SCIENCE: What if a small, non-invasive device could help regulate your nervous system, reduce inflammation, improve cognitive function, and support recovery from chronic illness?
Dr Elisabetta Burchi, psychiatrist, entrepreneur, and Head of Research at Parasym, is helping advance the growing field of neuromodulation, using gentle electrical stimulation to influence the body's nervous system through the vagus nerve.
Often described as the body's communication superhighway, the vagus nerve plays a key role in regulating heart rate, inflammation, mood, cognition, and overall resilience.
Parasym has developed a transcutaneous vagus nerve stimulation (tVNS) device that stimulates the nerve through the tragus, a point on the outer ear, providing a non-invasive alternative to implanted technologies.
Backed by more than 100 studies and clinical trials, vagus nerve stimulation has been investigated across a wide range of conditions, including Long Covid, ME/CFS, hypertension, depression, fatigue, anxiety and cognitive dysfunction, with promising results.
Parasym has also explored how vagus nerve stimulation may enhance cognitive performance and mental clarity in healthy individuals, raising interesting questions about the future of health and human performance.
In this episode, we explore:
- What the vagus nerve is and why it matters
- How vagus nerve stimulation works
- The science behind neuromodulation
- The difference between non-invasive ear stimulation and implanted devices
- How stimulation may affect heart rate variability (HRV), inflammation, and neuroplasticity
- What the evidence says about effectiveness, safety, and adherence
- The potential role of vagus nerve stimulation in both chronic illness and everyday health
Whether you're interested in chronic illness, neuroscience, longevity, or optimising brain and body function, this conversation explores one of the most exciting and rapidly evolving areas of health science.
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Elisabetta Burchi (00:00):
I'm particularly excited about this
technology, because it's aparadigmatic change. It's really
a theoretical paradigm shift.One is trying to fill the gap
and provide a treatment approachand technology, because it is a
(00:22):
technology that can give optionsto patients to people that have
unmet clinical needs forsyndromes and conditions that
are complex and that arecurrently missing treatments
that are inter systemic.
Emily Kate Stephens (00:38):
Welcome to Make visible the podcast shining
a light on complex chronicillness. I am your host, Emily
Kate Stephens.
Welcome to another episode.Hello, Gez. How are you?
Gez Medinger (00:57):
I'm suffering a little bit, but I've been mostly
functional today. I think I madetoo much of the slight
functionality I had, and now I'mhanging on a little bit. I get
to that point, like in the olddays, people's look, I say, all
the old days, everybody else whodoesn't have complex chronic
illness probably does thisalready. They look forward to
Friday, right? For me, I stillhave in my, in my head the idea
that I have to be productive,but once it gets to 5o'clock or
(01:18):
so, I let myself off the hook,so I'm looking forward to that
sort of 5o'clock moments ofactually releasing myself from
the psychological pressure offeeling like I need to be doing
useful things.
Emily Kate Stephens (01:29):
I do want to talk to you about how you got
to this place on a Friday. Werecord on a Friday, and today we
are doing an episode that isabout a specific technique for
nervous system regulation, and Iwanted to talk to you about that
in terms of your activity,because you left me a message
(01:53):
earlier in the week. You had areally busy few days, and I'd
just love for you, because I'msure it's very similar to a lot
of us share what happens to yourbody when you have that kind of
intense period of activity thatyou had this week.
Gez Medinger (02:09):
So, Tuesday I had a shoot out in South Wales,
which is a long way away. So,Monday I've got to get out
there. Tuesday's full on, it'svery exciting, it's wonderful,
it makes me feel alive. So,that's why I do it, and that's
why I subject my body toarguably the risk of doing so,
but it certainly over stimulatesthe nervous system. So, what do
(02:30):
I notice in my body? Well, Inotice that I can't fall asleep
that night because my body justcan't shut off. My heart rate's
still going mad, my brain'sstill going mad.
Emily Kate Stephens (02:37):
There's something about the adrenaline,
isn't there, that -
Gez Medinger (02:40):
Yeah, it doesn't switch off. My night sleep is
then very shallow as well. Iwake up a lot. I was awake for
three hours during the night,and the sleep I do have is very
shallow. I never managed to getinto deep sleep, the deep
restorative sleep. And then thenext day I'm also, I'm exhausted
by a function of having had abusy day and the lack of sleep,
but I'm also still quite wired,and that wiredness just about
(03:01):
compensates for the exhaustionto get me home, which is what to
do the next day, and then whathappens after that, that's when
I crash. Hey, crash. So, thereis this, this weird thing of
this retained nervous systemgoing haywire, whether that's
doing things with cortisol andadrenaline, potentially. I don't
know, I wasn't doing blood drawson myself to find out, but
that's what it feels like, asensory perspective. And then
(03:23):
there's the delayed crash afterthat, where the body does slow
down, and then goes, "Oh, you'vereally done it now."
Emily Kate Stephens (03:28):
Yeah, it's almost like your body set goes
into some kind of overdrive thatthinks, "Oh, I've been operating
at this level, I need to keepgoing, I need to do this big
push." And when you were talkingto me about it, I actually
realized that I think I had thathistorically, before I had Long
Covid, when I did shoots, that Iwould sometimes work for 36
hours without sleeping, or Iwould do these shoots, say six
(03:51):
days straight, and I'd maybe besleeping three hours each night,
and then you're busy for thewhole of the rest of the time,
and after that I would have, oreven after my wedding, I would
have three or four nights whereI absolutely could not shut
down, just push your nervoussystem to such a level of
activation it's very hard toretract from, and I was just
(04:14):
thinking about this with theLong Covid. Do you feel like I
used to feel like it was abuzzing, like my whole body was
buzzing for several days when Iwas in that activated state.
Gez Medinger (04:25):
That's quite common with people Long Covid. I
don't personally feel like that,but that's something I've been
told so many times from otherlong haulers about how they
experience it.
Emily Kate Stephens (04:33):
Yeah, so I thought that was a useful way
for us to enter today'sinterview and discussion, which
is with a psychiatrist calledElisabetta Burchi, who works
with Parasym, and they are thecompany behind the
neuromodulation device, Nurosym,what is called a transcutaneous
(04:54):
auricular vagus nervestimulation device, and what
they are trying to do with thistechnology is is a small device
that you clip on your ear and itsends electrical pulses through
your tragus. And just tomention, for those of you not
familiar, your tragus is thissmall piece of cartilage that
protrudes at the front of yourear. This interview does contain
(05:17):
some scientific language fromthings like homeostasis, which
is the body's ability tomaintain a stable internal
environment, to locus coeruleus,which is a small region in the
brainstem that producesnoradrenaline, and it plays a
key role in attention andalertness, but rather than
(05:40):
breaking the flow of theconversation, I have included a
glossary of some of the morescientific terms in the show
notes. So, do have that openalongside the episode? And
please let me know if that ishelpful to you when we delve
into these science episodes, andin that vein, please keep
(06:03):
feeding back, engaging, andsharing your stories. They are
so helpful as we try to shapethis podcast to be of greatest
help to you. Have you hadexperience with such devices or
such electrical stimulationneuromodulation?
Gez Medinger (06:24):
I have. Yeah, so I have an alpha stim device, which
is, I guess, a competitor atsome level for the neurosim one,
and I find it's quite helpful.So, let's say, for example, that
I'm on my way back from havingdone a shoe, or from having done
something that's strenuous, I'min the car. The first thing I'll
do is to put it on, and forhowever long I've got to get
home, I need to calm this bodydown, and it does seem to help,
(06:47):
but yes, the answer is I do haveexperience of using them, and I
do continue to do so.
Emily Kate Stephens (06:52):
Okay, so let us listen to Elisabetta
Burchi talking about the devicethat they have developed for
neurosim the way in which itstimulates the vagus nerve to
calm the nervous system, and wetalk about some of the studies
(07:12):
that they have done to look atthe efficacy of the device that
they've created.
So tell me, how you have endedup working in this bioelectronic
(07:32):
space, coming from thepsychiatry space, because we're
going to talk today, and ouraudience is quite focused on
complex chronic illness, but youhave a history of interest in
more - I don't want to call thempsychological - you have a very
wide-ranging history in terms ofyour interest. You've done
(07:54):
studies into alcohol usedisorder, you've looked at OCD,
so you kind of look across theboard at these conditions, and
then parasim has gone down rootsof very, very medicalized things
like heart failure, chronicheart heart failure. What I
really, really love about whatyou've done is it's so broad,
(08:16):
you're approaching it from apsychiatrist perspective, but
you kind of marrying this veryphysical. Talk to me about that
rooting.
Elisabetta Burchi (08:25):
I like that you like that. Maybe the main
reason, which taps into myorigins, is that I'm Florentine,
so you know, Renaissance style,multifaceted. I've always had an
understanding of reality andthings, which is three fully 360
degrees, or the largestpossible. I will always have
(08:48):
this aspiration to embrace moreand more. So, I've always tried
to acquire multiplemethodologies, paradigms to look
at things. And of course, as adoctor, I decided to become a
doctor because I wanted to helppeople in the first place, but
at the same time I was enticedby the object of study, not the
(09:13):
human being, and specificallythe human mind and brain, and
I'm deciding to become apsychiatrist, which is one of
those were already related tothe neuromodulation field. Why,
why neuromodulation? So,neuromodulation techniques in
general can be consideredtreatment approaches that
(09:34):
directly targets neuralcircuits, and if we think about
the brain, the brain mindobject, maybe the most
privileged level of analysis isthe circuit level, which is in
between, you know, the cellular,molecular, genetic level, and
the behavioral, phenomenologicallevel of the other side.
Emily Kate Stephens (09:57):
Is that really looking at it as an
electrical? When you saycircuits, are you looking at it
as an electrical system?
Elisabetta Burchi (10:06):
Yes, because we know that neurons used in a
certain way, electrical ways ofinteracting between them. There
are also neurotransmittersinvolved, so there is also a
chemical level, but I guess,yes, when we talk about the
circuit level, we talk about theelectrical functioning of these
systems, which is the way inwhich that's a very interesting
(10:29):
question, yours, but yes, if youthink about, if you think about
the way we measure functioning,narrow circuits, we use multiple
techniques, like techniqueswhich uses different ways of
measuring activities in thecircuits, so it's very complex,
but if we have to name one, Iwould say electrical functioning
(10:51):
is is one of the main featuresor way of looking at them. So,
so, yes, I thought that theneural circuits was one of the
privileged access way to theunderstanding of mental states,
and then also mental healthdisorders, not only to
understand them, an access wayto understand, but also to
(11:13):
affect their functioning andtreat these conditions. So
that's why I got interested inthe space, and once I completed
my fellowships, so I did someresearch in the neuroscience
space, coming back to my broaderaspiration of embracing a little
bit everything. I decided to goto get an MBA, a master in
(11:36):
business administration, sototally unrelated to medicine,
Emily Kate Stephens (11:38):
that is the thing, isn't it? The vagus nerve
because I wanted to magnify theimpact of my practice, the more
is essentially the connectionbetween what we perceive to be
systemic level to affect thewell-being, I guess, of more
people, so compared to theindividual level, which I
the physiological and thepsychological, essentially the
usually operate with mypatients, so I completed my MBA
concept of mind body, butactually we are just one, we are
and got some innovation skills,which then I wanted to
(11:59):
just one body, we are all one.
consolidate in the concreteworld, so I turned myself to the
biotech med tech space, and Iwas looking for interesting
companies that connected to theneuroscience space, and then I
Elisabetta Burchi (12:10):
Absolutely.
reduced have published so far with our
discovered Parasym which was atthe beginning, I think I joined
the company where we were onlythree, so I started working with
them. I was excited about whatthey were doing, not only
because they were dealing withneuromodulation, a specific
(12:32):
neuromodulation technique, whichis on invasive vagus nerve
stimulation, but I will say alsotalking about the vagus nerve,
which is the longest cranialnerve in humans, and carries the
majority of the fibers of theparasympathetic nervous system.
