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UNIVERSITY OF CHICAGO SUMMER 2006 BIOLOGICAL SCIENCES DIVISION AN ENEMY IN OUR MIDST ⌴␫⌵␦ ⌴␣␶␶⑀r MIND OVER MATTER: MOVING OBJECTS WITH YOUR MIND HAS LONG BEEN FODDER FOR SCIENCE FICTION STORIES. NOW, RESEARCH IS TURNING IT INTO REALITY. By Kelli Whitlock Burton ⌵icholas Hatsopoulos adjusts university research groups working on the volume on his computer and looks the problem in the United States. around. “Hear that?” he asks. There’s Ten years ago, Hatsopoulos and a steady crackling noise coming from John Donoghue, his former postdoctoral the speakers, like hail on a tin roof. advisor at Brown University, became the Hatsopoulos smiles. The crackling first scientists to teach monkeys how to chorus is as satisfying to his ear as a move a computer cursor with their minds. good guitar riff by Jimi Hendrix, one Two years ago, they taught a person to do of his favorite musicians. it—a quadriplegic who was able to turn What seems like a hail storm actually on a television, check e-mail and wiggle is the sound of neurons firing inside the fingers of an artificial hand, all with the motor cortex, the part of the brain his thoughts alone. The patient is part responsible for movement—a symphony of an FDA clinical trial of the BrainGate™ that just 15 years ago Hatsopoulos system, the product of a company could only dream of hearing, much Donoghue and Hatsopoulos launched less composing. in 2000. Listening to the brain is no small In a nutshell, the researchers have feat, and if that were the brightest note found a way to turn thought into action— in this little concert, it would be worth without moving a muscle. an ovation. But Hatsopoulos, an assistant professor of organismal biology and WHEN SCIENCE TICKLES anatomy at the University of Chicago, If his dark curly hair, deep brown eyes and can do more than eavesdrop. Along distinctive surname aren’t clue enough to with colleagues at Brown University, his ancestry, the strains of Mediterranean he has developed a way to record signals music coming from his office are a dead sent out by large groups of neurons— giveaway. Hatsopoulos’ parents grew up in commands telling the body how and Athens, Greece, but didn’t meet until the where to move—and to translate the orders into a language a computer understands and acts on. The technology is called a brain- computer interface—BCI for short—and it’s not a new phenomenon. Scientists have tinkered with BCI since the 1970s, but it’s only in the past decade that the technology’s true potential has been realized. The main thrust today is devel- oping BCI systems to aid people who are y r D paralyzed by injury or illness. While these n a D patients’ limbs may be stilled, studies show y b o t that the motor cortex is not. Hatsopoulos’ o h team is one of only about half a dozen P Chicago researcher Nicholas Hatsopoulos 19 early 1950s after each traveled separately to Boston to attend college, his father at MIT and his mother at Wellesley. With a mechanical engineer and physicist for a dad as well as a mathematician for a mother, Hatsopoulos was surrounded by science while he grew up in Lincoln, Mass., just outside Boston. He even chose to major in physics at Williams College. Still, when it came time to make plans after graduation, he wasn’t quite ready s o l to launch a scientific career. Instead, u o p o s Hatsopoulos decided to teach physics t a H and computers for a year in Greece. s a l o h c When he wasn’t in class, he dabbled i N f o with the bouzouki, an instrument similar y s e t to a mandolin. He even toyed with the r u o c o idea of staying in his parents’ homeland t o h to become a professional bouzouki player. P But something about science tickled his Hatsopoulos’ appreciation for science subconscious, so he returned to Boston is much like his love of music. While the “As soon as I recorded and took a job as a research assistant to a individual instruments are beautiful to my first cell and saw Harvard mathematical psychologist. Soon hear, it’s the combination of their sounds he enrolled in the psychology master’s that Hatsopoulos enjoys most. Similarly, the electrical spikes on program at Brown. By 1992 he’d earned the actions of one brain cell may be the oscilloscope and a PhD in cognitive science. Skilled in interesting, but the possibilities that physics, psychology, cognition and the abound when cells work together are listened to the crackle bouzouki, Hatsopoulos headed to Caltech downright fascinating. of a neuron spiking, I