# Risks associated with rTMS to the right VLPFC



## teal (Oct 9, 2019)

What are the risks associated with this treatment?

Reading on rTMS one could easily get the impression that it's risk free. But alas. There are patients with other conditions who have deteriorated following finger twitch navigated rTMS for other regions of the brain. So. I guess you Mayer-Gross know the most about it, but anyone is free to chime in.


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## 35467 (Dec 31, 2010)

There are very few trails done at this location as it is difficult to locate without neuronavitation. There are under 20.publications about rTMS at this location. There are facials nerves over the location to stimulation with high frequency is difficult to tolerate for 50%. The nerves begins to contracts during stimulation and it can be painful. In depersonalisation it is low frequency but theta burst inhibitory stimulation might not be tolerated by many due to this side effect. Normal rTMS should be no problem. But it is an area central for emotional regulation so you are inhibiting the brains ability to make emotional suppression. So, in theory people can experience negative emotions, anxiety that they didn't feel before.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6345398/


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## teal (Oct 9, 2019)

Hmm. Funny. I did a search for right VLPFC and found 20 studies, but the one on depersonalization wasn't among them. It didn't appear in the search results page.

The side effects you describe jives well with the other patient I mentioned in the OP. His rTMS wasn't like the one for DPDR, but the side effects are still lasting years after, giving the patient twitching legs and neck, a tingling face and sleep problems. He took five treatments a week though, non-neuronavigated to another part of the brain. So a much higher frequency than the twice a week schedule for in the right VLPFC DPDR trial.

I think spacing out treatments like that sounds resonable.


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## 35467 (Dec 31, 2010)

The "case" you are mentioning don't sound to be related to rTMS alone. The person could suffer from another condition that starts progressing due to rTMS, was diagnosed wrongly. The are several trials with rTMS at the right VPLFC and two by E.Jay in relation to depersonalisation. But, this one don't come up.https://www.sciencedirect.com/science/article/abs/pii/S0013700619301551?fbclid=IwAR3wxZyn9wPQH1vhWT0I3lwSd3x8Zqc2zN4rLz8H2Yv2SAn7lupshFJuQHA


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## 35467 (Dec 31, 2010)

The "risk" in depersonalisation is that the right VLPFC might not take the emotional numbing is 20-30% and you have to look for an alternative. It could be the medial prefrontal cortex that is likely very active in depersonalisation. From DTI scans of white matter in depersonalisation there is indication of suppression of emotions from this area. The right VLPFC can mobilise regulation of this area but in some it might not work to make a inhibition of it. So, if no response that could be an alternative and go directly towards the medial prefrontal cortex.


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## teal (Oct 9, 2019)

Mayer-Gross said:


> The "case" you are mentioning don't sound to be related to rTMS alone. The person could suffer from another condition that starts progressing due to rTMS, was diagnosed wrongly.


Could very well be. He had ME/CFS and his MCS got exacerbated after the rTMS as well. The patient in case did high frequency rTMS to the left DLPFC and then both high frequency left DLPFC and low frequency to the right DLPFC.

If the risks are low, then this really seems like something to try. I guess stopping if deteriorating would also minimize the risk of long term side effects - if indeed one would get some sort of side effects. The patient in case had doctors who administered the treatment five times a week, so there's less of an opportunity to pull the emergency break, in case something would happen. Of the protocols for rTMS for the right VLPFC, do you think the protocol described here is the best we have?



Mayer-Gross said:


> But it is an area central for emotional regulation so you are inhibiting the brains ability to make emotional suppression. So, in theory people can experience negative emotions, anxiety that they didn't feel before.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6345398/


Yeah, for sure. I don't feel now. I am flat. It's almost such that I'd rather feel miserable than nothing at all.


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## 35467 (Dec 31, 2010)

rTMS has been given in some trails to very servilely depressed 5.times a day. There are no large trails in treatment of depersonalisation and that includes rTMS trails -lack of funding. I have in the letter I wrote to the doctor reviewed all trials, their locations, reductions in symptoms clusters and put them in a context of cognitive regulation of emotions in the brain. The medial prefrontal cortex could be an alternative to the VLPFC for numbing -but for dissociation it is either the right TPJ or the right angular gyrus -likely angular gyrus as embodies regulated emotions. One likely has to work with two locations within a network for emotional regulation to take the disorder. So, people who has read into the disorder is necessary. There is likely need for repeated treatment with 10.sessions every 9-12.months.


