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People who survive a painful event should express their feelings soon after so the mem ory isn't "sealed over" and repressed, which could lead to post-traumatic stress disorder. In recent years. CISD has become exceed ingly popular, used by the US Department of Defense, the Federal Emergency Management Agency, the Israeli army, the
United Nations, and the American Red

are trained in the technique. (After the September H attacks, 2,000 facilitators
descended on New York City.)

and ruining the future. So, in theory, the act of sharing those memories is an act of
forgetting them.

Even though PTSD is triggered by a stressful incident, it is really a disease of memory. The problem isn't the traumait's that the trauma can't be forgotten. Most
memories, and their associated emotions,
fade with time. But PTSD memories remain

A typical CISD session lasts about three

hours and involves a trained faciUtator who

Cross. Each year, more than 30,000 people

horribly intense, bleeding into the present

encourages people involved to describe the event from their perspective in as much detail as possible. Facilitators are trained to probe deeply and directly, asking questions such as, what was the worst part of the

happens after a memory is formed, when

we attempt to access it, was much less well understood. In the late 1990s, Karim Nader, a young neuroscientist studying emotional response at New York University, realized

new proteins were needed for the making

of memoriesproteins are cellular bricks and mortar, the basis of any new biologi cal constructionwere additional proteins
made when those memories were recalled?

His boss, the famed neuroscientist Joseph LeDoux, couldn't have been more discourag ing. "I told Karim he was wasting his time," LeDoux says. "I didn't think the experiment
would work." To LeDoux, the reason was

that no one knew. "My big advantage was that I wasn't trained in memory," Nader says. "I was very naive about the subject. Even though the field wasn't that inter
ested in the mechanisms of recall, it struck

Nader hypothesized that they were, and

he realized that he could test his notion

me as a mystery worth pursuing." He began with the simplest question

he could think of While it was clear that

by temporarily blocking protein synthesis in a brain and looking to see if that altered recEill. "This is the kind of question you ask when you don't know how else to approach the subject," Nader says. "But I had to do
something, so why not this?"

obvious: Even if Nader blocked protein syn thesis during recall, the original circuitry would still be intact, so the memory should
be too. If Nader could induce amnesia, it

would be temporary. Once the block was removed, the recall would return as strong as
ever. And so LeDoux and Nader made a bet:

If Nader failed to permanently erase a set of

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discovered what came to be called memory reconsolidation, the brain's practice of re creating memories over and over again.
But by the mid-1970s, neuroscientists had

eyewitness testimony shouldn't be trusted

(even though it's central to our justice sys tem), why every memoir should be classi

fied as fiction, and why it's so disturbingly

easy to implant false recollections. (The

largely stopped investigating reconsolida tion. Other researchers failed to replicate several of Lewis' original experiments, so the phenomenon was dismissed as an experimental error "These guys had discov ered it all way before me," Nader says. "But they had been left out of all the textbooks."
Nader was convinced that Lewis' work

psychologist Elizabeth Loftus has repeat edly demonstrated that nearly a third of subjects can be tricked into claiming a made-up memory as their own. It takes
only a single exposure to a new fiction for
it to be reconsolidated as fact.)
And this returns us to critical incident

had been rejected unjustly. But no one

wanted to hear it. "Man, it was brutal,"

Nader says. "I couldn't get published any

where." He was shunned at conferences

ONCE YOU START QUESTIONING the reality of memory, things fall apart pretty quickly. So many of our assumptions about the human mindwhat it is, why it breaks, and how
it can be healedare rooted in a mistaken

and accused in journal articles of "forget ting the lessons of the past." By 2001, just a few years after his experimental triumph, he was on the verge of leaving the field. He thought of Thomas Kuhn, the philosopher of science who famously observed that overturning paradigms is always a fear some task. "Why put up with this shit?" Nader says. "I finally understood what
Kuhn was talking about. I'd run straight

beUef about how experience is stored in the brain. (According to a recent survey, 63 per
cent of Americans believe that human mem

ory "works like a video camera, accurately recording the events we see and hear so that we can review and inspect them later") We want the past to persist, because the past gives us permanence. It tells us who we are
and where we belong. But what if your most
cherished recollections are also the most

