The Remember project provides new insights into post-traumatic stress disorder © Inserm
Following a shocking, dangerous or frightening experience, such as a terrorist attack, many people develop post-traumatic stress disorder (PTSD). In order to improve its management, numerous scientific studies are examining the neurobiological processes underlying the development of this disorder. The Remember study, directed by Pierre Gagnepain and sponsored by Inserm, was set up in the months following the November 13 attacks. It focuses on protective factors and brain markers associated with trauma resilience. In a new scientific paper published in Science Advances, the research team at the Inserm Neuropsychologie et imagerie de la mémoire humaine laboratory (Inserm/Université de Caen Normandie/École pratique des hautes études/CHU Caen/GIP Cyceron) highlights the plasticity of brain mechanisms for coping with trauma. These change over time, and their reconfiguration leads to a reduction in post-traumatic stress symptoms.
The attacks in Paris and Saint-Denis on November 13, 2015 left lasting marks, not only on the survivors and relatives of the victims, but also on French society as a whole.
The Remember study, conducted as part of the transdisciplinary 13-November program [1] , is a study comparing brain imaging results conducted in 120 participants exposed to the attacks and 80 unexposed who have been followed since 2015.
The research team is exploring the effects of a traumatic event on brain structures and function, identifying neurobiological markers of both post-traumatic stress and trauma resilience. Ultimately, the aim is for this work to lead to new therapeutic avenues, complementary to those already available, for people suffering from PTSD.
"Why do some people who have experienced trauma suffer from post-traumatic stress disorder (PTSD), while others never develop it? What is it about the brain that explains why some people recover from PTSD while others suffer chronically?
Memory control mechanisms
One of the most characteristic symptoms of PTSD is the frequent intrusion of images, smells and sensations associated with the traumatic experience. These intrusive memories, which often arrive without warning and disrupt daily life, are a source of great distress.
In previous work, the team has shown that PTSD sufferers exhibit dysfunction in the brain control networks that normally regulate the activity of memory regions, and in particular the activity of the hippocampus.
In individuals with this disorder, these memory "control mechanisms" fail to inhibit hippocampal activity, allowing intrusive memories to resurface. Conversely, the functioning of these mechanisms is largely preserved in individuals without PTSD, who are able to effectively combat intrusive memories.
Following on from these results, Pierre Gagnepain and his colleagues set out to understand in their new study [2] whether memory control mechanisms could be reshaped and improved over time, contributing to recovery from the disorder.
A total of 100 people, who had been exposed to the terrorist attacks of November 13, 2015, took part in this work. Of these, 34 suffered from chronic PTSD, while 19 had recovered from an initial disorder. The study also included 72 participants not exposed to the attacks, serving as a control group.
All these people were invited to participate twice in brain imaging studies (in 2016/2017 and again in 2018/2019) to study structural and functional changes in their brains over time. They also answered a questionnaire about their possible PTSD symptoms in 2020/2021.
Based on these data, the research team was able to highlight the plasticity of the brain networks involved in memory control, which regulate the resurgence of intrusive memories.
Researchers have shown that, in people recovering from PTSD, these memory "control mechanisms" are reshaped over time and eventually "normalize" to resemble those of "control" people. In concrete terms, this translates in brain imaging into more effective action by prefrontal regions to inhibit hippocampal activity and prevent access to intrusive memories.
In participants with chronic PTSD, these phenomena are still impaired. Nevertheless, the onset of plasticity in memory control mechanisms, observed during the second stage of imaging in some of them, predicts a future reduction in the intrusive symptoms reported in the third part of the study, in the questionnaire.
Finally, at a structural level, this normalization of memory control mechanisms is also associated with an interruption in hippocampal atrophy, helping to limit the negative effects of stress on the brain.
" Our study shows that nothing is set in stone. Human resilience to trauma is characterized by the plasticity of memory control circuits, notably those that regulate hippocampal activity and the resurgence of intrusive memories. It also highlights that altered control mechanisms, which we identified in our previous study as central to understanding variation in response to trauma, are far more likely to be the cause than the consequence of PTSD ," stresses Giovanni Leone, first author of the study.
From a clinical point of view, this study could have interesting implications. " We could imagine new therapies, complementary to those already in use, to stimulate memory control mechanisms and encourage plasticity. The advantage of this approach would be to act on cerebral networks without acting on the emotional system, and without making the patient relive traumatic emotions", adds Pierre Gagnepain.
The team is continuing to work on the subject: the next step will be to study the role of a particular brain receptor (called "GABA alpha 5"), mainly located in the hippocampus. Scientists believe that this receptor may be involved in forgetting and silencing memories. They are keen to explore this avenue, which would not only help them better understand the mechanisms of TPST, but also enable them to consider this receptor as a potential new therapeutic target.
[1] A vast transdisciplinary research program, the 13-November program is co-directed by neuropsychologist Francis Eustache, director of the Inserm laboratory Neuropsychologie et imagerie de la mémoire humaine (Inserm/Université de Caen Normandie/École pratique des hautes études/CHU Caen/GIP Cyceron), and historian Denis Peschanski, director of research at the CNRS. The aim is to study the construction and evolution of individual and collective memories of these traumatic events, as well as to better understand the factors that protect individuals from post-traumatic stress.
[2] This study was funded by the Normandy Region as part of the Reseau d’Interet Normand (RIN) Label d’excellence.