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## teal (Oct 9, 2019)

Mayer-Gross, you've mentioned five locations for rTMS treatment. Would you accept treatment on either of those five if you got it for free?

I dunno what the risks are for either, or the benefits, like not needing neuronavigation, thus making it easier to target.

• right VLPFC
• left DLPFC
• right DLPFC
• the right TPJ 
• and soon the right angular gyrus


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## 35467 (Dec 31, 2010)

No, only the right VLPFC and angular gyrus.- that is within lines of what we know of brain imaging of depersonalisation and cognitive regulation of emotions by the brain. If i would try the right and/or left DLPFC and right TPJ i could have tried clinics in the Nederlands or the UK. They will try these locations.


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## teal (Oct 9, 2019)

I have had PET scan abnormalities in the frontal lobe and parietal lobes, where we find the right VLPFC and angular gyrus, so to me it makes perfect sense that those two are the places to start.

I assume the French trial got started as a consequence of some unpublished cases which responded (that's pretty common, though it could be based solely on theory).

Do you have word from anyone in touch with the French lady, who's responsible for the angular gyrus trial?

Either a yay or nay about whether they still believe the angular gyrus is the way to go.


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## 35467 (Dec 31, 2010)

The trail was formally finished in sept 2019 then writing and peer-review. It should be out the coming months.

Depersonalisation is a disorder related to cognitive regulation of emotions. There are models based to basic research on how the brain regulates emotions. In these models the right VLPFC plays the role as the "need of emotional regulation". So, in might not regulate emotions itself but tells other areas of the prefrontal cortex to regulate. So, in some case reports some people have seen reduction with rTMS at the right DLPFC of 25%, -and so it stops. The right DLPFC regulates emotions so the might be some suppression of emotions from the medial prefrontal cortex that still will be there and will suppress. By, going to the right VLPFC alone you are in reality addressing the whole prefrontal cortex regulation of emotions and not just one area. So, the reductions becomes more significant like 45%.

The angular gyrus is active in depersonalisation like the TPJ. The angular gyrus is more central to cognitive regulation of emotions and a central part of the default mode network. The TPJ is a sub hub . So, there is likely to be a higher response at the angular gyrus than the TPJ trial. The angular gyrus is a part of embodiment of regulated emotions, -putting them into action. So, if you do rTMS at this location some clusters with go away but not emotional numbing because the VLPFC will still be hyperactive. If you do the right VLPFC alone the emotional numbing will go away but not so much derealisation. My theory is you have to work with locations within the framework of emotional regulations. So, start with the right VLPFC and emotional numbing. When that is gone go to the angular gyrus and work from there. rTMS might be like 35% at the right VLPFC and 65% at the angular gyrus. I hope the evaluation of the french trial will point towards this. That is why I will wait for it before going any further. These models of cognitive regulation of emotions are very helpful.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4801480/

This is about cognitive regulation of emotion in depression and anxiety disorders and one can see that these disorders are opposite to depersonalisation with under regulation of emotions.Depersonalisation is a disorder related to overregulation.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5145785/


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## 35467 (Dec 31, 2010)

teal said:


> I have had PET scan abnormalities in the frontal lobe and parietal lobes, where we find the right VLPFC and angular gyrus, so to me it makes perfect sense that those two are the places to start.


In depersonalisation both the frontal lobes and parietal lobes are overactive. In most depressive states it is the opposite, -they are under-active. The overactivity in the parietal area is relation to embodiment of emotions.Many areas in the frontal lobes are overactive in depersonalisation but the right VLPFC stands out in depersonalisation and it can mobillize emotional regulation from other areas in the frontal lobe. So to inhibit and normalise the right VLPFC should affect other areas in the frontal lobes too. So, a overactivity in the right DLPFC and medial prefrontal cortex (expresses dyrnorphins to stress and anxiety) should normalise too. The small reduction seen when talking drugs like naloxone and naltrexone is likely to be related to the emotional regulation done by the medial prefrontal cortex. Why take drugs and only get the medial prefrontal cortex and 20% of symptoms when you can take it out at the right VLPFC and get a 44% reduction with 6.rTMS session at the right VLPFC?


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