Intrinsically, this nerve, whichwith this technique we modulate,
(12:56):
is involved in manyphysiological processes across
Emily Kate Stephens (12:57):
and an implanted vagal nerve
stimulation. So I would love youto talk to me about
the body, and so having thepossibility to modulate its
function allow us to reallyovercome the usual boundaries in
transcutaneous auricular vagusnerve stimulation, which is what
medicine. So my aspiration toembrace was found a little bit
parasim does. There are alsoother transcutaneous methods,
(13:17):
but talk to me about the methodthat you
about what parasin was doingmultiple levels, so with the
technique which could actuallyredesign the understanding of
technique more than 50 clinicalstudies, and we have a similar
diseases and disorders, not justdiseases of a specific
physiological system, but asdiseases, illnesses of
number of ongoing clinicalstudies with more than 100
multi-systemic disease, which isthe in truth what I believe
(13:39):
about many chronic conditions,or also mental health
research collaborationsworldwide, so we are really
conditions,
(16:07):
heavy on science, and we'vealways put research at the core
of our what we do.
Do you have a lot of heavy claims on your
website about how all of whatyou do is backed up by
scientific studies, and Ithought, okay, well, I'm gonna
dig into this, and yes, Parasym,it..
Elisabetta Burchi (16:27):
was real, yeah, absolutely,
Emily Kate Stephens (16:31):
and it's not just that it's been you
testing it for Parasym. Parasymas been used to test this
technique across multipleconditions, and we can go into
some of that in more detail, butI just wanted to mention at this
juncture that they are actually
Elisabetta Burchi (16:48):
verified.
Emily Kate Stephens (16:50):
Yeah,
Elisabetta Burchi (16:50):
Absolutely. Since the inception of the
company, I was not there, but Ijoined the 2021 I believe, at
the beginning. They've always,you know, the founders, they've
really cared about
Emily Kate Stephens (17:02):
Scientific rigour?
Elisabetta Burchi (17:04):
Yeah, scientific rigour, exactly. So
we developed the system, whichis capable of modulating the
vagus nerve through the traverseof the ear, so through the
surface of the of the skin hereat the level of the tragus,
where underneath lies thisauricular branch of the vagus
(17:25):
nerve, which is an afferentbranch. What does it mean,
afferent, which bringsinformation up to the brain,
specifically the brain stem,where you find the nucleus of
tract solitaris, which is closeof the of the brainstem, and we
have developed signal deliverysystem, which is capable of
(17:45):
delivering electricalstimulation, so it speaks the
same language of the of theneurons as we mentioned before,
and is capable of doing it in anon-invasive fashion, in a
safely manner. When I say safelybacked up by science versus a C
marked medical device deemed notdeemed no significant risk by
(18:07):
the FDA multiple clinicaltrials, and effectively simply
and effectively we have datashowing that we actually
modulate the vagus nerve. Thereare multiple ways of
corroborating this claim. One ofthe main biomarkers is this, I
would say, now renowned markets,HRV, heart rate variability,
(18:27):
which is measured by manywearables, and all that we all
have, and we use for trackingour well-being overall. That's
one of the main markers, gaugingthe parasympathetic tone, and as
we mentioned, the vagus nerve isthe main component of the
parasympathetic nervous system,which is a branch of the
(18:49):
autonomic nervous system. Ithink, although let's reframe
everything, which has a centralrole in dynamically controlling
the homeostasis of the bodythrough action on multiple
systems, from the cardiovascularsystem to the respiratory
system, to the gastrointestinalmotility, metabolic balance,
(19:11):
regulation, etc. So the vagusnerve is the main component of
this autonomic nervous system,and so basically, our device,
which is wearable, can be usedat home, very easy to use, has
been designed for at home use.Indeed, people can buy it
(19:32):
without prescription. This isbased on the safety, I would
say, mainly, and I think thedevice we have designed this
very, very intuitive to be used.Yes, so that's that's how it
works. It works initially, sothe stimulation of the duocular
branch of the vagus nerve, thenthe signal, yes, the brainstem.
(19:56):
And and then there are a series,a cascade of physiological
effects across these othersystems we mentioned, the
cardiovascular, the immunesystem. If we want to
categorize, maybe the effects, Ilike to see three many areas.
One is the modulation of theautonomic tone, so this balance
(20:18):
between the sympathetic and theparasympathetic tone. Another
category of effects is theanti-inflammatory action, which
is implemented through specificpathways, multiple pathways. One
of those is the cholinergicanti-inflammatory pathway to the
spin, and the third category ofeffects is the neuroplastic one,
(20:40):
which is more involved in allthe applications regarding
psychiatry, neurology, etc. Sothese are the three main areas,
and we have gathered data in allof this, and if you think about
these effects, you can imaginealready the plethora of the of
the potential applications ofthis technology.
Emily Kate Stephens (21:00):
So when Parasym was first developed,
because you are talking aboutsomething that is used for
multiple applications, and youcurrently have research ongoing,
I believe a lot into this sortof neuro, but you've also been
using it, looking at atrialfibrillation, and so it very
(21:20):
much a physiological in terms ofthe heart. When Parasym was
first developed, what was theidea behind it? What was the
primary focus in terms ofdeveloping something of that
neuromodulation? Was it forcomplex chronic conditions, such
as we deal with at Visible, orwas it for a much wider purpose?
Elisabetta Burchi (21:42):
It's a very good question. I don't know if
initially the no.. the visionwas clear, already defined, for
sure. Currently, the vision isto.. it's a broad one, it's a
broad one, and it taps onto twodifferent. I will say broad
scopes. One is for sure tryingto fill the gap and provide a
(22:07):
technology treatment approach,and technology, because it is a
technology that can give optionsto patients to people that have
unmet clinical needs forsyndromes and conditions that
are complex and that arecurrently missing treatments
that are inter systemic, so thisis one of the scopes. The other
(22:30):
one, and maybe we can see how wecan pursue both goals, is to
improve and boost the well-beingof the majority of the people
out there, even without the needof specific diagnosis, and we
can actually pursue both ofthese goals because of the
functional characteristics ofthe value snack, because if we
(22:52):
think about this capability tomodulate all these internal
processes with the goal ofmaintaining homeostasis, namely
the stability of the internalenvironment while adapting to
external challenges, we canthink how this is relevant in
disorders, but also when thereare no overt clinical
(23:15):
conditions, because we didn'tmention that if we think about
maintaining homeostasis inresponse to challenges, we think
about the stress spots. Maybeit's not up to me to say, but I
believe that in our contemporarysociety, all of us is involved,
engaged, interested in this,because we are constantly under
(23:38):
pressure, we are constantlystressed out because of demands
need to perform in multiple anddifferent ways, so what the
vagus nerve does, and theparasympathetic nervous system
does is working as a break onthe stress response. So even if
we just think about that in ahealthy person, the healthy
(24:02):
potential potentially a littlebit chronically stressed,
because of just the environment.You can imagine that we can
potentiate the vagues nerve, theparasympatheric response could
actually boost well-being. Soit's possible to pursue these
two visions, providing newtreatment approaches that can be
(24:24):
combined, that's another keypoint with many other
approaches. Now, becauseneuromodulation techniques, I'm
sorry, call a VNS can becombined with pharmacotherapy
and can be combined withbehavioral therapies. In a way,
there are differences betweenthese approaches, clearly one of
the main one I will say that,while with some exceptions, but
(24:47):
broadly speaking,pharmacotherapy is less precise,
especially and temporarily. Inour description of the
modulation techniques, we weresaying all the targeted
stimulations, specific neuralcircuits, so it's complementary,
directed, and so complementaryto the other approaches, so we
are providing something that canbe combined with other
(25:07):
approaches, but at the same timeyou're providing approach that
can empower people in theireveryday life with a tool that
can help them boost theirresilience, if you think about
the stress response, and we havedata, and that there is a
theoretical rationale behindwhat I'm saying, but there are
(25:30):
already some pilot findings thatwe have that this is possible.
Emily Kate Stephens (25:35):
If we look at that, we are all, as humans
in the current society, to adegree dysregulated in terms of
our stress response, and look atwhat you've developed here in
terms of neuromodulation. Inyour opinion, are many of the
conditions that you are able tohelp with a result of a
(25:57):
dysregulation of the nervoussystem due to life in general,
rather than very specifically,I'm not saying that some of
these conditions aren't directlycorrelated with a viral hit, or
that there is not a driver, butare we all more prone to these
(26:17):
conditions because of thatsocietal stress dysregulation?
Elisabetta Burchi (26:23):
Very good question. I think you already
give the answer. There aredifferent triggers. If you think
about one of the main chronicconditions that arose in the
last year's long COVID, isdefinitely there a trigger,
viral trigger, but in a certainway the syndrome that arose from
that Long Covid arose from theacute infection, in a way, is
(26:45):
kind of independent of thetrigger, no.
Emily Kate Stephens (26:46):
The point is, why did some people, why
were some people absolutely ableto recover from it? And some
people have a residual impactfrom these things that our body
should theoretically be able toprocess evolutionarily, we
should be able to either processthem and survive, or or not.
(27:08):
research over
Elisabetta Burchi (27:08):
Yes, yes, we are so complex that then there
is this shade of graze inbetween, even if evolution
doesn't care about us anymore,once we are not really
functional from a reproductiveperspective. No, but then
gladly, gladly, we do not in ourlives, I think, we are not
(27:28):
subjugated to these evolutionaryrules. So now we can survive
such conditions, and etc, etc.But no, yours is a very good
point. I believe that among thevarious factors that can trigger
these conditions is definitelythe environmental pressure,
which makes us more vulnerableto this kind of conditions that
(27:51):
have in the dysautonomic... thedysautonomias, as the common
but is it sort of six six toeight days into it, things
denominator, since you areinterested in this kind of
started to happen, repercussionsof the neuromodulation continued
conditions, Long Covid,fibromyalgia, they present the
same phenotypic features. Thinkabout fatigue and think about
after the treatment ended, sothe trajectory this
cognitive dysfunction, so-calledbrain fog, widespread pain,
neuromodulation put patients ona an upward trajectory in terms
(28:13):
orthostatic intolerance, whichis clearly a dysautonomic
feature, but even the otherones, that I mentioned, and they
present with similar features,and all the post-variant
syndromes, they are just tocorroborate the fact that then
the syndrome is in a wayindependent on the trigger, but
(28:35):
then at least evaluates thehypothesis that the autonomic
nervous system is pivotal in thepathogenesis, in whichever ways
it becomes disrupted, but thenit becomes disrupted. And I
agree with you, probably beingconstantly chronically stressed,
stimulated on the stressresponse, it can be one of the
(28:57):
main reasons why we have suchprevalence of these conditions,
and the fact that the unmetclinical need, I believe is
related to the fact that wedidn't have much approaches to
address specifically andtemporarily, especially the
autonomic nervous system, tillwe develop an approach that
(29:19):
could actually specificallytarget the vagus nerve and
non-invasively, that's animportant feature of that.
(30:39):
of their symptoms. Talk to meabout what were the most marked
improvements in that, becauseyou've already mentioned fatigue
just now. What were the mostmarked improvements, and how
does that neuromodition impactthese patients directly?
