both of our twoprior interviews, on both the
Funk Med Nation podcast as wellas the podcast the Inflammation
Nation, which is the generalpublic, and I'll probably do the
same thing because I, though, Iwant today, to be more

(01:07):
technical and more clinicallyoriented.
I think it's important for thegeneral public to hear your name
, see your faces and know thatthere are doctors out there that
are thinking and operating atthe level that we're going to
reveal and share today, and thetopic is immunosception.
And then, as I had mentioned toyou guys before, I want to

(01:29):
start with a quote from one ofthe papers from Kevin Tracy,
who's one of the big namesbehind immunosception research,
and the quote is it's from a2018 paper in Annual Reviews in
Immunology and it goes like thisit says the nervous system
regulates immunity andinflammation.
The molecular detection ofpathogen fragments, cytokines

(01:51):
and other immune molecules bysensory neurons generates
immunoregulatory responsesthrough efferent autonomic
neuron signaling.
The brain integratesneuroimmune communication and
brain function is altered indiseases characterized by
peripheral immune dysregulationand inflammation.
And like there's so much justin that quote.

(02:13):
Right, there's just a ton ofstuff right there, but I want to
open it up with a question andpose it, not rhetorically.
I really would like your opinionand your answers.
But why is it that we, asclinicians, so readily accept
the brain's role in controllingvisceral function, like the gut,
the pancreas and so on, andeven, to a certain extent, the

(02:36):
hormones?
Because we recognize, forexample, the adrenal system is
the hypothalamic, pituitary,adrenal axis, and that tends to
get forgotten, but it's stillthere.
Why is it we have such a hardtime recognizing or even
accepting the idea that thebrain controls and regulates the
immune system.
I guess almost like we treatthe immune system as something

(02:57):
completely different, almost aforeign entity.
Why is that?
What do you think that is Um?
Why?
Why is that?

Speaker 2 (03:04):
Why do you think that is?
Well, I'm going to say first ofall, I I don't think that, like
you said, people are reallythinking that much of the brain
regulating the gut.
I still think people, you know,aren't thinking that way.
I just did a lecture down inthe Dominican Republic and I had
two other doctors One was afunctional medicine pediatrician

(03:27):
, Dominican Republic and I hadtwo other doctors One was a
functional medicine,pediatrician and pretty good,
and the other one was aneurologist who was a
neuroimmunologist and you knowshe did a whole presentation on
autoimmune encephalopathies and,you know, really went through
it in pretty good detail,although it was the more severe

(03:50):
type things and things thatcould clearly be measured in the
cerebral spinal fluid.
But everything both of theirperspectives were that there's a
problem in the gut, that thisleads to certain issues that
lead to inflammation,inflammation comes up and
affects the brain and theinflammation in the brain
produces a bunch of symptoms.

(04:11):
So it was purely from astandpoint of going up and that
was the neuroimmune piece.
And one of the things I thinkthat we like about Kevin Tracy's
work is he's one of the firstpeople to come out and talk
about the brain coming down andactually regulating and being
the initiator, and I thinkthere's so much, like you said

(04:33):
in that quote about that.
You know, in the periphery, inthe peripheral sentry nerves,
just like we pick up pain andinflammation, so we have
inflammation in our body, in ourjoints, we feel it in our brain
.
That also is.
There's immune signals thattravel similar pathways that get

(04:56):
to the brain and then the brainis going to respond from a top
down standpoint and have someregulation.
And I think you know, peter andI have gone about through this
because you know the immunesystem is incredibly complex and
as we discuss it and you knowthere's some really good people
and they really describe howeverything is and it doesn't

(05:18):
seem like anything's missingfrom that piece on the overall.
And so I think that's the thingis that you know the immune and
the immune communication withinthe immune system is pretty
well documented, even thoughthere are gaps that we've picked
up on.
And so I think it's easy to getlulled into the thinking that

(05:42):
the immune system operatescompletely independent and that
it may create inflammation inthe body that affects the brain.
But there isn't, I think, verymany people that have the
knowledge of the neurology tounderstand the downward
influence and control that thebrain has from the brainstem and
from the brain itself, and Ithink that's where the gap is

(06:05):
Peter.

Speaker 1 (06:06):
what's your opinion on this and your feedback?

Speaker 3 (06:09):
Yeah, well, one.
You know.
Keep in mind that thepsychoneuroimmunology community
has only been around, I think,maybe at best not even 30 to 40
years, okay, when they reallystarted and Richard Adler and a
couple of those people reallystarted looking at this.
And so, you know, for thelongest time these super systems

(06:30):
I mean they've referred to thatin many papers like the immune
system in the right hand and thenervous system in the left hand
, were just separate of eachother and there was.
And now obviously, like KevinTracy points out, that we now
know, and you know I rememberRob and I were sitting in his
house a couple of months agolooking at that same quote and
saying, okay, hey, we're gettingthe toll-like receptors talking

(06:54):
to the brain, we got thesecytokines talking to the brain,
we got these chemokines.
And you know, for a long part,you know, of classic education
no one was really talking about.
They were just saying, ok,these are these inflammation or
these inflammation aspects ofinflammation, or these ways that

(07:17):
we're telling the immune systemto do this.
But, as Rob's pointed out, it'slike who's the conductor, who's
signaling to the immune systemto do this?
And I think that the biggestthing is I came across a new
paper a couple days ago, whereit's probably a 2019, 2020 paper
, I think, that was now lookingat the role of the brain in the

(07:38):
innate immune system.
Was now looking at the role ofthe brain in the innate immune
system?
Okay, and they're actually.
We're studying frogs andlooking at actually taking frogs
and separating the brain to tryto figure out, you know, what
happens if they disconnect thebrain to the immune system and
they they put it, you know, athey were using E coli as the

(08:03):
antigen to see what happens andwhat they found out that was, if
the brain wasn't present, theywouldn't get macrophage
differentiation.
Ok, there was no way themacrophages would actually maybe
split to an M1 position or M2position, and so I mean, there

(08:23):
it is, and the paper was talkingabout how we've studied, you
know, a certain amount of thebrain to the adaptive immune
system, but we really haven'tbegun to really explore the role
of the brain in the innateimmune system, and I think
that's where I think you knowyou talk about where the
literature is going.
I think that in theimmunosceptive world I think
that's what we're trying tounderstand now is more of what's

(08:44):
the brain's role on theimmediate immune response to
recognizing the differenttoll-like receptors recognize.
How's that signaling to thenatural killer cells?
What's that telling themacrophages to do?
But you know, trying tounderstand what particular
anatomical areas and I think themajor thing that we're going to

(09:07):
be looking at over the nextcouple of years that gets lost
in some of the translation isKevin's Tracy whole idea of the
immuno homunculus.
Okay, and really getting tolook at these definitive areas
in the brain.
I mean we've talked about asensory homunculus, a motor
homunculus, but now can weactually begin to fully put that
together?
I mean we've talked about asensory homunculus, a motor
homunculus, but now can weactually begin to fully put that

(09:31):
together?
I mean that's a hypothesis thathe put together about 10 years
ago and I think now you knowwe're trying to unravel that.

Speaker 1 (09:35):
Yeah, let's hold on to that one because I think we
need to work our way towardsthat.
But you know, for cliniciansthat are listening, they'll
remember back in their earlytraining days they learned a
little bit about sensory,homunculus and motor and how we
have these maps of our body upin the brain so the brain can
understand.
You know how to connect todifferent pieces and parts.