for a postdoc with a scientist who studied Take the bouzouki, for example. “I insects’ brains. have always been enamored by the finger was hooked.” There, Hatsopoulos made his first work these musicians do and how they recording of a neuron—a single cell in a coordinate their fingers that way,” locust’s brain. “As soon as I recorded my Hatsopoulos mused. How do the millions first cell and saw the electrical spikes on the of neurons in the motor cortex work 6 0 0 oscilloscope and listened to the crackle of a together to allow someone to strum sweet 2 r e neuron spiking, I was hooked,” he said. music on a bouzouki? m m u S y a w d i M e h t n o e n i c i d e The silicone chip—part of the brain-computer interface— M that’s implanted in the brain’s motor cortex. Photo courtesy of Nicholas Hatsopoulos 20 “What really turns me on in this Things started to come together when All this and the researchers weren’t research is understanding how these large Donoghue met Richard Normann from even sure the device would collect the groups of cells result in motor behavior the University of Utah. Normann had multi-cell data they needed. They trained or thought,” Hatsopoulos said. Studying developed a sensor array—a silicone chip a monkey to move a computer cursor by single cells, as he was doing at Caltech, about the size of a breath mint with 100 maneuvering a joystick with its arm, set would not help him find the answer. tiny electrodes, each capable of recording up their system, and watched. So in 1995, Hatsopoulos returned neuronal impulses. The array not only worked, it func- to Brown for a second postdoc with Donoghue and Hatsopoulos modified tioned better than the scientists had Donoghue. The neuroscientist was bent the array, which had only been used in hoped. In 1996, the team recorded signals on figuring out how to record as many cats and Petri dishes, for their studies from multiple brain cells in a monkey— neurons in the motor cortex as possible. with monkeys. Each electrode on the the first time anyone had collected data Hatsopoulos was more than happy to help. chip, which is implanted on the surface from the monkey using this array. “I of the motor cortex, picks up signals remember that moment as really exciting THE RECORDING from nearby neurons. Those impulses are from more of a scientific point of view,” INDUSTRY carried by gold wires that connect the Hatsopoulos said. “We were looking at Scientists had developed a way to listen chip to a titanium pedestal that protrudes the brain on a more global level, looking in on single brain cells years before about an inch from the monkey’s scalp. at a group of neurons that make up the Donoghue began his studies. Many tech- A cord extends from the top of the neural ensemble that is responsible for niques were employed, but one of the pedestal to a device that amplifies the everything that we do as thinking beings.” most successful was a mechanism created signals. A fiber-optic cable hooks the The next step was to identify patterns by Philip Kennedy, a scientist at Georgia amplifier to an acquisition system, which in neuronal activity related to movement. State University, who launched the first captures the neural impulses and sends Hatsopoulos’ job was to create algorithms human clinical trial of an implanted BCI them to a computer. that translated the chatter between the device. Consisting of glass cones with two microelectrodes designed to pick up neural impulses in the brain, the device was implanted in the motor cortex of a paralyzed patient. The woman was asked to think about moving a computer cursor. The device captured the cell signals and, using a radio transmitter under the scalp, sent them to a computer that decoded them and moved the cursor. s o l But Kennedy could only record data u o p o from one or two neurons with his device; s t a H Donoghue’s sights were set much higher. s a l o h He wanted to capture signals from dozens, c i N f perhaps hundreds, of brain cells. Monitor- o y s e t ing more neurons would provide a clearer r u o c picture of brain activity, Donoghue believed. o t o h P A titanium pedestal connects to the implanted chip. “We were looking at a group of neurons that make up the neural ensemble that is responsible for everything that we do as thinking beings.” 21 neurons in the motor cortex into a A RELUCTANT language the computer could understand ENTREPRENEUR —language that conveys information His father’s dream had been to come to about movement.

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