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The Myth of Mind Control: Will Anyone Ever Decode the Human Brain?

DISCOVER MAGAZINE COVER STORY, OCTOBER 2004

THE MYTH OF MIND CONTROL

Will anyone ever decode the human brain?

by John Horgan

All it took was a few jolts of electricity to turn ordinary rats into roborats and for pundits to leap to the conclusion that ordinary humans will soon be transformed into robohumans. Scientists at the State University of New York Downstate Medical Center in Brooklyn sparked a media frenzy two years ago when they demonstrated that rats with electrodes implanted in their brains could be steered like remote-controlled toy cars through an obstacle course. Using a laptop equipped with a wireless transmitter, a researcher stimulated cortical cells governing whisker sensations and reinforced those signals by zapping the rats’ pleasure centers. Presto! With this simple setup, the team had created living robots.

Publications around the world promptly proclaimed the imminence of those familiar science-fiction staples, surgically implanted devices that electronically monitor and manipulate our minds. The Economist warned that neurotechnology may be on the verge of “overturning the essential nature of humanity,” and New York Times columnist William Safire brooded that neural implants might allow a “controlling organization” to hack into our brains. In a more positive vein, MIT’s artificial-intelligence maven Rodney Brooks predicted in Technology Review that by 2020 implants will let us carry out “thought-activated Google searches.”

Hollywood’s remake of The Manchurian Candidate raises the specter of a remote-controlled soldier turned politician. In fact, officials at the Defense Advanced Research Projects Agency, which funds the roborat team, have suggested that cyborg soldiers could control weapons systems--or be controlled—via brain chips. “Implanting electrodes into healthy people is not something we’re going to do any time soon,” says Alan Rudolf, the former head of the DARPA brain-machine research program. “But 20 years ago, no one would have thought we’d put a laser in the eye either. This agency leaves the door open to what’s possible.”

Of course, that begs the question: Just how realistic are these futuristic scenarios? To achieve truly precise mind reading and control, neuroscientists must master the syntax or set of rules that transform electrochemical pulses coursing through the brain into perceptions, memories, emotions, and decisions. Deciphering this so-called neural code—think of it as the brain’s software--is the ultimate goal of many scientists tinkering with brain-machine interfaces. “If you’re a real neuroscientist, that’s the game you want to play,” says John Chapin, a co-leader of the roborat research team.

Chapin ranks the neural code right up there two other great scientific mysteries: the origin of the universe and of life on Earth. The neural code is arguably the most consequential of the three. The solution could, in principle, vastly expand our power to treat ailing brains and to augment healthy ones. It could allow us to program computers with human capabilities, helping them become more clever than HAL in 2001: Space Odyssey and C-3PO in Star Wars. The neural code could also represent the key to the deepest of all philosophical conundrums--the mind-body problem. We would finally understand how this wrinkled lump of jelly in our skulls generates a unique, conscious self with a sense of personal identity and autonomy.

In addition to being the most significant mystery in science, the neural code may also be the hardest to solve. Despite all they have learned in the past century, neuroscientists have made little headway figuring out exactly how brain cells process information. “It’s a bit like saying after a hundred years of researching the body, ‘Do you know if testes produce urine or sperm?’” says neuroscientist V.S. Ramachandran of the University of California at San Diego. “Our notions are still very primitive.”

The neural code is often likened to the machine code that underpins the operating system of a digital computer. Like transistors, neurons serve as switches, or logic gates, absorbing and emitting electrochemical pulses, called action potentials, which resemble the basic units of information in digital computers. But the brain’s complexity dwarfs that of any existing computer. A typical brain contains 100 billion cells—almost as numerous as the stars in the Milky Way galaxy. And each cell is linked via synapses to as many as 100,000 others. The synapses between cells are awash in hormones and neurotransmitters that modulate the transmission of signals, and the synapses constantly form and dissolve, weaken and strengthen, in response to new experiences.

Assuming that each synapse processes one action potential per second and that these transactions represent the brain’s computational output, then the brain performs at least one quadrillion operations per second, almost a thousand times more than the fastest supercomputers. Many more computations may occur at scales below or above that of individual synapses, says Steven Rose, a neurobiologist at England’s Open University. “The brain may use every possible means of carrying information.”

Optimists recall that in the middle of the last century, some biologists feared the genetic code was too complex to crack. Then in 1953 Francis Crick and James Watson unraveled the structure of DNA and researchers quickly established that the double helix mediates an astonishingly simple genetic code governing the heredity of all organisms. The neural code is not likely to yield such an elegant, universal solution. The brain is “so adaptive, so dynamic, changing so frequently from instant to instant,” says Miguel Nicolelis, a neural-prosthesis researcher at Duke University, that “it may not be proper to use the term ‘code’.”

Nicolelis has faith that science will one day ferret out all of the brain’s information-processing tricks—or at least enough of them to yield huge improvements in neural prostheses for people who are paralyzed, blind, or otherwise disabled. Yet he believes that certain aspects of our minds may remain inviolable because our most meaningful thoughts and memories are written in a code, or language, that is unique to each of us. “There will always be some mystery,” Nicolelis says.