Yeah, actually, yes, you are very well
prepared. Yes, these twostudies, there is a third one
(31:00):
down in Mount Sinai in New York,and we have been pioneering the
field of transit recollection ofVNS in Long Covid with these two
tasks, one, three studies, andand we were very excited,
because the first study, as youmentioned, that was done in 2021
pretty early on, and is that tothe researchers and all that
(31:23):
wanted, I was just joining thecompany at the time, so it was
really set up the first study,so in the research community
there was really interested forthis technology, and they
thought about it, even so earlyon, they thought that they could
have been beneficial in thesyndrome, and so they set up the
(31:45):
study. Of course, these are twopile of studies that they
already showed in as it's veryshort period of treatment, 10
days of simulation. I'm notwrong, talking about one hour 35
minutes of simulation day, whichis not much if you think that
you can have the stimulationwhile you are doing other
(32:06):
things, that's part of theaccessibility and low barrier
for patients, for people to usethe device, you know, so it was
really not a demandingtreatment, so in a short as 10
days of simulation in this way,they could have significant
improvement in mainly fatigue,but many other symptoms as well.
(32:27):
And I would, I will say thesecond study, the one did a
later one, the one done at CasaColina in California, which
studied a female cohort, theywere female patients, we know
that Long Covid is more frequentin females. In any case, and
that second study focused oncognitive improvement, and I
(32:49):
think that was, of course, theimprovement in fatigue central,
because it's central core of thesyndrome and affects many other
overall functionality, I willsee, but the cognitive, the
brain fog, too, is the other keysymptom, and we passed out, we,
the researchers, passed out thecognitive impairment into the
(33:11):
multiple cognitive dimensions,and they saw improvement across
all of them, which, in a way,because our studies are mainly
clinical, namely, we generallyare interested in providing
clinical improvement because wewant to improve the well-being
of the patients, but at the sametime we try to elucidate the
(33:33):
pathophysiology underpinningthese improvements, right? So
the idea is that in order to getthese results, leverage those
two pathways I mentioned before,all of these, but mainly I will
focus on the anti-inflammatoryeffect, because know that we
know these are hypotheses,because we are still early on
(33:55):
the research around long COVID,for instance, but we think that
long COVID is definitely alsoassociated to neuroinflammation,
right? Then we think we alsoaverage the neuroplastic
pathway, so if you think aboutthe nucleus of tract storytaris,
which is the nucleus wementioned before the brains, and
(34:17):
it is connected to any area, anyother areas in the brain, so
it's a particle area, which,though, is connected to many
cortical areas, which alsoexplains the effect on multiple
cognitive dimensions, not onlycognitive, there is also the
emotional side, which is morein, because of subcortical, but
(34:38):
specifically thinking about theeffect on brain form. What we
think happens actually isstimulation of the locus
cheruleus, which is anothernucleus in the brainstem now,
which produces no adrenaline,and we know that no adrenaline
is connected to attention, andso improvement of attention
(34:59):
might have boosted improvementin many other cognitive
dimensions that we measureclinically in this study.
Emily Kate Stephens (35:07):
Yeah, and you actually relied on the NIH
cognitive toolbox to do theassessment of the cognitive
improvements.
Elisabetta Burchi (35:14):
Yeah,
Emily Kate Stephens (35:15):
it's quite rigorous for things.
Elisabetta Burchi (35:18):
Yeah, no, absolutely. And I always like to
highlight that all these studiesthat we mentioned also in our
website, all done with ourtechnology, so we do not
translate results obtained withother devices. That's important,
because neuromodulation spacefield is cutting edge. There is
still a lot of confusion. Oftenwe see people mentioning studies
(35:44):
done with other devices, but youcannot really do that, because
each and every device has adifferent signal delivery
system, now differentstimulation parameters. So we
need to be careful when wetranslate results. Everything we
mention, everything we cite isachieved with our own
technology, but at the sametime, the studies are all
(36:05):
independent. We have not fundedthe study, so the researchers
publish whatever they want, andwe do not emanate anything. So
that's another important facet,the transparency and the
independency of the research. SoI heard about saying that we
collaborate on the protocoldesign, we give, of course,
advice they suggest that we knowthe technology, but the
(36:28):
implementation of the trials isfully on the shoulders of the
researchers, so it's fullyindependent, so that's another
relevant process. Talk to
Emily Kate Stephens (36:36):
me about speaking to someone before who
said that one of the mainproblems with transcutaneous,
whether auricular or otherwise,vagal nerve stimulation is the
adherence. It's reliant onpatient fitting it properly,
wearing it for the correctamount of time, and that is
something that will have impacton its efficacy and impact on
(37:01):
some of these studies. How areyou able to ensure the best
results, the best adherence foryour patients? Is it very simple
to use? Is it that you have veryclear instruction for how people
are able to get the bestresults? It's different from
just taking a
Elisabetta Burchi (37:20):
pill
Emily Kate Stephens (37:20):
drug once a day, and that allowing your
body, it is reliant on humans,
Elisabetta Burchi (37:26):
so yes, adherence compliance. We
actually have a very highcompliance in our studies, it
reported the very, very highcompliance. So I think the
relative difficulty in using itis compensated, but this is my
psychiatric side, by the factthat people are engaged in the
(37:47):
treatment, which you know, Ithink it's important for care,
for care in general, inengagement of the
Emily Kate Stephens (37:54):
kind of willingness
Elisabetta Burchi (37:55):
of the person, you know, so I think
these two aspects are complicit,and then explain the compliance.
Compliance is also explained bythe fact that the treatment,
that despite everything, ispretty easy to use. It, we do
have clear instructions, we havecrafted them, but it's actually
very easy. The stimulationparameters are already set
there. The patients, each andevery session, just have to
(38:20):
place the electrode, theearpiece at the trabus, and
regarding the precision of that,it's not like since we mentioned
other Chinese approaches, no,the other one is the cervical
one, I can delve into why,according to us, the auricular
approach is superior to thecervical one, but for sure, on
(38:41):
the precision side, that'spretty clear, because the tragus
is spread smaller, despiteanatomical differences between
people, but tragus is thetragus, the cervical area is
wider, so we had not seen a lotof variability, heterogeneity
based on the different wayspeople plug the ear pieces on
(39:03):
the tragic,
Emily Kate Stephens (39:05):
great,
Elisabetta Burchi (39:05):
yeah, and so, yes, the only thing that
patients have to do, plug theear pieces and set up the
current intensity. We have aclear guidance on that. You need
to find the sensitivitythreshold, because we have seen
that around that threshold,which can change at each and
every session, because of theenvironmental conditions, the
(39:28):
humidity in the air, yourbaseline parasympathetic
activation, multiple factors ledus to decide that at each and
every session patients shouldset up the current intensity,
and the guidance given is tolook for a present sensation of
the stimulus, which doesn't haveso
Emily Kate Stephens (39:48):
That was going to be my question. Is it
painful? What is that? What isthe sensation of it? Because I'm
someone who's used a 10s machineon pain, is it that similar
electrical pulsing?
Elisabetta Burchi (39:59):
It's an electrical tingling session that
you should look for, so itdoesn't have to be painful,
otherwise you trigger thesympathetic nervous system,
right, which we don't want. So Iwould say it's in between the
sensitivity threshold, the painthreshold, much below the pain
threshold. Now you want to feelit, but it has to be pleasant,
and it's like the tinglingsensation, but yes, it's pretty
(40:22):
simple to use it, pretty simple,but in the patient is to be
engaged. Yes, and I think it's aplus.
Emily Kate Stephens (40:28):
In different studies, there have
been different methods used,sometimes using it 10 times a
day for a shorter period,sometimes just using it twice a
day, for I think it's for 30minutes. Is there a different
application that you havedeveloped for different
conditions, or is there just asun size fits, or or this is
(40:50):
targeting your Vegas? So dothis.
Elisabetta Burchi (40:53):
Another very good question. I have to praise
you for the level of thequestions you, I can tell you're
very much prepared in thisplace, even here it's a little
bit in between plug and play, tobe honest. We are furthering the
research to optimize protocolsfor the different clinical
applications. In a way, thetechnology is the same, and we
(41:20):
know we aim to stimulate thevagus nerve, and that's it, but
depending on which kind ofpathways we want to leverage, we
have to optimize and change theprotocol of stimulation. So,
yeah, we have done studies inwhich we have very intense
treatments, short in timecumulatively intense, but in a
(41:41):
short period of time, I canthink about studies done in
acute settings. Now, in thehospital, for instance, it's
also related to the feasibility,but it's also related to the
clinical conditions. If we wantto achieve a change in HIV,
let's suppose now we can achievethis in as short as five minutes
(42:02):
of stimulation. We seen that ifwe want to achieve
anti-inflammatory effect, wemight probably need a longer
period of stimulation. So now,do you measure
Emily Kate Stephens (42:11):
the anti-inflammatory effect?
Because I know that in the 2021study, which was very early on,
it was inconclusive in terms ofits anti-inflammatory effect,
but it said it is definitelysomething that we need to
research, and we need to lookinto, and it definitely has a
positive effect. We just can'tsay that it's necessarily
working on theanti-inflammatory. How do you
measure that anti-inflammatoryeffect? Because it's not as easy
(42:32):
as a wearable,
Elisabetta Burchi (42:34):
exactly. So, you need to have a blood draw as
a minimum. So, you're
Emily Kate Stephens (42:39):
talking about CRP,
Elisabetta Burchi (42:40):
right, or many other cytokines, the NFL,
fatality one six. These havebeen measured in other trials in
the cardiovascular space, wherewe had much longer period of
stimulation, three six months,and we actually measured
significant improvements, soreduction of these
anti-inflammatory systemiccytokines in the blood.
Emily Kate Stephens (42:59):
In relation to that, this study was not
actually necessarily relating tothe that our patients will
necessarily have, but you did doa study into it, was 2024 into
cardiovasal baroreflex, whichwas in chronic heart failure
patients, and something reallyinteresting I noticed from that
(43:21):
is that most of these techniquesare reliant on using the left
tragus. Am I right in sayingthis revealed that the left
tragus was ineffective in this,but the right tragus was
effective in helping in chronicheart failure. Talk to me about
that, that difference there, the
Elisabetta Burchi (43:40):
laterality, so it's true that the majority
of our studies have been done onthe left side, but the majority
of our cardiac studies are doneon the right side. The reason is
a little bit historical and alittle bit functional, and there
are some differences, anatomicaldifferences between the left and
right side, but we are stillfurthering the results there,
(44:03):
because that study gave goodresults, other studies give
slightly different results,saying that both sides were
equivalent types of effects,
Emily Kate Stephens (44:13):
so the left, for the majority of your
studies, and for the majority ofthe recommendation to the
patients, seems effective, butit's not necessarily that the
right is always ineffective,
Elisabetta Burchi (44:23):
no, no, no, no. Actually, both sides should
be pretty effective, and then,of course, there is some
variation, inter-individualvariation, heterogeneity, but
anatomically speaking, bothsides should be equivalent in
terms of the effects we aretalking about. Yes.
Emily Kate Stephens (44:39):
Okay. Sorry, I think I interrupted you
there, but I wanted to knowabout that bilateral effect of
it.
Elisabetta Burchi (44:46):
Yeah, but yes, in any case, it's really
lateral. So, in each level,start, we had never stimulated
both sides at the same time,just one side. We had talked
about the effectiveness of ourapproaches, for instance, in
improving resilience tostressful events, the stress
response, etc. There is anotherway. Just came into my mind, we
(45:07):
didn't talk about, yes, it's notrelated to chronic conditions,
but I think it can beinteresting in any case to
everyone. No, because we arewho's not interested in the
cognitive enhancement side, no,maintaining our cognitive
reserve and cognitivecapabilities. No, talking about
as a psychiatrist. Yes, I'mbiased, but I think the core of
(45:28):
our identity lies here. No, in acertain way. So, there is not
much to protect our cognitivereserve. If we think about in
general, in our performanceenhancement techniques, there is
not much, and so I'mparticularly excited about some
of our pilot results in healthypeople at the population using
(45:51):
the our device while performingcertain activities, such as
reading a text or doing acognitive task, so we have seen
that we could improve theperformance, such as the reading
comprehension or memoryprevention. So, another
interesting use case is exactlythat we mentioned a little bit,
(46:15):
not how we use the device somany times a day, for how long.
