Neuroscientist Theodore Berger is working real hard to be the
     first person to implant microchips between your ears.

     By Samuel Greengard

     Clad in slacks and a dress shirt, Theodore Berger sits in his
     cluttered office, surrounded by the flotsam and jetsam of his
     work: modems, Zip drives, electrostatic bags, manuals, floppy
     disks, white cotton gloves, books. The intense neurobiologist is
     talking neurons and silicon chips, dendrite tissue and advanced
     photonics. Beneath the wall-mounted photographs of brain tissue
     and schematic diagrams of VLSI chips sit a pair of Gateway 2000
     Pentium PCs. Their hard plastic outer cases have been removed, the
     inside electronics ready for quick exploration. It's an
     unmistakable metaphor for a guy who finds the bony cranium an
     incidental obstacle to studying gray matter.

     During the past four years, Berger and a seven-member team of
     scientists - experts in everything from semiconductors to the
     neurophysiology of tissue cultures - have worked ceaselessly at
     the University of Southern California in Los Angeles to unlock the
     brain's complex mathematical model so they can bridge the gap
     between silicon and cerebrum. "If we can speak to the brain in its
     own language then we begin to understand the biological basis of
     thought and learning," says the 46-year-old scientist. "It's a
     matter of understanding the way neurons act and react in every
     conceivable situation, then building a device that can duplicate
     their basic functions and transmit the appropriate electrical
     impulses."

     If Berger can link the two - computer and brain - he may create a
     parallel- processing network that could function as a brain
     implant. Such a device would restore physical and mental functions
     lost to stroke, head trauma, Alzheimer's, epilepsy, and an array
     of other maladies. His plan to create a bionic brain is bold,
     brash, and just a bit, well, mind-blowing. Berger - scientist,
     tinkerer, dreamer - wants to be the man who implants microchips
     between your ears. And the amazing thing is that he just might
     succeed.

     Simple problem, complex solution

     Understanding the human brain is a formidable task. Parked inside
     the average cranium are between 1 and 10 billion neurons.
     Extensions called dendrites relay electrical impulses to other
     neurons, the brain cells that serve as the basic building blocks
     of thought and activity. The electrical impulses are carried on
     fibers called axons. The result is a neural network of remarkable
     complexity.

     The power of neurons is that they can work together in different
     ways to produce speech, vision, hearing, and thought. Only when
     something goes terribly wrong are we aware of how serious it is to
     lose these connections. Only then are we able to recognize how
     difficult it is to regain what's lost and how much therapy may be
     required.

     Neuroscience, a field that didn't exist until the mid-1960s, has
     struggled to map the human brain and comprehend how all the
     piecesfit together. It's analogous to a space alien dissecting
     computers, robots, and other devices stuffed with semiconductors.
     Without a road map, it would be virtually impossible to know what
     each chip does and how it interacts with other microprocessors.

     A decade ago, when Berger began studying "wet" brain tissue taken
     from animals, he saw how little was known about the way neurons
     process information, or how populations of neurons can work
     together. Although scientists know a great deal about the
     functioning of the individual nerve cells that compose the
     hippocampus - the part of the brain that oversees memory - there's
     still no clear idea of how their interaction produces the
     cognitive function known as learning. "A great deal of classical
     neurophysiology is devoted to trying to understand how the neurons
     process the signal and what the output represents," he explains.

     That's not a nagging concern for Berger. Instead, he spends 12 to
     14 hours a day identifying and cataloging predictable and
     repeatable neural electrical patterns, continuing a pattern of
     neural/technical intervention that has been explored for decades.
     In the 1950s, for instance, a stir was caused by a famous
     experiment on rats by J. Olds and P. Milner. Electrodes were
     implanted in each rat's lateral hypothalamus and connected to a
     stimulator that could be activated by pressing a small button.
     Since the electrical stimulation caused feelings of pleasure, the
     rats soon learned to stimulate themselves, choosing that button
     rather than another that would provide them with food, even when
     they were hungry.

     A decade later, American neurophysiologist J. M. R. Delgado used
     stereotactic instruments to implant microelectrodes in precisely
     targeted areas within the brain. Their signals were transmitted
     wirelessly, making it possible to send high-voltage current. That
     led to drastic changes in emotional, sexual, and social behavior.

