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i will try next week neuronavigated tms


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#13 Mayer-Gross

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Posted 31 December 2020 - 11:16 AM

There are no coils that can go 5.cm into the brain. There are several scientific articles about locations for stimulation, other about coil design for deeper stimulation. The coil used for the rTMS approved in Europe,  USA and elsewhere have a stimulation depth of 1.cm. Coils that can go deeper was not developed until 5.years ago and are yet not approved for clinical use. They have been used for research until now and one have just been approved in the USA for OCD. The response rate for depression with normal rims is around 50% at two locations with the coil used. Research have shown that other with depression have regulation of emotions in structures deeper in the prefrontal cortex and when they are given rTMS at these two other locations with a deep coil they have a response. So, you might cure 85% of depressions if you also use a deep coil at other locations. There is only one place in Europe where they use such a coil. Because it is not approved for clinical use they are breaking the law in a way by using it. I think they  might have said that the size of the trials in depression where such a coil is used makes it sufficient for them to use. It has been approved in the US to use this year for OCD. I have seen videos by a psychiatrist in New York from 2017 with such a coil used on a patient. It was not legal then. I think they have got these coil though connections to research facilities at universities. So, it is a research facility that have ordered from the producer and not a rTMS clinic. It might explain why the are almost absent elsewhere. 

 

The rTMS researcher who works with depression, Jonathan Downar have addressed this problem about stimulation depth, locations and coils years ago. He writes this about the right VLPFC;

 

"The VLPFC also presents a challenging target for conventional rTMS, as much of it lies deep within the frontal operculum, or along the orbital surface of the prefrontal cortex. However, even for superficial VLPFC regions, tolerability remains a problematic issue, due to the proximity of the extraocular and temporalis muscles. There are several alleviating measures that may be effective in improving the tolerability of stimulation at this region, as reviewed in detail below. With appropriate measures to alleviate discomfort, conventional figure-8 coils may be suitable for stimulating some VLPFC regions, and newer coil designs should be able to address the depth-of-target issue in future. Hence, the VLPFC could also serve as a practical target in future studies of rTMS for depression, with appropriate refinements to technique."

 

https://dribrahimyil...emik-Makale.pdf

 

You psychiatrist might mean that the effects of stimulation might go as deep as 5.cm. There he is right. When you stimulate an area it will have affects on areas It is in networks with that is much deeper into the brain. But, a direct stimulation might that can go 5.cm might never be possible to develop as it will diffuse from the areas it shall pass (it will affect them too) and the stimulation will also spread over a larger area and become weak. Around 2-2,5.cm for a coil for deep rTMS is likely maximum and H-coils design for a specific locations might go close into 3,5-4.cm the brain.

 

In Western Europe a rTMS session can very in price between 100.euros to 300.euros. In the UK it close to 300.euros. In Eastern Europe from 50-55. euros. 

 

He is right to call out a placebo effect. But, the TPJ trial was much larger is size than the right VLPFC. In depersonalization the placebo effect is much smaller than in depression. To see reductions of 20-50% in depression trials relate to placebo is normal. That is also why many says that SSRIs don't work for depression because the response rate in placebo group is very high in in many trials. But, the placebo effect in other conditions is much smaller. In obsessive conplusive disorder the placebo effect is much less and a response of 25% is regarded as valid. It is not the case in depression trials. Depersonalization placebo effect is similar to obsessive compulsive disorder. It is there but low and likely not sustainable over time. You can see it on the posts of this forum. Some tries a drug and makes a post here a day after about feeling better. It is often drug that are normally many weeks to work and in larger doses than tried. But, people feel better. Here on the forum they can not understand a week or two later that is stopped working. It is the placebo effect that stopped working. Many posts about feeling better on something also changes within weeks. So, the placebo effect is there but it do not last for a very long time. Never take posts from anyone who have taken a drug for a very few weeks seriously. 

 

But, the reductions in a TPJ trial is much larger in those who respond. The problem with all trials in depersonalization is they are very small and not placebo controlled. Likely due to lack of funding into research into depersonalization. That is a problem. A bias from the researcher can also play a role. They hope their patients gets better and want to see a response. So, their perceptions can color the trail. 

