John Horgan

Biography Writings=20 Appearances = =20

"Can a Single Brain Cell Think?"

Discover, June 2005

In the = neurosurgery=20 ward of the David Geffen School of Medicine at UCLA, Danny, a = stocky=20 21-year-old college student wearing blue pajamas and sporting a = wispy=20 goatee, sits on a bed watching one photo after another flash on a = laptop=20 screen. Several macho movie stars appear in rapid succession, = including=20 Arnold Schwartzenegger, Steven Seagal, Sylvester Stallone, and Mr. = T, the=20 mohawked brawler who plays Stallone=92s rival in the boxing film = Rocky III.=20 At first glance, one might guess that Danny has volunteered for a=20 Hollywood survey: Who=92s your favorite action hero? In fact, = Danny is the=20 real hero. The black cables emerging from the white turban wrapped = around=20 his skull hint at his role in investigating a truly profound = question: How=20 do thoughts form in the human brain?

Danny suffers from = epilepsy,=20 and he has had electrodes temporarily implanted into his brain to = monitor=20 seizures; ideally, the electrodes will pinpoint the neural defect=20 triggering his seizures so it can be surgically removed. During = the week=20 or so that the electrodes remain in Danny=92s brain, he has = volunteered to=20 participate in experiments aimed at understanding the = underpinnings of=20 cognition. Such research is quite rare; for obvious ethical = reasons,=20 neuroscientists have few opportunities to gather data from deep = inside a=20 living human brain.

This particular experiment touches on = one of=20 the most challenging puzzles of neuroscience: How do brain cells = recognize=20 items as complicated as a toaster oven, the number nine, a zebra, = Bill=20 Clinton, or the film character Rocky? Are single cells like = transistors in=20 a computer, or pixels on a television screen, contributing just = minute=20 pieces of information that only when combined with the output of = thousands=20 or millions of other cells form the complex pattern that means = Rocky? Or=20 can a single neuron learn to recognize that face?

Most=20 neuroscientists adhere to the pixel view of neurons, arguing that=20 individual cells can=92t possibly be clever enough to make sense = of a=20 concept as subtle as Rocky; after all, the world=92s fastest = supercomputers=20 have difficulty performing that pattern-recognition feat. But = Itzhak=20 Fried, the neurosurgeon who implanted the electrodes in Danny=92s = brain and=20 who leads this UCLA research program, believes he has found = "thinking=20 cells" in the brains of subjects like Danny. If he=92s right,=20 neuroscientists may be forced to overhaul their view of how the = human=20 brain works.

A true thinking cell should be able to = recognize a=20 person or fictional character even in many different guises. Danny = is a=20 big fan of Hollywood action heroes, especially Rocky; he owns DVDs = of all=20 four films in the series and never tires of watching them. So, = amid the=20 images that flash on the laptop screen, the research team has = included=20 shots that show Rocky running through the streets of Philadelphia, = staring=20 longingly at his girlfriend Adrian, or draped in the American flag = after=20 defeating his Russian rival. Now and then, to test whether a = cell=92s=20 recognition cuts across sensory modes, Rocky or some other name is = spelled=20 out on the laptop screen or uttered by an eerie synthesized=20 voice.

As Danny peers at the laptop, signals stream from = more than=20 100 ultra-thin electrodes, each sensitive enough to detect the = murmuring=20 of a single cell=97and into the cables that emerge from his head. = The cables=20 ferry the signals across the room to a cabinet crammed with = amplifiers. A=20 computer atop the cabinet displays the readouts from Danny=92s = cells as a=20 series of multi-colored lines unfolding across a screen. Every now = and=20 then, a line jerks upward, as one of Danny=92s cells sputters in = response to=20 an image or name. Rodrigo Quian Quiroga, the Argentinian = neuroscientist=20 overseeing this research session, points to one especially = energetic=20 squiggle and whispers, "That=92s Rocky."

The vast majority = of modern=20 brain research involves technologies such as magnetic = resonance-imaging,=20 positron emission tomography, and electroencephalography. All = measure=20 neural activity from outside the skull. Figuring out how brains = work with=20 external scanners is like studying life on a cloud-shrouded planet = with=20 satellites. Implanted electrodes, by contrast, are like probes = that drop=20 down to the planet=92s surface. Electrode studies of monkeys and = other=20 animals whose brains resemble ours have yielded valuable insights, = but=20 these creatures cannot describe their subjective = sensations.