(09:56):
You use the word immunosception.
I'm going to ask you in asecond to back up, but I want to
share with you.
I did a webinar for Vibrant Labs, probably three weeks ago, and
the topic was an effectiveclinical model for complex
disease, complex clinical cases,and I shared with Vibrant and

(10:19):
all the people that werelistening the clinical model
that I use.
And this is going back to whatyou were just saying about the
brain is the top dog andeverything is interconnected.
And I started by quoting TomiOtada, who was the guy who
coined the phrase super systemback in 1997.
And so I put up a graphic thatshowed the brain, hormones and

(10:41):
immune systems, started drawingthese connections and even now,
like going back and looking atthat, it's very easy for me to
draw out and to map outconnections on the
neuroendocrine side, right, it'seasy for us to even kind of
dissect the brain, so to speak,and look at the lobes and look
at networks and how thingsinterconnect.
But the part of the diagramthat represents the neuroimmune

(11:04):
interactions is kind of sparse,right, and you know, I'm
certainly no expert in this area.
I think I know a little bit morethan the average clinician, but
I'm no expert in this field andI'm struggling to put that to
like to fill in that side of thegraphic and I'd be happy to
share that with you guys and getyour feedback on it.
I would love your feedback,actually, and maybe I'll put a

(11:26):
link in the episode descriptionthat people can go to the web
and look at that.
But it's so, as clinicians,it's so helpful to have a
roadmap, right?
And what I'm hearing from youis that maybe this is where the
research is going.
It's just like we have aroadmap from the brain to the
motor system, we have a roadmapfrom the brain to the visceral

(11:47):
system and so on, that maybewe'll have a roadmap to the
immune system, right.
So, pausing that idea, and I'lltoss this up for either one of
you guys define interoception,contrast that to exteroception
and explain to me to us why it'sso important for the brain to

(12:11):
understand and have an interfacewith both internal and external
environments.

Speaker 2 (12:19):
Well, interoception is really the ability for the
brain to perceive what'shappening in the body, really
from a homostasis standpoint,and this is really critically
important because, from the timea child is born and we know
that that right hemisphere isactive, more active in the first

(12:43):
three years.
So, when the child is born,non-verbally, they need to be
able to perceive and express totheir parents or caregivers, you
know, when they're in pain,when they're hungry, when
they're thirsty, when they'recold, when they're hot, when
they need to be changed, youknow, or if they have gas or

(13:04):
something going on in theirstomach, when they're tired.
And smell and taste are verymuch around this right.
So we need to be able to feelthose things or sense them right
from the beginning for survivalright To be able to know when
something is wrong, when we needto eat, when we need to drink,

(13:25):
when things are too hot, if I'min pain.
All of that really isregistered in the right brain
and all of it is registeredprimarily in the insula on both
sides, but finally in the rightinsula and the right brain is
online, you know, early on inthat in reason, and we need to
be able to do that because,obviously, again, as the brain

(13:47):
is maturing and as we'rebuilding from the bottom up the,
you know, whatever, whateverlittle seeds start in the
brainstem as the precursorsultimately grow up and create
different areas of the brain, sothen the brain can come down
and regulate everything, andthat's the way you know it's
supposed to work.

(14:08):
That's the way this wholecomplex system works.
We need to have, you know, thiskind of internal map of our body
and proprioception the abilityto know where our body is in
space and feel our body andcreating these sentry maps also

(14:28):
starts in that insula area, sothat all of this kind of is in
that area there, and it's veryimportant.
And so you know it makes senseto us.
We think about this but wedon't think about, well, what
does that look like?
Meaning, what areas of thebrain are registering this?
As you said, what are thenetworks from the bottom up that

(14:48):
transmit this information?
I think there's a lot of overlapwith the neuroendocrine, the
neuroautonomic system and theimmune system, because if you
hear what Kevin Tracy said, hesaid basically these efferent
top-down pathways through theautonomic system, so through the

(15:09):
balance of the sympathetic andparasympathetic.
That's what regulates the immunesystem and I think he's done a
fairly good job of even talkingabout the input from the
sympathetic and parasympatheticinto the actual immune tissues
and how it actually, you know,may start the process of what's

(15:31):
going on in the lymphatic tissueto, you know, start this
process.
So we do have a fairly good mapof this from both the afferent
and afferent pathway both theafferent and afferent pathway.
But interoception is reallycritical for that because also

(15:53):
all of our right brain emotionsand most of our emotions are
built on top of that.
So first we sense things andthen we start to sense feelings
that are superimposed on thoseand then we're able to read
those same things on otherpeople and that's the foundation
of nonverbal communication andsocialization and ultimately,
emotional regulation andattachment, and then that leads

(16:16):
to the desire for verbalcommunication.
So this whole idea of beingable to survive and be around
other people and all reallystarts with interoception and
what we see is that, I think, isthe biggest piece missing in
severe autism, in nonverbalautism.

Speaker 1 (16:35):
Peter, I think that you and I probably have the same
mindset on this and in fact Iwas just in San Francisco last
weekend teaching our brainchemistry course and I really
made a big effort to try tochange the framework, like the
conceptual framework, of thedocs that were there, and not

(16:56):
just go through the standardmaterial that we presented for
15 years, but do it, you know,kind of in light of some of the
work that you guys are doing,and attach it to developmental,
neurodevelopmental issues and soon.
And so with this concept ofinteroception, which is
immunoception is one componentof that, like some very common

(17:18):
clinical manifestations ofinteroception would be, you know
, someone having their bloodsugar drop and then triggering
some kind of an anxiety event,right, and I don't know that.
There are many clinicians thatmake the connection that it's
actually the brain that'scausing all of this.
Right, they think, well, it'san adrenaline dump and that's

(17:39):
why.
But really still it's, you knowit's driving in the brain.
So we have all kinds ofdifferent types of interoception
.
Rob, you mentioned a wholebunch of them, like hunger and
thirst and temperature and allthese different things.
But we also have thesechemoreceptors that sense the
constituents of the blood right,Glucose levels, hormone levels,
all this kind of stuff.

(17:59):
And now?
So let's focus in on thisconcept of immunoception, Peter,
and I know that this is likeyour deal Of course you're a
more well-rounded, you're not aone-dimensional clinician, but
this seems to be like a passionproject of yours is to really
understand immunoseption andbring that into the world of

(18:21):
functional neurology.
So define it in maybe morediscrete terms than what we've
defined so far and what I'd liketo get at.
Rob, you mentioned that thishappens.
It's mediated through thesympathetics and the
parasympathetics, and you alsomentioned the insular cortex.
So where does all of this stuffhappen?
Is it a discrete network?

(18:41):
How highly organized is thesystem?
How predictable andreproducible is it from one
person to the next?
That was for you, Rob.
I'm sorry, Sorry, sorry, sorry,Peter.

Speaker 3 (18:55):
Go ahead.
Well, I mean, I think, forstarters, I think the challenge
for me right now is trying tofigure out, like, how do we
measure some of this stuff right?
How are we measuring thedifferent relationships of the
immune system?
I mean, I think that's whereyou know I'm looking at.

(19:15):
When I'm looking at a client,you can obviously see like
sickness behaviors.
Sickness behaviors you couldbegin to see how people are
perceiving their reality, oftheir, you know, somebody with
anxiety, or somebody withdepression, or somebody comes
down with a cold and you knowthey adopt these behaviors that,

(19:41):
oh, I'm feeling sick today I'mgoing to go lay down, you know,
I feel.
You know, once we have thesethings where we say like, oh, I
feel like I'm getting a headcold, OK, well, how do you feel
that?
Well, that's the whole idea ofwhat interoception is, and this
immunosception component of itis that I'm getting these, these
signals that are coming from mybody.
Or, you know, I sprain my ankle.
Ok, you know, can you?