Looking at the studies, we havea different, very wide range of
possibilities there. One ofthese use cases is using the
device while performing sometasks where you want to boost
learning. That's, I think, it'sa very exciting use case, and
(46:37):
next to the many other usecases, such as improving sleep
quality and quantity sessionbefore going to bed. The various
nerve is involved in switchingfrom awake stays to sleep
states, so now we boost depthswitch. So that's another one
talking about healthy, healthypeople, no, or or not, not only
(46:57):
healthy, but in general, we candefinitely apply to healthy as
well, another use case is to useit after stressful situation to
help store rebalance, or forinstance, before stressful
situation, thinking aboutperformance anxiety, and there
are people that suffer out ofit, me included, so before
performing physically ormentally, you know, a
(47:19):
performance can affect both whenwe talk about performance, we
can think about athletes, but wecan think about, you know,
speakers, we can think aboutother kind of mental
performances before such anactivity to rebalance there for
people that have a high stressreactivity. There is this
(47:40):
personalization piece, ofcourse, that we always need to
take into account
Emily Kate Stephens (47:44):
from those various different applications
that you've mentioned. Is therethe suggestion, therefore, that
this would have application inafter-the-fact anxiety? Would it
also have application inpreventing cognitive decline?
You've done studies into thingslike Parkinson's and that
physical thing, but what aboutAlzheimer's, and going into,
(48:07):
does it have the idea ofapplication for those kinds of
things in the future?
Elisabetta Burchi (48:12):
There is the hypothesis there. We have not
published yet anything inneurodegenerative disorders, but
as you mentioned, we havestudies ongoing Parkinson
disease, and we have somethinggoing on in my cognitive
impairment, so there is the isthe mechanistic rationale, so
there is the hypothesis that ourtechnology could, in a way, have
(48:35):
an effect on preventingimpairment through the
neuroplastic effects to theanti-inflammatory effect, so
that's a super interestingfield, and thinking about unmet
clinical needs, there is reallyhuge, right? So we are working
on that. I
Emily Kate Stephens (48:55):
think what is hugely exciting for me,
hopefully for our audience isthe way in which this sort of
technology has such a wideranging potential application
that indicates that really startto draw together how we need to
stop treating so many of theseconditions as being completely
(49:17):
disparate and being completelyseparate, because actually it's
bringing them all back in topotentially being activated or
able to be helped by one pointof the body, which is the vagal
nerve, and that idea that if wereally, really considered this
to be an integral part of ourbody rather than just something
(49:37):
that we didn't even know about,that we have the potential to
add some power over our bodies.
Elisabetta Burchi (49:44):
That's exactly right. That's exactly
right. I'm particularly excitedabout this technology, because
it's a paradigmatic change. Now,beside the technological part in
itself, it's really atheoretical paradigm shift,
because in the way we understandillnesses and in the way we
(50:04):
understand treatment, so yes,and it all made sense if we
think about the functionalphysiological role of the
economic nervous system, whichis so trans systemic, but even
if we think about, we mentionedthat VNS was initially approved
in depression, right, depressionis not just a mental disorder.
(50:26):
The mental features are madelike features of the disease,
but it's a systemic condition.In a relevant group of patients
with major depression, we findinflammatory biomarkers,
systemic biomarkers. So it isconsidered a systemic condition,
similarly so-called somaticconditions. They have mental
(50:48):
features. Now you mentionedabout the body and mind divide,
which now we go back toDescartes or Cartesio in
Italian, which now we havealways had this hard problem in
science, where do the mind andthe body connect, for sure. In
order to have the mind, you needan organic substrate, but it is
(51:10):
necessary. So, we are talkingabout the same matter. Then, of
course, there are emergentproperties, like the mind, the
consciousness. They can beunderstood as emergent
properties, but we are stilltalking about the same soma, the
same body, so doesn't make anysense to think about health and
(51:32):
diseases in scotomized fashion.This way of understanding the
vagus nerve, its function in thephenomenal system as a whole and
as a central player in themaintenance of metastasis allow
us to really to redefinetreatments, and I think it's
really exciting, and we want togo deeper into this, even
(51:54):
putting more effort in acquiringmore data, strengthening all the
data we already have gathered,we didn't mention all our
cardiovascular studies, just to,just to mention one, which can
be interesting to many people,is one study we have done in
hypertension in young peoplewith the essential hypertension
(52:16):
first grade, is at the verybeginning of the disease, we
have shown reduction in bothsystolic and diastolic pressure,
and this also now taps into allthe cardiovascular conditions,
which are the main causenowadays of death worldwide.
Emily Kate Stephens (52:34):
But there's also ties into the people who
have ended up withinfection-associated chronic
conditions end up withhypertension, so the way that
these all tie together,
Elisabetta Burchi (52:46):
It's mind blowing.
Emily Kate Stephens (52:48):
It is.
Elisabetta Burchi (52:49):
it is complex. It is complex, and we
are trying to pass it out, butmost of all, we are interested
in the clinical impact, and weare seeing clinical impact. We
are trying to elucidate why wedo have a clinical impact, or we
do have a clinical impact. So itis exciting, and I'm happy that
(53:10):
now you also contribute to thisadventure, spreading the word
and educating people anddistillating the knowledge
behind this complex studies andresearch. I think it's very,
very important. I'm glad youinvited me to your podcast.
Emily Kate Stephens (53:26):
Well, it has been such a pleasure talking
to you.
Gez, what did the conversationwith Elisabetta reveal to you
that perhaps was not somethingthat you already knew about the
nervous system or vagal nerve stimulation.
Gez Medinger (53:47):
Well, I didn't know that they worked so hard on
looking at how it could helpother conditions, and it makes
perfect sense, right, that itcould help other conditions,
because the autonomic nervoussystem is tied into so much of
your bodily functions, whetherimmune or metabolic or
cardiological.
Emily Kate Stephens (54:07):
Yeah,
Gez Medinger (54:07):
so, so it stands to reason that you should test
it against some of these otherconditions to see if actually
you can help the symptoms ofthem or help those resolved,
depending on what they are. Mycontact with this line of
science has only ever been fromthe perspective of complex
chronic illness, so I haven'thad that wider perspective on
it, but it makes perfect senseto me.
Emily Kate Stephens (54:28):
It does correlate with the research
that's done into thesubcutaneous vagal nerve
stimulation, which is licensedin depression and epilepsy, so I
feel that this space issomething that is ripe for us to
be only learning more, more,because, as I mentioned in that
(54:48):
the hypertension that people arehaving from these complex
chronic illnesses, there is thisbig crossover, isn't there, in
so many of these conditions, andit's interesting to consider
what the driver is of some ofthe symptoms, and if something
like this nervous systemregulation in various forms can
(55:09):
alleviate some of thosesymptoms, then I think we're
making strides forward. Onething that I would say on this
is that it is effectivelyexpensive.
Gez Medinger (55:18):
These devices are expensive, yeah, and there's,
and there's, there's a largerquestion here about what's the
difference in efficacy betweenone of these expensive devices,
like an alpha stem or like aNurosym, and a simple vagal 10s
device that you can maybe pickup for 10s of pounds or 10s of
dollars on eBay, as opposed to hundreds.
Emily Kate Stephens (55:37):
Yeah,
Gez Medinger (55:37):
and we don't know what the difference is in terms
of efficacy, ultimatelystimulating the vagus nerve is
stimulating the vagus nerve, anddo you have to play a certain
tune on it to have the effectfont, or will any tune do? So
that's a big question. We don'thave the answer to that.
Emily Kate Stephens (55:50):
However, I do love when I see that a device
or a methodology genuinely doeshave the research behind it, and
I really did go into thatinterview, I prepared so hard
for that to go in and try andrefute their claims. I genuinely
did. I went through all of theirstudies, and I was pleasantly
(56:11):
surprised to see they really dohave the results that they say,
which is something that somebodyelse just do not have behind
them. However, that doesn'tnecessarily mean that they don't
work. It also means that theydon't have the huge marketing
and power behind them to go outand get that kind of attention
(56:31):
within the research market.
Gez Medinger (56:32):
Exactly, I think one of the most interesting
things that came out theresearch was the potential
anti-inflammatory effects. Nowthat wasn't something I was
aware that this could do before,but again it makes sense. I
think part of the challenge whenit comes to using these devices
is around habit forming. So, howdo you make sure that you use it
for x amount of time a day,every day, when the effects are
(56:53):
sometimes very subtle and alsocumulative?
Emily Kate Stephens (56:55):
Yeah, it's that cumulative thing that is
incredibly interesting.
Gez Medinger (56:58):
The other thing about the cumulative thing is it
makes it harder to measure in aresearch setting because there's
so many other factors that canfeed into any cognitive or
fatigue improvements
Emily Kate Stephens (57:09):
- or worsening -
Gez Medinger (57:10):
or worsening over that period, so it's very hard
to control for everything elsein a condition, any of these
complex chronic conditions, butcertainly I think the thing that
I'm with the most is that I feellike my alpha stem does help,
but am I disciplined enoughabout using it? Probably not. I
probably ought to use it more,but when I don't immediately see
the benefits of it, it'ssomething that you have to be
(57:31):
encouraged to do, or to try andpersuade yourself to do it, or
put it into your life in a waywhere you always do it at x time
for x long. Otherwise, it justdoesn't happen.
Emily Kate Stephens (57:39):
But Gez, you have built into your life
taking 72 different supplementsor going downstairs and stepping
outside on your grass firstthing in the morning, so it is
one of those things thattheoretically we simply need to
build that discipline into ourlives. I think one of the things
(57:59):
for me, I actually really enjoywearing it, and I do think I
feel some benefits, but, likeyou, I am erratic in it, because
there are certain, for example,breath work practices, or
there's certain yoga practicesthat I do that I will have an
immediate shift in my nervoussystem, a marked immediate shift
(58:22):
following that practice, and Idon't get that with the
neurosim, so I guess we're allslightly seeking that
confirmation as soon as possible.
Gez Medinger (58:32):
And that's the hard thing with just about any
intervention you can ever trywith complex chronic illness.
You want to have something thattells you this works, this
helps, and so much of the timeit's very difficult to put your
finger on it, and it sends youcrazy trying to look for signs
of whether something helps ornot. That's actually one of the
reasons. Regarding, youmentioned supplements are pretty
big, all of mine. I don't takeany now, because I just came to
(58:55):
a conclusion I had all of them,and were they actually doing
anything? Got rid of them all,and I don't think it's made any
difference. It's so, it's sohard, we do. We do so much, we
try so many things just based onhope. I guess the positive thing
about a solution or anintervention like this is there
is technical evidence to showthat it does have an impact,
even if that impact is slight. Ithink any of us will take a
(59:15):
percentage improvement in oursymptoms. The question is just
whether that percentage is worthx high pounds or not at the end
of the day.
Emily Kate Stephens (59:21):
Yeah, and I think, particularly when that is
helping with the fatigue,helping with the cognitive
problems, and potentiallyhelping with what you and I have
described in slightly differentways, but this really, really
overwhelms nervous system. Ourconversation makes me want to do
better with it, and actually tryto be more strict about it, and
(59:44):
monitor the progress I make, orlack of progress.
Gez Medinger (59:47):
Yeah, same with me.
Emily Kate Stephens (59:48):
Okay, so what we've done today is we're
just now gonna hold each otheraccountable for trying to build
that into our routine, let's sayover the next two weeks, yeah,
and see if it, if it makes anydifference for us.
Gez Medinger (01:00:01):
Yeah, I'm up for that. Yeah, fair. To be fair,
straight after listening to thatinterview, I went and got on my
Alpha stim for 45 minutes, so itencouraged me to do that.