 

I think that that the right TPJ might play a role but is not the "core" location. It is likely in network with it and it might have some effect in some. The angular gyrus trial is with a 100. patients and half of them will get placebo. So, it the first real trial in depersonalization ever.  If the rumor holds that the response rate is 50% it might again be related to networks connections. There is a locations that turns up in many studies with drugs that can make depersonalization and that is also found larger in people with symptoms with depersonalization. It is also connected to and close to angular gyrus and the TPJ. That is a location called "Precuneus". In a PET study from 2000 it came out as active along with the angular gyrus and TPJ. It is found larger in in MRI study at the depersonalization research unit. In people with borderline disorder with dissociation it is also affected. When people are given  sedation and lose consciousness, it is turn off. Drugs like ketamine and cannabis that can make depersonalization highly effects this location. But almost all drugs that have affect the the consciousness affect the precuneus. It plays a centrai role in consciousness and self-awareness.

 

There was a publications in "Nature" this year about a experiment where mouse was given ketamine and immobilized into dissociative state. They found an area changes the frequencies in the brain called "Retrosplenial" in mouse. The same area in humans are called "posteromedial cortex" and coveres two locations; precuneus and posterior cingulate cortex. In publication about the effect of cannabis those who experienceed a bad trip with depersonalization, anxiety, ego death found to have changes in frequencies in the precuneus and prosterior cingulate/posteromedial cortex. 

https://www.ecnp.eu/...8/P.1.b.009.pdf

 

I hope that angular gyrus trial might go into the role that the precuneus might play. You need a deep coil to stimulation of this area. 



#14 leminaseri

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Posted 01 January 2021 - 06:17 AM

There are no coils that can go 5.cm into the brain. There are several scientific articles about locations for stimulation, other about coil design for deeper stimulation. The coil used for the rTMS approved in Europe, USA and elsewhere have a stimulation depth of 1.cm. Coils that can go deeper was not developed until 5.years ago and are yet not approved for clinical use. They have been used for research until now and one have just been approved in the USA for OCD. The response rate for depression with normal rims is around 50% at two locations with the coil used. Research have shown that other with depression have regulation of emotions in structures deeper in the prefrontal cortex and when they are given rTMS at these two other locations with a deep coil they have a response. So, you might cure 85% of depressions if you also use a deep coil at other locations. There is only one place in Europe where they use such a coil. Because it is not approved for clinical use they are breaking the law in a way by using it. I think they might have said that the size of the trials in depression where such a coil is used makes it sufficient for them to use. It has been approved in the US to use this year for OCD. I have seen videos by a psychiatrist in New York from 2017 with such a coil used on a patient. It was not legal then. I think they have got these coil though connections to research facilities at universities. So, it is a research facility that have ordered from the producer and not a rTMS clinic. It might explain why the are almost absent elsewhere.

The rTMS researcher who works with depression, Jonathan Downar have addressed this problem about stimulation depth, locations and coils years ago. He writes this about the right VLPFC;




"The VLPFC also presents a challenging target for conventional rTMS, as much of it lies deep within the frontal operculum, or along the orbital surface of the prefrontal cortex. However, even for superficial VLPFC regions, tolerability remains a problematic issue, due to the proximity of the extraocular and temporalis muscles. There are several alleviating measures that may be effective in improving the tolerability of stimulation at this region, as reviewed in detail below. With appropriate measures to alleviate discomfort, conventional figure-8 coils may be suitable for stimulating some VLPFC regions, and newer coil designs should be able to address the depth-of-target issue in future. Hence, the VLPFC could also serve as a practical target in future studies of rTMS for depression, with appropriate refinements to technique."


https://dribrahimyil...emik-Makale.pdf


You psychiatrist might mean that the effects of stimulation might go as deep as 5.cm. There he is right. When you stimulate an area it will have affects on areas It is in networks with that is much deeper into the brain. But, a direct stimulation might that can go 5.cm might never be possible to develop as it will diffuse from the areas it shall pass (it will affect them too) and the stimulation will also spread over a larger area and become weak. Around 2-2,5.cm for a coil for deep rTMS is likely maximum and H-coils design for a specific locations might go close into 3,5-4.cm the brain.


In Western Europe a rTMS session can very in price between 100.euros to 300.euros. In the UK it close to 300.euros. In Eastern Europe from 50-55. euros.


He is right to call out a placebo effect. But, the TPJ trial was much larger is size than the right VLPFC. In depersonalization the placebo effect is much smaller than in depression. To see reductions of 20-50% in depression trials relate to placebo is normal. That is also why many says that SSRIs don't work for depression because the response rate in placebo group is very high in in many trials. But, the placebo effect in other conditions is much smaller. In obsessive conplusive disorder the placebo effect is much less and a response of 25% is regarded as valid. It is not the case in depression trials. Depersonalization placebo effect is similar to obsessive compulsive disorder. It is there but low and likely not sustainable over time. You can see it on the posts of this forum. Some tries a drug and makes a post here a day after about feeling better. It is often drug that are normally many weeks to work and in larger doses than tried. But, people feel better. Here on the forum they can not understand a week or two later that is stopped working. It is the placebo effect that stopped working. Many posts about feeling better on something also changes within weeks. So, the placebo effect is there but it do not last for a very long time. Never take posts from anyone who have taken a drug for a very few weeks seriously.