(20:01):
You know, sometimes you don'thave to just look down and see
that your ankle is swelling, butyou actually can perceive that,
hey, I'm hurting, I'm feelingpain, and so I think that you
know, trying to get patients tounderstand that you know one,
when we have, when our immunesystem turns on and begins to

(20:23):
activate, it's going to gothrough these very stereotypical
responses.
And I think that that's wheresome of the immunodeception
research is going is that wehave these very specific
responses that the immune systemmakes, and makes it in a very
stereotypical way, very muchlike our motor system does, Like
we have our motor system thatdoes these particular outputs

(20:46):
that are somewhat reflexive, orwe know that they're reflexive,
and then over time we can builda complex motor task and that in
itself becomes a very learnedresponse.
So I think that that's whatwe're seeing in the immune
system is that we're now seeingthis choreography that happens
within the innate immune systemand the adaptive immune system,

(21:07):
where, when we engage ourself ina certain type of response to
maybe a pathogenic response orwe're dealing with some damaged
tissue and we're getting a dampresponse, that we're going to
have this very specific responsethat the immune system is going
to coordinate using a variousamount of cells that are in the

(21:28):
innate immune system or callingon the adaptive immune system.
But then what happens is thatthen the immune system now makes
this memory of it Okay, so thatway, when it happens again, we
now can mobilize much faster.
And this is not necessarily liketalking about our adaptive
immune system and our antibodiesbeing made.

(21:49):
We're talking about thechoreography of all the
responses of the immune systemthat happen to that given moment
of tissue damage or apathogenic response.
In that aspect, and I thinkthat's what we're beginning to
figure out about this wholeconcept of immunosception is the
idea of how it's allchoreographed, okay, and how

(22:11):
you're seeing.
You know what cells that arecoming online at certain moments
, and I think you know back tohow we do things in movement.
You know we know when we go tomove our body in a certain way,
we know it's going to involveour cerebellum and what parts of
our cerebellum and our basalganglia and our frontal lobe.
So now you know, when weencounter a certain pathogen or

(22:32):
a certain inflammatory response,we're going to get this very
stereotypical choreography ofthe immune response and then the
immune system is then going toin the insular cortex, going to
have these kind of like filesthat they have now and they know
that.
Okay, we do thisimmunologically when we
encounter this, and that's howI'm looking at explaining the

(22:54):
concept of immunosuppression.

Speaker 1 (22:55):
Right and you and I did just the two of us we did a
couple of interviews on one ofthe podcasts and we talked about
we use the word engram right onone of the podcasts and we
talked about we use the wordengram right, which is that
brain's memory of some kind of aperipheral immune event,
whether it's an injury orsomething like that
no-transcript in the traditionalway that memories are stored,

(23:19):
or are they stored in theinsular cortex.
Is this a completely becauseit's immune-based memory.
It's not like cognitive memory,it's something completely
different but it's memorynonetheless.
So is this interlinked with, oris this completely separate
from our, let's say, ourtraditional memory systems?

Speaker 2 (23:38):
I think it's within our traditional memory systems.
But remember, we have differentmemory systems between our left
and right hemisphere.
The right hemisphere has moreof a subconscious, unconscious
memory, where the hub of it isreally around the amygdala,
which is really more of anemotional type of memory or
experiential memory.

(23:59):
We remember what somethingfeels like but we don't recall
it as a memory, whereas factualmemory, episodic memory,
declarative memory, consciousmemory, is really generated more
through the left hemispherehippocampal networks.
So I think it's within thosesystems.
But I think, like most righthemisphere memories, it's

(24:20):
implicit, it's subconscious,it's not something that we
consciously say oh, this is amemory.
But our body responds tosomething as a memory, meaning
we know that it's there, likewe've been hurt once before.
That's what happens in trauma.
Trauma tends to live in thatright brain.
Happens in trauma Trauma tendsto live in that right brain and

(24:43):
even though people may notremember the memory of the
traumatic event exactly, that,it can get triggered over and
over and over and over again.
Or if they have a memory,that's literally a flashback
where they literally go back tothat moment.
But you know, one of the thingsthat I think is cool is again,
with the interoception.
You asked what was importantabout that.
Well, again, that, and theinsula and the anterior

(25:06):
cingulate is where we becomeembodied, right, that's where we
become an individual person.
We become self-aware.
One of the most unique featuresof human intelligence is
self-awareness, right, meaningthat homo sapien sapien, the
wise man that knows he's wise.
It means that level ofself-awareness is what is unique

(25:28):
to human intelligence.
Right now we don't believe,ever believe, artificial
intelligence will have that.
But that's the fear that theymay someday become self-aware,
right, but without a body.
The belief is you can't becomeself-aware.

Speaker 1 (25:42):
Yeah, you can't be embodied if you don't have a
body.

Speaker 2 (25:45):
Exactly.
And you can't be self-aware ifyou don't have a body and you
become embodied in that insulaand that's where you recognize
yourself from other Around.
Two years of age, your childsuddenly recognizes themselves
in a mirror.
Now, if we look at autoimmunity, what's the concept of
autoimmunity when you lose, whenthe immune system loses, the

(26:06):
ability to recognize self?

Speaker 3 (26:08):
from other.

Speaker 2 (26:09):
So where would that and where would the memory of
that or the concept of that beregulated?
In the same area that weunderstand our self from other
as a body, we also understandour immune system from self from
other, and so you look at thatand say if there's a dysfunction
in one.

(26:30):
When you have lack ofinteroception, you often see,
you know this very high level ofautoimmune reactions eczema,
food sensitivities, pans orPANDAS reactions, you know
autoimmune encephalitis and allof it is really related to that
regulation of those things.

Speaker 1 (26:51):
So, if I heard you correctly, the right brain and
you've said this many times inyour interviews that the right
brain develops preferentiallyright in the first three years
of life.
It's not that the left braindoesn't develop, just the right
brain develops more efficientlyand faster.
And the right insular cortexand, I would imagine, to a

(27:11):
certain extent, the parietallobe, because they would have to
communicate together to havethis sense of self.
What I'm hearing you saying isthat that has influence over
what we would say from afunctional immunology standpoint
, the concept of self-tolerance,and when we lose self-tolerance
we start to generateautoimmunity.
So I guess what I'm trying toask is how predictable are these

(27:38):
relationships Like the rightbrain controls or generates
tolerance, and when we lose that, we lose tolerance and we have
the expression of autoimmunity.
Is that always a right brain orright hemisphere function?
And if that's true, what is theleft brain responsible for?
And again back to a question Iasked before how repeatable and

(27:59):
reproducible is that from personto person?
Is this part of ourdevelopmental blueprint, meaning
that it's predetermined thatthose parts of the brain are
going to control these aspectsof the immune system, or is that
much more experiential, likedevelopmental from the
standpoint of as I have livedand experienced these inputs

(28:20):
into my system.
My immune system and brain havedeveloped this relationship and
it might be different fromsomebody else's.

Speaker 2 (28:30):
I mean, I think personally because the insula is
online so early.
These are all developmental.
So even when we talk about theright brain and the left brain
becoming the right brain andleft brain, it's almost all
experiential, it's almost allnon-genetic.
That's what makes the rightbrain the right brain and the
left brain the left brain.
The timing of it is what makesthe difference right and I think

(28:53):
it's very, very predictable.
But what we often see is thatwhen something alters that
timing mechanism, it may alterhow the brain is developing and
regulating itself and that iswhat leads to these different
developmental imbalances that wesee.
So I think it is veryreproducible from a standpoint

(29:16):
of that.
You know, we know that the rightbrain will in general, if it
develops appropriately, will dothings.
It's more involved with bottomup.
It's, you know it has a lot todo with, you know,
proprioception and feeling ourbody.
And there is an overlap, as yousaid, with the parietal lobe,
because the insula parietalvestibular cortex, the border of

(29:39):
the insula and the parietallobe, is the primary vestibular
cortex on the right side, whichagain helps us to develop a
vestibular and sensory map aswell as a somatic topic map.
So it is reproducible and so itis predictable, and so,
therefore, we can use this toactually change things.

(30:02):
But when this is altered insome way, that's where we see a
problem, and it's almost alwaysfrom a developmental perspective
that this is altered.