Emily Kate Stephens (01:00:09):
Amazing, brilliant. Thank you so much for
joining me, Gez. Pleasure,
Gez Medinger (01:00:13):
As always. Bye.
Emily Kate Stephens (01:00:23):
Thank you for listening to Make Visible.
(01:00:44):
Please do like, follow, orsubscribe to listen to our next
(01:01:13):
episode, where we'll beuncovering more insights into
(01:01:40):
complex chronic illness. Thiswas brought to you by the team
(01:02:11):
at Visible, a group ofscientists and engineers whose
(01:02:38):
lives have been affected byenergy limiting health
(01:03:04):
conditions. We're buildingwearable technology that's
(01:03:31):
helping 100,000 people measureand manage their complex chronic
(01:04:03):
illness. To find out about whatwe're working on and how Visible
(01:04:35):
could help you, visit ourwebsite at makevisible.com
I'm particularly excited about this
technology, because it's aparadigmatic change. It's really
a theoretical paradigm shift.One is trying to fill the gap
and provide a treatment approachand technology, because it is a
(00:22):
technology that can give optionsto patients to people that have
unmet clinical needs forsyndromes and conditions that
are complex and that arecurrently missing treatments
that are inter systemic.
Emily Kate Stephens (00:38):
Welcome to Make visible the podcast shining
a light on complex chronicillness. I am your host, Emily
Kate Stephens.
Welcome to another episode.Hello, Gez. How are you?
Gez Medinger (00:57):
I'm suffering a little bit, but I've been mostly
functional today. I think I madetoo much of the slight
functionality I had, and now I'mhanging on a little bit. I get
to that point, like in the olddays, people's look, I say, all
the old days, everybody else whodoesn't have complex chronic
illness probably does thisalready. They look forward to
Friday, right? For me, I stillhave in my, in my head the idea
that I have to be productive,but once it gets to 5o'clock or
(01:18):
so, I let myself off the hook,so I'm looking forward to that
sort of 5o'clock moments ofactually releasing myself from
the psychological pressure offeeling like I need to be doing
useful things.
Emily Kate Stephens (01:29):
I do want to talk to you about how you got
to this place on a Friday. Werecord on a Friday, and today we
are doing an episode that isabout a specific technique for
nervous system regulation, and Iwanted to talk to you about that
in terms of your activity,because you left me a message
(01:53):
earlier in the week. You had areally busy few days, and I'd
just love for you, because I'msure it's very similar to a lot
of us share what happens to yourbody when you have that kind of
intense period of activity thatyou had this week.
Gez Medinger (02:09):
So, Tuesday I had a shoot out in South Wales,
which is a long way away. So,Monday I've got to get out
there. Tuesday's full on, it'svery exciting, it's wonderful,
it makes me feel alive. So,that's why I do it, and that's
why I subject my body toarguably the risk of doing so,
but it certainly over stimulatesthe nervous system. So, what do
(02:30):
I notice in my body? Well, Inotice that I can't fall asleep
that night because my body justcan't shut off. My heart rate's
still going mad, my brain'sstill going mad.
Emily Kate Stephens (02:37):
There's something about the adrenaline,
isn't there, that -
Gez Medinger (02:40):
Yeah, it doesn't switch off. My night sleep is
then very shallow as well. Iwake up a lot. I was awake for
three hours during the night,and the sleep I do have is very
shallow. I never managed to getinto deep sleep, the deep
restorative sleep. And then thenext day I'm also, I'm exhausted
by a function of having had abusy day and the lack of sleep,
but I'm also still quite wired,and that wiredness just about
(03:01):
compensates for the exhaustionto get me home, which is what to
do the next day, and then whathappens after that, that's when
I crash. Hey, crash. So, thereis this, this weird thing of
this retained nervous systemgoing haywire, whether that's
doing things with cortisol andadrenaline, potentially. I don't
know, I wasn't doing blood drawson myself to find out, but
that's what it feels like, asensory perspective. And then
(03:23):
there's the delayed crash afterthat, where the body does slow
down, and then goes, "Oh, you'vereally done it now."
Emily Kate Stephens (03:28):
Yeah, it's almost like your body set goes
into some kind of overdrive thatthinks, "Oh, I've been operating
at this level, I need to keepgoing, I need to do this big
push." And when you were talkingto me about it, I actually
realized that I think I had thathistorically, before I had Long
Covid, when I did shoots, that Iwould sometimes work for 36
hours without sleeping, or Iwould do these shoots, say six
(03:51):
days straight, and I'd maybe besleeping three hours each night,
and then you're busy for thewhole of the rest of the time,
and after that I would have, oreven after my wedding, I would
have three or four nights whereI absolutely could not shut
down, just push your nervoussystem to such a level of
activation it's very hard toretract from, and I was just
(04:14):
thinking about this with theLong Covid. Do you feel like I
used to feel like it was abuzzing, like my whole body was
buzzing for several days when Iwas in that activated state.
Gez Medinger (04:25):
That's quite common with people Long Covid. I
don't personally feel like that,but that's something I've been
told so many times from otherlong haulers about how they
experience it.
Emily Kate Stephens (04:33):
Yeah, so I thought that was a useful way
for us to enter today'sinterview and discussion, which
is with a psychiatrist calledElisabetta Burchi, who works
with Parasym, and they are thecompany behind the
neuromodulation device, Nurosym,what is called a transcutaneous
(04:54):
auricular vagus nervestimulation device, and what
they are trying to do with thistechnology is is a small device
that you clip on your ear and itsends electrical pulses through
your tragus. And just tomention, for those of you not
familiar, your tragus is thissmall piece of cartilage that
protrudes at the front of yourear. This interview does contain
(05:17):
some scientific language fromthings like homeostasis, which
is the body's ability tomaintain a stable internal
environment, to locus coeruleus,which is a small region in the
brainstem that producesnoradrenaline, and it plays a
key role in attention andalertness, but rather than
(05:40):
breaking the flow of theconversation, I have included a
glossary of some of the morescientific terms in the show
notes. So, do have that openalongside the episode? And
please let me know if that ishelpful to you when we delve
into these science episodes, andin that vein, please keep
(06:03):
feeding back, engaging, andsharing your stories. They are
so helpful as we try to shapethis podcast to be of greatest
help to you. Have you hadexperience with such devices or
such electrical stimulationneuromodulation?
Gez Medinger (06:24):
I have. Yeah, so I have an alpha stim device, which
is, I guess, a competitor atsome level for the neurosim one,
and I find it's quite helpful.So, let's say, for example, that
I'm on my way back from havingdone a shoe, or from having done
something that's strenuous, I'min the car. The first thing I'll
do is to put it on, and forhowever long I've got to get
home, I need to calm this bodydown, and it does seem to help,
(06:47):
but yes, the answer is I do haveexperience of using them, and I
do continue to do so.
Emily Kate Stephens (06:52):
Okay, so let us listen to Elisabetta
Burchi talking about the devicethat they have developed for
neurosim the way in which itstimulates the vagus nerve to
calm the nervous system, and wetalk about some of the studies
(07:12):
that they have done to look atthe efficacy of the device that
they've created.
So tell me, how you have endedup working in this bioelectronic
(07:32):
space, coming from thepsychiatry space, because we're
going to talk today, and ouraudience is quite focused on
complex chronic illness, but youhave a history of interest in
more - I don't want to call thempsychological - you have a very
wide-ranging history in terms ofyour interest. You've done
(07:54):
studies into alcohol usedisorder, you've looked at OCD,
so you kind of look across theboard at these conditions, and
then parasim has gone down rootsof very, very medicalized things
like heart failure, chronicheart heart failure. What I
really, really love about whatyou've done is it's so broad,
(08:16):
you're approaching it from apsychiatrist perspective, but
you kind of marrying this veryphysical. Talk to me about that
rooting.
Elisabetta Burchi (08:25):
I like that you like that. Maybe the main
reason, which taps into myorigins, is that I'm Florentine,
so you know, Renaissance style,multifaceted. I've always had an
understanding of reality andthings, which is three fully 360
degrees, or the largestpossible. I will always have
(08:48):
this aspiration to embrace moreand more. So, I've always tried
to acquire multiplemethodologies, paradigms to look
at things. And of course, as adoctor, I decided to become a
doctor because I wanted to helppeople in the first place, but
at the same time I was enticedby the object of study, not the
(09:13):
human being, and specificallythe human mind and brain, and
I'm deciding to become apsychiatrist, which is one of
those were already related tothe neuromodulation field. Why,
why neuromodulation? So,neuromodulation techniques in
general can be consideredtreatment approaches that
(09:34):
directly targets neuralcircuits, and if we think about
the brain, the brain mindobject, maybe the most
privileged level of analysis isthe circuit level, which is in
between, you know, the cellular,molecular, genetic level, and
the behavioral, phenomenologicallevel of the other side.
Emily Kate Stephens (09:57):
Is that really looking at it as an
electrical? When you saycircuits, are you looking at it
as an electrical system?
Elisabetta Burchi (10:06):
Yes, because we know that neurons used in a
certain way, electrical ways ofinteracting between them. There
are also neurotransmittersinvolved, so there is also a
chemical level, but I guess,yes, when we talk about the
circuit level, we talk about theelectrical functioning of these
systems, which is the way inwhich that's a very interesting
(10:29):
question, yours, but yes, if youthink about, if you think about
the way we measure functioning,narrow circuits, we use multiple
techniques, like techniqueswhich uses different ways of
measuring activities in thecircuits, so it's very complex,
but if we have to name one, Iwould say electrical functioning
(10:51):
is is one of the main featuresor way of looking at them. So,
so, yes, I thought that theneural circuits was one of the
privileged access way to theunderstanding of mental states,
and then also mental healthdisorders, not only to
understand them, an access wayto understand, but also to
(11:13):
affect their functioning andtreat these conditions. So
that's why I got interested inthe space, and once I completed
my fellowships, so I did someresearch in the neuroscience
space, coming back to my broaderaspiration of embracing a little
bit everything. I decided to goto get an MBA, a master in
(11:36):
business administration, sototally unrelated to medicine,
Emily Kate Stephens (11:38):
that is the thing, isn't it? The vagus nerve
because I wanted to magnify theimpact of my practice, the more
is essentially the connectionbetween what we perceive to be
systemic level to affect thewell-being, I guess, of more
people, so compared to theindividual level, which I
the physiological and thepsychological, essentially the
usually operate with mypatients, so I completed my MBA
concept of mind body, butactually we are just one, we are
and got some innovation skills,which then I wanted to
(11:59):
just one body, we are all one.
consolidate in the concreteworld, so I turned myself to the
biotech med tech space, and Iwas looking for interesting
companies that connected to theneuroscience space, and then I
Elisabetta Burchi (12:10):
Absolutely.
reduced have published so far with our
discovered Parasym which was atthe beginning, I think I joined
the company where we were onlythree, so I started working with
them. I was excited about whatthey were doing, not only
because they were dealing withneuromodulation, a specific
(12:32):
neuromodulation technique, whichis on invasive vagus nerve
stimulation, but I will say alsotalking about the vagus nerve,
which is the longest cranialnerve in humans, and carries the
majority of the fibers of theparasympathetic nervous system.
Intrinsically, this nerve, whichwith this technique we modulate,
(12:56):
is involved in manyphysiological processes across
Emily Kate Stephens (12:57):
and an implanted vagal nerve
stimulation. So I would love youto talk to me about
the body, and so having thepossibility to modulate its
function allow us to reallyovercome the usual boundaries in
transcutaneous auricular vagusnerve stimulation, which is what
medicine. So my aspiration toembrace was found a little bit
parasim does. There are alsoother transcutaneous methods,
(13:17):
but talk to me about the methodthat you
about what parasin was doingmultiple levels, so with the
technique which could actuallyredesign the understanding of
technique more than 50 clinicalstudies, and we have a similar
diseases and disorders, not justdiseases of a specific
physiological system, but asdiseases, illnesses of
number of ongoing clinicalstudies with more than 100
multi-systemic disease, which isthe in truth what I believe
(13:39):
about many chronic conditions,or also mental health
research collaborationsworldwide, so we are really
conditions,
(16:07):
heavy on science, and we'vealways put research at the core
of our what we do.