If so, the bad news is that brains chips will never be sophisticated enough for us to learn new languages instantly or have a “mental telephone” conversation with a friend “simply by thinking about talking,” as Popular Science has prophesied. The good news is we are not on the verge of what the Boston Globe called a “Matrix-like cyberpunk dystopia” in which we all become robohumans, controlled by implants that “impose false memories” and “scan for wayward thoughts.”

All the loose speculation provoked by roborats is ironic considering that the experiment is just a small-scale replay of a major media event that is 40 years old. In 1964, Jose Delgado, a neuroscientist from Yale University, stood in a Spanish bullring as a bull with a radio-equipped array of electrodes, or “stimoceiver,” implanted in its brain charged toward him. When Delgado pushed a button on a radio transmitter he was holding, the bull stopped in its tracks. Delgado pushed another button, and the bull obediently turned to the right and trotted away. The New York Times hailed the event as “probably the most spectacular demonstration ever performed of the deliberate modification of animal behavior through external control of the brain.”

Delgado also conducted stimoceiver experiments in cats, monkeys, chimpanzees, and even human psychiatric patients. He showed that he could jerk the limbs of patients like marionettes, as well as induce sensations such as euphoria, sexual arousal, sleepiness, garrulousness, terror, and rage. In his1969 book Physical Control of the Mind: Toward a Psychocivilized Society, Delgado extolled the promise of brain-stimulation for curbing violent aggression and other maladaptive traits.

Delgado’s work—partly funded by the Pentagon—provoked fears of government plots to transform citizens into robots. He dismissed this “Orwellian possibility,” pointing out that the technology was still much too unreliable and crude for precise mind control. The major impediment to progress, he wrote, is that “our present knowledge regarding the coding of information... is so elemental.” Now 89 and living in San Diego, Delgado still follows research on brain-machine interfaces. The potential of brain-stimulation “has not been fully developed,” he says, because the neural code remains “very difficult to untangle.”

In Delgado’s heyday, neuroscientists believed that the brain employed just a single, simple coding scheme discovered in the 1930’s by Lord Edgar Adrian, a British neurobiologist. After isolating sensory neurons from frogs and eels, Adrian showed that as the intensity of a stimulus increases, so does a neuron’s firing rate, which can peak as high as 200 spikes per second. In the next few decades, experiments confirmed that the nervous systems of all animals employ this method of conveying information, called a rate code. Researchers also demonstrated that specific neurons are dedicated to extremely specific tasks, such as seeing vertical lines, hearing sounds of a specific pitch, or flexing a finger. Together, these findings suggested that controlling the brain might be a simple matter of delivering the right jolt of electricity to the right clusters of brain cells.

It turns out that things are not so simple. Recent research has undermined two basic assumptions about how the brain processes information. One is the view of neurons as drones single-mindedly carrying out specific tasks. Cells can be retrained for different jobs, switching from facial expressions to finger flexing, or from seeing red to hearing squeaks. Our neural circuits keep shifting “massively and continuously” not only during childhood but throughout our lives, says Michael Merzenich of the University of California at San Francisco, whose research has helped expose just how plastic neurons really are.

Neuroscientists are also questioning whether the firing rate serves as a brain cell’s sole means of expression. Rate codes are extremely inefficient. They are analogous to a language that conveys information only through modulations of a voice’s loudness, and they imply that the brain is inherently noisy and wasteful. What counts as a genuine signal is a surge in the firing rate of a cell from, say, 2 to 50 times a second; variations in the intervals between successive spikes in a surge are considered irrelevant. But just as some geneticists suspect that the junk DNA riddling our genomes actually serves hidden functions, so some neuroscientists believe that information may lurk within the fluctuating gaps between spikes. Schemes of this sort, which are known as temporal codes, imply that significant information may be conveyed by just a spike or two.

Another time-sensitive code involves groups of neurons firing in precise lockstep, or synchrony. Some evidence suggests that synchrony helps us focus our attention. If you are at a noisy cocktail party and suddenly hear someone nearby talking about you, your ability to eavesdrop on that conversation and ignore all the others around you could result from the synchronous firing of cells. “Synchrony is an effective way to boost the power of a signal and the impact it has downstream on other neurons,” says Terry Sejnowski, a computational neurobiologist at the Salk Institute. He speculates that the abundant feedback loops linking neurons allow them to synchronize their firing before passing messages on for further processing.

Then there is the chaotic code championed by Walter J. Freeman of the University of California at Berkeley. For decades, he has contended that far too much emphasis has been placed on individual neurons and action potentials, for reasons that are less empirical than pedagogical. The action potential “organizes data, it is easy to teach, and the data are so compelling in terms of the immediacy of spikes on a screen.” But spikes are ultimately just “errand boys,” Freeman says; they serve to convey raw sensory information into the brain, but then much more subtle, larger-scale processes immediately take over.

