John Krakauer's Stroke of Genius

To break new ground in post-stroke rehabilitation techniques, Krakauer employs an eclectic mix of engineers and computer scientists.

BALTIMORE—To say John Krakauer is a maverick in the world of academic medicine errs on the side of caution.

His presentation "Motor Recovery After Stroke in Mice and Men" at a Johns Hopkins University seminar on brain science research got off to this start: "If you have a stroke in the United States in 2014, you're better off if you're a rodent than if you're a human being."

It was arresting, glib, and, based on what Krakauer has learned through experiments with rats and mice, true. When receiving intensive therapy in a stimulating environment—through interaction with toys, chutes, mirrors, rodent friends, interesting areas to explore—lab rats get better faster. Though humans unquestionably get excellent care at the time of a stroke with the delivery of clot-busting drugs and surveillance for complications, in Krakauer's opinion, standard post-stroke care for humans is intolerably backward.

Current rehabilitation therapies are medieval, Krakauer, a professor of neurology and neuroscience at Hopkins, told the audience of science writers. "It's time for a revolution."

A Rebel With a Cause

John Walter Krakauer is 47 years old and wears narrow rectangular blue eyeglasses that confer a kind of wry, postmodern look. The tone (British in accent) is by turns ironic, questioning (science, he says, is all about doubts and questions—not methodology), and supremely self-assured. To his patients he is compassionate, respectful, and accessible. He does not wear a white coat when making rounds and will unhesitatingly order a neurology resident who is more focused on email than on the patient to leave the room. (Related: "Virtual Dolphin on a Mission".)

When the British medical journal The Lancet asked Krakauer which famous person he would most want to have dinner with, he opted for Spanish filmmaker Pedro Almodóvar or Joss Whedon, creator of Buffy the Vampire Slayer.

Asked what career he would have chosen besides one in medicine, he listed art historian, literary critic, or Alvin Ailey dancer. The last may have been a stretch, but considering his knowledge base ("huge," says his department head) and literacy in humanities (he is as likely to quote Thomas Aquinas as Beavis and Butt-Head), he might very well have become the first or second.

When Krakauer arrived at Hopkins in 2010 to set up a center for stroke recovery research, one of the first things he jettisoned was the traditional composition of a research lab. Typically a neurology lab in an academic institution consists of a principal investigator, then a descending hierarchy of postdocs, graduate students, a medical student perhaps, all with essentially the same training and background as the principal investigator.

The staff roster in the Krakauer lab, on the second floor of the Carnegie Building, at the Johns Hopkins Medical complex in East Baltimore, upends that convention. It includes a robotics engineer, an animator, a software engineer, a mathematician, a computer scientist, and, as adjunct consultants, an animal intelligence expert and the director of animal programs at the National Aquarium. (There is, of course, collaboration with researchers from other neurology labs.) "To do something new, you need to bring people together who don't normally stand cheek by jowl," Krakauer says.

In Krakauer's BLAM lab (the acronym stands for brain, learning, animation, and movement), the something new being created is computer games for post-stroke rehabilitation and neurological research, developed by a cadre of young, Google/Pixar/Apple-grade talent.

His recruitment approach for what is known as the Kata Project ("kata" is a Japanese term relating to mastery and training) baffled the hospital administration at first. When he hired Kat McNally, an animator, from the Maryland Institute College of Art, it took two weeks to convince Human Resources it wasn't a mistake.

"You mean a medical illustrator?" they asked.

"No, an animator."

"I don't think we have anyone quite like John. Certainly not in this department and certainly not in the hospital," says Justin McArthur, director of the Department of Neurology at Hopkins. "He's not afraid to challenge thinking and ruffle feathers."

He has a streak of irreverence? I suggest.

"A streak? More like a river."

Stroke, Sports, and Science

Stroke is a stranglehold on the supply of blood, and thus oxygen, to the brain that cripples the body and sometimes the mind. Most strokes—80 percent or so—are ischemic and caused by a blood clot. The remainder are hemorrhagic, the result of a leaking or ruptured blood vessel, caused, for example, by an aneurysm or high blood pressure.

The disease afflicts—perhaps the better word is devastates—nearly 800,000 people in the United States each year. Krakauer stresses that it is not just a disease of the elderly. Some 32,000 of those stricken are under 45. On average, an American dies from a stroke every four minutes. More than half who survive suffer disabilities that can include paralysis or weakness, usually on one side, and difficulty in speech, swallowing, and memory. The economic burden is huge: about $37 billion in care a year.

