The Idea of Kindling, and the possibility of Deep Brain Stimulation

[[ra...]]

Dear Nov3 and all,

 

I am still in a wave, and still using reading and research as a distraction, but hanging here. 

 

Before we get to the Deep Brain Stim (DBS) article, I read the other article Nov3 posted (another great find Nov) from Discover Magazine on the addicted brain. For those of you that have not read it, I highly recommend it.  But it makes one REALLY important mistake.  It explains in terms that are pretty easy to follow how glutamate, AMPA and NMDA lead to LTP which they call the “maladapted” learning of addiction.  I really liked their explanation of the “migrating” of AMPA receptors.  That is how LTP works.  The problem with that paper is what it is actually showing is how glutamate, AMPA and NMDA lead to the LTP of learning ANYTHING.

 

These articles focus on LTP’s important but negative learning of fear:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3985283/

https://www.pnas.org/content/108/30/12503

 

And this one by one of the scientists sited in the addiction paper

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3367554/#__ffn_sectitle

And a very complex but much more recent article:

https://www.nature.com/articles/s41539-019-0048-y

 

Show that LTP is how we learn everything we learn.  LTP and LDP are really what neuroplasticity is all about.

 

It is the where those things happen, and of course to what, that lead to addiction.

 

First the where.  The Ventral Tegmental Area (VTA) and Nucleus Acumens (NAc) are the addiction centers of the brain.  Then the what.  Dump dopaminergic substances like cocaine, amphetamines, or the complex mix of tobacco chemicals (nicotine by itself is not all that addictive) and the dopamine in those centers use the LTP process to make us love cocaine and tobacco forever.

 

What was really interesting in the addiction paper was how they were able to target the EXACT area of the rat brains in the VTA and NAc that made the rats love cocaine with chemicals that literally made those areas of their brain glow, and then hit them with LFS (more on that below) and they cured the rats craving for cocaine.

 

What was also interesting is how the response to need or craving grows STRONGER over time.  I think this is very analogous to what we experience, only instead of craving, it is our health issues.

 

The key take aways from this slightly misguided but still really good paper is find the areas that are INAPPROPRIATELY LTP, and reset them with LFS, and you cure addiction.

 

Let’s look at the need for Deep Brain Stimulation (DBS).

I do not believe there is a “center” of our brains that is “responsible” for our damage.  I can only speak for myself when I say I have never “craved” a benzo.  In 3 ½ years, I have had a few “lapses” on alcohol.  I actually did them on purpose in a crude system “reset.” It sometimes works, but sometimes does not, so I do not recommend it.  And a few lapses on cigs, and consequently I sometimes feel cravings for them.  I also sometimes feel cravings for something I cannot identify.  I do not have a desire to smoke or drink, but I CRAVE and I get furious about it.  I honestly have no idea what that is. I think it might be glutamate dumped on my VTA and NAc from something I ate that contained glutamate like grains.  Maybe that would require DBS to fix.

 

The other exception would be the amygdala area of our brain responsible for anxiety and panic.  But when I am “glutamated,” I can get anxiety or craving, but I personally feel in mostly in my spine and gut.  Can we use LFS on our spines and vagus nerves?  I intend to put that in my email to the DBS authors later today.

 

I watched the video on Elon Musk's Neuralink.  It is nit the company’s intention, but if we need to reach a place in the brain like the VTA and amygdala to apply LFS, that is probably the technology that will get us there.

 

Remember there are no bad ideas to talk about, and discussion is good, and nothing is personal.  I have looked at Transcranial Direct Current Stimulation (TDCS), and Transcranial Magnetic Stimulation (TMS) in the recent past.  At the present state of technology, those ideas are the equivalent of swatting mosquitos with a wrecking ball.  I was going to say “slicing tomatoes with a chainsaw,” but that is not enough hyperbole to describe how blunt an instrument TDCS and TMS really are.  I am not saying that one day we will not discover how they “really” work, and be able to tune them to do what a doctor wants them to do.  I am saying right now, as best I can tell the technology is literally, “We tried this on some brain injured and brain diseased (like Parkinson’s) people and some of them got a little better and hardly any of them got worse.”  If someone wants to dig deeper and find some articles that show otherwise, have at it.  I looked at it, got really scared, and moved on.  That doesn’t mean I might have missed something, so if you like those ideas, do not let me dissuade you from looking.