But, the reductions in a TPJ trial is much larger in those who respond. The problem with all trials in depersonalization is they are very small and not placebo controlled. Likely due to lack of funding into research into depersonalization. That is a problem. A bias from the researcher can also play a role. They hope their patients gets better and want to see a response. So, their perceptions can color the trail.


I think that that the right TPJ might play a role but is not the "core" location. It is likely in network with it and it might have some effect in some. The angular gyrus trial is with a 100. patients and half of them will get placebo. So, it the first real trial in depersonalization ever. If the rumor holds that the response rate is 50% it might again be related to networks connections. There is a locations that turns up in many studies with drugs that can make depersonalization and that is also found larger in people with symptoms with depersonalization. It is also connected to and close to angular gyrus and the TPJ. That is a location called "Precuneus". In a PET study from 2000 it came out as active along with the angular gyrus and TPJ. It is found larger in in MRI study at the depersonalization research unit. In people with borderline disorder with dissociation it is also affected. When people are given sedation and lose consciousness, it is turn off. Drugs like ketamine and cannabis that can make depersonalization highly effects this location. But almost all drugs that have affect the the consciousness affect the precuneus. It plays a centrai role in consciousness and self-awareness.


There was a publications in "Nature" this year about a experiment where mouse was given ketamine and immobilized into dissociative state. They found an area changes the frequencies in the brain called "Retrosplenial" in mouse. The same area in humans are called "posteromedial cortex" and coveres two locations; precuneus and posterior cingulate cortex. In publication about the effect of cannabis those who experienceed a bad trip with depersonalization, anxiety, ego death found to have changes in frequencies in the precuneus and prosterior cingulate/posteromedial cortex.
https://www.ecnp.eu/...8/P.1.b.009.pdf

I hope that angular gyrus trial might go into the role that the precuneus might play. You need a deep coil to stimulation of this area.

there is a little probability i can get a fmri. it will be fucking expensive but i dont care. if i wont respond to the stimulation of the rvlpfc, a fmri can maybe make out, which other locations i can stimulate.

do you think a pet or spect can also make out activities in the brain? maybe its cheaper than fmri.

3 people in this forum have very abnormal qeegs. mine was highly normal. what do you think is the difference? maybe mine is pure psychological?

#15 Mayer-Gross

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Posted 01 January 2021 - 06:48 AM

as it stands and from what we know about depersonalization a scan will likely not be of any use like it could be in depression. The problem is that many locations show up as active. You do not know with is the "core" location among them. That is also why a review of brain imaging studies from this year recommended a study where a combination of fMRI with rTMS was done. You could then pick some of these locations a make a stimulation and see if it makes a difference in symptoms and in a new brain scan. That knowledge about depression comes form a decade of research where a combination of rTMS and fMRI was done in many hundreds of patients . In depression there are 3-4.networks affected and locations. So, you can scan a depressed and see what kind they are as you know what to look for. That we do not know in depersonalization. A SPECT is almost not used in psychiatry but neurology as it is not sensitive enough. Psychiatric symptoms are much "softer" than neurological symptoms. But, the problem is also can you intervene in these locations. Conventional rTMS have the limitation of stimulation depth of 1.cm and that rules out many areas for stimulation that are central in many states. Many with depression can not be treated with conventional rTMS as the emotional regulation in the prefrontal cortex is too deep. Many locations showing up in depersonalization as active is too deep for conventional rTMS. 



#16 Mayer-Gross

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Posted 01 January 2021 - 06:54 AM

in SPECT and PET scans you used a radioactive tracer that have a brief short life that is out of the body with some hours. This tracer has to be made prior to the scan. This tracer is given as a infusion or a tablet. In a fMRI you don't need that. It can measure the use of oxygen in the brain. 



#17 Mayer-Gross

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Posted 01 January 2021 - 07:13 AM

a conventional rTMS 8.coil that can stimulate at 1.cm depth that is the one approved with look flat like this. 