The current model for stroke therapy is too little and, sometimes, too late and driven by economics, not science. The standard of care in a hospital setting is an hour of speech, an hour of physical, an hour of occupational therapy. That model is 150 years old, McArthur says, and "not adequate or up to today's scientific knowledge."

But before addressing the impairment of movement caused by stroke and the attempt to regain what's been lost, Krakauer would have us appreciate the other end of the continuum: the beauty and braininess of movement in its healthy state, particularly in professional athletes.

"We are obsessed with movement," he says, "yet we marginalize it, though we spend hours watching grown men jump around with a ball.

"We think jocks are inferior people, even though we pay athletes more than we pay anyone else in our culture. When Michael Jordan threw the ball behind him, he knew there would be someone there to catch it. He looked around the court, played it five seconds ahead, then acted on it."

That deft pass-off, Krakauer wants us to know, is high-level cognition at work, intersecting with the ability to execute it.

"People think it's all unconscious, automatic, and reflexive," he says. "They speak of muscle memory. Muscle memory is meaningless. Muscles don't have memory."

In short, movement is cognitive. This is not to suggest, he says, that sports are a substitute for the study of literature—simply a proposition that through the lens of neuroscience, a jock is far from dumb.

To Krakauer, the skill behind a Roger Federer pinpoint slam into the corner of an opponent's court is one end of an arc that spans a space between stroke, the ability to perform the tasks of everyday life, and the masterly performance of a professional athlete.

"It seems obvious," he says, "that they all have to share general principles. We have to study the whole spectrum, because they mutually inform themselves."

To figure out those principles, both how they are different and how they are the same—to understand motor planning and how a goal like picking up a coffee cup leads to the right muscle contractions and forces to actually move the arm and fingers, to deconstruct the anatomy and physiology of brain injury and repair—is the task of the neuroscientist, and the first order of business. Next comes application to the affliction of stroke, thief of the beautiful calculus of motion: the elegantly executed parabola of a golf swing, the seemingly casual reach for a cup of coffee, the gentle brush of a hand on a lover's face.

A Therapist With Fins

The ambassador of healing developed in the BLAM lab is a simulated dolphin named Bandit, based on three real bottlenose dolphins at the National Aquarium (with a dash of spinner dolphin thrown in) that the lab spent hundreds of hours studying, then turned into cybernetic form. Movement of a stroke patient's arm, placed in a robotic sling, manipulates the digital dolphin on a screen. Bandit swims with the fluidity of a real dolphin (and an aquatic swagger), catches fish, and swallows them in a symphony of crunching sounds. The reward comes in the chance to make Bandit leap—in a verisimilitude of twists, turns, and somersaults—for points. "It feels like you are being jacked into the creature," explains Omar Ahmad, who is the director of the Kata Project. "It's visceral feedback; every subtle movement you do is reflected in the dolphin." The player becomes the dolphin. It's engaging, much more so, than, say, the repetitive lifting of dumbbells in conventional therapy. (See: "Virtual Dolphin on a Mission.")

Clinical trials begin in a few months, but Bandit is already creating buzz even outside the medical arena. The game has a future as an iPad and iPhone app with a conservation message (if you become the dolphin, you empathize with the animals and don't want to see them in captivity, says Krakauer).

The lab has also developed an iPad "ant game." The game—the goal is to maneuver an ant along a hairpin-curve course—is being used to track motor skill recovery after traumatic brain injury and also as crowdsourced research to follow players as they get better at the skill. "I call it a lab on a pad," Krakauer says.

Do dolphins belong in a stroke unit? Isn't "hospital game" an oxymoron?

It shouldn't be, says Krakauer. Hospitals don't have to be bleak. "Why shouldn't a hospital be more like a gaming arcade? Why can't it be a place where you want to explore and play? People think it's frivolous or childish, [but that's] a kind of lurking puritanism."

And so the therapeutic utopia, as imagined by the BLAM lab, is equipped with engaging and healing games in an immersive and beautiful universe.

Brain Healing

To understand stroke therapy also requires an appreciation of the difference between repair and compensation. An injured brain can get better, like a cut that triggers an immune response and heals itself. The brain essentially reconfigures itself by way of a cascade of unique genetic, molecular, and physiological events. There's a roadblock in the circuitry, so the post-stroke brain maps out a detour that gets you to where you need to be, just by a different route. This spontaneous process happens during a post-stroke period of unusual brain plasticity that lasts one to three months. That, says Krakauer, is when therapy needs to be most intense. Instead "that sensitive window is being frittered away."

Miss that window of opportunity for endogenous repair and it's too late.