The most vital components of cognition, Freeman believes, are the electrical and magnetic fields, generated by synaptic currents, that constantly ripple through the brain. These fields are chaotic, in the sense that they conceal a hidden, complex order and are subject to minute influences--the so-called butterfly effect. A sound enters the ear and triggers a stream of action potentials, which nudge the waves of electrical activity coursing through the cortex into a particular chaotic pattern, or attractor. The result is fantastically precise, almost instant comprehension. “You pick up the telephone and hear a voice,” Freeman says, “and before you even know the meaning of the words, you know who you’re talking to and what her emotional state is.”

Although none of these alternatives to rate codes has been proven yet, so little is known about how the brain processes information that “it’s difficult to rule out any coding scheme at this time,” argues neuroscientist Christof Koch of Caltech. Koch and Itzhak Fried, who is both a neuroscientist and practicing neurosurgeon at UCLA Medical School, recently uncovered evidence for a coding scheme long ago discarded as implausible. This scheme has been disparaged as the “grandmother cell” hypothesis, because in its reductio ad absurdum version it implies that our memory banks dedicate a single neuron to each person, place, or thing that inhabits our thoughts, such as Grandma. Most theorists assume that such a complex concept must be underpinned by large populations of cells, each of which corresponds to one component of the object (the bun, the bifocals, the leather mini-skirt).

Yet Fried and Koch have found neurons that act very much like grandmother cells. The subjects were epileptics who had electrodes temporarily inserted into their brains to provide information that could guide surgical treatment. The researchers monitored the output of the electrodes while showing the patients images of animals, people, and other things. A neuron in the amygdala of one patient spiked only in response to three quite different images of Bill Clinton: a line drawing, a presidential portrait, and a group photograph. A cortical cell in the other patient responded in a similar way to images of characters from The Simpsons. In future experiments, Koch and Fried plan to show patients photographs of their grandmothers to see if they can locate actual grandmother cells.

It makes intuitive sense, Koch says, that our brains should dedicate some cells to people or other things frequently in our thoughts. He adds that his findings might seem less surprising if one realizes that neurons are much more than simple “threshold” switches that fire whenever incoming pulses from other neurons exceed a certain level. A typical neuron receives input from thousands of other cells, some of which inhibit rather than encourage the neuron’s firing. The neuron may in turn encourage or suppress firing by some of those same cells in complex positive or negative feedback loops.

In other words, a single neuron may resemble less a simple switch than a customized minicomputer, sophisticated enough to distinguish your grandmother from Grandma Moses. If this view is correct, meaningful messages might be conveyed not just by hordes of neurons screaming in unison but by small groups of cells whispering, perhaps in a terse temporal code. Discerning such faint signals within the cacophony of the brain will “incredibly difficult,” Koch notes, no matter how much neurotechnology advances.

Efforts to detect the whispers amid the cacophony are further complicated by the improvisational dexterity of the brain. Studies of the motor cortex, which underpins body movement, have shown that the brain invents entirely new coding schemes for novel situations. In the 1980’s, researchers discovered neurons in a monkey’s motor cortex that peak in their firing rate when the monkey moves its hand in a specific direction. Rather than falling silent when the hand diverges even slightly from its so-called preferred direction, the cells’ firing rate diminished in proportion to the angle of divergence.

Several teams, including one led by Andrew Schwartz of the University of Pittsburgh, have sought to exploit these findings to create neural prostheses for paralyzed patients. They have demonstrated that electrodes implanted in a monkey’s motor cortex can detect signals accompanying a specific arm movement; these same signals—after being processed by an algorithm--can initiate similar movements by a robot arm. If the monkey’s arm is tied down, it can learn to control the robot arm through pure thought—but with an entirely different set of neural signals. These findings dovetail with others showing that neurons’ coding behavior shifts in different contexts. “What you’re aiming at is sort of a moving target,” Schwartz elaborates. “If you make an estimate of something at one point in time, that doesn’t mean it’s going to stay that way.”

The mutability of the neural code is not necessarily bad news for neural-prosthesis designers. In fact, the brain’s capacity for inventing new information-processing schemes is thought to explain the success of artificial cochleas, which have been implanted in more than 50,000 hearing-impaired people. Commercial versions typically employ a half-dozen electrodes, each of which channels sounds of a different pitch to electrodes embedded in the auditory nerve. Like an old telephone party line, the electrodes can stimulate not just a single neuron but many simultaneously.

When cochlear implants were introduced in the mid-1980’s, many neuroscientists expected them to work poorly, given their crude design. But they work well enough for some deaf people to converse over the telephone, particularly after a break-in period during which channel settings are adjusted to provide the best reception. Patients’ brains somehow figure out how to make the most out of the strange signals.

There are surely limits to the brain’s ability to make up for scientists’ ignorance, as the poor performance of other neural prostheses suggests. Artificial retinas, light-sensitive chips that mimic the eye’s signal-processing ability and stimulate the optical nerve or visual cortex, have been tested in a handful of blind subjects who usually “see” nothing more than phosphenes, or flashes of light. And like Schwartz’s monkeys, a few paralyzed humans have learned to transmit commands to computers via chips embedded in their brains, but the prostheses are still slow and unreliable.