 

https://www.magventu...coils/c-b70-2-2

 

 coil for deeper stimulation at a depth of 2.cm will look like this. It has been used for research in 5-6.years but is not approved for clinical used in Europe yet. Just been in the US. Magventure rTMS machines only. 

 

https://www.magventu...oils/cool-d-b80



#18 Mayer-Gross

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Posted 01 January 2021 - 07:35 AM

You can in a way divided rTMS into 2.generations.

 

 The first generation with conventional rTMS will use a flat 8.coil with a stimulation depth of 1.cm. The machines are primarily made for stimulation of either the left or right DLPFC. It can only location these two locations so there are no navigation system used as it is restricted to two locations. 

 

2. generation will use both a conventional coil and a deep coil for deeper stimulation . It will have a computer based navigation system that is either based on MRI of the patient or a computer algorithm. It will be able to locate all areas on the brain surface. It will use theta burst as stimulation. Normal rTMS typically takes between 25.min to 45.min. With theta burst stimulation it can be done in 3.min. It gives another economy to rTMS treatment. So, the cost a treatment should also be reduced with 50% or more. It will the time of calibration of the equipment and not the treatment that takes time. This equipment will be able to treat 85% of depression, many mental disorders, reduce symptoms in neurological disorders. 

 

95% of rTMS machines used today are the first generation. There are some places where there are some features used in 2.generation like neuronavigation or theta burst stimulation. 



#19 tomenko

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Posted 01 January 2021 - 07:39 AM

You can’t. I have disabled the messenger function this summer and it will never be activated again. I had several contacts at that time close to 2-3.a day. I have used much time in reply’s to many only to see that many didn’t read my replies, asked about the same thing again and again. I had replied one person with 7.pages within 24.hours. So, You are ending up in conversations with many that only cause frustrations. 

 

ok.

 

if I well remember you said there was a clinic in Italy that used the neuronavigation system.

you remember the name of the clinic?

 

take care

 

tom



#20 Numb_1993

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Posted 01 January 2021 - 07:44 AM

Good luck laminaseri ..i can't wait to hear your report !

#21 Mayer-Gross

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Posted 01 January 2021 - 08:09 AM

ok.

 

if I well remember you said there was a clinic in Italy that used the neuronavigation system.

you remember the name of the clinic?

 

take care

 

tom

That is right. I was in contact with them in 2019. A professor who is an adviser to the clinic replied me and said he would look into depersonalization and reply me shortly. He never did. Depersonalization is not on their site either. I think, they have looked into the rTMS case reports and trials done. These are based of two small trials at two different location and two case reports at another location; The right TPJ, right VLPFC and the right DLPFC. If they are aware of the angular gyrus trials then it is 4.different locations. Conclusion; we will not try to treat depersonalization as the disorder is purely understood as seen in 4.different locations tried.The risk of non-response is too high. The publication of the French trial might change that if is has more information. If the French trial follow their design they should also do some fMRI scans in some of the patients and they might come up with some information that does they might be open to try it.



#22 Mayer-Gross

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Posted 01 January 2021 - 08:30 AM

The location in Italy has four centers and one of them have equipment you only find in a research facility. Neuronavigation system from "Localite", deep coil for deep stimulation, use of theta burst that is likely why the take 100.euros pr. session. They treat people with depression with 2.session a day the first week and one session a day the 2.week. They are the only clinic in Europe that can stimulate the dorsomedial prefrontal cortex and the right orbitofrontal cortex. So, they can likely treat 85% of depressions. Not, 50%.

 

There is a German on this site with depression who have the obsession that he has depersonalization disorder. He have been seen by a German professor who have done research into depersonalization and written two books about depersonalization. He have said to him that he suffers from major depression with secondary symptoms of depersonalization. I have written to him that he should contact the Italian clinic as they could likely treat him. He have tried the right DLPFC so two other locations with a deep coil could be tried. He would not do that and asked me for the rTMS clinic in Hungary and I said to him that they for depression could not offer him what he already had tried and he should try other locations for depression. He said "are your a doctor?" since I said he should be treated for depression. No, but a professor who knows about depersonalization have said you have depression and I have tried to help you with that. They would likely have taken him in for depression but he have the idea of having depersonalization so they would likely have rejected him for that. 

 

It is my estimate that 20-30% active on this site do not have depersonalization as a primary disorder but a secondary symptom to another condition. 



#23 leminaseri

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Posted 04 January 2021 - 10:11 AM

first session done. nothing noticeable

#24 leminaseri

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Posted 05 January 2021 - 05:25 AM

second session done. no benefits.




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