"You live with what's left." At that point of no return, rehabilitation turns into compensation. "If your right arm is paralyzed, you compensate by learning to be left-handed. If your legs are affected, you learn to use a walker." One promising avenue of research is directed at extending that period of plasticity (sometimes the patient is so sick, therapy can't begin right away) through the use of fluoxetine, an antidepressant.

In clinical trials to come, Bandit the dolphin will be deployed during that critical period of sensitivity when the brain is able to self-repair. If the immersive, aesthetic experience of making Bandit swim and leap helps stroke patients recover lost motor function faster than conventional therapy, it could very well provoke the revolution Krakauer envisions.

In the Stroke Unit

One day I followed Krakauer around the Brain Recovery Unit as he made rounds. Four to six times a year he steps into his clinical role as attending physician on the service. "I like being in the wards," he says. "The marvelous thing about Hopkins is that everyone is treated the same. Everyone gets love and respect."

Making rounds is a ritual of medical training—a Socratic dialogue between teacher (the attending) and students (the house staff residents). On that day there was a small, but varied, spectrum of patients. The first patient, a man in his 70s, had suffered a massive brain hemorrhage. He lay motionless on the bed, eyes shut, minimally responsive. ("What do you think is going on here?" Krakauer quizzed one of the residents, who examined the scans before entering the room. "What would you do next?") Every patient is a narrative, but in this instance the ending was expected to be grim: Large bleeds are usually fatal.

The last patient the group visited had suffered a stroke caused by high blood pressure and complicated by diabetes. His right hand had been affected, with loss of strength and mobility. Although the man was supposed to go home, Krakauer decided to delay his discharge so he could learn how to give himself insulin with his unaffected hand.

We had crossed into the dark land of illness. In the case of stroke, that shift occurs in an instant. A fleck of plaque breaks loose and lodges in a vessel leading to the brain. A life changes. The narrative becomes one of vulnerability and dependence.

"Think of it," Krakauer said as rounds ended and the entourage of neurologists-in-training dispersed. "You are in a hospital, regressed, scared, and surrounded by ten people hovering over you."

That soon-to-be-discharged patient with an impaired hand was particularly frustrating for Krakauer. "The high functioning individuals like him drive me to despair," he said afterward. "He needs a hand robot and a dolphin."

If all goes well with the clinical trials, that need for "dolphin therapy" will be met.

Prognosis?

Grand visions take time to be accepted. Bandit has a long swim ahead. There are leaps over clinical trial regulations, not to mention the negative feelings computer games evoke. When Krakauer appeared on Diane Rehm's radio talk show for a panel on video games and mental health, most guests talked about games as addictive and violence inducing. Krakauer had a different viewpoint. "Like any other interesting, complex technology, it can be abused or it can be highly beneficial," he said. "I am saying it is an unbelievable scientific instrument."

Then there are the ruffled feathers—academics in the field of physical therapy who challenge his contention that "current therapy is medieval."

"I think John is definitely a trailblazer," says Carolee Winstein, a professor of biokinesiology and physical therapy at the University of Southern California in Los Angeles. "But he sometimes exaggerates, in part to get people to pay attention. I think there have been significant advances in rehabilitation, though research does lag behind."

The use of computer games in rehab is not new, she adds, citing research groups at McGill University in Montreal, Carnegie Mellon in Pittsburgh, and Rutgers University in New Jersey, but Krakauer says there's no comparison, that superior technology, a conceptual framework that emphasizes movement exploration and enjoyment, and his work as a neuroscientist set his lab apart.

Both agree that stroke is woefully underfunded, which leads to a final hurdle for Bandit. Funding, the perpetual worry of the investigator, often goes to research of a more conservative nature.

"Everyone talks about innovation and interdisciplinary collaboration, but it's easier to talk about that than go through the pain of doing it," says Krakauer, noting that in a world of risk aversion and the easy slide into mediocrity, there is always a manager with a PowerPoint presentation lurking around the corner.

So what new ideas are lurking around the corner of Krakauer's mind? Not surprisingly, he'd like to see hospitals reinvent themselves—and not just for stroke patients. "Hospitals have become more like hotels with private rooms," he says. "This may work for certain areas of medicine, but we really need a space for interaction. The game is a form of enriched environment, but so is some kind of central café or gym."

And he'd like to extend the Kata Project into a "Bell Labs-like" center for movement, one that might—among other things—build better robots, study the pleasure principles of sport, and create an animal simulation center for conservation (think of Bandit as an ambassador for nature education).

In short, Krakauer—flamboyantly opinionated, controversial, and undeniably passionate about his work—will continue to battle against the ossification caused by the easy-to-slip-into adherence to the status quo.

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