# rTMS Questions



## Rmontgomery (Aug 31, 2020)

I have had marijuana-induced DPDR since 2012, which I have been able to manage the anxiety around but have not been able to get rid of the depersonalization-derealization. I have consultations set up with the TMS treatment centers in the area. I am very fortunately in a position, where I can afford to find the best possible treatment. What questions should I ask the doctors?

1) I know one says he uses StimGuide for navigating to find the location. Is this the same as the neural navigation/localite that others have mentioned?

2)If I give the doctor the exact coordinates from the Jay study for right TPJ and right VPLFC, will that allow them to find the location or is it trickier than that? I know the one video on YouTube mentioned that he had the wrong part of the TPJ stimulated.

3) What is difference between theta burst / rTMS? Which should I choose?

4)Is there any way to direct the doctor to the correct location on the right angular gurus from the yet-to-be-published French study? It should also be inhibitory right?

5) Do any of these brain locations require the so-called deep coil? If so, how do I ask if they have it? It sounds like it is very rare to have it, is there anywhere in the U.S. that is known to have it (would travel to a Europe if necessary after COVID ends.

6) If I am a willing guinea pig and able to pull a few strings, is there anyway to find a location that could do inhibitory rTMS to the VMPFC?

7) what are your thoughts on this wild speculation on the SCN's role in DPDR in this article? Is it plausible? https://selfhack.com/blog/depersonalization-its-causes-and-potential-solutions/

Thanks for your help! I know there are some very knowledgeable people on this forum.


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## 35467 (Dec 31, 2010)

1) StimGuide navigation is a system developed by Magstim that is one of the oldest makers of rTMS. Likely ok. There might be an option in the system to find the location without a MRI scan. Locations will be based on a artificial brain made from data from the average of several hundreds.

https://www.magstim.com/product/stimguide/

2) yes, both coordinates are in the study and both locations are not to deep for a normal coil to reach.

3) theta burst is much faster like 40.sec instead of 35. min and is likely a little more effective. It is likely more painful to do on the right VLPFC as there are facial nerves above the right VLPFC that will make fast contactions to tms and theta burst effect is likely slightly more painful.

4) angular gyrus is just behind the right TPJ slightly over you right ear. Talairach coordinates is mostly used and for the right angular gyrus it can likely be looked up. https://en.wikipedia.org/wiki/Talairach_coordinates

The design of the French trial is here. https://clinicaltrials.gov/ct2/show/NCT02476435

5) Magstim do make a deep coil and it is not approved for treatment and therefor they likely do not have it. It is the competitor to Magstim, Magventure who have a coil that can go deeper than a normal coil. This coil have just been approved for the use in the US by the FDA for OCD. It is not approved in Europe yet, - likely within a year. You have to find a rTMS provider that uses Magventure. There are in some brain scans in depersonalization found overactivity in the anterior cingulate cortex and the medial prefrontal cortex similar to in OCD. This coil is approved for OCD at this location. Never tried in depersonalization. A woman wrote in a Facebook group some years ago the she had made her depersonalization go away. She had tried rTMS at the pre-SMG that is also a location used for OCD. So, to run a rTMS protocol for OCD might be a alternative as there is many OCD like components in depersonalization.

6) not likely as the coil is not approved for treatment yet. The coil approved for OCD will likely could affect most parts of the ventromedial prefrontal cortex. The reason there is a interest in the area is also because there are connections to the periaqueductal gray in the midbrain. Recent research into the dissociative subtype of PTSD shows that the ventral part of the periaqueductal gray is active in dissociative and likely is the core to the anatomical immobilization response and it is done from the ventromedial prefrontal cortexSo, you have to find areas in the prefrontal cortex that can affect the periaqueductal gray to fear and anxiety. The right VLPFC might also have connections to it.

https://www.magventure.com/component/k2/news/magventure-received-fda-clearance-for-ocd-2

7) The activity recently found in the ventral part of the periaqueductal gray is a parasympathetic immobilization response to danger. It might explain the HPA axis changes in depersonalization ( fight and flight dysfunction), changes in heart rate variability, skin conducdence. It is more related to that than the SCN.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5167004/


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## 35467 (Dec 31, 2010)

You will be limited to what locations have been tried and the equipment you have. So, it is likely the right VLPFC and the right TPJ or angular gyrus is what you can try right now until a coil for deeper stimulation is more likely available. Clinics that uses Magventure is what to look for.