     In one dramatic demonstration, Delgado implanted an electronic
     receiver in the medial region of the hypothalamus of a bull and
     then challenged the animal to do battle in a bullfighting ring.
     Delgado stopped the charging bull at the last minute by activating
     electrodes with a radio transmitter.

     More recent experiments by researchers like Caltech's Carver Mead
     have shown that the elementary operations found in the nervous
     system can be realized by analog circuits created with standard
     silicon fabrication technology. Many neural areas are organized as
     thin sheets and carry two-dimensional representations of their
     computational space. These structures map well onto the
     two-dimensional silicon surface. Coincidentally, in both neural
     and silicon technologies, the active devices (synapses and
     transistors) occupy no more than a small percentage of the space -
     "wire" fills the remaining area.

     Berger and fellow team member Vasilis Marmarelis, a professor of
     biomedical engineering, have built on those insights through an
     elaborate game of copycat, developing a complicated mathematical
     model that precisely replicates the input and output signals that
     a natural neural system uses. Just as a basketball player doesn't
     require a degree in advanced trigonometry to toss a jump shot
     through a hoop, Berger doesn't need to unlock the vast secrets of
     the brain to make an implant work.

     Wander into Berger's lab and you begin to see where he's going
     with all this. Alongside a workbench covered with beakers and
     tubes, a researcher (in the finest tradition of a Carnegie Deli
     chef) slices human brain tissue into ultrathin sections. These
     samples are then inserted into test tubes filled with oxygen and
     artificial cerebral-spinal fluid, which keeps the fresh tissue
     alive for several hours. The sample is transported to another part
     of the lab, where a series of electrodes and probes are inserted.
     This leads to a smorgasbord of electronic amplifiers and
     oscilloscopes.

     For the next few hours, the tissue is subjected to a series of
     electronic impulses designed to simulate every possible
     combination that the brain can throw at it. A Pentium computer
     charts the data, creates a unique profile for each piece of
     tissue, and then slots the information into an enormous database.

     Berger & Co. repeat this process thousands of times. It's not
     enough to know how a piece of brain tissue reacts to different
     circumstances. They must understand the range of responses to the
     same stimulus at different times.

     Hardwiring the head

     Constructing a brain implant is more than a meat-and-test-tube
     operation, however. Even with a growing understanding of the
     mathematics involved in driving such a system, today's digital
     microprocessors are not fast enough to execute the complex
     instructions in real time. Minutes, hours, even days could elapse
     before a software-driven brain implant could process even the most
     basic task, such as moving a finger that has been paralyzed by
     stroke or restoring a fragment of memory lost to Alzheimer's.
     Imagine trying to surf the Web on a 300-bps modem or commute to
     work in a go-cart. Possible? Yes. Practical? Definitely not.

     That's where silicon and hybrid analog/digital microchips enter
     the picture. By hardwiring the algorithms that represent, say, 100
     neurons onto a microchip, it is possible to rapidly accelerate the
     data processing. A calculation that might have taken 10 seconds or
     more in the past is now completed in only about 100 nanoseconds.
     What's more, these neural microchips can operate as
     parallel-processing devices.

     But there's still a long way to go. Putting the function of
     perhaps 100 or 200 neurons on a single chip and then hardwiring
     tens of thousands of chips together would replicate only a
     fraction of the 4 or 5 million neurons in the hippocampus. You'd
     need an implant device the size of a pickup to get anywhere near
     the processing power of the brain.

     Armand R. Tanguay Jr., director of the Center for Neural
     Engineering at USC and a key member of the team, hopes to solve
     the scaling and bandwidth problems through a combination of
     holography and laser optics. By using light signals to replace
     physical wiring, it's possible to tightly stack 1-by-1-centimeter
     chips, which can then communicate with each other. This tiny
     parallel-processing network potentially allows for real-time
     response, and might eventually fit into a space the size of a
     peanut or, more important, the human skull.

     Such an implant could be tailored to replace a lost ability in
     humans. "Because the brain is such an adaptive organ," Berger
     says, "the device wouldn't have to precisely mimic the lost
     functions. If the brain is provided with a basic set of
     instructions, it would fill in the blanks and regain the lost
     functions. Over days and weeks, the person might make a full
     recovery."

     It's tough, time-consuming work, but engineering an implant from
     the silicon up is a bit easier when you've got your own photonic
     fabrication facility on the premises. Just a few hundred feet from
     Berger's lab is a US$10 million setup that has the ability to make
     the photonic elements that "wire" the silicon chips together, as
     well as the multielectrode probes that act as an interface between
     living and man-made neural circuits.