 

Now LFS I love, but we need to understand what it is.  I hate long quotes, but we need this one.  From the DBS paper:

“Each LFS consisted of 4 packages at 5-minute intervals. Each package contained 200 monophasic square wave pulses of 0.1 milliseconds (ms) in duration at 1 Hz.  The intensity of LFS was equal to the after discharge (AD) threshold of each animal.”  It previously defined the AD threshold, “determined by 1 millisecond (ms) monophasic square wave of 50 Hz with a 3 s train duration. The stimulating currents were initially delivered at 30 microAmps (μA), then intensity was increased in increments of 10 μA at 10 min intervals until ADs of at least 8 s were recorded. ADs were defined as spikes with a frequency of at least 1 Hz and amplitude of at least twice the baseline activity originating immediately post stimulation.”

 

If that explanation makes your mind numb, do not feel bad.  That is a very difficult definition to understand, which is why I left it out of my original summary.  But it is clearly not just a low current pulse delivered at less than 100 Hz.  It is painfully specific and difficult to find, and complex to generate and deliver.  I am going to ask a little about it in my email to the authors.

 

So in summary:

The addiction paper was a great but misguided explanation of LTP.  LTP is learning.

Per my previous post, I think LFS has potential to reverse all of what is wrong with our glutamatergic and GABAergic neurons.

I think it would need to be tailored to the areas of concern to us, and not just the brain.  My top 4 would be Amygdala, VTA, spine, and vagus nerve.

I am going to compose the email later today, with all of the questions we discussed, and I will get back with anything I learn from the authors.

 

In the immortal words of Arnold Schwarzenegger, “I shall return.”

 

Ramcon1

[[Po...]]

Hi Ramcon1- thank you very much.

 

 

Regarding fear, and these 2 articles below, wanted to hopefully hear your thoughts...

 

I have become more and more fearful over the past few months. It’s crazy, absurd, and 100% debilitating. I can’t go out of my house, can’t ride in a car, etc. etc. it’s so frickin’ bizarre!

 

I don’t think I am “learning” fear. It seems like a benzo / chemical thing. I think fear is primarily in the amygdala?

 

What do you think is the process that’s increasing fear over time, rather than it diminishing? Is there anything that’s helpful in breaking the fear cycle?

 

 

Thanks again,

 

 

 

 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3985283/

https://www.pnas.org/content/108/30/12503

[[ra...]]

Power,

 

There is only one thing that can beak the fear cycle and you are not going to like it: face your fear head on.  Get on the horse.  Whatever it is you fear, you must expose yourself to it and see that nothing bad is going to happen (unless you fear poisonous snakes.  Do not face that fear.  It is very healthy.  )

 

But leaving your house, riding in a car etc.  Leave your house for a short while. See that nothing bad happened.  Remember that nothing bad happened and leave again.

 

This DOES work for "fake chemical" fear.  That fake chemical fear is unnatural LTP (and all the other stuff in the DBS article), and facing it will depress the potential.  The catch is you have to be "ready."  If you go out and just get scared and run back inside, you reinforce the fear learning.  You have to go out with a plan.  "I am going out to smell flowers.  I am going out to speak with a friend I really like. Or even, I am going to listen to my favorite song in my back yard."  Doesn't matter what it is, just some type of positive reinforcement or reward.  In a month, the fear will be gone.

 

No pills required.

 

Good luck,

 

Ramcon1

[[Po...]]

Ramcon1 - thanks buddy - made my day 

 

 

[[ra...]]

Not everything is "DBS LFS" level profound.  Often, the simplest things work best.  And if that made your day, you made mine.

[Guest [Sk...]]

I have become more and more fearful over the past few months. It’s crazy, absurd, and 100% debilitating. I can’t go out of my house, can’t ride in a car, etc. etc. it’s so frickin’ bizarre!