A=20 handful of other hospitals are carrying out electrode research = that=20 piggybacks on the clinical treatment of patients with epilepsy,=20 Parkinson=92s disease, and other neurological disorders. But no = research=20 program approaches UCLA=92s in experience, sophistication, or = published=20 results, says Christof Koch, a neuroscientist at the California = Institute=20 of Technology who has been collaborating with the UCLA group since = 1998.=20 "There is no one technique that=92s going to give you all the = answers" to=20 the riddle of cognition, Koch says. "But this is one that=92s = very, very=20 good, and we=92re getting better at it."

Fried, the driven = yet=20 affable commander-in-chief of the program, founded it in 1992 = after=20 leaving Yale. Since then more than 100 of his epileptic patients = with=20 electrodes implanted in their brains for diagnostic purposes have=20 volunteered as subjects for basic research. From the outset, Fried = has=20 been protective of his patients and their privacy; this is the = first time=20 he has allowed a reporter to watch him and his team at = work.

Fried=20 was born and raised in Israel, and he spends several months a year = working=20 at a hospital in Tel Aviv as well as at UCLA. He flew from Israel = to Los=20 Angeles on a Sunday, and during a three-hour operation on Monday = he=20 drilled ten holes in Danny=92s skull and inserted the electrodes = into his=20 brain. The following day, wearing a white lab coat over aqua = scrubs, Fried=20 strode into a conference room packed with researchers who had = gathered to=20 discuss plans for Danny. The team included two undergraduates who = flew=20 here from the University of Pennsylvania, a few graduate students = from=20 UCLA and Caltech, a couple of postdocs, and two = physicians.

Fried=20 briskly provided background on the patient: Danny is a bright, = friendly=20 young man, he said, who is looking forward to working with the = research=20 team as a way to "break the boredom" of his hospital stay. "Okay, = let=92s=20 get down to practical issues," he continued in his distinctive = Israeli=20 accent. Rapid-fire, he queried the researchers on the status of = their=20 "paradigms." He prefers that term to "experiments," which might = suggest=20 electrodes had been implanted in Danny=92s brain primarily for = research=20 rather than diagnostic purposes.

The discussion keeps = returning to=20 problems with data storage and analysis. Several researchers asked = for=20 upgrades in equipment for storing data=97which the microelectrode=20 experiments generate by the terabyte--and Fried said he=92d see = what he=20 could do. The researchers also received detailed instructions on = how to=20 grapple with a major technical challenge: electrodes in = patients=92 brains=20 often detect pulses from two or more nearby neurons at the same = time,=20 which may show up in the computer as one big signal. Quiroga has = written a=20 program that mathematically unravels overlapping pulses. The = process,=20 called cluster-cutting, makes it possible to extract more = information from=20 the data, at least in principle. But some of Quiroga=92s = colleagues were=20 still trying to familiarize themselves with the fine points of = what the=20 team has dubbed "Rodrigo=92s code."

The researchers had = prepared=20 more than enough studies to keep Danny from becoming bored. One = called for=20 him to view computer-generated pictures of celebrities morphing = into each=20 other: Mr. T into Will Smith, and Sly into Arnie. The objective: = to see if=20 a cell that lights up for Sly fires more slowly as the photo = gradually=20 morphs into Arnie, or just abruptly falls silent. In other words, = are=20 face-recognition cells like simple on-off switches, or can they = act like=20 dimmers?

Another paradigm, called X-Cab, is designed to = yield=20 insights into how we navigate. More than a decade ago = microelectrode=20 studies of rats and monkeys revealed place cells that light up = when the=20 animals move to a particular spot in a maze. Previous versions of = X-Cab,=20 which involves driving a virtual taxi through a cyber-city, have = confirmed=20 that humans have place cells, too, as well as view cells that = respond to=20 specific landmarks, and goal cells that respond to the driver=92s = ultimate=20 destination.