Speaker 1 (30:11):
So I'm sorry, go ahead, peter.

Speaker 3 (30:29):
Yeah, I think to Rob's point.
You know, one of the thingswe've seen over his career and
what we've seen over my careeris when you look at these kids
and you look at thesedevelopmental imbalances, there
tends to be these almost liketrademark symptoms that they
have.

Speaker 2 (30:37):
That you know, we look at autism, for example.

Speaker 3 (30:38):
We always see for the majority of cases, if not all
of them, you know, underdevelopment in their GI system,
in their GI system, so many ofthem have upregulated atopic
presentations of eczema or skinrashes or history of that, and
then they tend to be a, they getan immune response and, you

(31:02):
know, is it enough to knock downthe infectious agent or it
lingers more and they don't geta contraction of their immune
response.
And so I think that that's youknow.
And when you look at thelaterality research, I mean the
research goes back 30 years.
Unfortunately, the major brainlaterality research for the

(31:22):
immune system passed awayseveral years ago from cancer
and unfortunately not manypeople picked up his work.
But you know, the basis of itwas that you know, the left
brain tends to be more theactivator of the immune response
and the right brain tends to bemore the inhibitor of that.
And I think what we've seenover the years is that when you
have a more dominant leftcortical development, especially

(31:45):
a progressively early onset ofthat left brain development,
okay, you know, are we seeingthese higher instances of
autoimmune types ofpresentations with these young
children?
And our experience has taughtus is, as we start to establish
more right brain dominancy ofthe immune response.

(32:07):
You know that we tend to bringthat back in line Now.
There's definitely some nuancesthat now to where we look at
the T cell positions a littlebit different than we did maybe
20 years ago, and the simplicityof the, the t-helper cell one
and two and three and th17, youknow now we know there's some
subsets, so there's definitelygot that has to be accounted for

(32:30):
a little bit more in a waydifferently than we've done in
the past.
But I think that from atotality of what I've seen and
what rob's seen, is that youknow, a lot of these kids tend
to be classically more Th2dominant or classically Th17
dominant.
They don't have a very, verystrong Th1 response or a natural

(32:52):
killer cell response and youknow, and especially if their
Th2 system is really revved up,they're going to have more
autoimmune expression.
And you know, one of the thingsthat I've been teaching, now
that you know Dr Yannick's beentalking about for quite a while
now, is the whole idea of, like,an increased Th22 expression,
where you now you get, you know,high level of glycation of

(33:14):
antibody expression so that theymake the antibodies more
stickier, and so then do we geta more activation of these
antibodies, especially in thebasal ganglia that we may see in
the PANS presentation.
But I don't think the answer isjust purely trying to promote a
polarization shift.
I think that's part of theanswer.

(33:34):
But the bigger thing is thistop-down modulation of the
immune response and trying toget that right brain to come
online more so we do get a moredeveloped gastrointestinal
system, so that every child thatwe treat doesn't have to stay
on, you know, glutamine and drylicorice and all these products

(33:55):
for years and years and years totry to treat their gut.
Because what is, you know, ifyou're looking at this from like
Rob's point of view and saying,okay, you know, are we looking
at this autonomic dysfunctionand are we looking at really
more a heightened sympatheticresponse and the fact that the
parasympathetics tends to beseems to be more governed by the

(34:16):
right side of the brain, Okay,so if we're shifting towards a
left-sided early development, dowe get increased sympathetic
outflow and obviously we'reseeing that decreased
parasympathetic aspect.
So I think for us, you know, Ithink our database is much
different than most people and Ithink that's why we can be
probably very more convicted tosay listen, you know, you fix

(34:38):
the laterality, you address thelaterality to say listen, you
know, you fix the laterality,you address the laterality.
You are going to addressdownstream neuroimmune
consequences.
And we do see children, youknow, do better with gut
function and do have betteroverall intestinal function.
They don't seem to getintestinal inflammation quite as
much, they don't seem to haveto constantly be on guard for so

(35:04):
much contamination to foodresponses because their system
does finally calm down.

Speaker 1 (35:09):
And is that the brain work that you're referencing
there and the changes in guthealth and function?
Is that with or in the absenceof, say, nutraceuticals that are
designed to get rid ofinfections or support healing?
Permeability issues?

Speaker 3 (35:27):
I think you know from , my approach has always been
you kind of using those as amodulating.
You're modulating the immuneresponse, you're trying to
modulate the T cell polarizationand you're trying to maybe cut
down on the gut inflammatorystuff.
While you're trying to maybecut down on the gut inflammatory
stuff, while you're trying tobuild the brain, okay, and but
as long as you cause, if you donothing but just do that like

(35:49):
most of the functional medicineworld, we see it all the time
their parents are walking in onsupplement after supplement and
they haven't changed that immuneresponse or they haven't
changed that gastrointestinaldevelopment because they haven't
done the bottom up developmentof the brain and then getting
that bottom up interference outof the way.

(36:10):
So that way now you can getthose higher cortical networks
to finally come on and do theirinhibition and maturation of
certain areas.
And so I think that's thebiggest thing is that, yeah, you
do those.
We use these T cell supplementsand way we're trying to

(36:32):
modulate the immune response butto quote unquote get a more
permanent effect, it's got tocome down from the maturation of
that right hemisphere.

Speaker 2 (36:45):
I think a good practical example, steve, is
kind of jump on what Peter wassaying before.
You know, most of us know, likeI mean, we've all experienced
where we go.
Oh my God, I feel like I'mgetting sick.
My throat starts to get alittle thicker feeling and I'm
just not feeling great Right.

(37:05):
And that leads to what we callsickness behavior Any behavior
for us to be able to perceivethat it has to be happening in
the brain.
Absolutely.
We have to register that wheresomewhere we go oh, my throat
doesn't feel good and I'm not,and I know I'm getting sick, and

(37:26):
so the immune system and noone's ever really thought about
that or really said, oh well, ok, so we must be perceiving it in
the brain.
So then the brain is going toreact some way.
That's what it does, right, itfeels things and then it reacts.
And that's what Tracy's workwas really, I think, really on

(37:46):
the forefront of.
But he still stayed kind of lowdown in the brainstem and the
lower part of the brain didn'treally completely bring in, you
know, the upper part of thebrain as much like the orbital
frontal cortex, which plays arole in that and and other
things that play a role in it.
But you know, it's just forsomebody to think about it like
you know, okay, your stomachdoesn't feel good, or you ever

(38:09):
had a chance where you atesomething and you just didn't
feel right, and then you know afew hours later you're puking
your brains out, but right, assoon as you ate it you didn't
feel right.
Right, you perceive thatsomewhere.
We have to perceive it in ourbrain, and where we perceive it
is in that insula and in thehumunculus.

Speaker 1 (38:30):
If we can localize it , it's in our humunculus, and
then there's an efferentreaction to that and there are
pretty well-known pathways thatwe know that do all of that, rob
, I'll direct this to youbecause I made the point when I
was teaching in San Franciscothat there's so many cases and
I'm not talking about kids onthe spectrum right now, but just

(38:52):
generally across functionalmedicine clientele that people
come in and they have a leakygut, they might have an altered
circadian rhythm, and we do somesupplements, we make some
lifestyle adjustments and thosethings sort themselves out.
And I made the point thatwhenever you are doing what you
think you know to be right froma nutraceutical, dietary,

(39:13):
lifestyle standpoint and you getthese resistant patterns like
you get the leaky gut thateither never goes away or always
comes back resistant patternsLike you get the leaky gut that
either never goes away or alwayscomes back, or you get that
abnormal circadian rhythm thatjust doesn't smooth itself out
with the standard practices.
I made the point like you'vegot to think about the brain in
those circumstances.
Would you agree?
And how might you modify thatsentiment?

