16 THE SCIENTIST | the-scientist.com
NOTEBOOKParis 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 experi-
ment 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.
These word-image pairs were designed
to represent neutral memories—there was
nothing emotionally charged about seeing
the word “Favor” and thinking about a pic-
ture of an elephant. But the idea the research-
ers wanted to test was whether individuals
with PTSD were somehow less able to sup-
press neutral memories, just as they struggled
to suppress the traumatic ones that underlie
their disorder. Once participants had com-
pleted such a “no think” trial, the research-
ers asked them whether they’d involuntarily
thought of the image, what the researchers
considered an intrusive memory.
There was no difference between indi-
viduals 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 intru-
sions 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 underly-
ing that suppression isn’t the same for
people with PTSD and controls (Science,
367:eaay8477, 2020).The researchers found that partici-
pants 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 connec-
tions between these regions than did people
without the disorder. “It seems that vulner-
able individuals have a problem with con-
trol,” 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 k e y.”After being asked to suppress cer-
tain images, the participants completed
a different sort of test. They were shown
scrambled versions of those same images,
which then slowly came into focus. Par-
ticipants with PTSD were quicker to dis-
cern the familiar but suppressed images,
suggesting that their suppression was
somehow disrupted. It seems that not
thinking about something is more dif-
ficult 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 non-
emotional, implicit memories that aren’t
consciously recalled but influence behav-
ior 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 regula-
tion 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 research-
ers have noted similar neural signatures in
cases of attention deficit hyperactivity dis-
order and obsessive-compulsive disorder.
Scanning the literature, Ersche also found
evidence of weak inhibitory control over
the amygdala, the brain’s emotional pro-
cessing 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 reg-
ulatory control over all of one’s memories,
not just the traumatic ones, could signal a
new avenue to explore for potential thera-
pies, 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 emo-
tional 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 stim-
uli, 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 par-
ticipants 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 [pat-
terns],” he says. “We are extremely grate-
ful to all the participants who volunteered.... I think most of them were happy to
participate and feel they were doing some-
thing right. It’s important to make positive
things out of a traumatic event.”
—Jef Akst
When you listen to the
reports of the survivors,
it was shocking.
—Karen Ersche, University of Cambridge