Arne Ekstrom, a UCLA postdoc, and Indra = Viskontas, a=20 graduate student, had made preparations for Danny to test drive a = new=20 version of the X-Cab program, which allows the driver to pick up = and=20 discharge passengers. Fried asked if they had made the changes he=20 requested in the paradigm. "Almost all of them," Viskontas = replied, adding=20 that she and Ekstrom "respectfully" disagreed with some of = Fried=92s=20 requests and wanted to discuss them with him.

Fried nodded. = "Any=20 more questions?" he asked, scanning the room one last time. "If = not, to=20 work."

Back in his office, Fried recalled how he ended up=20 overseeing this unusual program. One of his role models was Wilder = Penfield, the Canadian surgeon who carried out pioneering = operations on=20 epileptics in the 1950=92s and 1960=92s. After removing the = skull-cap of=20 patients, Penfield electrically tickled different spots of their = brains=20 with wires and asked them what they felt; because the brain lacks = pain=20 receptors, the patients needed no anesthesia. They could report = feeling a=20 tingle in their left forefinger, seeing a blue flash, hearing a=20 low-pitched hum.

This procedure not only helped to guide = Penfield=92s=20 surgical treatment of each patient; it also yielded clues to what=20 different parts of the brain do. "Here was somebody who was really = looking=20 at the human mind," Fried said, "but at same time he was helping a = human=20 being." Fried=92s method is much more refined than Penfield=92s. = Fried=20 typically drills a dozen holes in the patient=92s skull and = inserts a dozen=20 hollow macroelectrodes, which can detect large-scale electrical = waves=20 emanating from a seizure.

Protruding from the end of each=20 macroelectrode are as many as ten flexible microelectrodes that = can detect=20 the pulses of individual neurons. The patient=92s clinical status = dictates=20 the placement of the macroelectrodes. In Danny=92s case, tests = suggest that=20 his seizures originate in his frontal lobes, so Fried inserted = most of the=20 macroelectrodes in that region. He embedded one macroelectrode in = Danny=92s=20 hippocampus, a minute region that underpins memory and is often = implicated=20 in epileptic seizures.

The patient=92s clinical health and = comfort,=20 Fried emphasized, take precedence over research objectives. Even = the most=20 carefully planned paradigm must be set aside if the patient = becomes bored,=20 tired, frustrated, gets a headache, or just wants to be left = alone. Fried=20 carefully screens prospective colleagues to ensure that they treat = his=20 patients like human beings rather than laboratory animals. "The = person who=20 will not do well," he said, "is a compulsive-obsessive animal = physiologist=20 who, if he doesn=92t control all the variables, falls apart." But = Fried also=20 said he believes that "there is a responsibility" to take = advantage of=20 these rare chances to learn more about the behavior of individual = neurons,=20 which he calls the building blocks of cognition.

Following=20 Penfield=92s example, Fried occasionally does studies that involve = stimulating brain cells with minute electrical jolts. In 1998, he = and=20 three colleagues discovered that a female patient burst into = laughter=20 every time they stimulated a spot at the top of her brain called = the=20 supplementary motor area. Her hilarity was not just physiological; = the=20 woman felt subjective sensations of "merriment or mirth." She = displaying a=20 syndrome known as confabulation=97she invented reasons for her = hilarity,=20 telling the researchers at one point, "You guys are just so = funny...=20 standing around."

But most of Fried=92s findings, which he = has=20 described in more than a dozen papers in such leading journals as = Nature,=20 Neuron, and Proceedings of the National Academy of Sciences, = involve not=20 electrically stimulating neurons but passively listening to their = chatter=20 as a patient performs various tasks. In one set of experiments, = Fried,=20 Koch, and Gabriel Krieman, a Caltech grad student, found cells = that light=20 up both when a subject looks at an image=97of a baseball, say, or = a woman=92s=20 face--and when he closes his eyes and recalls the image in his = minds=92 eye.=20 The results provide the most convincing evidence yet that human = perception=20 and imagination share neural circuitry.

The experiments = that have=20 attracted the most attention are those supporting the existence of = "thinking cells." The possibility of such cells has been debated = at least=20 since the 1950s, when researchers found single neurons in the = visual=20 cortex of cats and other animals that respond to simple stimuli, = such as=20 lines oriented at a certain angle or moving in a specific = direction or=20 light of a particular wavelength. Some theorists wondered whether = single=20 neurons might also respond to much more complicated stimuli, such = as=20 specific people.