Speaker 2 (39:37):
Yeah, I think you know from the very beginning.
You know, when I was down therein the DR and listening to
these doctors, they both did agood job and it really started
with there's this problem in thegut and there's a leaky gut and
there's intestinal permeabilityand there's a breakdown and
there's not the production ofenzymes and acid.

(39:57):
But my question is okay, well,why is there a leaky gut beyond
a certain age and why aren'tthey producing these acids and
the enzymes?
There's a step and that's whereI think it starts in the
brainstem.
The brainstem is not comingdown from the beginning and the
gut starts out leaky and openand the sympathetic nervous

(40:22):
system is on full when we'reborn and the parasympathetic
nervous system isn't.
So that's how we start life.
And if somebody's still likethat, where they still have a
leaky gut, they still have asympathetic dominance, they're
not producing theparasympathetic then it most
likely starts in the brainstembecause that nuclei that would

(40:46):
regulate those things, thenucleus ambiguous of the
parasympathetic nervous systemand the nucleus tractus
solitarius, isn't developing tobegin with, right.
So it's not that that happensto the gut.
The gut just isn't maturingbecause the brainstem is not
maturing.
So, right from the beginning.
The idea that it starts fromthe gut and works up is false.

(41:09):
It starts in the brainstem andit goes down.

Speaker 1 (41:15):
Yeah, I'm sorry to interrupt.
I just had two thoughts as youwere going through that.
We know that babies are bornwith a leaky gut and that goes
away spontaneously as long asthings develop.
That's the key there, steveyeah exactly, and so I don't
know the answer to this, but atwhat neurodevelopmental stage

(41:39):
does that newborn leaky gutresolve, if you know?

Speaker 2 (41:44):
When the nucleus ambiguous comes fully online,
right, it's a parasympatheticresponse as we start to eat food
and as we start to have a needto digest food and absorb it.
Now we start the rest anddigest system, which is the
parasympathetic, which is thenucleus ambiguous.

(42:04):
Before that we have the rostralventral lateral medullary
nucleus, which is thesympathetic nervous system, and
we have the dorsal motor nucleusof the vagus, which is what
starts it all.
Right, but ultimately, thenucleus ambiguous is what causes
the gut to close up.

(42:25):
It's what produces or allowsfor the production of, by either
inhibiting the sympatheticnervous system or activating the
dorsal motor nucleus, wherewe're producing digestive
enzymes and acid in the gut.
So that's where it starts onthe way down, and that doesn't

(42:45):
happen if that isn't maturing,meaning a child still eating
food.
But it's not just the eating offood that causes it to close up,
because if that was the case,then no one who's eating solid
food would have a leaky gut,right, because that's the point.
So there's something other thanthat that isn't developing,

(43:06):
even though now we're eatingsolid food, but yet we're not
closing up that gut, we're notproducing the enzymes, we're not
producing the acid and we'renot increasing the blood flow to
the gut for absorption, andthis is everything you see in
kids with autism and this iseverything you see in kids with
autism and this is everythingyou see in most kids in the
neurobehavioral spectrum,especially with the right

(43:26):
hemisphere delays.

Speaker 3 (43:28):
And I would add that you know the relationship of the
orbital frontal system to allthat.
You know that one of the thingsthat we constantly see is that
they have suppressed the outputof their orbital frontal
function.
And so, and as Rob was saying,this early development of that

(43:49):
orbital anterior cingulateinsular mechanisms that are
happening in that first year,you know, first, 18 months of
life, you know 36 months of lifeand so I think that's you know,
when we look at kids withautism, they don't smell, most
of them don't have any sense ofsmell.
You hold up a canister and youask them to blow sniff in.

(44:10):
They don't sniff in.
Parents will talk to you allthe time they don't relate, the
ones that are even verbal, theydon't talk about smelling mom's
cookies or come into the kitchenand say, hey, you know what's
cooking today.
You know that smells reallygood, okay.
And then you look at the orbitalfrontal relationship to

(44:31):
self-regulation and being ableto, you know again, modulate
those internal visceral statesof being Okay, internal visceral
states of being okay.
That you know again, you knowwe all get upset or we all can
get anxious.
We all can get, you know, asense of I want to go towards
something very aggressively, butyou know what hemisphere really

(44:53):
begins to regulate all that isthe right hemisphere and more
specifically, the right orbitalfrontal, and so, as Rob has been
talking about this idea ofembodiment, attachment and
self-regulation, it's all comingfrom the right side, and so I
think that we're going tocontinue to probably find out.
Not only is the right insularcortex a major player in the

(45:18):
immune modulation, but I thinkwe're also going to probably
uncover that the orbital frontalarea has a lot to do with this
immune modulation as well.

Speaker 2 (45:28):
And we can map this out from the bottom up.
I mean we can kind of gothrough that yeah let's do it,
okay.
So again.
So in the periphery, as Tracytalked about, we have these
peripheral nerves that are inour tissue and sensing.
We have an infection, we haveinflammation, we have something
going on and just like weperceive pain, we perceive that

(45:52):
there's inflammation going on,we perceive that you know what's
happening, we perceive thepresence of these foreign
invaders through the sentryneurons and all of that afferent
input really comes through thevagus nerve.
There was a recent paperrecently that showed that the
use of probiotics had a directrelationship on activating the

(46:16):
vagus nerve right.
So from there it goes up and itgoes into the solitary nucleus
in the medulla, in the brainstem, and from there then there is a
regulation of, like I said, therostral ventral lateral
medullary nucleus, which is thesympathetic, the dorsal motor

(46:38):
nucleus and the nucleusambiguous right.
So from the NTS it's going togo to those areas and it's going
to feed information to eitheractivate the sympathetic or
parasympathetic there.
But then from the NTS it goesinto the parabrachial nucleus
near the dorsal vagal complex.

(46:59):
From the parabrachial nucleusthat goes to the paraventricular
nucleus of the hypothalamus andagain, what they showed was,
with probiotics, when itactivates the vagus nerve, that
goes to the paraventricularnucleus and can cause a release

(47:20):
of oxytocin and vasopressin.
But also that's the start ofthe HPA axis, which is an
anti-inflammatory pathway.
But then it goes up from thereinto the periaqueductal gray and
then it goes to the amygdalaand then it goes to the anterior

(47:40):
cingulate and then it goes tothe insula and the orbital
frontal cortex and then from theorbital frontal cortex
ultimately will come down andgenerate much of the efferent
control along with the insula.
So we go up and we see that, aswe said, this is called the

(48:01):
central autonomic network.
It's a network that's beenmapped out, we know it exists
and that's also thatperibrachial nucleus is also
where we initiate sicknessbehavior in the brainstem.
That's where it starts, sogetting a fever.
You know we have some people,some kids, on the autism
spectrum that when they get afever they start speaking.

(48:25):
I believe the reason why manykids don't speak is because the
lack of that insula andinteroception and proprioception
and not having a map of theirbody and not having that drive
to communicate and not havingthat drive to communicate.
But it would be interestingbecause when they get sick and
they have inflammation itultimately gets picked up

(48:46):
through the parasympatheticnervous system in the vagus into
the insula and the right insula, activating it, and now they
feel their body better too andthey speak, and then that
initiates the HPA axis, which isgenerating anti-inflammatory

(49:06):
and it's generating thecorticosterone, which is our own
most powerful anti-inflammatorysystem.
So that's the way this networkworks, and the left hemisphere
is more activating through theinsula of the sympathetic
nervous system and theinflammatory, pro-inflammatory
cytokines and pathways, wherethe right hemisphere and the

(49:29):
right insula is more through theanti-inflammatory pathways.
And that is the way we see itworking right now.