In some fMRI scans done at the depersonalization research unit the medial prefrontal cortex and anterior cingulate was also found active. These locations are to deep for a normal coil to go to- especially anterior cingulate. It is also a OCD location and there are strong OCD component in depersonalization. So, to treat on that location could be an option.This review point to these locations as central: https://www.sciencedirect.com/science/article/pii/S0022395620300224?via%3Dihub#bib3

There have been some recent structural scans done of white and gray matter and there are some indication from there that the ventromedial prefrontal cortex in central. This is not confirmed by fMRI studies. She who did these studies says that the fMRI studies done are very small in size ( and in many ways old) that there can be errors and might explain some conflicts. More new and resent scanning s could likely be of some use. I think the French angular gyrus trail will also include some fMRI scannings. Also until recently there was only fMRI scanners that could run at 3.tesla. So, many structures in the midbrain could not be studied as they are too small. Scanner that can run 7.tesla is now developed but only used for research. They cost around 4mio.dollars. We have only one in Denmark for research-not clinical use. To look at the periaqueductal gray in depersonalization or SCN you need such a scanner. A recent study in chronic fatigue syndrome found that the periaqueductal gray was affected. People are immobilized as they are sick. Might explain they feel tried all the time. To look at the midbrain in depersonalization could be interesting too.


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## RunToMe (May 30, 2019)

At Mayer-Gross:

Do you know from people who worsened their symptoms for example from depression protocoll ?

I can get actually again rtms on right dlpfc with 1 hertz (because it had juvenile epilepsy, so they dont wanna do the left dlpfc with 10 hertz). Can understimulation from areas near around right dlpfc makes brain functioning worser ? Thanks !


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## Rmontgomery (Aug 31, 2020)

Thanks so much for your thoughtful response! Is the medial prefrontal cortex the same as the ventromedial cortex? Are both the medial prefrontal cortex and anterior cingulate OCD locations able to be targeted by the treatment for OCD?


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## 35467 (Dec 31, 2010)

I think that the risk of a seizure is very low. Inhibitory rTMS on an area where there is a seizure will inhibit a seizure. You can in theory reduce the risk of a seizure if the location is in the upper cortex with 50%. It is only high frequency rTMS where that theoretical risk is. If you have not have a seizure for more that 5. Years without medicine you are not likely to be an epileptic any more. You have grown from it. I do not know if high frequency rTMS will do any benefit at all. I think that most cases with depersonalization where there have been reports of a reduction have been at the right DLPFC. The response rate is very low, - less than 20%. In depression I have the impression that if you are refractory at the right DLPFC you will likely also be it at the left with high frequency.

Better to try some other locations but that is difficult to as most can only locate and treat at the left and right DLPFC.


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## 35467 (Dec 31, 2010)

Rmontgomery said:


> Thanks so much for your thoughtful response! Is the medial prefrontal cortex the same as the ventromedial cortex? Are both the medial prefrontal cortex and anterior cingulate OCD locations able to be targeted by the treatment for OCD?


No, the medial and ventromedial prefrontal cortex is not the same. Yes, there are a special designed helmet for deep tms made by "Brainsway" designed especially for OCD that stimulate the medial prefrontal and anterior cingulate at once. To find a provider go to this location and chose "OCD"( not "MDD") as your indication and a provider close to you can be found. https://www.brainsway.com/find-a-provider/

https://www.brainsway.com/wp-content/uploads/2019/09/Carmi_American-Journal-of-Psychiatry-2019_H7_OCD.pdf

there should also be some connections to the periaqueductal gray from the anterior cingulate.


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## RunToMe (May 30, 2019)

Thanks MG:i meant it not to seizures because I am proofed full to it because I had in netherlands the full 10 hertz. I meant it more that inhibition from 1 hertz can cause reduce functioning in right dlpfc or Region nearly around it in the Kind that the activities for cognitive function like planning or something else will go down


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## 35467 (Dec 31, 2010)

Don't think so.


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## Rmontgomery (Aug 31, 2020)

Mayer-Gross said:


> No, the medial and ventromedial prefrontal cortex is not the same. Yes, there are a special designed helmet for deep tms made by "Brainsway" designed especially for OCD that stimulate the medial prefrontal and anterior cingulate at once. To find a provider go to this location and chose "OCD"( not "MDD") as your indication and a provider close to you can be found. https://www.brainsway.com/find-a-provider/
> 
> https://www.brainsway.com/wp-content/uploads/2019/09/Carmi_American-Journal-of-Psychiatry-2019_H7_OCD.pdf
> 
> there should also be some connections to the periaqueductal gray from the anterior cingulate.


To make sure I am understanding correctly, the deep TMS from Brainsway is not the same as the Magventure? I.e. it can target the medial prefrontal and anterior cingulate, but it cannot target the ventromedial prefrontal cortex?


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## 35467 (Dec 31, 2010)

Rmontgomery said:


> To make sure I am understanding correctly, the deep TMS from Brainsway is not the same as the Magventure? I.e. it can target the medial prefrontal and anterior cingulate, but it cannot target the ventromedial prefrontal cortex?


No, the deep coil from Magventure likely have the same target, at least anterior cingulate. "Brainsway" coil is formed like one big helmet called a H-coil that runs a specific programme of stimulation for one disorder. For depression they use another helmet. They try to design different helmets for different conditions. Brainway do deep TMS and Magventure do deep rTMS. Brainsway might go some few centimeters deeper than a deep rTMS coil and affect a larger area.