Nevertheless, the surprising effectiveness of artificial cochleas—together with other evidence of the brain’s adaptability and opportunism—has fueled much of the recent optimism over the prospects for brain-machine interfaces. “This is very relevant to why we think we’re going to be successful,” says Ted Berger of the University of Southern California in Los Angeles, who is leading a project to create implantable brain chips that can restore or enhance memory. “We don’t need a perfectly accurate model of a memory cell,” he remarks. “We probably just have to be close, and the rest of brain will adapt around it.”

Thus far, Berger’s experiments have been confined to slices of rat brain in petri dishes. For more than a decade, he has embedded arrays of electrodes in slices of hippocampus--which plays a role in learning and memory--and recorded neurons’ responses to a wide range of electrical stimuli. His observations have made him a firm believer in temporal codes; hippocampal cells seem to be exquisitely sensitive not only to the rate but also to the timing of incoming pulses. “The evidence for temporal coding is indisputable,” Berger says. Within three years, he hopes to have chips that mimic the signal-processing properties of hippocampal tissue ready for testing in live rats.

Berger boldly predicts that someday chips like his might restore memory capacity to stroke victims or help soldiers instantly learn complex fighting procedures, like the characters in The Matrix. But in some respects Berger is quite modest. He acknowledges that his memory chips could not be used to identify and manipulate specific memories. His chips can simulate “how neurons in a particular part of the brain change inputs into outputs. That’s very different from saying that I can identify a memory of your grandmother in a particular series of impulses.” To achieve this sort of mind-reading, scientists must compile a “dictionary” for translating specific neural patterns into specific memories, perceptions, and thoughts. “I don’t know that it’s not possible,” Berger says. “It’s certainly not possible with what we know at the moment.”

“Don’t count on it in the 21st century, or even in the 22nd, ” says Bruce McNaughton of the University of Arizona. With arrays of as many as 50 electrodes, McNaughton has monitored neurons in the hippocampus of rats as they run through a maze. Once a rat learns to navigate a maze, its neurons discharge in the same patterns whenever it runs the maze. Remarkably, when the rat sleeps after a hard day of maze running, the same firing pattern often unfolds; the rat is presumably dreaming of the maze. This pattern could be said to represent--at least partially--the rat’s memory of the maze.

McNaughton emphasizes that the same maze generates a different firing pattern in different rats; even in the same rat, the pattern changes if the maze is moved to a different room. He thus doubts whether science can compile a dictionary for decoding the neural signals corresponding to human memories, which are surely more complex, variable, and context-sensitive than those of rats. At best, McNaughton suggests, one might construct a dictionary for a single person by monitoring the output of all her neurons for years while recording all her behavior and her self-described thoughts. Even then, the dictionary would be imperfect at best, and it would have to be constantly revised to account for the individual’s ongoing experiences. This dictionary would not work for anyone else.

Delgado hinted at the problem more than 30 years ago in Physical Control of the Mind when he raised the knotty question of meaning. With new and improved stimoceivers and a better understanding of the neural code, he said, scientists might determine what we are perceiving—a piece of music, say—based on our neural output. But no conceivable technology will be subtle enough to discern all the memories, emotions, and meanings aroused in us by our perceptions, because these emerge from “the experiential history of each individual.” You hear a stale pop tune, I hear my wedding song.

This is one point on which many neuroscientists agree: The uniqueness of each individual represents a fundamental barrier to science’s attempts to understand and control the mind. Although all humans share a “universal mode of operation,” says Freeman, even identical twins have divergent life histories and hence unique memories, perceptions, predilections. The patterns of neural activity underpinning our selves keep changing throughout our lives as we learn to play checkers, read Thus Spoke Zarathustra, fall in love, lose a job, win the lottery, get divorced, take Prozac.

Freeman thinks the prospects are good for relatively simple neural prostheses, such as devices that restore vision to the blind or that let paralyzed people send simple commands to a computer. But he suspects that our brains’ complexity and diversity rule out more ambitious projects, such as mind-reading. If artificial-intelligence engineers ever succeed in building a truly intelligent machine based on a neural coding scheme similar to ours, “we won’t be able to read its mind either,” Freeman says. We and even our cyborg descendants will always be “beyond Big Brother, and I’m very grateful for that.”

[BOX]

HARDWARE HURDLES

Last year, the engineering journal IEEE Spectrum proclaimed that magnetic-resonance imaging and electroencephalography are “bringing us closer to a world where mind reading is possible.” In reality, detecting specific thoughts with these external scanners is like trying to eavesdrop on individual conversations at a baseball game while standing outside the stadium and listening to the roar of the crowd.

Similarly, a technique called transcranial magnetic stimulation, which excites specific brain regions with electromagnetic fields, has been touted for its potential to curb depression, heighten artistic ability, and otherwise alter our minds. But this external stimulation method will never be precise enough to, for instance, pinpoint and delete specific memories, in spite of what films such as Total Recall and Eternal Sunshine of the Spotless Mind have suggested. Most neuroscientists believe that conversing with the brain in its own language will require implanted electrodes.