Speaker 1 (49:37):
Peter, on that last note, with pro and
anti-inflammatory systems, do wehave it?
I remember back when I firstheard about this brain immune
connection, people were talkingabout lesional studies where,
for example, the one that sticksout in my mind is if you damage

(49:59):
the cerebellum, you lose yournatural killer cell population,
for example and I don't know ifthat's been borne out or if that
was a theoretical model.
But is it a circumstance where,going back to a very simplistic
T helper cell model of TH1, th2, th3, for example, if the right

(50:19):
brain, particularly rightinsular cortex, is
anti-inflammatory and gives ustolerance, would we expect that
part of the brain to have morecontrol over TH2 systems, over
regulatory T cells, for example,over TH2 systems over
regulatory T cells, for example.

Speaker 3 (50:40):
I think we're still trying to dissect that all out.
Because, again, I think thatwhen we look at, for example, we
know that the TH2 system for along time was considered like
this anti-inflammatory system,but yet it's.
But when it's overactive it canreally be super inflammatory.

(51:04):
Right, it can.
It's driving more of theseatopic presentations, it's
driving more of these asthmaticaspects.
Okay and so.
And then in the presence of areal dominant th2 response,
where you're pumping a lot ofinterleukin 4 out OK, and then
you're also pumping out IL-5,IL-13.

(51:24):
If you get intestinalinflammation, you can pump out,
like TSLP and other interleukinsthat are going to even promote
a greater shift of that TH2system, that are going to even
promote a greater shift of thatTH2 system.
And then from there, if in thepresence of a bunch of IL-4 and
TGF-beta do we shift over to aTH9 expression and that may

(51:45):
drive more of a mucosal response, Okay.
So I think that's where youknow, where I'm at least trying
to process through that a littlebit, Okay, To kind of say,
because the way I'm looking atit now is where you know, where
I'm at least trying to processthrough that a little bit okay,

(52:06):
to kind of say, because the wayI'm looking at it now is that
you know, a lot of these kidsare coming in with more of a Th2
dominancy to begin with.
Okay, so what's driving thatTh2 dominancy that we see where
we have the asthma, we have theatopic presentations, okay, we
have the over responsiveness toseasonal allergens and stuff.
So we tend to see that.
And then you know, when you dohave a, you know, a higher level
of a TH2 system, you're goingto kind of basically stop

(52:27):
autophagy and mitophagy in itstracks and you're not even going
to be able to promote as muchof a TH1 response.
So now you know, do you get abit a bigger burden of of this
bacterial situation in the gisystem where now you're, you're,
you're allowing that bacteriato go and you got more gut
dysbiosis?

(52:47):
Um, you know, maybe you'regetting more viral load burdens.
That are going on.
And and then you, the moreaspects you get.
Because the one thing thatwe're seeing with the T cells,
it's not they, they can morph inand out.
You know it's based on thecytokine presentation that they
have that they can be dumping.
If IL-4 is really present, it'sgoing to, it's going to shift

(53:08):
that naive T cell to to TH2.
But if all of a sudden IL-6comes floating along, IL-6 is
going to shift it to a th17system.
So I I think that I don't wantto be linear yet in that, in
that construct I think that westill have to unravel that a
little bit more.
To try to see now with how youknow how rapid and again the

(53:32):
idea that it's not like yourwhole body is systematically Th2
dominant.
You're having it in verylocalized areas.
You could be needing a Th2response in your nasal pharynx,
but in response to a fungi youneed a Th17 response in your GI,

(53:52):
system response in your GIsystem, okay, but I, but I think
where we're looking at, atleast, is the perspective of are
we shifting to where thosesystems are too dominant, okay,
too overexpressive?
Now the question is, how is thebrain not regulating those two
systems?
I think that's the biggerquestion for us now is trying to

(54:14):
figure that that we know thatwe can shift into a TH17
dominancy, we can shift into aTH2 dominancy.
We can lose the integrity ofour TH1 system.
Okay, we may not have enough ofthat T regulatory, that TH3
that we used to call, but now weit's really dominantly called t

(54:34):
regulatory system, but we losesome of that integrity of that
system to modulate.
But, um, I think for me itwe're trying to figure out how
to pull it back but then at thesame time, probably really
relying on that right brain tocome down and calm down the th2
and the th17 systems yeah, Ithink that the way you describe

(54:57):
that is that you know you canhave, remember what.

Speaker 2 (55:00):
How do we know what's happening in the blood?
We draw it out and we look at itoutside the body.
So typically we test blood notin the presence of the nervous
system and if we did would weget completely different
responses but also, as Peter'ssaying, you know if you can have
an infection or somethinghappening in one area and then a

(55:23):
different one in the other andyou need different immune
responses.
You know the immune system andthe metabolic system usually
isn't that specific, it'susually more of a globality.
When you need specificity, youneed the brain to regulate it.
You need some sort of likesomatotopic map in our brain,

(55:44):
like a humunculus of our immunesystem that would say okay, I'm
perceiving this in my rightshoulder and I need to do this
there to the immune system.
And the immune system and thebrain can regulate the release
of these cytokines so that itpromotes more of an inflammatory
response here or maybe ananti-inflammatory response here,

(56:08):
and that they're likeneurotransmitters being released
or being modulated by the brainmodulating the release of those
cytokines which isorchestrating what's happening
in the T-cell polarization andwhat they're doing and where
they're going and all of that.
So I think the fact that it maybe that specific just speaks to

(56:30):
more and more that the brainhas to be taking the main role
in.

Speaker 1 (56:33):
So is the primary role of the brain in the
neuroimmune axis.
Is it to assist in T-cellpolarization, to shift the
population of different types ofcells, or is it to change the
behavior of cells that arealready there, to make them more
active or less active?

Speaker 3 (56:54):
I think that's a great question.
I think it's probably both, tobe honest, I think that you're
trying to because, again,especially with these T cells
now, I mean we're finding outthey're not static, right, they
can change on a dime.
And then they can, let's say,you go from a naive T cell and
you shift to a TH2 cell and thateffector cell relationship, but

(57:17):
these effector cells over herecan then change on a dime to
another T cell position, right,based on the climate of what's
happening and and really youknow, based on the signaling
probably from the innate immunesystem, and how antigen
presenting cells is happeningand what is the co-activation
that's happening there and whattoll-like receptor is presenting

(57:40):
that relationship that changesthe morphology of that T cell.
But again, I think that, as Robhas said, is that I think the
elegancy is going to be here,the idea of how the brain is
signaling down, and I thinkwe're going to see some
breakthroughs in how the brainis telling, because the innate
immune system is giving theinstructions to the adaptive

(58:02):
immune system, right.
And so we now, I think, aretrying to look at what is the
brain doing to the innate immunesystem, and I think Kevin Tracy
was beginning to kind of andhis team there were beginning to
put some of the understandingto okay, what can happen with a
certain macrophage or what canhappen to a certain neutrophil,

(58:25):
or this whole classification ofinnate lymphoid cells that you
know have just been discoveredover the last, say, 10 or 15
years, that we're barelybeginning to understand what
they do Like.
We have innate immune lymphoidcell one, two and three.
One tends to be associated witha Th1 system.
Innate lymphoid cell two tendsto be associated with Th2.

(58:46):
And Th3 tends to be the innatelymphoid cell three.
So I mean that's a whole otherscenario now.
So again, I think that we'regoing to be starting to see
where we're going to understanda little bit more of the way the
brain is discreetly instructingthe cells of the innate system
to do what they need to do andthen how they're going to go and

(59:09):
then tell, ok, the T cellsystem to do what they have to
do or the B cell population todo.
I think we're going to have amuch clearer picture on that
over the next couple of years.

Speaker 2 (59:21):
Yeah, what you just raised, Steve, was really our
primary question around research.
Right now We've come to thesame point.
We're like, wait a second, ok,and nobody that we're aware of
yet has really answered thatquestion that you just asked.
And it's really great that yougot there because, again, you
only because you have a lot ofknowledge.
You're like, ok, yeah, so thisand so we don't know the answer

(59:43):
to that yet, but that's where wewant our research to go.