There is more flexibility in Magventures deep coil to use it at other locations like orbito frontal cortex, ventromedial cortex ect. It is approved for OCD but my guess is that it will also be used in depression in people who not respond to the left or right DLPFC. Location like the dorsomedial or orbito frontal cortex have a high response rate in those refractory to the other location in depression.


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## Rmontgomery (Aug 31, 2020)

Sorry to keep asking so many questions, but when thinking about such a major financial decision with mental health implications I really don't want to mess this up haha. I really appreciate your hel, MG. Does the right angular gyrus stimulation require either neural navigation or a deep coil?


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## 35467 (Dec 31, 2010)

It only need neuronavigation for location. You shall be aware that everything in research done into depersonalization is small. The number of patients scanned in different examinations. so, there can be error or conflicting data.

The rTMS trails are also very small with no follow up months after the trail so we do know if people became symptomatic after some time. The locations found like angular gyrus and the right TPJ are partly based on brain scan but also that neurological patients with epilepsy or a tumor can have derealisation from these locations. At the time that the depersonalization research unit did their trail in 2014 there was no coils that could go deeper than 1.5 cm. So, they where likely forced to think in locations they could stimulate and that excludes some locations.

In the model used for depersonalization in PTSD it starts at the ventromedial prefrontal cortex that suppresses that amygdala, limbic system and insula and activate the ventral part of the periaqueductal. The periaqueductal gray will release opiopates that will affect areas like the right TPJ and angular gyrus. Some the activation of these locations is likely in the finial stange of a process. So, prefrontal cortex is likely where it starts.


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## 35467 (Dec 31, 2010)

I have by the way tried rTMS at both the right VLPFC and the right TPJ without any effect, 12.session with 900.stimulations at each location with 1.mz at 120% power each time and each location. In the trail at depersonalization research unit they only treated 7.patients and that is a very small group. The reason they choose the right VLPFC was because in some brains scans this location was active in the depersonalization group and not in the control group when show aversive pictures. But, depersonalization is constant and not only related to stimulation. So, the location might not show up as active to stimulation as it might be active all the time. In structural scanners the ventromedial shows to be active as the area is much larger as it is used more compared to normal. The ventromedial cortex is also active when we sleep, when the left ventromedial is active the parasympathetic system is stimulated and when the right is active in sympathetic system is suppressed. It have connections to the periaqueductal gray so it can likely make a chronic immobilization response.


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## Rmontgomery (Aug 31, 2020)

I just got this in response from one of the MagVenture clinics in my area that I reached out to. Does this sound right? I had previously thought that the OFC was the same as the VMPFC and not the same as the VLPFC.



> I have received some information about the areas and protocols you were asking about. Please see below (I am sorry for the delay)
> 
> "Dr. Downar reports having success with patients with a depersonalization diagnosis and referred us to a study done by Antonio Mantevini in New York City.
> 
> ...


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## 35467 (Dec 31, 2010)

No, everything is wrong. 
the right VLPFC is not same as VmPFC nor the Orbitofrontal cortex. I have recently written with a Canadian girl who have been seen and tried treated by Jonathan Downar. She tried the right DLPFC and the right Orbitofrontal cortex without any effect. I think his research clinic for depression is restricted and only approved for treatment at the left and right DLPFC, the dorsomedial prefrontal cortex and the right Orbitofrontal cortex. So, he can not go to other locations as he then makes an experiment he have no approval for. So, he has no experience in treatment of depersonalization with a clinical response.

The coil they refers to is a normal flat 8-coil and it can not treat as deep as the Orbitofrontal cortex. They do likely not have neuronavigation for locations or planing to get a coil for deep rTMS.Have looked at their site. The setup for their treatment is only depression with a response rate of 60%. That is "normal" to write for a clinic that can only treat at the left and right DLPFC. All their treatment is likely built around these two locations. Very easy to find without neuronavigation and treat with a normal 8.coil.

This text by Jonathan Downar from addresses different locations in the prefrontal cortex and the dept of the locations and coils.

http://dribrahimyilmaz.com/site/wp-content/uploads/Depresyonda-TMS-Tedavisi-Akademik-Makale.pdf


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## 35467 (Dec 31, 2010)

Look I myself is waiting for the publication of a very large French trail at the angular gyrus. It might be published within 3-6.months. It might have a high response rate in people with a recent outset of depersonalization. You can treat at the angular gyrus with the coil they write they have. I think that the design and size of the French trail might rise awareness about depersonalization and cast some light on the networks at play. I would wait until it was published.


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## 35467 (Dec 31, 2010)

You are assuming that because a deep coil from Magventure is approved from OCD by the FDA a Clinic that uses Magventure intent to get such a coil. But, if you look at their site they only treat for depression. It can be related to insurance coverage. That insurances companies will only pay for rTMS treatment for depression at the left or right DLPFC. So, they only offers treatments that can get insurance coverage. FDA might have approved such a coil for the use in OCD but the insurance companies have not. So, many might not get it for that reason as long as it is the case.


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