The American Commute By Alasdair Rae.

Helping Hand

Robots, video games, and a radical new approach to treating stroke patients.

BY KAREN RUSSELL

In late October, when the Apple TV was relaunched, Bandit’s Shark Showdown was among the first apps designed for the platform. The game stars a young dolphin with anime-huge eyes, who battles hammerhead sharks with bolts of ruby light. There is a thrilling realism to the undulance of the sea: each movement a player makes in its midnight-blue canyons unleashes a web of fluming consequences. Bandit’s tail is whiplash-fast, and the sharks’ shadows glide smoothly over rocks. Every shark, fish, and dolphin is rigged with an invisible skeleton, their cartoonish looks belied by the programming that drives them—coding deeply informed by the neurobiology of action. The game’s design seems suspiciously sophisticated when compared with that of apps like Candy Crush Soda Saga and Dude Perfect 2.

Bandit’s Shark Showdown’s creators, Omar Ahmad, Kat McNally, and Promit Roy, work for the Johns Hopkins School of Medicine, and made the game in conjunction with a neuroscientist and neurologist, John Krakauer, who is trying to radically change the way we approach stroke rehabilitation. Ahmad told me that their group has two ambitions: to create a successful commercial game and to build “artistic technologies to help heal John’s patients.” A sister version of the game is currently being played by stroke patients with impaired arms. Using a robotic sling, patients learn to sync the movements of their arms to the leaping, diving dolphin; that motoric empathy, Krakauer hopes, will keep patients engaged in the immersive world of the game for hours, contracting their real muscles to move the virtual dolphin.

Many scientists co-opt existing technologies, like the Nintendo Wii or the Microsoft Kinect, for research purposes. But the dolphin simulation was built in-house at Johns Hopkins, and has lived simultaneously in the commercial and the medical worlds since its inception. “We depend on user feedback to improve the game for John’s stroke patients,” Ahmad said. “This can’t work without an iterative loop between the market and the hospital.”

In December, 2010, Krakauer arrived at Johns Hopkins. His space, a few doors from the Moore Clinic, an early leader in the treatment of AIDS, had been set up in the traditional way—a wet lab, with sinks and ventilation hoods. The research done in neurology departments is, typically, benchwork: “test tubes, cells, and mice,” as one scientist described it. But Krakauer, who studies the brain mechanisms that control our arm movements, uses human subjects. “You can learn a lot about the brain without imaging it, lesioning it, or recording it,” Krakauer told me. His simple, non-invasive experiments are designed to produce new insights into how the brain learns to control the body. “We think of behavior as being the fundamental unit of study, not the brain’s circuitry. You need to study the former very carefully so that you can even begin to interpret the latter.”

Krakauer wanted to expand the scope of the lab, arguing that the study of the brain should be done in collaboration with people rarely found on a medical campus: “Pixar-grade” designers, engineers, computer programmers, and artists. Shortly after Krakauer arrived, he founded the Brain, Learning, Animation, Movement lab, or BLAM! That provocative acronym is true to the spirit of the lab, whose goal is to break down boundaries between the “ordinarily siloed worlds of art, science, and industry,” Krakauer told me. He believes in “propinquity,” the ricochet of bright minds in a constrained space. He wanted to create a kind of “neuro Bell Labs,” where different kinds of experts would unite around a shared interest in movement. Bell Labs is arguably the most successful research laboratory of all time; it has produced eight Nobel Prizes, and inventions ranging from radio astronomy to Unix and the laser. Like Bell,BLAM! would pioneer both biomedical technologies and commercial products. By developing a “self-philanthropizing ecosystem,” Krakauer believed, his lab could gain some degree of autonomy from traditionally conservative funding structures, like the National Institutes of Health.

The first problem that BLAM! has addressed as a team is stroke rehabilitation. Eight hundred thousand people in the U.S. have strokes each year; it is the No. 1 cause of long-term disability. Most cases result from clots that stop blood from flowing to part of the brain, causing tissue to die. “Picture someone standing on a hose, and the patch of grass it watered dying almost immediately,” Steve Zeiler, a neurologist and a colleague of Krakauer’s, told me. Survivors generally suffer from hemiparesis, weakness on one side of the body. We are getting better at keeping people alive, but this means that millions of Americans are now living for years in what’s called “the chronic state” of stroke: their recovery has plateaued, their insurance has often stopped covering therapy, and they are left with a moderate to severe disability.

In 2010, Krakauer received a grant from the James S. McDonnell Foundation to conduct a series of studies exploring how patients recover in the first year after a stroke. He was already well established in the worlds of motor-control and stroke research. He had discovered that a patient’s recovery was closely linked to the degree of initial impairment, a “proportional recovery rule” that had a frightening implication: if you could use early measures of impairment to make accurate predictions about a patient’s recovery three months later, what did that say about conventional physical therapy? “It doesn’t reverse the impairment,” Krakauer said.