In the past decade, the technology of tiny electrodes that can touch individual brain cells has leaped forward. Researchers have crafted arrays of hundreds and even thousands of electrodes, each of which can monitor a separate cell. However, implanting electrodes through holes in the skull poses a risk of infection and brain damage, so testing on healthy humans is not allowed. Electrodes also constantly lose contact with neurons; at any one moment an array of 100 electrodes may make contact with only half that many cells. “Getting a stable connection,” says William Heetderks, a neural-prosthesis expert at the National Institutes of Health, “is still a bit of an issue.”

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John Horgan

"Can a Single Brain Cell Think?"

Discover, June 2005

In the neurosurgery ward of the David Geffen School of Medicine at UCLA, Danny, a stocky 21-year-old college student wearing blue pajamas and sporting a wispy goatee, sits on a bed watching one photo after another flash on a laptop screen. Several macho movie stars appear in rapid succession, including Arnold Schwartzenegger, Steven Seagal, Sylvester Stallone, and Mr. T, the mohawked brawler who plays Stallone’s rival in the boxing film Rocky III. At first glance, one might guess that Danny has volunteered for a Hollywood survey: Who’s your favorite action hero? In fact, Danny is the real hero. The black cables emerging from the white turban wrapped around his skull hint at his role in investigating a truly profound question: How do thoughts form in the human brain?

Danny suffers from epilepsy, and he has had electrodes temporarily implanted into his brain to monitor seizures; ideally, the electrodes will pinpoint the neural defect triggering his seizures so it can be surgically removed. During the week or so that the electrodes remain in Danny’s brain, he has volunteered to participate in experiments aimed at understanding the underpinnings of cognition. Such research is quite rare; for obvious ethical reasons, neuroscientists have few opportunities to gather data from deep inside a living human brain.

This particular experiment touches on one of the most challenging puzzles of neuroscience: How do brain cells recognize items as complicated as a toaster oven, the number nine, a zebra, Bill Clinton, or the film character Rocky? Are single cells like transistors in a computer, or pixels on a television screen, contributing just minute pieces of information that only when combined with the output of thousands or millions of other cells form the complex pattern that means Rocky? Or can a single neuron learn to recognize that face?

Most neuroscientists adhere to the pixel view of neurons, arguing that individual cells can’t possibly be clever enough to make sense of a concept as subtle as Rocky; after all, the world’s fastest supercomputers have difficulty performing that pattern-recognition feat. But Itzhak Fried, the neurosurgeon who implanted the electrodes in Danny’s brain and who leads this UCLA research program, believes he has found "thinking cells" in the brains of subjects like Danny. If he’s right, neuroscientists may be forced to overhaul their view of how the human brain works.

A true thinking cell should be able to recognize a person or fictional character even in many different guises. Danny is a big fan of Hollywood action heroes, especially Rocky; he owns DVDs of all four films in the series and never tires of watching them. So, amid the images that flash on the laptop screen, the research team has included shots that show Rocky running through the streets of Philadelphia, staring longingly at his girlfriend Adrian, or draped in the American flag after defeating his Russian rival. Now and then, to test whether a cell’s recognition cuts across sensory modes, Rocky or some other name is spelled out on the laptop screen or uttered by an eerie synthesized voice.

As Danny peers at the laptop, signals stream from more than 100 ultra-thin electrodes, each sensitive enough to detect the murmuring of a single cell—and into the cables that emerge from his head. The cables ferry the signals across the room to a cabinet crammed with amplifiers. A computer atop the cabinet displays the readouts from Danny’s cells as a series of multi-colored lines unfolding across a screen. Every now and then, a line jerks upward, as one of Danny’s cells sputters in response to an image or name. Rodrigo Quian Quiroga, the Argentinian neuroscientist overseeing this research session, points to one especially energetic squiggle and whispers, "That’s Rocky."

The vast majority of modern brain research involves technologies such as magnetic resonance-imaging, positron emission tomography, and electroencephalography. All measure neural activity from outside the skull. Figuring out how brains work with external scanners is like studying life on a cloud-shrouded planet with satellites. Implanted electrodes, by contrast, are like probes that drop down to the planet’s surface. Electrode studies of monkeys and other animals whose brains resemble ours have yielded valuable insights, but these creatures cannot describe their subjective sensations.

A handful of other hospitals are carrying out electrode research that piggybacks on the clinical treatment of patients with epilepsy, Parkinson’s disease, and other neurological disorders. But no research program approaches UCLA’s in experience, sophistication, or published results, says Christof Koch, a neuroscientist at the California Institute of Technology who has been collaborating with the UCLA group since 1998. "There is no one technique that’s going to give you all the answers" to the riddle of cognition, Koch says. "But this is one that’s very, very good, and we’re getting better at it."

Fried, the driven yet affable commander-in-chief of the program, founded it in 1992 after leaving Yale. Since then more than 100 of his epileptic patients with electrodes implanted in their brains for diagnostic purposes have volunteered as subjects for basic research. From the outset, Fried has been protective of his patients and their privacy; this is the first time he has allowed a reporter to watch him and his team at work.