Speaker 1 (01:00:02):
And we think you know that4, cd8 populations for
decades, right, and then in thelast, say, five to seven years
we've had labs offering expandedT cell or lymphocyte subsets.
But these are still populationsof different types of cells and
they show us numbers, theydon't show us function.
And we have other labs thatwill show us cytokine levels.

(01:00:24):
All of these are taken, as yousaid, rob, from a blood sample,
separate and removed from themoment-to-moment influence of
local environmental signals anddescending regulation from
brainstem and let's say, theorbital frontal cortex and the
insular cortex.
But on top of that they're anamalgamation of all the

(01:00:48):
different compartments of thebody right, and, for example, if
you're working with, like anautistic kid with a gut problem,
you would love to know what'shappening immunologically in the
gut, not just the cellpopulations but their activity
levels.
And if we're dealing with anadult, say with Hashimoto's,
we're trying to understand theimmune system.

(01:01:09):
We pull a blood sample and itdoesn't show kind of a classic
Th1 dominance that we tend toexpect.
And it doesn't show kind of aclassic TH1 dominance that we
tend to expect, like we can'treally make any conclusions
about the thyroid and theHashimoto's process from a
sample of blood that shows theamalgamation of all the immune
processes that we're able tomeasure Right, and so the more

(01:01:29):
that I learn about immunologyand now bringing the brain piece
in, the less satisfied I amwith those as clinical tools.
Now, that's I was going to say.
That's my opinion.
I'd love to hear yours.

Speaker 3 (01:01:43):
This has been a discussion that Robert and I
have been having for, you know,three to four years now, as I
really dug into this deeper, myfrustration with standardized
labs that allow us to look at,you know, flow cytometry and
look at, because again, we lookat IL-6, for example.
Il-6 has to really be in theacute state to probably see it

(01:02:05):
elevated if we draw it.
I mean, I know it's becomepopular since COVID and so many
funk med practitioners are goingaround.
Oh, you know, run this througha standard lab corp request.
But I can tell you, I mean, ifyou do, you're probably not
going to see it.
I think that you know the thingthat I've seen more reliable

(01:02:26):
has been number one, theclinical presentation of the
case.
Okay, and looking at what youknow tends to seem to be, you
know, are the patients more Th2dominant in their symptom
presentation?
Again, are we seeing that thehistory of atopic type of
presentation?
Are we seeing asthma?
Are we seeing, you know,sinusitis, you know rhinitis,

(01:02:47):
kind of things, utis?
You know those things that tendto be more of those classic Th2
dominancies.
You know, periodically, youknow, again, if you're in maybe
an acute state, you'll probablysee the eosinophils elevate or
you'll see the basophils elevate, okay, and they'll start
getting upwards of 4%, 5%.

(01:03:08):
I mean right now the researchout there on mast cell testing.
I mean people talk about it, Iknow there's a couple companies
out there.
On mass cell testing, I meanpeople talk about it and I know
there's a couple of companiesout there that are saying, oh,
you know, they can look at masscell activation and pinpoint it.
Maybe they can and maybe it's auseful test.
But I just go, based off thesymptoms of what I perceive to
be more of a mass cell type ofactivation and start down

(01:03:30):
regulating Again.
Sometimes you'll see where youknow, in the Th17 shift there'll
be really, you know, acute Th17.
So you'll see a high CRP thatcan indicate a Th17 shift.
Or you'll see an elevatedneutrophil level that's gone up
in the upper 60s.

(01:03:50):
You know low 70s where you canbegin to say, okay, is this
patient in a TH17-mediatedimmune response?
Do you get, you know, maybe,their fibrin level?
That's elevated, you know.
Do you see an elevated ferritinlevel?
That's elevated?
You know again, those classicacute phase reactants.
But in a chronic case you maynot see all that completely

(01:04:13):
elevated.
So I think for me may not seeall of that completely elevated.
So I think for me it's comingback to trying and then trying
to catch the interval of it too.
I think that's.
The other big thing I'velearned over time is that with
lab testing, especially likewith antibody testing, I like
what seems to be what Vibrant'strying to do and even cyrix is

(01:04:34):
trying to do, but to me I thinkthe problem with those two is
that they're cost prohibitive tobe able to try to catch the
contraction and expansion of theantibodies.

Speaker 1 (01:04:44):
Yeah, and it's like it's a it's a snapshot in time
and, like you said, like um, youknow, these are very dynamic
environments, right, veryresponsive to shifts and changes
in those local environments,and it's like-.

Speaker 3 (01:05:00):
And just like you brought up with the autoimmune
patient with the Hashimoto'sokay, at least with TPO
antibodies right, that's apretty, you know you can get
that through a conventional laband get a fairly inexpensive
number and you can serial it.
You can look at that over aperiod of a two week, 30 day, 60
day window, whatever thatwindow is, and be able to look
at it more.
And then again the question hasbecome like, if we're looking

(01:05:24):
at it now more from the antibodyglycation standpoint, is that
you might have a low antibodylevel and it's out of range, but
it's low, but yet it's a veryaggressive response, okay, as
opposed to the person that has ahigh antibody level and maybe
they not having a lot ofsymptoms.
So again back to this, thisshifting of the the other, the

(01:05:48):
TH17 system, into a moreadvanced, you know, a TH21 shift
.
You're going to get thatresponse to where, you know now
the antibodies are more, youknow, more glycated and they're
more sticky, and so now they'rethey may be more, you know,
attacking that particular targettissue, and so so I think, you
know, I think with labs I getfrustrated, because I do, you

(01:06:10):
know, dr Rob, and I get askedall the time like will you use
this lab, will you use that lab?
And I'm like I don't know yetI'm not convinced that those
labs are going to give me theclinical picture that a good
case history is going to give me.
And especially when workingwith you know some of these
children that you know coming inright off the bat that at two,

(01:06:31):
three years old they alreadyshifted to a Th2 dominance and
we can see it pretty quickly.
And so we start modulating thatdown with some of the
supplements we're using.
And then, you know, as we'retreating the brain more and we
can get around that prettyquickly.

Speaker 1 (01:06:47):
Yeah, rob, going back to the idea of neurodevelopment
and progressive stages, wouldyou go so far as to say that, as
the right brain comes onlinefirst, that it has a
preferential influence overinnate immunity, like
neutrophils and monocytes andnatural killer cells, for

(01:07:08):
example?
Or are we still in that placeof we just don't know, like we
have suspicions, but nothing'struly mapped out with high
detail yet?

Speaker 2 (01:07:19):
I think the way it works, steve, is that you know,
from a bottom up perspective,you know, all of the again,
seeds of what will become areasof the brain start in the
brainstem and then they maketheir way up right and, as the
brain is developing, as thechild is developing, make their
way up right and as the brain isdeveloping, as the child is
developing, and they make theirway up into the brain.

(01:07:42):
And we know that bottom-updevelopment mostly favors right
brain development, right?
So I mean that's pretty clear.
And so you know, we mapped allof this out this way and you
know, I think, that so initiallythe brainstem, just like the
vestibular, spinal, thereticulospinal, you know, some
of these descending autonomicpathways, start in the brainstem

(01:08:07):
and make their way down, and Ithink at the lower level we tend
to have a bias towards beingmore sympathetic on both right
and left.
But then as we get this up andthen as it starts to come down,
if we get that, that's when thebrain becomes more in control
and regulates it and we get more.

