Finding treatment options for Post-Traumatic Stress Disorder Finding treatment options for Post-Traumatic Stress Disorder

Finding treatment options for Post-Traumatic Stress Disorder

Researchers at INSERM use Cool 40 Rat Coil for PTSD-study

 

4 years ago, researchers at the French Institute of Health and Medical Research (INSERM) were among the first in the world to perform TMS on mice with the Cool 40 Rat Coil specifically designed for TMS on rodents. Their goal was to take a vital step towards finding new treatment options for Post-Traumatic Stress Disorder (PTSD).

“We expect to make useful findings for the practical application of TMS for treating depression and PTSD”. Those were the words of Professor Wissam El-Hage when he and his research team members sat out to examine how TMS could be applied in mouse models of PTSD. 4 years down the road, the researchers have completed the study involving 155 mice and the results were recently published in the journal “Brain Stimulation”. We have asked Dr. Marc Legrand who was a prominent part of the research team if the initial expectations have been met and if he thinks it will be possible to find an effective TMS protocol for the treatment of PTSD in humans.

Relevance of new cortical targets

“The studies carried out in mice provided useful insights on the application of rTMS in humans for the treatment of depression and PTSD. The experimental findings obtained in mice models of depression and PTSD allowed us to better characterize neurobiological mechanisms at play following chronic rTMS treatment and underlines the relevance of new cortical targets,” says Marc Legrand whose main objective for doing TMS research was to further the efficacy of TMS in humans and define new cortical targets that could prove relevant in the treatment of neuropsychiatric disorders and continues:

“The fundamental mechanisms at play in the therapeutic efforts still remains poorly understood even though TMS has been widely used and studied in the past decades”.

The result: TMS reverses stress-induced behavioral impairment

“To step back from clinical trials to study such mechanisms in rodents was essential to improve the therapeutic efficacy of rTMS in future human research,” says Marc Legrand of the PTSD study which was the first study to use prefrontal cortex rTMS in mouse models of PTSD. The main result of the study was that rTMS reversed stress-induced behavioral impairments and acted on distributed networks of fear extinction up to 10 days after treatment.   

Targeting both hemispheres at the same time

Since the mouse brain is a lot smaller compared to the human skull, both hemispheres were stimulated when the vmPFC was targeted. According to Marc Legrand this could be of interest in terms of finding new treatments for humans.

“Most TMS clinical trials focus on one hemisphere, but our study approach where both hemispheres were targeted produced beneficial effects and might indicate that bilateral stimulation of the vmPFC could be of therapeutic interest in humans,“ says Marc Legrand.

Successes and challenges

Looking back at how it was to apply TMS on mice, Marc Legrand stresses that the most satisfying part of the study was applying the high-intensity/high-frequency (12 Hz) protocol while maintaining spatial precision and be able to target specific subparts of the prefrontal structures.

“This was allowed by the active cooling properties for the coil and the use of a stereotaxic frame to position the coil at the given coordinates,“ Marc Legrand explains and stresses that the most challenging aspect of doing TMS on mice was to effectively target the prefrontal cortex:

“We managed to target the prefrontal cortex and extensively study the stimulation of the motor cortex. The latter showed that, in mice, the most effective part of the magnetic field was located on the periphery of the coil rather than in the center of the coil. Establishing this coil-to-brain relation was the most difficult part of developing relevant targeted TMS in mice,” Marc Legrand says.

Upcoming TMS research on mice

Coming from a double academic background of medicine and neuroscience and having worked with TMS since 2014, Marc Legrand is interested in doing more TMS research in mice models. Currently, translational experiments are being designed on the application of rTMS in mice models of depression.

“The effects of bilateral vmPFC stimulation on subcortical limbic structures/neurobiology, such as the amygdala, the hippocampus and hippocampal neurogenesis, are of prime interest for me in future TMS research, ends Marc Legrand.

In detail: the main results of the study

Marc Legrand: “The chronic application of high-intensity/high-frequency rTMS (12 Hertz) to bilateral ventromedial prefrontal cortex (vmPFC) produced beneficial effects on behaviors, enhancing short-term memory and reducing the expression of fear behaviors (freezing) during a second exposition to the fear context. Chronic rTMS treatment (5 sessions, 3750 pulses) modified brain activity during this second exposition as seen with c-Fos immunohistochemistry, increasing the activity scores in the infralimbic cortex (i.e. vmPFC), the basolateral amygdala and the ventral hippocampus, which are cortical and subcortical structures involved in fear neurocircuitry and the expression of fear-related behaviors."

More info:
Website:www.inserm.fr


The views and opinions expressed in this article do not necessarily reflect the official policy or position of MagVenture or any of its affiliates. The usage of rTMS for any other purpose than the cleared indication, in the country in which the product is intended to be used, is considered investigational.

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