Fried was born and raised in Israel, and he spends several months a year working at a hospital in Tel Aviv as well as at UCLA. He flew from Israel to Los Angeles on a Sunday, and during a three-hour operation on Monday he drilled ten holes in Danny’s skull and inserted the electrodes into his brain. The following day, wearing a white lab coat over aqua scrubs, Fried strode into a conference room packed with researchers who had gathered to discuss plans for Danny. The team included two undergraduates who flew here from the University of Pennsylvania, a few graduate students from UCLA and Caltech, a couple of postdocs, and two physicians.

Fried briskly provided background on the patient: Danny is a bright, friendly young man, he said, who is looking forward to working with the research team as a way to "break the boredom" of his hospital stay. "Okay, let’s get down to practical issues," he continued in his distinctive Israeli accent. Rapid-fire, he queried the researchers on the status of their "paradigms." He prefers that term to "experiments," which might suggest electrodes had been implanted in Danny’s brain primarily for research rather than diagnostic purposes.

The discussion keeps returning to problems with data storage and analysis. Several researchers asked for upgrades in equipment for storing data—which the microelectrode experiments generate by the terabyte--and Fried said he’d see what he could do. The researchers also received detailed instructions on how to grapple with a major technical challenge: electrodes in patients’ brains often detect pulses from two or more nearby neurons at the same time, which may show up in the computer as one big signal. Quiroga has written a program that mathematically unravels overlapping pulses. The process, called cluster-cutting, makes it possible to extract more information from the data, at least in principle. But some of Quiroga’s colleagues were still trying to familiarize themselves with the fine points of what the team has dubbed "Rodrigo’s code."

The researchers had prepared more than enough studies to keep Danny from becoming bored. One called for him to view computer-generated pictures of celebrities morphing into each other: Mr. T into Will Smith, and Sly into Arnie. The objective: to see if a cell that lights up for Sly fires more slowly as the photo gradually morphs into Arnie, or just abruptly falls silent. In other words, are face-recognition cells like simple on-off switches, or can they act like dimmers?

Another paradigm, called X-Cab, is designed to yield insights into how we navigate. More than a decade ago microelectrode studies of rats and monkeys revealed place cells that light up when the animals move to a particular spot in a maze. Previous versions of X-Cab, which involves driving a virtual taxi through a cyber-city, have confirmed that humans have place cells, too, as well as view cells that respond to specific landmarks, and goal cells that respond to the driver’s ultimate destination.

Arne Ekstrom, a UCLA postdoc, and Indra Viskontas, a graduate student, had made preparations for Danny to test drive a new version of the X-Cab program, which allows the driver to pick up and discharge passengers. Fried asked if they had made the changes he requested in the paradigm. "Almost all of them," Viskontas replied, adding that she and Ekstrom "respectfully" disagreed with some of Fried’s requests and wanted to discuss them with him.

Fried nodded. "Any more questions?" he asked, scanning the room one last time. "If not, to work."

Back in his office, Fried recalled how he ended up overseeing this unusual program. One of his role models was Wilder Penfield, the Canadian surgeon who carried out pioneering operations on epileptics in the 1950’s and 1960’s. After removing the skull-cap of patients, Penfield electrically tickled different spots of their brains with wires and asked them what they felt; because the brain lacks pain receptors, the patients needed no anesthesia. They could report feeling a tingle in their left forefinger, seeing a blue flash, hearing a low-pitched hum.

This procedure not only helped to guide Penfield’s surgical treatment of each patient; it also yielded clues to what different parts of the brain do. "Here was somebody who was really looking at the human mind," Fried said, "but at same time he was helping a human being." Fried’s method is much more refined than Penfield’s. Fried typically drills a dozen holes in the patient’s skull and inserts a dozen hollow macroelectrodes, which can detect large-scale electrical waves emanating from a seizure.

Protruding from the end of each macroelectrode are as many as ten flexible microelectrodes that can detect the pulses of individual neurons. The patient’s clinical status dictates the placement of the macroelectrodes. In Danny’s case, tests suggest that his seizures originate in his frontal lobes, so Fried inserted most of the macroelectrodes in that region. He embedded one macroelectrode in Danny’s hippocampus, a minute region that underpins memory and is often implicated in epileptic seizures.

The patient’s clinical health and comfort, Fried emphasized, take precedence over research objectives. Even the most carefully planned paradigm must be set aside if the patient becomes bored, tired, frustrated, gets a headache, or just wants to be left alone. Fried carefully screens prospective colleagues to ensure that they treat his patients like human beings rather than laboratory animals. "The person who will not do well," he said, "is a compulsive-obsessive animal physiologist who, if he doesn’t control all the variables, falls apart." But Fried also said he believes that "there is a responsibility" to take advantage of these rare chances to learn more about the behavior of individual neurons, which he calls the building blocks of cognition.

Following Penfield’s example, Fried occasionally does studies that involve stimulating brain cells with minute electrical jolts. In 1998, he and three colleagues discovered that a female patient burst into laughter every time they stimulated a spot at the top of her brain called the supplementary motor area. Her hilarity was not just physiological; the woman felt subjective sensations of "merriment or mirth." She displaying a syndrome known as confabulation—she invented reasons for her hilarity, telling the researchers at one point, "You guys are just so funny... standing around."