 

I don’t think I am “learning” fear. It seems like a benzo / chemical thing. I think fear is primarily in the amygdala?

 

What do you think is the process that’s increasing fear over time, rather than it diminishing? Is there anything that’s helpful in breaking the fear cycle?

 

Thanks again,

 

 

PowerMM 

I think it goes deeper than just facing the fear,

we often have to examine what is causing the fear,

and it is not something outside ourselves,

however I have found it is often  more within us.

 

Using the benzos diminishes the fears, gives us a false sense of  safeness maybe,

without any learning ability to overcome them,

so  they give us  some  chemical respite,

and  more courage to face things

without the understanding of ourselves often I have found for me.

 

I use this when facing a fear  ( and its getting easier to deal and diminish my fears)

 

"FACE MY FEAR..... OF ..........MY OWN FEARS" 

 

what exactly do I fear,

is it danger out there, is it judgements by others,

is it doing the wrong thing,

is it fear  I might make a mistake or do the wrong thing.

fear of not knowing what might happen (  often lack of belief in ourselves)

etc etc

EVEN the fear we might not HEAL  :'(

 

All coming from within

ourselves as we seek other opinions.

We have to learn to trust ourselves again

As adults we know what is dangerous for us,

not what we think MIGHT be harmful/dangerous

and its unraveling the differences,

and processing how WE then deal with things.

 

If we delve deeper,

we see they are often learned in life

or manufactured fears applied to us by others

and not based on reality. 

 

  Sadly the benzos took the learning away,

created the dependance,

and now we have to learn to evaluate again

and trust ourselves again as we learn to live

without the benzos which did the work for us

often in the past.

 

Also agree there are possibly some damage to receptors

that the body has to heal, however for now no one really knows

how to fix this, and for me just accepting my body is smart enough to

help heal that I give it the added tool

of  sussing out  within my  own inner Fears

Face them myself and erase them and develop new tools to function

so that maybe the receptors can heal faster.

Nature is a wonderful things.

 

Just what helps me as I heal.  Might help someone hopefully

[[Po...]]

Skyblue2 - thank you 

 

 

I guess one of the things I find so frustrating - I seem to be getting worse.

 

No matter how I was feeling, I was able to push thru and do things. Years on the drug, tolerance, taper, and first 16 months benzo free I was able to push thru.

 

Now for past 12 months plus - anxiety to another level (feel like I’m plugged into an electrical socket), vertigo that keeps me bed bound, and entire body feels like it’s in contraction. Add in the fear component now.

 

At the time the symptoms ramped up 12 months ago, I increased Zoloft, and added remeron. I’m tapering off those now.

 

Maybe the two combined created a Serotonin Syndrome situation? Or maybe I have zero real need for Zoloft? I’ve read that those ADs could cause those symptoms... but who knows?

 

 

Once again - thank you very much!

 

 

[[ea...]]

Here is my take. I found that there is a difference between normal fear/anxiety, and benzo withdrawal caused fear/anxiety. BIG difference. BWD caused fear is irrational, and comes from our brains who are trying to regulate themselves back into normalcy.

Or brains deal with fear in a specific place: The amygdala. A walnut sized part of your brains, that controls the "fight or flight" response. When you try to deal with a scary situation, the amygdala sends out chemicals and "nerve signals" that tell you that you need to either fight - or flight. Benzos work on that part of your brain. Benzos disrupt the normal flow of chemicals and other stuff. Benzos make you feel calmer, maybe let you go to sleep. But OH! what a price we pay for that.

IMO, a lot of benzo withdrawal is simply letting the amygdala "right itself." And for some reason, that can take a very long time.

 

On SSRIs and other ADs: I no longer believe in them. For me....and listen up here! - I took ADs for 12 years. I had NO relief from those pills whatsoever. BUT: when I got OFF benzos, I did not HAVE any depression or major anxiety! ALL of it was caused by my nightly benzos. I am now off ALL of those drugs, and I have NO depression, no anxiety except mild, I sleep fine, etc.

