November 13, 2015, will be remembered in France and around the world as the day that Paris fell under attack by a group of terrorists. More than 130 people died. Many others survived to carry on lives in the wake of this categorically traumatic experience. “When you listen to the reports . . . of the survivors, it was shocking,” says Karen Ersche, a neuroscientist at the University of Cambridge. “It was gruesome. It was worse than a horror film.”
The head of the French National Centre for Scientific Research (CNRS) at the time, Alain Fuchs, wrote a letter imploring researchers to respond to the attacks with science. After reading the letter, cognitive neuroscientist Pierre Gagnepain felt moved to do something. Although he didn’t study post-traumatic stress disorder (PTSD), his work was “extremely connected to the question of how the brain [controls] unwanted memory experience,” says Gagnepain, a researcher in Francis Eustache’s lab in the Neuropsychology and Imaging of Human Memory department at the French National Institute of Health and Medical Research (INSERM). “I wanted to focus . . . on what could protect and increase resilience” in people who suffered a trauma.
In January 2016, Eustache and CNRS research director Denis Peschanski met with Fuchs to discuss launching a national program to study the survivors of the November 13 attacks. Gagnepain soon joined in the conversations, as did Yves Lévy, head of INSERM at the time, and the 13-Novembre Programme was born. Researchers involved in the project, which is ongoing, aim to film testimonies from 1,000 volunteers—including those who survived the attacks, people from targeted neighborhoods, and inhabitants of surrounding areas and other cities—about their experiences that night. They have also begun using fMRI to look at the brains of some of those participants.
One question the researchers want to explore through the lens of the Paris attacks is why some people who experience trauma develop PTSD, while others do not. Gagnepain, Eustache, Peschanski, and their colleagues worked with a subset of those individuals who were affected by the attacks and were part of the 13-Novembre Programme—including 55 who had developed PTSD following the incident and 47 who had not. They also recruited 73 people who were not in Paris that day to participate in the study.
The researchers designed a behavioral experiment in which the volunteers memorized word-image pairs, to the point where, upon seeing one of the words on a screen, the participants would automatically think of the associated image. The researchers then had the participants lie down in an fMRI machine and try to avoid recalling some of the images they’d just been trained to think of: if a cue word appeared in red, they were to try to prevent the associated image from entering their awareness, or to push it out of their thoughts if it did so.
When you listen to the reports of the survivors, it was shocking.—Karen Ersche, University of Cambridge
These word-image pairs were designed to represent neutral memories—there was nothing emotionally charged about seeing the word “Favor” and thinking about a picture of an elephant. But the idea the researchers wanted to test was whether individuals with PTSD were somehow less able to suppress neutral memories, just as they struggled to suppress the traumatic ones that underlie their disorder. Once participants had completed such a “no think” trial, the researchers asked them whether they’d involuntarily thought of the image, what the researchers considered an intrusive memory.
There was no difference between individuals with PTSD and those without the disorder, or between those who had been exposed to the Paris attacks and those who had not, in terms of how often the intrusions happened—everyone was so well trained on the word-image pairs that the “intrusive images pop automatically,” says Gagnepain. All participants got better at blocking out intrusive memories over the course of the trials. But the fMRI data suggested that the mechanism underlying that suppression isn’t the same for people with PTSD and controls.
The researchers found that participants differed in the amount of connectivity between certain brain regions—specifically, between inhibitory control regions of the prefrontal cortex and structures involved in memory such as the hippocampus. People with PTSD showed much weaker connections between these regions than did people without the disorder. “It seems that vulnerable individuals have a problem with control,” says Ersche, who wrote a perspective article that accompanied the study but was not involved in the research. “What I really liked about this paper is it says it’s not the severity of the trauma that leads to PTSD; it’s the ability to control it. And that is key.”
After being asked to suppress certain images, the participants completed a different sort of test. They were shown scrambled versions of those same images, which then slowly came into focus. Participants with PTSD were quicker to discern the familiar but suppressed images, suggesting that their suppression was somehow disrupted. It seems that not thinking about something is more difficult for individuals with PTSD than it is for other people.
This was known to be true of explicit, emotional memories such as a traumatic event that may have triggered the PTSD, and the new study demonstrates a similar effect for nonemotional, implicit memories that aren’t consciously recalled but influence behavior or emotions. Gagnepain compares the brain’s ability to suppress memories to the brake in a car: “There is one brake, to be used should a dog run out into the road or simply because the light turned red. We believe it is the same in the brain.”
Kerry Ressler, chief scientific officer at McLean Hospital and a professor of psychiatry at Harvard Medical School, says the findings fit well with a “long-standing expectation from the literature—the psychological literature and the neuro-imaging literature—that people with PTSD have deficits in top-down regulation of emotion.”
Ersche notes that the findings are very much in line with her own research on drug addiction. She has found that those who struggle with addiction have less inhibitory control over the striatum, a brain region with links to impulsivity and drug-related compulsions. Other researchers have noted similar neural signatures in cases of attention deficit hyperactivity disorder and obsessive-compulsive disorder.
Scanning the literature, Ersche also found evidence of weak inhibitory control over the amygdala, the brain’s emotional processing center, in cases of depression. “It seems there’s a general pattern here,” she says, though she emphasizes that the idea of a common mechanism for such diverse disorders is just speculation.
The idea that PTSD involves loss of regulatory control over all of one’s memories, not just the traumatic ones, could signal a new avenue to explore for potential therapies, Ressler says. He explains that PTSD patients are often treated with methods that encourage the repeated recollection of the traumatic experiences in an attempt to desensitize the individual—“essentially retraining the brain to no longer have emotional over-responses to the triggers or the intrusive memories.” The new study suggests that patients could potentially be trained to control their memories using neutral stimuli, as opposed to having to relive their own traumatic experiences. “That that could be a different way of approaching PTSD that could be powerful,” Ressler says.
As for the INSERM study, Gangepain and his colleagues recently saw their participants a second time, and are using the latest data they collected to explore how brain activity changes over time. “We are interested in evolution of these [patterns],” he says. “We are extremely grateful to all the participants who volunteered. . . . I think most of them were happy to participate and feel they were doing something right. It’s important to make positive things out of a traumatic event.”