But most of Fried’s findings, which he has described in more than a dozen papers in such leading journals as Nature, Neuron, and Proceedings of the National Academy of Sciences, involve not electrically stimulating neurons but passively listening to their chatter as a patient performs various tasks. In one set of experiments, Fried, Koch, and Gabriel Krieman, a Caltech grad student, found cells that light up both when a subject looks at an image—of a baseball, say, or a woman’s face--and when he closes his eyes and recalls the image in his minds’ eye. The results provide the most convincing evidence yet that human perception and imagination share neural circuitry.

The experiments that have attracted the most attention are those supporting the existence of "thinking cells." The possibility of such cells has been debated at least since the 1950s, when researchers found single neurons in the visual cortex of cats and other animals that respond to simple stimuli, such as lines oriented at a certain angle or moving in a specific direction or light of a particular wavelength. Some theorists wondered whether single neurons might also respond to much more complicated stimuli, such as specific people.

Once known as gnostic cells, after the Greek word for knowledge, they were dubbed grandmother cells in the late 1960s by neuroscientist Jerry Lettvin of the Massachusetts Institute of Technology. Lettvin meant to make fun of—if not to dismiss--speculation that single cells could be dedicated to recognition of family members or other individuals who loom large in an individual’s mental universe. [fnc: There's apparently a long history on this.  Found this reference:  Gross, C. (2002). Genealogy of the Grandmother Cell. The Neuroscientist 8, 512-518.]  In one paper, he joked that mother-smothered neurotics such as Portnoy, the hero of Phillip Roth’s novel Portnoy’s Complaint, could be cured of their Oedipal disorders by having all the mother cells purged from their brains.

Many neuroscientists found it hard to believe that a single cell could recognize an inanimate object, let alone a human being. Even objects as simple as chairs, trees, or buildings come in an almost infinite variety of forms, and the same object looks different from different perspectives or in different contexts. Neuroscientists were therefore startled in the early 1970s when experiments on monkeys by Charles Gross of Princeton turned up cells that respond selectively to hands and faces--not specific faces but faces in general.

No one had really followed up on Gross’s findings, however, until the late 1990s, when Fried and his colleagues started reporting how epileptic patients reacted to various images. Some neurons were apparently smart enough to comprehend the highly abstract concept "non-human animal." Their neurons fired when the patient was shown a picture of a tiger, eagle, antelope, and rabbit, but not when shown pictures of humans or inanimate objects. Other cells favored images only of food, or of buildings, or of human faces. Some cells responded to all faces, but others were picky, firing for male faces but not female ones, or scowling faces but not smiling ones—or, finally, faces of specific individuals.

One of the first neurons of this type was the so-called Bill Clinton cell, which was buried deep in the amygdala of a female patient. The cell responded to three very different images of the former President: a line drawing of Clinton laughing; a formal painting of him; and a photograph of him mingling with other dignitaries. The cell remained mute when the patient viewed images of other people, including male politicians and celebrities. Fried’s group found cells in other volunteers that responded in this same highly selective way to actors, including Jennifer Anniston, Brad Pitt, and Halle Berry.

One reason celebrities have played a prominent role in Fried’s experiments is that their photographs are often easier to come by than images of a patient’s own relatives. But as part of her dissertation project on biographical memory, the UCLA graduate student Viskontas has for several years been showing patients photographs of family members. Viskontas is reluctant to reveal details about her results, which have not been published yet. But she confirms that she has found neurons that respond to a particular relative: father, mother, brother, sister, grandfather, and, yes, grandmother. The experiments have also found cells that light up when a patient sees an image of himself. Call them narcissism cells.

Viskontas is wary of over-interpreting these results or others emerging from the UCLA program. She does not believe, for example, that they support the most extreme version of the grandmother-cell hypothesis, in which cells are exclusively and permanently assigned to one person, place, or thing. The past few decades, she adds, have revealed that brain cells are versatile, or "plastic," changing their roles in response to new experiences. The UCLA experiments may not be detecting long-term memory but so-called working-memory, in which cells are temporarily assigned to the job of representing Grandma, Jennifer, Aniston, or Rocky only as a result of the stimulation provided by the experiment.

Koch isn’t so sure. It would make sense, he argues, for our brains to dedicate some cells to people or other things frequently in our thoughts. The larger significance of the UCLA experiments, he says, is that neuroscientists may have to change their view of neurons as simple switches, transistors, or pixels. Each neuron may be more like a sophisticated computer, running customized software. After all, individual neurons can receive input from hundreds of thousands of other cells, some of which inhibit rather than encourage the neuron’s firing. The neuron may in turn encourage or suppress firing by some of those same cells in complex positive or negative feedback loops.

What excites Koch most about the thinking-cell results is the possibility that they may illuminate a fundamental component of cognition. Our comprehension of the world, he says, requires that we ignore much of the data flooding in through our senses. When we turn on a TV or reminisce about a movie, our brains somehow instantly compress raw sensory data into meaningful concepts and categories. This feat may be accomplished at least in part, Koch says, by cells that represent not just this or that particular image of Rocky but "the platonic ideal of Rocky."