Nick Ward, a British stroke and neurorehabilitation specialist who also works on paretic arms, told me that the current model of rehabilitative therapy for the arm is “nihilistic.” A patient lucky enough to have good insurance typically receives an hour each per day of physical, occupational, and speech therapy in the weeks following a stroke. “The movement training we are delivering is occurring at such low doses that it has no discernible impact on impairment,” Krakauer told me. “The message to patients has been: ‘Listen, your arm is really bad, your arm isn’t going to get better, we’re not going to focus on your arm,’ ” Ward said. “It’s become accepted wisdom that the arm doesn’t do well. So why bother?”

Krakauer and his team are now engaged in a clinical trial that will test a new way of delivering rehabilitation, using robotics and the video game made by Ahmad, Roy, and McNally, who make up an “arts and engineering” group within the Department of Neurology. Krakauer hopes to significantly reduce patients’ impairment, and to demonstrate that the collaborative model of BLAM! is “the way to go” for the future study and treatment of brain disease.

Reza Shadmehr, a Johns Hopkins colleague and a leader in the field of human motor-control research, told me, “He’s trying to apply things that we have developed in basic science to actually help patients. And I know that’s what you’re supposed to do, but, by God, there are very few people who really do it.”

“You bank on your reputation, in the more conventional sense, to be allowed to take these risks,” Krakauer said. “I’m cashing in my chits to do something wild.”

In 1924, Charles Sherrington, one of the founders of modern neuroscience, said, “To move things is all that mankind can do; for such the sole executant is muscle, whether in whispering a syllable or in felling a forest.” For Sherrington, a human being was a human doing.

Yet the body often seems to go about its business without us. As a result, we may be tempted to underrate the “intelligence” of the motor system. There is a deep-seated tendency in our culture, Krakauer says, to dichotomize brains and brawn, cognition and movement. But he points out that even a movement as simple as reaching for a coffee cup requires an incredibly sophisticated set of computations. “Movement is the result of decisions, and the decisions you make are reflected in movements,” Krakauer told me.

Motor skills, like Stephen Curry’s jump shot, require the acquisition and manipulation of knowledge, just like those activities we deem to be headier pursuits, such as chess and astrophysics. “Working with one’s hands is working with one’s mind,” Krakauer said, but the distinction between skill and knowledge is an ancient bias that goes back to the Greeks, for whom techne, skill, was distinct from episteme, knowledge or science.

Keep reading

This tutorial shows simple step-by-step instructions to get the BMP180 pressure sensor wired up and programmed with the Arduino Microcontroller. We show how …

Arduino with Python LESSON 9: Measuring Pressure and Temperature with the BMP180 Sensor

This map shows where 25 iconic movies were filmed in New York City

Geos-1 being tested at ESTEC

A vintage view of ESA’s Geos-1 satellite being prepared for flight at ESA’s technical centre in the Netherlands, which was launched 40 years ago this month.

Keep reading

Muscle-controlling Neurons Know When They Mess Up

Whether it is playing a piano sonata or acing a tennis serve, the brain needs to orchestrate precise, coordinated control over the body’s many muscles. Moreover, there needs to be some kind of feedback from the senses should any of those movements go wrong. Neurons that coordinate those movements, known as Purkinje cells, and ones that provide feedback when there is an error or unexpected sensation, known as climbing fibers, work in close concert to fine-tune motor control.   

A team of researchers from the University of Pennsylvania and Princeton University has now begun to unravel the decades-spanning paradox concerning how this feedback system works.

At the heart of this puzzle is the fact that while climbing fibers send signals to Purkinje cells when there is an error to report, they also fire spontaneously, about once a second. There did not seem to be any mechanism by which individual Purkinje cells could detect a legitimate error signal from within this deafening noise of random firing. 

Using a microscopy technique that allowed the researchers to directly visualize the chemical signaling occurring between the climbing fibers and Purkinje cells of live, active mice, the Penn team has for the first time shown that there is a measurable difference between “true” and “false” signals.

This knowledge will be fundamental to future studies of fine motor control, particularly with regards to how movements can be improved with practice. 

The research was conducted by Javier Medina, assistant professor in the Department of Psychology in Penn’s School of Arts and Sciences, and Farzaneh Najafi, a graduate student in the Department of Biology. They collaborated with postdoctoral fellow Andrea Giovannucci and associate professor Samuel S. H. Wang of Princeton University.

It was published in the journal Cell Reports.