stress debriefing. When we experience a traumatic event, it gets remembered in two separate ways. The first memory is the event itself that cinematic scene we can replay at will. The second memory, however, consists entirely of the emotion, the negative feelings triggered by what happened. Every memory is actually kept in many different parts of the brain. Memories of negative emotions, for instance, are stored in the amygdala,
an almond-shaped area in the center of the brain. (Patients who have suffered damage to the amygdala are incapable of remember ing fear) By contrast, all the relevant details that comprise the scene are kept in various sensory areasvisual elements in the visual cortex, auditory elements in the auditory cortex, and so on. That flhng system means that different aspects can be influenced independently by reconsolidation. The larger lesson is that because our memories are formed by the act of remem bering them, controlling the conditions under which they are recalled can actu ally change their content. The problem
with CISD is that the worst time to recall

into a very stubborn paradigm." But Nader was so angry at his scientific opponents that he refused to let them win, and by 2005 other researchers had started to take his side. Multiple papers demon strated that the act of recall required some
kind of protein synthesisthat it was, at the molecular level, nearly identical to the initial creation of a long-term recollection. Tobemorespeciflc:! can recall vividly the

ephemeral thing in your head? Consider the study of flashbulb memo ries, extremely vivid, detailed recollections. Shortly after the September 11 attacks, a

team of psychologists led by William Hirst and Elizabeth Phelps surveyed several hun dred subjects about their memories of that awful day. The scientists then repeated the
surveys, tracking how the stories steadily decayed. At one year out, 37 percent of the details had changed. By 2004 that number was approaching 50 percent. Some changes were innocuousthe stories got tighter and
the narratives more coherentbut other

party for my eighth birthday. I can almost

taste the Baskin-Robbins ice cream cake and

summon the thrill of tearing wrapping paper off boxes of Legos. This memory is embed ded deep in my brain as a circuit of con nected cells that 1 will hkely have forever Yet the science of reconsolidation suggests that the memory is less stable and trustworthy than it appears. Whenever I remember the party, I re-create the memory and alter its map of neural connections. Some details are reinforcedmy current hunger makes
me focus on the ice creamwhile others

adjustments involved a wholesale retrofit. Some people even altered where they were
when the towers fell. Over and over, the act

of repeating the narrative seemed to cor rupt its content. The scientists aren't sure
about this mechanism, and they have yet to analyze the data from the entire 10-year survey. But Phelps expects it to reveal that many details will be make-believe. "What's

a traumatic event is when people are flush with terror and grief They'll still have all the bodily symptoms of fearracing pulse, clammy hands, tremorsso the intense emotional memory is reinforced. It's the opposite of catharsis. But when people wait a few weeks before discussing an eventas
Mitchell, the inventor of CISD, did himself

they give their negative feelings a chance to

fade. The volume of trauma is dialed down;

get erased, like the face of a friend whose name I can no longer conjure. The memory is less Uke a movie, a permanent emulsion of chemicals on celluloid, and more like a playsubtly different each time it's performed. In my brain, a network of cells is constantly being reconsolidated, rewritten, remade. That two-letter prefix changes everything.

most troubling, of course, is that these people have no idea their memories have changed this much," she says. "The strength
of the emotion makes them convinced it's

the body returns to baseline. As a result, the emotion is no longer reconsolidated in such a stressed state. Subjects will still remem ber the terrible event, but the feelings of pain associated with it will be rewritten in Ught of what they feel now.
LeDoux insists that these same prin

all true, even when it's clearly not." Reconsohdation provides a mechanis

tic explanation for these errors. It's why

ciples have been used by good therapists for decades. "When therapy heals, when it
MAR 2012 WIRED 091

could stop crying. "That was the difference," she says. "I still remembered everything that happened, and it still hurt so much, but now I felt like I could live with it. The feelings were just less intense. The therapy let me breathe." Such improvements, small though they may seem, are almost unheard of in psychia try. "We never cure anything," Brunei says. "All we do is try to treat the worst symptoms. But I think this treatment has the potential to be the first psychiatric cure ever. For many people, the PTSD really is gone." Propranolol, of course, is an imperfect drug, a vintage tool commandeered for a new purpose. Despite Brunei's optimistic assessment, many of his patients remain traumatized, albeit perhaps less so. While he is currently conducting a larger-scale, ran domized PTSD trial with the beta-blocker, future therapies will rely on more targeted compounds. "These norepinephrine inhibi tors are just what's available right now," LeDoux says. "They work OK, but their effect is indirect." What reconsolidation therapy really needs is a drug that can target the fear