Do you have a lot of heavy claims on your
website about how all of whatyou do is backed up by
scientific studies, and Ithought, okay, well, I'm gonna
dig into this, and yes, Parasym,it..
Elisabetta Burchi (16:27):
was real, yeah, absolutely,
Emily Kate Stephens (16:31):
and it's not just that it's been you
testing it for Parasym. Parasymas been used to test this
technique across multipleconditions, and we can go into
some of that in more detail, butI just wanted to mention at this
juncture that they are actually
Elisabetta Burchi (16:48):
verified.
Emily Kate Stephens (16:50):
Yeah,
Elisabetta Burchi (16:50):
Absolutely. Since the inception of the
company, I was not there, but Ijoined the 2021 I believe, at
the beginning. They've always,you know, the founders, they've
really cared about
Emily Kate Stephens (17:02):
Scientific rigour?
Elisabetta Burchi (17:04):
Yeah, scientific rigour, exactly. So
we developed the system, whichis capable of modulating the
vagus nerve through the traverseof the ear, so through the
surface of the of the skin hereat the level of the tragus,
where underneath lies thisauricular branch of the vagus
(17:25):
nerve, which is an afferentbranch. What does it mean,
afferent, which bringsinformation up to the brain,
specifically the brain stem,where you find the nucleus of
tract solitaris, which is closeof the of the brainstem, and we
have developed signal deliverysystem, which is capable of
(17:45):
delivering electricalstimulation, so it speaks the
same language of the of theneurons as we mentioned before,
and is capable of doing it in anon-invasive fashion, in a
safely manner. When I say safelybacked up by science versus a C
marked medical device deemed notdeemed no significant risk by
(18:07):
the FDA multiple clinicaltrials, and effectively simply
and effectively we have datashowing that we actually
modulate the vagus nerve. Thereare multiple ways of
corroborating this claim. One ofthe main biomarkers is this, I
would say, now renowned markets,HRV, heart rate variability,
(18:27):
which is measured by manywearables, and all that we all
have, and we use for trackingour well-being overall. That's
one of the main markers, gaugingthe parasympathetic tone, and as
we mentioned, the vagus nerve isthe main component of the
parasympathetic nervous system,which is a branch of the
(18:49):
autonomic nervous system. Ithink, although let's reframe
everything, which has a centralrole in dynamically controlling
the homeostasis of the bodythrough action on multiple
systems, from the cardiovascularsystem to the respiratory
system, to the gastrointestinalmotility, metabolic balance,
(19:11):
regulation, etc. So the vagusnerve is the main component of
this autonomic nervous system,and so basically, our device,
which is wearable, can be usedat home, very easy to use, has
been designed for at home use.Indeed, people can buy it
(19:32):
without prescription. This isbased on the safety, I would
say, mainly, and I think thedevice we have designed this
very, very intuitive to be used.Yes, so that's that's how it
works. It works initially, sothe stimulation of the duocular
branch of the vagus nerve, thenthe signal, yes, the brainstem.
(19:56):
And and then there are a series,a cascade of physiological
effects across these othersystems we mentioned, the
cardiovascular, the immunesystem. If we want to
categorize, maybe the effects, Ilike to see three many areas.
One is the modulation of theautonomic tone, so this balance
(20:18):
between the sympathetic and theparasympathetic tone. Another
category of effects is theanti-inflammatory action, which
is implemented through specificpathways, multiple pathways. One
of those is the cholinergicanti-inflammatory pathway to the
spin, and the third category ofeffects is the neuroplastic one,
(20:40):
which is more involved in allthe applications regarding
psychiatry, neurology, etc. Sothese are the three main areas,
and we have gathered data in allof this, and if you think about
these effects, you can imaginealready the plethora of the of
the potential applications ofthis technology.
Emily Kate Stephens (21:00):
So when Parasym was first developed,
because you are talking aboutsomething that is used for
multiple applications, and youcurrently have research ongoing,
I believe a lot into this sortof neuro, but you've also been
using it, looking at atrialfibrillation, and so it very
(21:20):
much a physiological in terms ofthe heart. When Parasym was
first developed, what was theidea behind it? What was the
primary focus in terms ofdeveloping something of that
neuromodulation? Was it forcomplex chronic conditions, such
as we deal with at Visible, orwas it for a much wider purpose?
Elisabetta Burchi (21:42):
It's a very good question. I don't know if
initially the no.. the visionwas clear, already defined, for
sure. Currently, the vision isto.. it's a broad one, it's a
broad one, and it taps onto twodifferent. I will say broad
scopes. One is for sure tryingto fill the gap and provide a
(22:07):
technology treatment approach,and technology, because it is a
technology that can give optionsto patients to people that have
unmet clinical needs forsyndromes and conditions that
are complex and that arecurrently missing treatments
that are inter systemic, so thisis one of the scopes. The other
(22:30):
one, and maybe we can see how wecan pursue both goals, is to
improve and boost the well-beingof the majority of the people
out there, even without the needof specific diagnosis, and we
can actually pursue both ofthese goals because of the
functional characteristics ofthe value snack, because if we
(22:52):
think about this capability tomodulate all these internal
processes with the goal ofmaintaining homeostasis, namely
the stability of the internalenvironment while adapting to
external challenges, we canthink how this is relevant in
disorders, but also when thereare no overt clinical
(23:15):
conditions, because we didn'tmention that if we think about
maintaining homeostasis inresponse to challenges, we think
about the stress spots. Maybeit's not up to me to say, but I
believe that in our contemporarysociety, all of us is involved,
engaged, interested in this,because we are constantly under
(23:38):
pressure, we are constantlystressed out because of demands
need to perform in multiple anddifferent ways, so what the
vagus nerve does, and theparasympathetic nervous system
does is working as a break onthe stress response. So even if
we just think about that in ahealthy person, the healthy
(24:02):
potential potentially a littlebit chronically stressed,
because of just the environment.You can imagine that we can
potentiate the vagues nerve, theparasympatheric response could
actually boost well-being. Soit's possible to pursue these
two visions, providing newtreatment approaches that can be
(24:24):
combined, that's another keypoint with many other
approaches. Now, becauseneuromodulation techniques, I'm
sorry, call a VNS can becombined with pharmacotherapy
and can be combined withbehavioral therapies. In a way,
there are differences betweenthese approaches, clearly one of
the main one I will say that,while with some exceptions, but
(24:47):
broadly speaking,pharmacotherapy is less precise,
especially and temporarily. Inour description of the
modulation techniques, we weresaying all the targeted
stimulations, specific neuralcircuits, so it's complementary,
directed, and so complementaryto the other approaches, so we
are providing something that canbe combined with other
(25:07):
approaches, but at the same timeyou're providing approach that
can empower people in theireveryday life with a tool that
can help them boost theirresilience, if you think about
the stress response, and we havedata, and that there is a
theoretical rationale behindwhat I'm saying, but there are
(25:30):
already some pilot findings thatwe have that this is possible.
Emily Kate Stephens (25:35):
If we look at that, we are all, as humans
in the current society, to adegree dysregulated in terms of
our stress response, and look atwhat you've developed here in
terms of neuromodulation. Inyour opinion, are many of the
conditions that you are able tohelp with a result of a
(25:57):
dysregulation of the nervoussystem due to life in general,
rather than very specifically,I'm not saying that some of
these conditions aren't directlycorrelated with a viral hit, or
that there is not a driver, butare we all more prone to these
(26:17):
conditions because of thatsocietal stress dysregulation?
Elisabetta Burchi (26:23):
Very good question. I think you already
give the answer. There aredifferent triggers. If you think
about one of the main chronicconditions that arose in the
last year's long COVID, isdefinitely there a trigger,
viral trigger, but in a certainway the syndrome that arose from
that Long Covid arose from theacute infection, in a way, is
(26:45):
kind of independent of thetrigger, no.
Emily Kate Stephens (26:46):
The point is, why did some people, why
were some people absolutely ableto recover from it? And some
people have a residual impactfrom these things that our body
should theoretically be able toprocess evolutionarily, we
should be able to either processthem and survive, or or not.
(27:08):
research over
Elisabetta Burchi (27:08):
Yes, yes, we are so complex that then there
is this shade of graze inbetween, even if evolution
doesn't care about us anymore,once we are not really
functional from a reproductiveperspective. No, but then
gladly, gladly, we do not in ourlives, I think, we are not
(27:28):
subjugated to these evolutionaryrules. So now we can survive
such conditions, and etc, etc.But no, yours is a very good
point. I believe that among thevarious factors that can trigger
these conditions is definitelythe environmental pressure,
which makes us more vulnerableto this kind of conditions that
(27:51):
have in the dysautonomic... thedysautonomias, as the common
but is it sort of six six toeight days into it, things
denominator, since you areinterested in this kind of
started to happen, repercussionsof the neuromodulation continued
conditions, Long Covid,fibromyalgia, they present the
same phenotypic features. Thinkabout fatigue and think about
after the treatment ended, sothe trajectory this
cognitive dysfunction, so-calledbrain fog, widespread pain,
neuromodulation put patients ona an upward trajectory in terms
(28:13):
orthostatic intolerance, whichis clearly a dysautonomic
feature, but even the otherones, that I mentioned, and they
present with similar features,and all the post-variant
syndromes, they are just tocorroborate the fact that then
the syndrome is in a wayindependent on the trigger, but
(28:35):
then at least evaluates thehypothesis that the autonomic
nervous system is pivotal in thepathogenesis, in whichever ways
it becomes disrupted, but thenit becomes disrupted. And I
agree with you, probably beingconstantly chronically stressed,
stimulated on the stressresponse, it can be one of the
(28:57):
main reasons why we have suchprevalence of these conditions,
and the fact that the unmetclinical need, I believe is
related to the fact that wedidn't have much approaches to
address specifically andtemporarily, especially the
autonomic nervous system, tillwe develop an approach that
(29:19):
could actually specificallytarget the vagus nerve and
non-invasively, that's animportant feature of that.
(30:39):
of their symptoms. Talk to meabout what were the most marked
improvements in that, becauseyou've already mentioned fatigue
just now. What were the mostmarked improvements, and how
does that neuromodition impactthese patients directly?
Yeah, actually, yes, you are very well
prepared. Yes, these twostudies, there is a third one
(31:00):
down in Mount Sinai in New York,and we have been pioneering the
field of transit recollection ofVNS in Long Covid with these two
tasks, one, three studies, andand we were very excited,
because the first study, as youmentioned, that was done in 2021
pretty early on, and is that tothe researchers and all that
(31:23):
wanted, I was just joining thecompany at the time, so it was
really set up the first study,so in the research community
there was really interested forthis technology, and they
thought about it, even so earlyon, they thought that they could
have been beneficial in thesyndrome, and so they set up the
(31:45):
study. Of course, these are twopile of studies that they
already showed in as it's veryshort period of treatment, 10
days of simulation. I'm notwrong, talking about one hour 35
minutes of simulation day, whichis not much if you think that
you can have the stimulationwhile you are doing other
(32:06):
things, that's part of theaccessibility and low barrier
for patients, for people to usethe device, you know, so it was
really not a demandingtreatment, so in a short as 10
days of simulation in this way,they could have significant
improvement in mainly fatigue,but many other symptoms as well.
