<!--intro-->Duke University Medical Center researchers and their colleagues have tested a neural system on monkeys that enabled the animals to use their brain signals, as detected by implanted electrodes, to control a robot arm to reach for a piece of food. The scientists even transmitted the brain signals over the Internet, remotely controlling a robot arm 600 miles away. <!--/intro--> According to the scientists, their recording and analysis system, in which the electrodes remained implanted for two years in one animal, could form the basis for a brain-machine interface that would allow paralyzed patients to control the movement of prosthetic limbs. Their finding also supports new thinking about how the brain encodes information, by spreading it across large populations of neurons and by rapidly adapting to new circumstances. In an article in the Nov. 16, 2000, Nature, Miguel Nicolelis, associate professor of neurobiology, and his colleagues described how they tested their system on two owl monkeys implanting arrays of as many as 96 electrodes, each less than the diameter of a human hair, into the monkeys' brains. The technique they used, called "multi-neuron population recordings" was developed by co- author John Chapin and Nicolelis. It allows large numbers of single neurons to be recorded separately, and then combines their information using a computer coding algorithm. The scientists implanted the electrodes in multiple regions of the brain's cortex, including the motor cortex from which movement is controlled. The scientists then recorded the output of these electrodes as the animals learned reaching tasks, including reaching for small pieces of food. The scientists fed the mass of neural signal data generated during many repetitions of these tasks into a computer, which analyzed the brain signals to determine whether it was possible to predict the trajectory of the monkey's hand from the signals. In this analysis, the scientists used simple mathematical methods to predict hand trajectories in real-time as the monkeys learned to make different types of hand movements. Said Chapin, who is at the State University of New York Health Science Center, "In a previous paper [published in the July 1, 1999, Nature Neuroscience], we found that rats were able to use their neuronal population activity to control a robot arm, which they used to bring water to their mouths. At the beginning of the experiments, the animals had to press down a lever to generate the brain activity needed to move the robot arm. Over continued training, however, their lever movements diminished while their brain activity remained the same." Said Nicolelis, "We found two amazing things, both in the earlier rat studies and in our new studies on these primates. One is that the brain signals denoting hand trajectory shows up simultaneously in all the cortical areas we measured. This finding has important implications for the theory of brain coding which holds that information about trajectory is distributed really over large territories in each of these areas even though the information is slightly different in each area. "The second remarkable finding is that the functional unit in such processing does not seem to be a single neuron," Nicolelis said. "Even the best single-neuron predictor in our samples still could not perform as well as an analysis of a population of neurons. So, this provides further support to the idea that the brain very likely relies on huge populations of neurons distributed across many areas in a dynamic way to encode behavior." Once the scientists demonstrated that the computer analysis could reliably predict hand trajectory from brain signal patterns, they then used the brain signals from the monkeys as processed by the computer to allow the animals to control a robot arm moving in three dimensions. They even tested whether the signals could be transmitted over a standard Internet connection, controlling a similar arm in MIT's Laboratory for Human and Machine Haptics informally known as the <a HREF="http://touchlab.mit.edu/">Touch Lab</a>. Said co-author Mandayam Srinivasan, director of the MIT laboratory, "When we initially conceived the idea of using monkey brain signals to control a distant robot across the Internet, we were not sure how variable delays in signal transmission would affect the outcome. Even with a standard TCP/IP connection, it worked out beautifully. It was an amazing sight to see the robot in my lab move, knowing that it was being driven by signals from a monkey brain at Duke. It was as if the monkey had a 600-mile-long virtual arm." Besides Nicolelis, Srinivasan and Chapin, other co-authors of the paper were, from Duke, Johan Wessberg, Christopher Stambaugh, Jerald Kralik, Pamela Beck and Mark Laubach; and from MIT, Jung Kim and James Biggs. The scientists' work is supported by the National Institutes of Health, National Science Foundation, Defense Advanced Research Projects Agency and the Office of Naval Research. "The reliability of this system and the long-term viability of the electrodes lead us to believe that this paradigm could eventually be used to help paralyzed people restore some motor function," Nicolelis said. "This system also offers a new paradigm to study basic questions of how the brain encodes information. For example, now that we've used brain signals to control an artificial arm, we can progress to experiments in which we change the properties of the arm or provide visual or tactile feedback to the animal, and explore how the brain adapts to it. Understanding such adaptation will allow us to make inferences about how the brain normally encodes information." Nicolelis and his colleagues will soon begin such "closed-loop" experiments, in which movement of the robot arm generates tactile feedback signals in the form of pressure on the animals' skin. Also, they are providing visual feedback by allowing the animal to watch the movement of the arm. The scientists' experiments with learning in rats that were reported in Nature last July have already indicated that the analysis system can detect adaptive brain changes associated with learning. Such feedback studies could also potentially improve the ability of paralyzed people to use such a brain-machine interface to control prosthetic appendages, said Nicolelis. In fact, he said, the brain could prove extraordinarily adept at using feedback to adapt to such an artificial appendage. "One most provocative, and controversial, question is whether the brain can actually incorporate a machine as part of its representation of the body," he said. "I truly believe that it is possible. The brain is continuously learning and adapting, and previous studies have shown that the body representation in the brain is dynamic. So, if you created a closed feedback loop in which the brain controls a device and the device provides feedback to the brain, I would predict that as people or animals learn to use the device, their brains will basically dedicate neuronal space to represent that device. "If such incorporation of artificial devices works, it would quite likely be possible to augment our bodies in virtual space in ways that we never thought possible," Nicolelis said. "For example, in our modest experiment at using brain wave patterns to control the robot arm over the Internet, if we extended the capabilities of the arm by engineering in feedback such as visual, force or texture such closed-loop control might result in the remote arm being incorporated into the body's representation in the brain. Once you establish a closed loop, you're basically telling the brain that the external device is part of the body representation. The major question in my mind now is what is the limit of such incorporation." Besides experimenting with such feedback systems, Nicolelis and his colleagues are planning to increase the number of implanted electrodes, with the aim of achieving 1,000-electrode arrays. They are also developing a "neurochip" that will greatly reduce the size of the circuitry required for sampling and analysis of brain signals. "We envision that this neurochip can become an essential component of the type of hybrid- brain-machine interfaces that may one day be used to restore motor function in paralyzed patients," said Nicolelis. "These activities will serve as the backbone of a new Center for Neural Analysis and Engineering currently being created at Duke."