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Mayer-Gross

Member Since 31 Dec 2010
Online Last Active Today, 08:28 PM
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Topics I've Started

Development of more advanced rTMS equipment.

08 December 2020 - 05:09 PM

So, some of you might know that i am very interested in rTMS. It is an intervention the former “Depersonalization research unit” had high hopes for and a German DTI brain imaging study from 2019 also point towards rTMS as the intervention in the disorder. 

 

rtms was developed 25.years ago but only approved to treatment for depression in Europe and the US around 2007. The technology has been very limited to two locations in the brain called the left and right DLPFC. These are very easy to find and stimulate as they are on the surface on the prefrontal cortex. 
 

Around 50% with depression respond to stimulation at these locations. RTMS clinics will often in their material claim a response rate of 70%. But, the reality is that significant number sees a reduction of only 20% of their symptoms- that is very close to placebo. Because these clinics runs a business they will take those who “feels a little better” as respondent. They run a business and it is easy to sell a product by saying it works in 70% and not 50%.

 

That rTMS only works in 50% with depression is one reason why most psychiatrists have been very skeptical of the intervention. In Denmark and in Europe it is offered as a eksperimental treatment at limited numbers of hospitals for depression. 
 

The reason why only 50% with depression respond is related to current technology used in rTMS. In many with depression (and also in depersonalization) the cognitive regulation of emotions is not done in the left or right DLPFC but other locations and networks in the prefrontal cortex. In depression the two other locations are the dorsomedial prefrontal and the right orbito frontal cortex. If you try these locations with a deep coil in depressed at a research facility the response rate for depression is closer to 90%. The reason why it is not a 100% is likely partly because the emotional regulation is done to deep in the brain for a deep coil used today to stimulate. 

 

The problems is that rTMS as it is approved and used today uses coil that can only stimulate 1.cm into the brain. So, it can not treat at deep locations and networks. This is a problem in depersonalization as the over regulation of emotions making a state of numbing is too deep in the brain. This goes for the right VLPFC that can only be partly stimulated with a normal coil-like 30%. Other locations found active in depersonalization and under suspicion like the anterior cingulate/dorsomedial prefrontal cortex and the ventromedial prefrontal is to deep in the brain to stimulate with a normal rTMS. So, one can say that with the current rTMS technology used depersonalization will have a very low response rate due to the areas in the brain where the regulation likely is done. Magventure makes a deep coil that is only used for research that might reasch these areas. But, has just been approved in the US for treatment of obsessive compulsive disorder. It might also be approved in Europe.

 

I read an interview with a danish professor in psychiatry who I have talked to and written when he was chairman of the danish psychiatrists association around 2004. My complaint back then was that they where not aware of the existence of depersonalization disorder. But, in a recent interview he addresses that 15-20% of people might have a depression in their lifetime and of 20% of those no medication will work. They will end up on social programs ect as they are resident to current treatments. He pointed towards rTMS as a treatment and a research program he was a part of for the development of more advanced rTMS equipment.

 

it is as I can see from the danish innovation fund site who have given 2.mio euros to the project and money from two companies will also go into it . It is a danish-German program divided into two sections. 
 

The danish producer of rTMS equipment, Magventure will with researchers from danish technical university( engineers) and a danish center for magnetic resonance and a research center in psychiatry develop a new coil, likely for a deeper and more selective stimulation in the brain that currently can not be stimulated. 

 

The German part of the project is the neuronavigation company “Localite” who shall develop more advanced software for more individual brain stimulation. It looks like they try to develop a navigation system that is not dependent on a MRI scan of individuals. University in Munich is also in the program.

It is a very broad and vague description they come with and I think it is for the protection of the project. We will know more when it a patented.

 

But, the ambitions is to develop rTMS equipment that can be used in refractory depression, other psychiatric conditions and to reduce neurological symptoms in neurological disorders. So, rTMS might end up being much more commonly used in the future if the project succeeds. 

 

 So, they are developing coils for more deeper stimulation and likely equipment that is more precise and easy to use. The program should run until 2023. They will likely start testing some of it in the coming years. So, equipment that can make a deeper stimulation and treat more conditions is under development. The project in danish is here.Try a autotranslate. 
 

https://innovationsf...tent-depression

 

english version of the project: https://www.drcmr.dk...tant-depression


Did you have seperation anxiety as a child?