     Surrounded by an array of equipment that would seem more fitting
     in Silicon Valley than downtown LA - including a bonding machine
     and clean room that can filter down to 10 particles per cubic foot
     - assistant professor Chris Kyriakakis shows off a hybrid optical
     electronic device that contains a set of stacked chips. "It has
     the built-in electronics to power the entire device," he explains.
     "The first chip drives another optical chip that can modulate
     light. Ultimately, that's what runs the tiny computer network."

     The final and most difficult step is placing such a device inside
     the skull and connecting it to a living brain. Crosswiring such
     wildly divergent universes - one brains, the other bytes - isn't
     for the faint of heart or the intellectually timid. It's certainly
     not difficult to let your imagination run amok and conjure up an
     image of some crazed zombie straight out of a Boris Karloff flick.
     But Berger is no Boris. Although Berger eschews much of the
     conventional wisdom that permeates the rarefied field of
     neuroscience - particularly traditional reductionist thinking that
     says every piece of the puzzle must be fully understood in order
     to build a scientific model - he also knows that it's crucial to
     retain credibility within the discipline by adhering to accepted
     standards and practices.

     You might call his attitude skeptically reverent. "History is
     littered with the debris of firmly established explanations that
     have suddenly been overturned by new information," he says. "There
     are countless cases where humanity believed that an explanation
     was absolutely right, and then someone else came along with a
     radically different explanation that washed the old theory down
     the drain. So, it is very difficult to accept the truth of the
     day. It's crucial to look at various perspectives and
     explanations, to always keep the big picture in mind."

     Berger seems to do that pretty well, though his approach perturbs
     some in the scientific community. Having grown up in a household
     that placed a high premium on introspection and accomplishment
     ("Not necessarily the accomplishment that comes with dollars, but
     the accomplishment of having an impact on the people around you,"
     he explains), and with a father who helped pioneer transistor
     research at IBM, he realized early on that he wanted to make a
     real difference in the world.

     Berger studied mathematics and psychology at college but shied
     away from a career in psychology, opting instead for the hands-on
     world of neuroscience. "I realized that psychology doesn't have
     the tools to fully understand the cause and effect of behavior,"
     he says. "It is a very incomplete part of the puzzle."

     Fast-forward a couple of decades, and Berger's life puzzle is
     mostly assembled. He lives in a pleasant split-level home
     overlooking the bluffs and beaches of Palos Verdes, commuting the
     40 minutes to work in a 1992 Honda Accord. He spends spare moments
     gardening or tinkering with computers; both allow him to further
     explore elaborate relationships as well as evolution. Then there's
     his wife and his 7-year-old daughter, the latter serving as his
     most prized experiment. "Watching her brain develop is
     fascinating," he observes. "You realize that there are some things
     you can influence and some things you can't. You can try to teach
     something to someone, but if the brain isn't ready or willing to
     accept it, it ain't goin' in."

     Which is precisely the challenge of Berger's odyssey into the
     mind. Dropping a functioning brain implant into a person's head
     and expecting it to work requires a voyage beyond the flat earth
     of today's neuroscience. For starters, the shape of the
     hippocampus doesn't remotely resemble a computer board, so
     inserting a conventional microchip into the brain and trying to
     send electrical waves back and forth would be like speaking into a
     telephone that's not connected to anything. Berger has
     circumvented this problem with a digital interface chip that will
     serve as the gateway between the brain's cells and the stacked set
     of chips that creates a group of artificial neurons.

     Since transistors and neurons both send and receive electrical
     signals, it all boils down to arranging the chip's conductors in a
     pattern that matches the layout of neurons in a particular part of
     the brain. The brain then believes it's receiving its own signals,
     when in fact they're originating from the computer network. "A
     transistor can send electricity and so can a neuron," Berger says.
     "So, instead of using a computer chip that has transistors on it,
     you build a chip with a piece of exposed metal. You place the
     metal right next to the neuron, so that it can sense the
     electrical signals sent out by the neuron and send signals to the
     neuron." By slightly overbuilding the device - designing a layer
     of electrodes that are perhaps 30 microns thick compared with the
     cell's layer of 20 microns - Berger increases the odds of a
     successful contact.