God Almighty, these drugs can do so much damage, and we take them out of "hope" and all they do is cause more problems.

east

[[Po...]]

EastCoast62 - thanks so much 

 

 

 

 

[[be...]]

All,

 

I know the concept and most of the mechanism of kindling pretty well.  However, ALL credit to Nov3 found a really good article that describes it pretty well, and then another concept that poses a a potential solution.

 

I am moving the posts from the Lithium thread here for further discussion.

 

As I state at the bottom, I am in a wave right now, but in teh immortal words of Douglass MacArthur:

 

I'll be baaack.

 

Ramcon1

 

(Someone cheer me up and tell me they like or even get that joke.  Please.  I need a smile.)

 

The Terminator lol 😂

[[...]]

I have looked at Transcranial Direct Current Stimulation (TDCS), and Transcranial Magnetic Stimulation (TMS) in the recent past.  At the present state of technology, those ideas are the equivalent of swatting mosquitos with a wrecking ball.  I was going to say “slicing tomatoes with a chainsaw,” but that is not enough hyperbole to describe how blunt an instrument TDCS and TMS really are

 

“Each LFS consisted of 4 packages at 5-minute intervals. Each package contained 200 monophasic square wave pulses of 0.1 milliseconds (ms) in duration at 1 Hz.  The intensity of LFS was equal to the after discharge (AD) threshold of each animal.”  It previously defined the AD threshold, “determined by 1 millisecond (ms) monophasic square wave of 50 Hz with a 3 s train duration. The stimulating currents were initially delivered at 30 microAmps (μA), then intensity was increased in increments of 10 μA at 10 min intervals until ADs of at least 8 s were recorded. ADs were defined as spikes with a frequency of at least 1 Hz and amplitude of at least twice the baseline activity originating immediately post stimulation.”

 

Forgive me, I am still trying to determine the exact difference between something like tDCS and DBS, aside from the fact that one is an electrode on your scalp and one is an electrode in your brain...

 

I have seen a lot of the tDCS machines online and I do understand that they are generally sold as pretty basic and standard deliverers of frequency. The LFS method described in the paper is clearly more complex in the way it delivers frequencies. But they are both delivering frequencies, and they both should be able to reach the places in the brain that we need them to. Hypothetically, could we not program a tDCS machine to deliver frequencies in a more complex manner? I have seen articles that use tDCS machines that deliver oscillating square waves or altering microAmps or a variety of frequencies and durations. Yeah, there's a lot of big words in the paper's description, but is it saying something that is really that complex or beyond what we could do with tDCS and someone who really knows how to personalize and program one? (I am genuinely asking here, not making any statements and have no idea myself.)

 

I just wonder if we had some sort of engineer on our team if we couldn't replicate those methods but just put the electrodes on our skull (or wherever else) instead of IN our skull. Yes, tDSC is not super precise or focused but if other parts of my brain get hit with frequencies while I am treating the amygdala, I don't really care as long as my amygdala gets fixed in the process (off site side effects would be temporary). Lol....Probably demonstrating my ignorance here, this brain stimulation stuff is new to me and I am still in the early days of reading about it and really understanding it.

 

Anyway, Ramcon,

Let us know if you have any other proposed ideas for LFS delivery.

If what you say is true, I'm not sure how else we could get LFS where it needs to be with current technology.

Might have to wait for these non-invasive DBS methods to mature, like Temporal Interference Stimulation or Optogenetics.

 

PS.

I'm super happy you are going to reach out to the authors. I hope they are communicative and helpful. We must try to determine any and every way that this low frequency stimulation could be recreated and any and every way such frequencies can be delivered. Again, I feel like we need an engineer on our squad, or neurologist who does these treatments, or someone who really knows the intricacies of how these types of machines work. I've begun reaching out to people ...I feel like we're onto something and it's just a FrEqUeNcY away...

 

......

EDIT: A lot of the top hospitals and Universities in the world are using tDCS and TMS with success. (Johns Hopkins and Harvard examples below).