22 November 2020 - 06:28 PM

With seperation anxiety it could be anxiety for being away from you parents, sleeping at places without your parents ect. I had seperation anxiety as a child and there are some research pointing towards the risk of developing panic anxiety is 3.times higher if one had separation anxiety as a child. Panic anxiety has been seen as a component in development  depersonalization. 

 

 


Lecture by Ruth Lanitus on dissociative subtype of PTSD

13 August 2020 - 04:20 PM

It has been very limited with the research into depersonalization disorder since the depersonalization research unit stopped in 2015. But, there has been a lot of research in PTSD and the dissociative subtype that features of depersonalization and derealization. Among people with PTSD it is estimated that 15% of the have the dissociative subtype. There are some significant overlapping between the dissociative subtype of PTSD and depersonalization disorder. They both share symptoms of emotional numbing, detachment, derealisation. So, it is assumed that the emotional regulation done by the brain is likely the same. So, findings in the dissociative subtype of PTSD can also be used in depersonalization. The leading researcher into the dissociative subtype of PTSD is the Canadian prof in psychiatry, Ruth Lanitus. Here is lecture with her from 2019 based in recent brain scans in PTSD and its dissociative subtype. The recording in not so good as it is recorded from distance but it can be seen. Her point is the dissociation comes from overregulation of emotion done by the ventromedial prefrontal cortex- emotions are suppressed. An area deep in the midbrain called the “periaqueductal gray”/PAG is in the ventral part active in the dissociative state, - all the time. It is a old structure in the brain we share with reptiles. A structure millions of years old.

In normal PTSD the periaqueductal gray is active in the dorsal part, -all the time. They are in a constant state of alert/fight and flight mode. Their emotions are under regulated as the ventromedial prefrontal cortex is underactive- opposite to the dissociative subtype. They can have emotional outburst, have range due to  this under regulation. Their constant state of alert does they have difficulty to find rest and be relaxed.

The dissociative state is a immobilization response that the brain have chosen because a fight and flight response could not be taken. Danger was perceived as being to close. Symptoms like out of body, derealisation is likely connected to the activation of the periaqueductal gray. Emotional numbing is likely result of the overactivity/emotional regulation done by the ventromedial prefrontal cortex. 
 

So, she have recent data from brain scan that shows the involvement of the periaqueductal gray. This is not found in other studies in depersonalization. They likely could scan that area until recently. She points towards ventromedial prefrontal cortex as central in this regulation. The ventromedial prefrontal cortex -both left and right have also been found overactive in studies in depersonalization. It is a location very difficult to manipulate with until recently, as it is to deep to stimulate with rTMS. There have been development of new coils that can likely affect it. But, it is not used by rTMS providers yet. 
 

her lecture is here. 
https://www.youtube....5uW5y4c8&t=270s


Review of brain imaging studies and dissociation published until today.

09 July 2020 - 02:58 PM

Those who have an interest in brain imageing studies, have questions like, “where do depersonlisation start in the brain”, why do rTMS fail in so many? This review of all different types of brain imageing studies done in, dissociative identity disorder, depersonalisation disorder, borderline disorder and the dissociative subtype of PTSD might give some ideas.

 

In reality one shall focus on the data for depersonalisation disorder and the dissociative subtype of PTSD. All emotional regulation in the brain is done by the prefrontal cortex. When you use rTMS you try to stimulate or inhibit a location in the prefrontal cortex. The model used for depersonalisation is it is a brain response to Anxiety and danger where there is no option to make a fight and flight. The brain makes a immobilisation and shots down so nothing can be felt. The price for this response is a sense of loss of self, emotional numbing and unreality.

 

The location in the brain from where this response is started have been conflicting over the years. It have been the hope that if this location could be found, it could be turn off with the use of rTMS.

 

At Depersonalisation research Unit They came with the right ventro lateral prefrontal cortex, though other location was found overactive in depersonalisation, like the medial prefrontal cortex. They chose the ventrolateral prefrontal cortex for their very small of rTMS. I have tried this location and it did not work. I have then thought that the location might be wrong. In this review here that have many more recent studies and the ventromedial prefrontal cortex is likely the location found in most studies to be overactive and make Depersonalisation.

This location is to deep in the brain for a normal rTMS coil to stimulate. Only after 2017 a coil was developed to go so deep in the brain. It might explain that many have a very poor response to rTMS. The location have never been the right one and the coil needed have not been avalible.

 

The review of brain scans is here: https://www.scienced...4?via=ihub#bib3