(01:08:29):
And just as you're describing,as we're describing this, you
know, peter, saying that theimmune system is so responsive.
There's no way it's going to bethat responsive purely through
metabolic reactions.
It can only be directed by thebrain.
Only the brain is going to movewith that much speed right.
So again, and that's why,looking at these things, when

(01:08:52):
we're looking at it outside ofthe brain, I've always been
frustrated by lab work.
I mean, I started I drew bloodon every patient when I was
first in practice over 30 yearsago and I, from the very
beginning, the labs didn'talways seem to jive.
And then I did.
I've done as much foodsensitivity testing as almost
anybody and again, it neverseemed to, always, like Peter

(01:09:13):
would say, sometimes a level onewould be more aggressive than a
level five.
And then even with the you know, finger prick antibody tests, I
think they're a good guidelinebut they've never really jived.
For me there's somethingmissing, and Peter has this term
that he would talk about that Ithink you learned from Sam what
was that term, peter?

(01:09:33):
Where it was like kind ofthere's this certain response
happening when it doesn't reallyfit the way you think it's
going to fit.

Speaker 3 (01:09:41):
I'm going to try to remember now what I termed it.

Speaker 2 (01:09:45):
What I'm talking about.
It's like you said, there wasthis, I don't know, some sort of
it's like this anomalous effect, and now there's a name for it,
right, when?
Okay, when the blood work isn'tlooking the way we look and the
response isn't the way weexpect it to respond.
So it falls onto this this nameum and I said to peter from the

(01:10:08):
beginning, I think that gap,that we've made this name up, is
actually the brain and thenervous system, that you're
right.
When it doesn't work the way,you don't think, and it's the
same thing in the brain, youknow, when people argue about
the whole, is there the rightbrain, left brain?
Um, because we don't see it ona qeg that way or whatever, I

(01:10:30):
don't.
Same thing in most of theimaging that we do, even in
highest level research, itdoesn't have the sensitivity to
pick up some of these subtlelittle differences in brain
activity that actually translateinto big differences in
behavior.
And that's why we have to lookat the behavior of the

(01:10:51):
individual.
We have to look at it, knowingwhat research has told us about
right and left brain, and thenit fits.
Same thing with the immunesystem.
We have to look at the behavior, the sickness behavior or the
lack of sickness behavior.
Kids with autism they don't getsick and even when they are
sick, even when they have raginginfections, they don't act like

(01:11:12):
they're sick.

Speaker 1 (01:11:13):
How do you explain that?
And then, like I said, whenthey do get know it.

Speaker 2 (01:11:15):
They don't know it.
Yeah, yeah, right, how do youexplain that?
And then, like I said, whenthey do get sick, they may
actually speak better.
So you know, you have to beable to explain all of that and
I, and I think that the labtesting and even brain testing
at this point is not at thatsensitivity, but that just
because we can't measure itdoesn't mean it doesn't exist,
that uh, yeah, and the rob'spoint too.

Speaker 3 (01:11:37):
I you know, one of the things I think the
frustration with labs too, isthat are they making their labs
even too sensitive, right Towhere you know that they are
wanting you to use theirservices, so much that are they
narrowing in their sensitivity alittle bit more?
So I think for me, I thinkwe're trying to put together an
immunological labs of what wecan hold our hand on the most

(01:12:03):
okay and say, all right, hey,this is, we feel very you know,
we run a vitamin D.
Okay, we can, you know we canput a lot of stock in that okay,
if we can run like a CRP number, I think there's, you know,
some real stability in that Okay.
So I think, where you're tryingto find stability markers, but

(01:12:24):
you know, I've run, you knowpanels where I've done TNB,
lymphocyte, natural killer cellpanels through Quest or LabCorp
and didn't come out to match thepresentation that I thought was
going to happen, and you know,and then you go over here and
you might run, you know whatCyrix has developed with their
cytokine panel and the samething.

(01:12:46):
It just doesn't seem to match.
So I think for me I'm alwaystrying to look at the clinical
picture of the case and thesymptomatology and then do the
best that I can with some labsthat I think are not too
overexpensive, that we canmeasure and then try to get a
serial pattern of thatrelationship.

(01:13:09):
And I think for me, and whatI've taught in Robert's course
over the last three to fouryears, is that you know, just
just doing a simple CBC becauseit's so simple to reproduce,
Okay, and kind of see the trendsand you can, and you can see
just the, the trends of theeosinophils, or you can see the
trends of the neutrophils andand stuff, and then you know if

(01:13:30):
you see a lymphocyte panel, thatis a lymphocyte number that
comes up, you know.
All right, maybe I do need torun a TMB natural killer cell
profile and see that.
But I mean, I don't think we'retrying to like tell families
that they got to run all thesesophisticated labs to get that.

Speaker 1 (01:13:50):
I mean, that's not where we're at right now we're
just unsatisfied, yeah, and Iwould agree, I would agree more
often than not, like alymphocyte subset panel doesn't
match my understanding of theclinical problem, and maybe the
problem is with my understanding.
But I've also found an issuewith you know.
Okay, so I have this pattern ofwhatever dominance or

(01:14:14):
deficiency, and you know, here'sa set of recommended
supplements to change that.
And I have not, I have notoften see that change within
what I consider to be areasonable period of time, even
though I might see clinicalprogress.
Right, and so that's for me.
That's when I started to gookay, really, where does this,
where does this fit in my bag oftricks?

(01:14:36):
And so I de-emphasized all ofthose things.

Speaker 3 (01:14:41):
And I think it's true .
I think there's an element ofyou know, one I always look at,
you know, one of the things I'vetalked to Rob about is that you
know, sometimes, you know,using just only a couple
products might be giving us achance to go vertical and be
able to push the physiologyenough.
And then at the other times,also the idea of you know how

(01:15:01):
underdeveloped is the brain, andeven in adults adults I mean
adults obviously can have thesedramatic hemispherical balances
and and and again.
If you feel confident that, hey, your clinical plan is, from a
metabolic or neuro-emologicallevel, solid on the emological
side of things, then probablythe other equation of it is the

(01:15:23):
neuro side of it and we haven'tdug deep enough into looking at
retaining primitive reflexes onthese adults under development
of these systems, these earlysystems of the brain that still
are impacting the way theirpsychoneuroimmunology is working

(01:15:44):
and their endocrinology.

Speaker 1 (01:15:46):
Do you guys have any time limits or do you want to
keep going?

Speaker 2 (01:15:51):
I got another call at 630 my time, so I only have
about another 20 minutes.

Speaker 1 (01:15:55):
So, as always, I have more questions.
Yeah, I got a few more minutes,and then I got to run Okay.
So are you guys okay to go?
Because here's what I wouldlike to do.
I'd like to dive into theinsular cortex.
I'd like to talk to you guysabout its functional
organization, its networkconnections, how you might

(01:16:18):
assess it, how you access it tochange its behavior and its
function, and then maybe talkabout some cases that you guys
have done.
And you know, obviously that'sa much longer conversation than
just 20 minutes.
So are you guys okay withscheduling another one?
Awesome yeah, that's awesomeyeah.

Speaker 2 (01:16:36):
That's awesome yeah.

Speaker 1 (01:16:37):
So I appreciate it, you guys.
You are both a wealth ofknowledge and the whole point of
Functional the Funk Med Nationis to share, learn, grow and be
inspired, and you guys arefitting the bill, so I
appreciate your time.

All Episodes

177 | Unlocking the Neuroimmune Connection: Exploring Immunoception, Brain Lateralization, and the Insular Cortex with Experts Drs. Peter Scire and Rob Melillo

Episode Transcript

Popular Podcasts

Crime Junkie

24/7 News: The Latest

Stuff You Should Know

.css-15opob5{left:0;position:absolute;top:0.8rem;} All Episodes

Episode Transcript

Popular Podcasts

.css-r6mb8g{margin:0;word-break:break-word;display:-webkit-box;-webkit-box-orient:vertical;box-orient:vertical;-webkit-line-clamp:1;overflow:hidden;}Crime Junkie

24/7 News: The Latest

Stuff You Should Know

All Episodes

Crime Junkie