     "The ever present scaling issue"

     In almost all cases, electrical signals trigger the release of
     chemical reactions in the brain, which in turn stimulate other
     cells to produce electrical reactions. These result in additional
     chemical activity. In fact, Berger points out that cells cannot
     talk to each other without the release of chemicals that
     effectively bridge the gap between neurons. So, the brain implant
     would need only to stimulate electrical activity to work. Many
     chemical imbalances would still be treated by medication, which
     allows the brain to restore the proper electrical activity.With
     all the parts in place, Berger will have essentially created a
     circuit between the device and the gray matter that operates much
     like a dedicated phone line. Brain cells could actually grow on
     top of the silicon or metal surfaces, further blurring their
     distinction. A pair of the team's scientists - Michel Baudry, a
     professor of biological sciences, and Roberta Brinton, an
     associate professor of molecular pharmacology - have begun
     developing such cultures with animal tissue. When their research
     is finalized, says Berger, "We will have created a physical
     connection, or synapses, between the brain cells and computer
     chips. We have the basic ingredients for a brain replacement."

     The most remarkable aspect of all, says fellow team member
     Tanguay, is that such a device represents the sheer oddity of
     today's science. Increasingly, researchers are able to find
     solutions without fully understanding the underlying process. "We
     may never really know how the brain works, but we might be able to
     understand enough about how neurons correlate and work together to
     run the mathematical model," he explains. "By connecting a silicon
     neural circuit to a probe chip and allowing it to 'learn' and then
     feed data back, it's possible to diagnose and fix the problem
     without having a clue how the system achieved the results. The
     brain would use its natural adaptive abilities to reestablish all
     the correct connections."

     In other words, the device could learn the brain's native language
     and speak it, but not interpret it to the outside world.

     The research is also yielding data that can be plugged into an
     array of other, seemingly divergent, scientific disciplines. Says
     Joel Davis, program manager at the Office of Naval Research: "Once
     you understand the algorithms that drive the brain, you can apply
     them to all sorts of real-world problems that require computing.
     You can use reverse engineering to solve problems in
     communications, sonar, and neural networks."

     One spin-off has been a new type of parallel-processing network
     that could dramatically improve the quality of wireless and
     cellular communication. By embedding an existing algorithm in a
     microchip that mimics a biological model, it is possible to
     drastically reduce the effects of noise and distortion. Yet
     another prototype design, which used the same biological
     processing model, promises to improve speech recognition.

     Of course, connecting all the dots on the brain implant remains
     the team's central focus - and their enormous challenge. For one
     thing, there's a dizzying array of experimental technologies that
     must intertwine and complement one another perfectly. It's one
     thing to create computer simulations onscreen in a highly
     controlled environment, but it's quite another to make them work
     in the real world of chemistry, biology, and neurophysiology.
     Stimulating a neuron or two in the brain is a pretty good
     achievement but mere child's play compared with stimulating
     thousands of neurons and running electrical channels through each.

     Then there's the profound question of how many artificial neurons
     scientists can fit on a microchip, and how many chips they can
     pack into a cranium. "The ever present scaling issue," as Tanguay
     puts it. Even the simplest prototype versions of the device will
     require far more exotic and sophisticated chips and
     interconnections than the group has so far managed to design and
     build. Alas, there's also the humbling reality that if any member
     of the highly skilled research team drops out or dies, the project
     could quickly crumble. So far, the team has steered remarkably
     clear of ego and turf battles, but the irony remains inescapable -
     the development of what could be the most advanced
     parallel-processing network on earth hinges on the most basic and
     tenuous: fellow humans.

     Berger believes the team is about five years away from designing a
     brain implant for animals and about 10 to 15 years away from the
     first device for humans. With custom microchip designs taking
     weeks or months and other technical hurdles at every turn, it's
     certainly not a project for anyone with less than the patience of
     Buddha and the persistence of someone who sells insurance.

     That suits Berger just fine. Nobody ever said that building an
     electronic brain would be easy, and it's clear that he's just as
     infatuated with the process as with the thought of changing
     people's minds."You build it neuron by neuron and chip by chip,"
     he says. "You enjoy each experiment and piece of the puzzle while
     keeping a focus on the bigger picture." Berger won't rest until he
     has built a bionic brain. He definitely wants to get inside your
     head.

     Samuel Greengard(samuelg@deltanet.com) is a Burbank, California
     writer specializing in science and technology.