It might have limitations..... But damn, it might be worth a shot?? Especially if we could somehow get more technical with it and closer replicate the delivery of the DBS paper? I understand it's not the best possible method of delivery, but I'm not yet convinced it is useless (though, further readings or explanations my provide convincing, lol)

 

https://www.hopkinsmedicine.org/physical_medicine_rehabilitation/services/programs/brain-stimulation.html

https://braintour.harvard.edu/archives/portfolio-items/noninvasive-brain-stimulation

[[ra...]]

Just FYI, I am going to have to take a day off from this.  I will send the email I promised, and I will address every question in this thread, but not today.  I just can't today. 

 

Thanks benzogirl.  MacArthur, "I shall return," Arnold, "I'll be baack."  I like to reverse them.  It makes me smile for a second on a tough day. 

[[be...]]

Queen. We are the Champions.....

[[ra...]]

:smitten:

[[to...]]

Nov, out of all the things I have experimented with and the things that I might potentially experiment with in the future, messing around with "shock therapy" is the one that would scare me the most.  People have come out of those types of sessions f'd up and I wouldn't even think about trying to rig something.  The brain is very intricate and I wouldn't want to see someone become effectively lobotomized because they were a millimeter or two too far to the left. 

[[...]]

Nov, out of all the things I have experimented with and the things that I might potentially experiment with in the future, messing around with "shock therapy" is the one that would scare me the most.  People have come out of those types of sessions f'd up and I wouldn't even think about trying to rig something.  The brain is very intricate and I wouldn't want to see someone become effectively lobotomized because they were a millimeter or two too far to the left.

 

took... yeah. I feel you.

Ironically, yesterday that 'Don Killian' post bumped up to the top of the 'chewing the fat' threads and I checked it out.

I had never heard of his situation and it freaked me out. He used binaural beats, which are a different beast, but also mess with delivering frequencies to the brain, and had a major setback after years in the clear. It's likely the case that my curiosity of things like tDSC should be abandoned. As Ramcon suggested. The lack of precision probably is more of a concern, especially for us being so fragile.

 

It would likely take DBS (or a more futuristic alternative) and maybe even a neurologist who is familiar with benzo effects specifically(?) to safely utilize a LFS treatment on us; putting it exactly where it needs to be, with the exact method of delivery, etc... Not something to be taken lightly. I got excited about this, but I think you're right. Still open to other ideas for LFS delivery though if anyone stumbles on anything.

 

All of this said, I also see you noticed the new posts on the Mesenchymal Stem Cell thread, took.

I suggest everyone following this thread go over there and check them out. They are really relevant to kindling and sensitized glutamate receptors.

I think they further my idea that MSC therapy has some of the strongest potential to heal us. But go look for yourself.

 

http://www.benzobuddies.org/forum/index.php?topic=232293.20

 

Also - Ramcom presented the question, 'how do we get LFS therapy to every damaged neuron/receptor in our body?' Welp, if mesenchymal stem cell therapy can address kindling and sensitization in a similarly exhaustive fashion that LFS does (and I think the articles I posted suggest that it could), then a high dose (300 million) IV of MSCs would do just that.....travel through the bloodstream and reach every place in the body.

 

Just some food for thought! Not to deter the progression of this thread of course. The more avenues for healing, the better!!

[[Po...]]

Hi everyone,

 

I’m rereading Norman Doidge’s book (The Brain’s Way of Healing).

 

Chapter 7 is about the PoNs device.

 

It’s a electrical device placed in the mouth.

 

It starts neuromodulation on the tongue, then it creates a cascading “reset” in the brain stem, brain, spinal cord, etc.

 

Neurons that are underperforming get turned in, neurons that are over stimulated get “turned down”, etc.

 

It’s show good results with symptoms of Parkinson’s, stroke, balance issues, etc.

 

It has not been approved by the FDA for use in the USA yet. I believe it is being used in Canada.

 

 

 

More is here - http://www.normandoidge.com/?page_id=1042

 

 

 

 

 

[[to...]]

Hi everyone,

 

I’m rereading Norman Doidge’s book (The Brain’s Way of Healing).

 

Chapter 7 is about the PoNs device.

 

It’s a electrical device placed in the mouth.