(32:27):
And I would, I will say thesecond study, the one did a
later one, the one done at CasaColina in California, which
studied a female cohort, theywere female patients, we know
that Long Covid is more frequentin females. In any case, and
that second study focused oncognitive improvement, and I
(32:49):
think that was, of course, theimprovement in fatigue central,
because it's central core of thesyndrome and affects many other
overall functionality, I willsee, but the cognitive, the
brain fog, too, is the other keysymptom, and we passed out, we,
the researchers, passed out thecognitive impairment into the
(33:11):
multiple cognitive dimensions,and they saw improvement across
all of them, which, in a way,because our studies are mainly
clinical, namely, we generallyare interested in providing
clinical improvement because wewant to improve the well-being
of the patients, but at the sametime we try to elucidate the
(33:33):
pathophysiology underpinningthese improvements, right? So
the idea is that in order to getthese results, leverage those
two pathways I mentioned before,all of these, but mainly I will
focus on the anti-inflammatoryeffect, because know that we
know these are hypotheses,because we are still early on
(33:55):
the research around long COVID,for instance, but we think that
long COVID is definitely alsoassociated to neuroinflammation,
right? Then we think we alsoaverage the neuroplastic
pathway, so if you think aboutthe nucleus of tract storytaris,
which is the nucleus wementioned before the brains, and
(34:17):
it is connected to any area, anyother areas in the brain, so
it's a particle area, which,though, is connected to many
cortical areas, which alsoexplains the effect on multiple
cognitive dimensions, not onlycognitive, there is also the
emotional side, which is morein, because of subcortical, but
(34:38):
specifically thinking about theeffect on brain form. What we
think happens actually isstimulation of the locus
cheruleus, which is anothernucleus in the brainstem now,
which produces no adrenaline,and we know that no adrenaline
is connected to attention, andso improvement of attention
(34:59):
might have boosted improvementin many other cognitive
dimensions that we measureclinically in this study.
Emily Kate Stephens (35:07):
Yeah, and you actually relied on the NIH
cognitive toolbox to do theassessment of the cognitive
improvements.
Elisabetta Burchi (35:14):
Yeah,
Emily Kate Stephens (35:15):
it's quite rigorous for things.
Elisabetta Burchi (35:18):
Yeah, no, absolutely. And I always like to
highlight that all these studiesthat we mentioned also in our
website, all done with ourtechnology, so we do not
translate results obtained withother devices. That's important,
because neuromodulation spacefield is cutting edge. There is
still a lot of confusion. Oftenwe see people mentioning studies
(35:44):
done with other devices, but youcannot really do that, because
each and every device has adifferent signal delivery
system, now differentstimulation parameters. So we
need to be careful when wetranslate results. Everything we
mention, everything we cite isachieved with our own
technology, but at the sametime, the studies are all
(36:05):
independent. We have not fundedthe study, so the researchers
publish whatever they want, andwe do not emanate anything. So
that's another important facet,the transparency and the
independency of the research. SoI heard about saying that we
collaborate on the protocoldesign, we give, of course,
advice they suggest that we knowthe technology, but the
(36:28):
implementation of the trials isfully on the shoulders of the
researchers, so it's fullyindependent, so that's another
relevant process. Talk to
Emily Kate Stephens (36:36):
me about speaking to someone before who
said that one of the mainproblems with transcutaneous,
whether auricular or otherwise,vagal nerve stimulation is the
adherence. It's reliant onpatient fitting it properly,
wearing it for the correctamount of time, and that is
something that will have impacton its efficacy and impact on
(37:01):
some of these studies. How areyou able to ensure the best
results, the best adherence foryour patients? Is it very simple
to use? Is it that you have veryclear instruction for how people
are able to get the bestresults? It's different from
just taking a
Elisabetta Burchi (37:20):
pill
Emily Kate Stephens (37:20):
drug once a day, and that allowing your
body, it is reliant on humans,
Elisabetta Burchi (37:26):
so yes, adherence compliance. We
actually have a very highcompliance in our studies, it
reported the very, very highcompliance. So I think the
relative difficulty in using itis compensated, but this is my
psychiatric side, by the factthat people are engaged in the
(37:47):
treatment, which you know, Ithink it's important for care,
for care in general, inengagement of the
Emily Kate Stephens (37:54):
kind of willingness
Elisabetta Burchi (37:55):
of the person, you know, so I think
these two aspects are complicit,and then explain the compliance.
Compliance is also explained bythe fact that the treatment,
that despite everything, ispretty easy to use. It, we do
have clear instructions, we havecrafted them, but it's actually
very easy. The stimulationparameters are already set
there. The patients, each andevery session, just have to
(38:20):
place the electrode, theearpiece at the trabus, and
regarding the precision of that,it's not like since we mentioned
other Chinese approaches, no,the other one is the cervical
one, I can delve into why,according to us, the auricular
approach is superior to thecervical one, but for sure, on
(38:41):
the precision side, that'spretty clear, because the tragus
is spread smaller, despiteanatomical differences between
people, but tragus is thetragus, the cervical area is
wider, so we had not seen a lotof variability, heterogeneity
based on the different wayspeople plug the ear pieces on
(39:03):
the tragic,
Emily Kate Stephens (39:05):
great,
Elisabetta Burchi (39:05):
yeah, and so, yes, the only thing that
patients have to do, plug theear pieces and set up the
current intensity. We have aclear guidance on that. You need
to find the sensitivitythreshold, because we have seen
that around that threshold,which can change at each and
every session, because of theenvironmental conditions, the
(39:28):
humidity in the air, yourbaseline parasympathetic
activation, multiple factors ledus to decide that at each and
every session patients shouldset up the current intensity,
and the guidance given is tolook for a present sensation of
the stimulus, which doesn't haveso
Emily Kate Stephens (39:48):
That was going to be my question. Is it
painful? What is that? What isthe sensation of it? Because I'm
someone who's used a 10s machineon pain, is it that similar
electrical pulsing?
Elisabetta Burchi (39:59):
It's an electrical tingling session that
you should look for, so itdoesn't have to be painful,
otherwise you trigger thesympathetic nervous system,
right, which we don't want. So Iwould say it's in between the
sensitivity threshold, the painthreshold, much below the pain
threshold. Now you want to feelit, but it has to be pleasant,
and it's like the tinglingsensation, but yes, it's pretty
(40:22):
simple to use it, pretty simple,but in the patient is to be
engaged. Yes, and I think it's aplus.
Emily Kate Stephens (40:28):
In different studies, there have
been different methods used,sometimes using it 10 times a
day for a shorter period,sometimes just using it twice a
day, for I think it's for 30minutes. Is there a different
application that you havedeveloped for different
conditions, or is there just asun size fits, or or this is
(40:50):
targeting your Vegas? So dothis.
Elisabetta Burchi (40:53):
Another very good question. I have to praise
you for the level of thequestions you, I can tell you're
very much prepared in thisplace, even here it's a little
bit in between plug and play, tobe honest. We are furthering the
research to optimize protocolsfor the different clinical
applications. In a way, thetechnology is the same, and we
(41:20):
know we aim to stimulate thevagus nerve, and that's it, but
depending on which kind ofpathways we want to leverage, we
have to optimize and change theprotocol of stimulation. So,
yeah, we have done studies inwhich we have very intense
treatments, short in timecumulatively intense, but in a
(41:41):
short period of time, I canthink about studies done in
acute settings. Now, in thehospital, for instance, it's
also related to the feasibility,but it's also related to the
clinical conditions. If we wantto achieve a change in HIV,
let's suppose now we can achievethis in as short as five minutes
(42:02):
of stimulation. We seen that ifwe want to achieve
anti-inflammatory effect, wemight probably need a longer
period of stimulation. So now,do you measure
Emily Kate Stephens (42:11):
the anti-inflammatory effect?
Because I know that in the 2021study, which was very early on,
it was inconclusive in terms ofits anti-inflammatory effect,
but it said it is definitelysomething that we need to
research, and we need to lookinto, and it definitely has a
positive effect. We just can'tsay that it's necessarily
working on theanti-inflammatory. How do you
measure that anti-inflammatoryeffect? Because it's not as easy
(42:32):
as a wearable,
Elisabetta Burchi (42:34):
exactly. So, you need to have a blood draw as
a minimum. So, you're
Emily Kate Stephens (42:39):
talking about CRP,
Elisabetta Burchi (42:40):
right, or many other cytokines, the NFL,
fatality one six. These havebeen measured in other trials in
the cardiovascular space, wherewe had much longer period of
stimulation, three six months,and we actually measured
significant improvements, soreduction of these
anti-inflammatory systemiccytokines in the blood.
Emily Kate Stephens (42:59):
In relation to that, this study was not
actually necessarily relating tothe that our patients will
necessarily have, but you did doa study into it, was 2024 into
cardiovasal baroreflex, whichwas in chronic heart failure
patients, and something reallyinteresting I noticed from that
(43:21):
is that most of these techniquesare reliant on using the left
tragus. Am I right in sayingthis revealed that the left
tragus was ineffective in this,but the right tragus was
effective in helping in chronicheart failure. Talk to me about
that, that difference there, the
Elisabetta Burchi (43:40):
laterality, so it's true that the majority
of our studies have been done onthe left side, but the majority
of our cardiac studies are doneon the right side. The reason is
a little bit historical and alittle bit functional, and there
are some differences, anatomicaldifferences between the left and
right side, but we are stillfurthering the results there,
(44:03):
because that study gave goodresults, other studies give
slightly different results,saying that both sides were
equivalent types of effects,
Emily Kate Stephens (44:13):
so the left, for the majority of your
studies, and for the majority ofthe recommendation to the
patients, seems effective, butit's not necessarily that the
right is always ineffective,
Elisabetta Burchi (44:23):
no, no, no, no. Actually, both sides should
be pretty effective, and then,of course, there is some
variation, inter-individualvariation, heterogeneity, but
anatomically speaking, bothsides should be equivalent in
terms of the effects we aretalking about. Yes.
Emily Kate Stephens (44:39):
Okay. Sorry, I think I interrupted you
there, but I wanted to knowabout that bilateral effect of
it.
Elisabetta Burchi (44:46):
Yeah, but yes, in any case, it's really
lateral. So, in each level,start, we had never stimulated
both sides at the same time,just one side. We had talked
about the effectiveness of ourapproaches, for instance, in
improving resilience tostressful events, the stress
response, etc. There is anotherway. Just came into my mind, we
(45:07):
didn't talk about, yes, it's notrelated to chronic conditions,
but I think it can beinteresting in any case to
everyone. No, because we arewho's not interested in the
cognitive enhancement side, no,maintaining our cognitive
reserve and cognitivecapabilities. No, talking about
as a psychiatrist. Yes, I'mbiased, but I think the core of
(45:28):
our identity lies here. No, in acertain way. So, there is not
much to protect our cognitivereserve. If we think about in
general, in our performanceenhancement techniques, there is
not much, and so I'mparticularly excited about some
of our pilot results in healthypeople at the population using
(45:51):
the our device while performingcertain activities, such as
reading a text or doing acognitive task, so we have seen
that we could improve theperformance, such as the reading
comprehension or memoryprevention. So, another
interesting use case is exactlythat we mentioned a little bit,
(46:15):
not how we use the device somany times a day, for how long.
Looking at the studies, we havea different, very wide range of
possibilities there. One ofthese use cases is using the
device while performing sometasks where you want to boost
learning. That's, I think, it'sa very exciting use case, and
(46:37):
next to the many other usecases, such as improving sleep
quality and quantity sessionbefore going to bed. The various
nerve is involved in switchingfrom awake stays to sleep
states, so now we boost depthswitch. So that's another one
talking about healthy, healthypeople, no, or or not, not only
(46:57):
healthy, but in general, we candefinitely apply to healthy as
well, another use case is to useit after stressful situation to
help store rebalance, or forinstance, before stressful
situation, thinking aboutperformance anxiety, and there
are people that suffer out ofit, me included, so before
performing physically ormentally, you know, a
(47:19):
performance can affect both whenwe talk about performance, we
can think about athletes, but wecan think about, you know,
speakers, we can think aboutother kind of mental
performances before such anactivity to rebalance there for
people that have a high stressreactivity. There is this
(47:40):
personalization piece, ofcourse, that we always need to
take into account
Emily Kate Stephens (47:44):
from those various different applications
that you've mentioned. Is therethe suggestion, therefore, that
this would have application inafter-the-fact anxiety? Would it
also have application inpreventing cognitive decline?