The cerebellum is one of the brain’s motor control centers. It contains thousands of Purkinje cells, each of which collects information from elsewhere in the brain and funnels it down to the muscle-triggering motor neurons. Each Purkinje cell receives messages from a climbing fiber, a type of neuron that extends from the brain stem and sends feedback about the associated muscles. 

“Climbing fibers are not just sensory neurons, however,” Medina said. “What makes climbing fibers interesting is that they don’t just say, ‘Something touched my face’; They say, ‘Something touched my face when I wasn’t expecting it.’ This is something that our brains do all the time, which explains why you can’t tickle yourself. There’s part of your brain that’s already expecting the sensation that will come from moving your fingers. But if someone else does it, the brain can’t predict it in the same way and it is that unexpectedness that leads to the tickling sensation.”

Not only does the climbing fiber feedback system for unexpected sensations serve as an alert to potential danger — unstable footing, an unseen predator brushing by — it helps the brain improve when an intended action doesn’t go as planned.    

“The sensation of muscles that don’t move in the way the Purkinje cells direct them to also counts as unexpected, which is why some people call climbing fibers ‘error cells,’” Medina said. “When you mess up your tennis swing, they’re saying to the Purkinje cells, ‘Stop! Change! What you’re doing is not right!’ That’s where they help you learn how to correct your movements.

“When the Purkinje cells get these signals from climbing fibers, they change by adding or tweaking the strength of the connections coming in from the rest of the brain to their dendrites. And because the Purkinje cells are so closely connected to the motor neurons, the changes to those synapses are going to result in changes to the movements that Purkinje cell controls.”

This is a phenomenon known as neuroplasticity, and it is fundamental for learning new behaviors or improving on them. That new neural pathways form in response to error signals from the climbing fibers allows the cerebellum to send better instructions to motor neurons the next time the same action is attempted.

The paradox that faced neuroscientists was that these climbing fibers, like many other neurons, are spontaneously activated. About once every second, they send a signal to their corresponding Purkinje cell, whether or not there were any unexpected stimuli or errors to report.

“So if you’re the Purkinje cell,” Medina said, “how are you ever going to tell the difference between signals that are spontaneous, meaning you don’t need to change anything, and ones that really need to be paid attention to?”

Medina and his colleagues devised an experiment to test whether there was a measurable difference between legitimate and spontaneous signals from the climbing fibers. In their study, the researchers had mice walk on treadmills while their heads were kept stationary. This allowed the researchers to blow random puffs of air at their faces, causing them to blink, and to use a non-invasive microscopy technique to look at how the relevant Purkinje cells respond.

The technique, two-photon microscopy, uses an infrared laser and a reflective dye to look deep into living tissue, providing information on both structure and chemical composition. Neural signals are transmitted within neurons by changing calcium concentrations, so the researchers used this technique to measure the amount of calcium contained within the Purkinje cells in real time.

Because the random puffs of air were unexpected stimuli for the mice, the researchers could directly compare the differences between legitimate and spontaneous signals in the eyelid-related Purkinje cells that made the mice blink.

“What we have found is that the Purkinje cell fills with more calcium when its corresponding climbing fiber sends a signal associated with that kind of sensory input, rather than a spontaneous one,” Medina said. “This was a bit of a surprise for us because climbing fibers had been thought of as ‘all or nothing’ for more than 50 years now.”

The mechanism that allows individual Purkinje cells to differentiate between the two kinds of climbing fiber signals is an open question. These signals come in bursts, so the number and spacing of the electrical impulses from climbing fiber to Purkinje cell might be significant. Medina and his colleagues also suspect that another mechanism is at play: Purkinje cells might respond differently when a signal from a climbing fiber is synchronized with signals coming elsewhere from the brain.   

Whether either or both of these explanations are confirmed, the fact that individual Purkinje cells are able to distinguish when their corresponding muscle neurons encounter an error must be taken into account in future studies of fine motor control. This understanding could lead to new research into the fundamentals of neuroplasticity and learning.    

“Something that would be very useful for the brain is to have information not just about whether there was an error but how big the error was — whether the Purkinje cell needs to make a minor or major adjustment,” Medina said. “That sort of information would seem to be necessary for us to get very good at any kind of activity that requires precise control. Perhaps climbing fiber signals are not as ‘all-or-nothing’ as we all thought and can provide that sort of graded information”

#DataMining

Poland A and Poland B might be real - Borders of Imperial Germany and the 2015 Polish Presidential Race Exit Poll Results.

Orange (Incumbent): PO (Civic Platform) Party - Liberal-Conservative

Blue: PiS (Law and Justice) Party - Interventionist & Social Conservative

More interesting correlations >>

DEC terminal finds itself viscously attacked by a bear. 

Leonardo DiCaprio accepts his award for Best Actor in a Drama Film for ‘The Revenant’ and dedicates it to indigenous communities.