 

It starts neuromodulation on the tongue, then it creates a cascading “reset” in the brain stem, brain, spinal cord, etc.

 

Neurons that are underperforming get turned in, neurons that are over stimulated get “turned down”, etc.

 

It’s show good results with symptoms of Parkinson’s, stroke, balance issues, etc.

 

It has not been approved by the FDA for use in the USA yet. I believe it is being used in Canada.

 

 

 

More is here - http://www.normandoidge.com/?page_id=1042

 

I think I read either that book or The Brain that Heals Itself and he was discussing the same device where people who had consumed a certain type of antibiotic could no longer walk again due to severe damage to the equilibrium and they used that device to retrain the brain.  It was very interesting stuff. 

[[...]]

The PoNs device has always intrigued me as well.

Last I checked though, the FDA actually declined approval of the device in April of this year.

This doesn't necessarily mean one thing or another because, well, the FDA clearly sucks. Hence a lot of us being here.

 

But I do remember it costing an absurd 30 thousand US dollars in Canada last I checked. 30 grand for a 2 week treatment. I don't imagine any of us are well off enough to give that a shot... The same treatment, however, is offered in Russia for only 5 thousand USD. If anyone is in Europe or willing to travel.

[[Sa...]]

Following and just adding this previous thread about the poNS device which intrigues me as well. 

 

 

http://www.benzobuddies.org/forum/index.php?topic=217186.msg2790897#msg2790897

 

 

 

[[va...]]

Following

[[va...]]

Hi everyone,

 

I’m rereading Norman Doidge’s book (The Brain’s Way of Healing).

 

Chapter 7 is about the PoNs device.

 

It’s a electrical device placed in the mouth.

 

It starts neuromodulation on the tongue, then it creates a cascading “reset” in the brain stem, brain, spinal cord, etc.

 

Neurons that are underperforming get turned in, neurons that are over stimulated get “turned down”, etc.

 

It’s show good results with symptoms of Parkinson’s, stroke, balance issues, etc.

 

It has not been approved by the FDA for use in the USA yet. I believe it is being used in Canada.

 

 

 

More is here - http://www.normandoidge.com/?page_id=1042

 

I think I read either that book or The Brain that Heals Itself and he was discussing the same device where people who had consumed a certain type of antibiotic could no longer walk again due to severe damage to the equilibrium and they used that device to retrain the brain.  It was very interesting stuff.

 

Jeez now I'm scared of antibiotics.

[[ra...]]

Hey all yall,

 

My wave is almost broken (which means of course I jinxed myself and will be sick tomorrow  )

 

Assuming I am not, the main difference between:

PoNS, TMS, TDCS and LFS was the insane precision of the LFS. 

 

Nov3 said "I wonder if we had some sort of engineer . . . " You do.  Me.  I am a self taught neuroscientist, but I am an MIT trained engineer.    Granted, I am a mechanical engineer, but we all had to take "electrical 101." I understand exactly what that pulse is.  I tried like a dozen times to explain it simpler so all of you could more fully "ride this ride with me" and I just gave up.  I can't cram a 150 hour course in electrical engineering into a paragraph.  It is just not possible.  You can either trust me or not.  That about which I have absolutely NO IDEA is how in the world they came up with a delivery that specific?"  What was the reason for finding that exact current sweet spot, and then a wave that precise?  I have promised you I will ask the authors and I will.

 

I also hope that once I ask and understand "why" it will help me explain what and how, but it might not.

 

That said, I am not going to hook myself up to any of the other things anytime soon, even if I were clean for months and had millions of dollars. But LFS looked "real."  And remember, the only reason it was Deep Brain, was that was the area they were trying to reach.  To me the easiest and most obvious human trial would be the celiac branch of the vagus nerve (part that enervates the colon) in people with IBS, and I will pose that exact question.

 

More next week,

 

ramcon1

[[be...]]

MIT? WOW well I’m impressed...

[[va...]]

Nov 3 have you recovered from your workout induced setback?

 

I'm trying to workout and stabilize and I notice I really have to watch the intensity of the exercises.