You've done studies into thingslike Parkinson's and that
physical thing, but what aboutAlzheimer's, and going into,
(48:07):
does it have the idea ofapplication for those kinds of
things in the future?
Elisabetta Burchi (48:12):
There is the hypothesis there. We have not
published yet anything inneurodegenerative disorders, but
as you mentioned, we havestudies ongoing Parkinson
disease, and we have somethinggoing on in my cognitive
impairment, so there is the isthe mechanistic rationale, so
there is the hypothesis that ourtechnology could, in a way, have
(48:35):
an effect on preventingimpairment through the
neuroplastic effects to theanti-inflammatory effect, so
that's a super interestingfield, and thinking about unmet
clinical needs, there is reallyhuge, right? So we are working
on that. I
Emily Kate Stephens (48:55):
think what is hugely exciting for me,
hopefully for our audience isthe way in which this sort of
technology has such a wideranging potential application
that indicates that really startto draw together how we need to
stop treating so many of theseconditions as being completely
(49:17):
disparate and being completelyseparate, because actually it's
bringing them all back in topotentially being activated or
able to be helped by one pointof the body, which is the vagal
nerve, and that idea that if wereally, really considered this
to be an integral part of ourbody rather than just something
(49:37):
that we didn't even know about,that we have the potential to
add some power over our bodies.
Elisabetta Burchi (49:44):
That's exactly right. That's exactly
right. I'm particularly excitedabout this technology, because
it's a paradigmatic change. Now,beside the technological part in
itself, it's really atheoretical paradigm shift,
because in the way we understandillnesses and in the way we
(50:04):
understand treatment, so yes,and it all made sense if we
think about the functionalphysiological role of the
economic nervous system, whichis so trans systemic, but even
if we think about, we mentionedthat VNS was initially approved
in depression, right, depressionis not just a mental disorder.
(50:26):
The mental features are madelike features of the disease,
but it's a systemic condition.In a relevant group of patients
with major depression, we findinflammatory biomarkers,
systemic biomarkers. So it isconsidered a systemic condition,
similarly so-called somaticconditions. They have mental
(50:48):
features. Now you mentionedabout the body and mind divide,
which now we go back toDescartes or Cartesio in
Italian, which now we havealways had this hard problem in
science, where do the mind andthe body connect, for sure. In
order to have the mind, you needan organic substrate, but it is
(51:10):
necessary. So, we are talkingabout the same matter. Then, of
course, there are emergentproperties, like the mind, the
consciousness. They can beunderstood as emergent
properties, but we are stilltalking about the same soma, the
same body, so doesn't make anysense to think about health and
(51:32):
diseases in scotomized fashion.This way of understanding the
vagus nerve, its function in thephenomenal system as a whole and
as a central player in themaintenance of metastasis allow
us to really to redefinetreatments, and I think it's
really exciting, and we want togo deeper into this, even
(51:54):
putting more effort in acquiringmore data, strengthening all the
data we already have gathered,we didn't mention all our
cardiovascular studies, just to,just to mention one, which can
be interesting to many people,is one study we have done in
hypertension in young peoplewith the essential hypertension
(52:16):
first grade, is at the verybeginning of the disease, we
have shown reduction in bothsystolic and diastolic pressure,
and this also now taps into allthe cardiovascular conditions,
which are the main causenowadays of death worldwide.
Emily Kate Stephens (52:34):
But there's also ties into the people who
have ended up withinfection-associated chronic
conditions end up withhypertension, so the way that
these all tie together,
Elisabetta Burchi (52:46):
It's mind blowing.
Emily Kate Stephens (52:48):
It is.
Elisabetta Burchi (52:49):
it is complex. It is complex, and we
are trying to pass it out, butmost of all, we are interested
in the clinical impact, and weare seeing clinical impact. We
are trying to elucidate why wedo have a clinical impact, or we
do have a clinical impact. So itis exciting, and I'm happy that
(53:10):
now you also contribute to thisadventure, spreading the word
and educating people anddistillating the knowledge
behind this complex studies andresearch. I think it's very,
very important. I'm glad youinvited me to your podcast.
Emily Kate Stephens (53:26):
Well, it has been such a pleasure talking
to you.
Gez, what did the conversationwith Elisabetta reveal to you
that perhaps was not somethingthat you already knew about the
nervous system or vagal nerve stimulation.
Gez Medinger (53:47):
Well, I didn't know that they worked so hard on
looking at how it could helpother conditions, and it makes
perfect sense, right, that itcould help other conditions,
because the autonomic nervoussystem is tied into so much of
your bodily functions, whetherimmune or metabolic or
cardiological.
Emily Kate Stephens (54:07):
Yeah,
Gez Medinger (54:07):
so, so it stands to reason that you should test
it against some of these otherconditions to see if actually
you can help the symptoms ofthem or help those resolved,
depending on what they are. Mycontact with this line of
science has only ever been fromthe perspective of complex
chronic illness, so I haven'thad that wider perspective on
it, but it makes perfect senseto me.
Emily Kate Stephens (54:28):
It does correlate with the research
that's done into thesubcutaneous vagal nerve
stimulation, which is licensedin depression and epilepsy, so I
feel that this space issomething that is ripe for us to
be only learning more, more,because, as I mentioned in that
(54:48):
the hypertension that people arehaving from these complex
chronic illnesses, there is thisbig crossover, isn't there, in
so many of these conditions, andit's interesting to consider
what the driver is of some ofthe symptoms, and if something
like this nervous systemregulation in various forms can
(55:09):
alleviate some of thosesymptoms, then I think we're
making strides forward. Onething that I would say on this
is that it is effectivelyexpensive.
Gez Medinger (55:18):
These devices are expensive, yeah, and there's,
and there's, there's a largerquestion here about what's the
difference in efficacy betweenone of these expensive devices,
like an alpha stem or like aNurosym, and a simple vagal 10s
device that you can maybe pickup for 10s of pounds or 10s of
dollars on eBay, as opposed to hundreds.
Emily Kate Stephens (55:37):
Yeah,
Gez Medinger (55:37):
and we don't know what the difference is in terms
of efficacy, ultimatelystimulating the vagus nerve is
stimulating the vagus nerve, anddo you have to play a certain
tune on it to have the effectfont, or will any tune do? So
that's a big question. We don'thave the answer to that.
Emily Kate Stephens (55:50):
However, I do love when I see that a device
or a methodology genuinely doeshave the research behind it, and
I really did go into thatinterview, I prepared so hard
for that to go in and try andrefute their claims. I genuinely
did. I went through all of theirstudies, and I was pleasantly
(56:11):
surprised to see they really dohave the results that they say,
which is something that somebodyelse just do not have behind
them. However, that doesn'tnecessarily mean that they don't
work. It also means that theydon't have the huge marketing
and power behind them to go outand get that kind of attention
(56:31):
within the research market.
Gez Medinger (56:32):
Exactly, I think one of the most interesting
things that came out theresearch was the potential
anti-inflammatory effects. Nowthat wasn't something I was
aware that this could do before,but again it makes sense. I
think part of the challenge whenit comes to using these devices
is around habit forming. So, howdo you make sure that you use it
for x amount of time a day,every day, when the effects are
(56:53):
sometimes very subtle and alsocumulative?
Emily Kate Stephens (56:55):
Yeah, it's that cumulative thing that is
incredibly interesting.
Gez Medinger (56:58):
The other thing about the cumulative thing is it
makes it harder to measure in aresearch setting because there's
so many other factors that canfeed into any cognitive or
fatigue improvements
Emily Kate Stephens (57:09):
- or worsening -
Gez Medinger (57:10):
or worsening over that period, so it's very hard
to control for everything elsein a condition, any of these
complex chronic conditions, butcertainly I think the thing that
I'm with the most is that I feellike my alpha stem does help,
but am I disciplined enoughabout using it? Probably not. I
probably ought to use it more,but when I don't immediately see
the benefits of it, it'ssomething that you have to be
(57:31):
encouraged to do, or to try andpersuade yourself to do it, or
put it into your life in a waywhere you always do it at x time
for x long. Otherwise, it justdoesn't happen.
Emily Kate Stephens (57:39):
But Gez, you have built into your life
taking 72 different supplementsor going downstairs and stepping
outside on your grass firstthing in the morning, so it is
one of those things thattheoretically we simply need to
build that discipline into ourlives. I think one of the things
(57:59):
for me, I actually really enjoywearing it, and I do think I
feel some benefits, but, likeyou, I am erratic in it, because
there are certain, for example,breath work practices, or
there's certain yoga practicesthat I do that I will have an
immediate shift in my nervoussystem, a marked immediate shift
(58:22):
following that practice, and Idon't get that with the
neurosim, so I guess we're allslightly seeking that
confirmation as soon as possible.
Gez Medinger (58:32):
And that's the hard thing with just about any
intervention you can ever trywith complex chronic illness.
You want to have something thattells you this works, this
helps, and so much of the timeit's very difficult to put your
finger on it, and it sends youcrazy trying to look for signs
of whether something helps ornot. That's actually one of the
reasons. Regarding, youmentioned supplements are pretty
big, all of mine. I don't takeany now, because I just came to
(58:55):
a conclusion I had all of them,and were they actually doing
anything? Got rid of them all,and I don't think it's made any
difference. It's so, it's sohard, we do. We do so much, we
try so many things just based onhope. I guess the positive thing
about a solution or anintervention like this is there
is technical evidence to showthat it does have an impact,
even if that impact is slight. Ithink any of us will take a
(59:15):
percentage improvement in oursymptoms. The question is just
whether that percentage is worthx high pounds or not at the end
of the day.
Emily Kate Stephens (59:21):
Yeah, and I think, particularly when that is
helping with the fatigue,helping with the cognitive
problems, and potentiallyhelping with what you and I have
described in slightly differentways, but this really, really
overwhelms nervous system. Ourconversation makes me want to do
better with it, and actually tryto be more strict about it, and
(59:44):
monitor the progress I make, orlack of progress.
Gez Medinger (59:47):
Yeah, same with me.
Emily Kate Stephens (59:48):
Okay, so what we've done today is we're
just now gonna hold each otheraccountable for trying to build
that into our routine, let's sayover the next two weeks, yeah,
and see if it, if it makes anydifference for us.
Gez Medinger (01:00:01):
Yeah, I'm up for that. Yeah, fair. To be fair,
straight after listening to thatinterview, I went and got on my
Alpha stim for 45 minutes, so itencouraged me to do that.
Emily Kate Stephens (01:00:09):
Amazing, brilliant. Thank you so much for
joining me, Gez. Pleasure,
Gez Medinger (01:00:13):
As always. Bye.
Emily Kate Stephens (01:00:23):
Thank you for listening to Make Visible.
(01:00:44):
Please do like, follow, orsubscribe to listen to our next
(01:01:13):
episode, where we'll beuncovering more insights into
(01:01:40):
complex chronic illness. Thiswas brought to you by the team
(01:02:11):
at Visible, a group ofscientists and engineers whose
(01:02:38):
lives have been affected byenergy limiting health
(01:03:04):
conditions. We're buildingwearable technology that's
(01:03:31):
helping 100,000 people measureand manage their complex chronic
(01:04:03):
illness. To find out about whatwe're working on and how Visible
(01:04:35):
could help you, visit ourwebsite at makevisible.com
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