to an injection of lithium). After just a few trials, the rats began studiously avoiding the did a bunch of other molecules. It took me a artificial sweetener. All it took was a single few years to figure out if my dad was right." injection of a PKMzeta inhibitor called zetaIn fact, it took Sacktor more than a interacting protein, or ZIP, before the rats decade. (He spent three years just trying to forgot all about their aversion. The rats went purify the molecule.) What he discovered back to guzzling down the stuff By coupling these amnesia cocktails to is that a form of protein kinase C called the memory reconsolidation process, it's PKMzeta hangs around synapses, the junctions where neurons connect, for an possible to get even more specific. Nader, unusually long time. And without it, stable LeDoux, and a neuroscientist named Jacek Debiec taught rats elaborate sequences memory itself "The perfect drug wouldn't recollections start to disappear. While sci of association, so that a series of sounds just tamp down the traumatic feeling," he entists like Nader had erased memories predicted the arrival of a painful shock to says. "It would erase the actual representa using chemicals that inhibited all protein the foot. Nader calls this a "chain of mem synthesis, Sacktor was the first to target a tion of the trauma in the brain." ories"the sounds lead to fear, and the Here's the amazing part: The perfect single memory protein so specifically. The animals freeze up. "We wanted to know if trick was finding a chemical that inhib drug may have already been found. ited PKMzeta activity. "It turned out to be making you remember that painful event remarkably easy," Sacktor says. "All we had would also lead to the disruption of related to do was order this inhibitor compound memories," Nader says. "Or could we alter from the chemical catalog and then give it to just that one association?" The answer was the animals. You could watch them forget." clear. By injecting aprotein synthesis inhibi What does PKMzeta do? The molecule's tor before the rats were exposed to only one crucial trick is that it increases the den of the soundsand therefore before they sity of a particular type of sensor called an underwent memory reconsolidationthe AMPA receptor on the outside of a neuron. rats could be "trained" to forget the fear It's an ion channel, a gateway to the interior associated with that particular tone. "Only of a cell that, when opened, makes it easier the first link was gone," Nader says. The for adjacent cells to excite one another. other associations remained perfectly (While neurons are normally shy strangers, intact. This is a profound result. While sci struggling to interact, PKMzeta turns them entists have long wondered how to target into intimate friends, happy to exchange specific memories in the brain, it turns out all sorts of incidental information.) This to be remarkably easy: All you have to do is ask people to remember them. THE CHEMISTRY OF THE BRAIN IS in constant process requires constant upkeepevery This isn't Eternai Sunshine of the Spotless flux, with the typical neural protein lasting long-term memory is always on the verge of Mind-style mindwiping. In some ways it's anywhere from two weeks to a few months vanishing. As a result, even a brief interrup potentially even more effective and more before it breaks down or gets reabsorbed. tion of PKMzeta activity can dismantle the precise. Because of the compartmentalizaHow then do some of our memories seem function of a steadfast circuit If the genetic expression of PKMzeta is tion of memory in the brainthe storage of to last forever? It's as if they are sturdier different aspects of a memory in different than the mind itself. Scientists have nar amped upby, say, genetically engineering areasthe careful application of PKMzeta rowed down the list of molecules that rats to overproduce the stuffthey become synthesis inhibitors and other chemicals seem essential to the creation of long-term mnemonic freaks, able to convert even that interfere I continued on page 120 memorysea slugs and mice without these the most mundane events into long-term
MAR 2012 WIRED 093

compounds are total amnesiacsbut until recently nobody knew how they worked. In the 1980s, a Columbia University neurologist named Todd Sacktor became obsessed with this mental mystery. His breakthrough came from an unlikely source. "My dad was a biochemist," Sacktor says. "He was the one who said I should look into this molecule, because it seems to have some neat properties." Sacktor's father had suggested a molecule called protein kinase C, an enzyme turned on by surges of calcium ions in the brain. "This enzyme seemed to have a bunch of prop erties necessary to be a regulator of longterm potentiation." Sacktor says. "But so

memory. (Their performance on a standard test of recall is nearly double that of normal animals.) Furthermore, once neurons begin producing PKMzeta, the protein tends to linger, marking the neural connection as a memory. "The molecules themselves are always changing, but the high level of PKMzeta stays constant," Sacktor says.
"That's what makes the endurance of the
memory possible."

Sacktor and scientists at the Weizmann Institute of Science trained rats to associate the taste of saccharin with nausea (thanks

For example, in a recent experiment,