Quiroga notes that a short story by a fellow Argentinian, Jorge Luis Borges, spelled out what would happen to us if we lacked this capacity for compression. Funes the Memorious tells the tale of a youth who, after falling from a horse and striking his head, becomes gifted, or cursed, with photographic recall of every minute experience. He is so overwhelmed by the infinitude of his perceptions that he retreats into a darkened room. "To think is to forget a difference, to generalize, to abstract," Borges writes. "In the overly replete world of Funes there were nothing but details." Unlike Danny, Funes had lost the capacity to perceive the platonic ideal of Rocky.

In Danny’s hospital room, weighty philosophical issues yield to more practical concerns, like getting a tray on rollers properly positioned over his lap. "I’m not an engineer, just a scientist," Quiroga says apologetically as he struggles with the balky tray. He eventually succeeds with the help of Emily Ho, who is an engineer, and the team’s chief troubleshooter.

As other researchers come and go, Ho remains in Danny’s room, manning the amplifiers, computers, and other equipment. When the readouts from Danny’s microwires go haywire, Ho starts checking lights and other appliances that might be causing electrical interference. Within minutes she traces the problem to the remote-controller that Danny uses to make his bed go up and down. After she unplugs it, the readouts return to normal.

The atmosphere in the room is surprisingly cheery. One reason is the frequent presence of Danny’s father, Bill, owner of a carpeting business. Although silence reigns during experiments, so that Danny doesn’t get distracted, between sessions Bill teases both the researchers and his son. At one point, Ho, watching signals from Danny’s neurons scroll across a computer screen, tells him that he’s got "great brain cells."

"Are you kidding?" Bill exclaims. "He’s got lousy brain cells!"

Danny grins, even more so later after his father fumbles a styrofoam container of Chinese food, sending chicken chunks skidding across the floor. "Who’s got the lousy cells?" Danny chortles.

Bill turns serious when asked why he and his wife agreed to let their son participate in these studies. "It’s a duty," Bill says. Danny, Bill points out, has benefited because many other patients before him have volunteered to be subjects for research. In the future, people suffering from epilepsy or other brain disorders may benefit from what the UCLA team learns from Danny.

For his part, Danny says he enjoys hanging out with the scientists and doing the experiments--"as long as there’s no math."

Brain cells more complex than we think

By Steve Connor

London - It only takes one brain cell to recognise a Hollywood celebrity, according to a study into how the human mind recalls a familiar face.

Scientists have shown that the faces of stars such as Halle Berry, Jennifer Aniston and Brad Pitt can each stimulate a nerve cell in the brain which seems to recognise that face alone.

Neuroscientists said the results suggest that present-day thinking about how the brain recognises and remembers familiar objects and people may have to be overhauled.

The findings suggest that individual brain cells are more complex than previously thought and rather than being mere electronic relays for transmitting signals, they are miniature computers in their own right, capable of processing complex information.

Instead of brain cells acting as a network of individual units which are not particularly important on their own, scientists may revitalise an older theory suggesting that a separate nerve cell is responsible for triggering the recognition of a familiar face.

The scientists who carried out the research said that along with the old idea of a "grandmother cell" responsible for recognising your grandmother, there may be an entire population of brain cells for recognising other people, such as the Halle Berry or Brad Pitt cell.

Itzhak Fried, professor of neurosurgery at the University of California in Los Angeles, said that the discovery, published in the journal Nature on Friday, could lead to new ways of augmenting a damaged brain or a failing memory with artificial aids.

"This new understanding of individual neurons as thinking cells is an important step toward cracking the brain's cognition code," Fried said.

"As our understanding grows, we one day may be able to build cognitive prostheses to replace functions lost due to brain injury or disease, perhaps even for memory," he said.

The study was carried out on eight epilepsy patients who were undergoing treatment with the help of micro-electrodes implanted deep into their brains. The scientists used the patients' clinical situation to test their ideas about recognition.

As the patients were shown images of famous people and landmarks, the scientists recorded electrical activity in individual brain cells or "units".

"For example, in one case, a unit responded only to three completely different images of the ex-president Bill Clinton.

"Another unit from a different patient responded only to images of The Beatles, another one to cartoons from The Simpson's television series and another one to pictures of the basketball player Michael Jordan," the scientists said.

In another patient a single brain cell responded to different pictures of Jennifer Aniston but not to other famous or non-famous faces, landmarks or animals.

Yet the same brain cell did not respond to Jennifer Aniston when she appeared together with her former husband Brad Pitt.

In another instance, an individual brain cell responded to a picture of Halle Berry, even with many of her features obscured when she was dressed as Catwoman. The same cell even responded to the words "Halle Berry".

Christof Koch, professor of computation and neural systems at the California Institute of Technology, said the results of the study were extremely surprising.

"Our findings fly in the face of conventional thinking about how brain cells function. Conventional wisdom views individual brain cells as simple switches or relays.

"In fact, we are finding that neurons are able to function more like a sophisticated computer," Koch said. - The Independent

• This article was originally published on page 10 of The Cape Times on June 24, 2005