Once known as gnostic cells, after the = Greek word=20 for knowledge, they were dubbed grandmother cells in the late = 1960s by=20 neuroscientist Jerry Lettvin of the Massachusetts Institute of = Technology.=20 Lettvin meant to make fun of=97if not to dismiss--speculation that = single=20 cells could be dedicated to recognition of family members or other = individuals who loom large in an individual=92s mental universe. = In one=20 paper, he joked that mother-smothered neurotics such as Portnoy, = the hero=20 of Phillip Roth=92s novel Portnoy=92s Complaint, could be cured of = their=20 Oedipal disorders by having all the mother cells purged from their = brains.=20

Many neuroscientists found it hard to believe that a = single cell=20 could recognize an inanimate object, let alone a human being. Even = objects=20 as simple as chairs, trees, or buildings come in an almost = infinite=20 variety of forms, and the same object looks different from = different=20 perspectives or in different contexts. Neuroscientists were = therefore=20 startled in the early 1970s when experiments on monkeys by Charles = Gross=20 of Princeton turned up cells that respond selectively to hands and = faces--not specific faces but faces in general.

No one had = really=20 followed up on Gross=92s findings, however, until the late 1990s, = when Fried=20 and his colleagues started reporting how epileptic patients = reacted to=20 various images. Some neurons were apparently smart enough to = comprehend=20 the highly abstract concept "non-human animal." Their neurons = fired when=20 the patient was shown a picture of a tiger, eagle, antelope, and = rabbit,=20 but not when shown pictures of humans or inanimate objects. Other = cells=20 favored images only of food, or of buildings, or of human faces. = Some=20 cells responded to all faces, but others were picky, firing for = male faces=20 but not female ones, or scowling faces but not smiling ones=97or, = finally,=20 faces of specific individuals.

One of the first neurons of = this=20 type was the so-called Bill Clinton cell, which was buried deep in = the=20 amygdala of a female patient. The cell responded to three very = different=20 images of the former President: a line drawing of Clinton = laughing; a=20 formal painting of him; and a photograph of him mingling with = other=20 dignitaries. The cell remained mute when the patient viewed images = of=20 other people, including male politicians and celebrities. = Fried=92s group=20 found cells in other volunteers that responded in this same highly = selective way to actors, including Jennifer Anniston, Brad Pitt, = and Halle=20 Berry.

One reason celebrities have played a prominent role = in=20 Fried=92s experiments is that their photographs are often easier = to come by=20 than images of a patient=92s own relatives. But as part of her = dissertation=20 project on biographical memory, the UCLA graduate student = Viskontas has=20 for several years been showing patients photographs of family = members.=20 Viskontas is reluctant to reveal details about her results, which = have not=20 been published yet. But she confirms that she has found neurons = that=20 respond to a particular relative: father, mother, brother, sister, = grandfather, and, yes, grandmother. The experiments have also = found cells=20 that light up when a patient sees an image of himself. Call them=20 narcissism cells.

Viskontas is wary of over-interpreting = these=20 results or others emerging from the UCLA program. She does not = believe,=20 for example, that they support the most extreme version of the=20 grandmother-cell hypothesis, in which cells are exclusively and=20 permanently assigned to one person, place, or thing. The past few = decades,=20 she adds, have revealed that brain cells are versatile, or = "plastic,"=20 changing their roles in response to new experiences. The UCLA = experiments=20 may not be detecting long-term memory but so-called = working-memory, in=20 which cells are temporarily assigned to the job of representing = Grandma,=20 Jennifer, Aniston, or Rocky only as a result of the stimulation = provided=20 by the experiment.

Koch isn=92t so sure. It would make = sense, he=20 argues, for our brains to dedicate some cells to people or other = things=20 frequently in our thoughts. The larger significance of the UCLA=20 experiments, he says, is that neuroscientists may have to change = their=20 view of neurons as simple switches, transistors, or pixels. Each = neuron=20 may be more like a sophisticated computer, running customized = software.=20 After all, individual neurons can receive input from hundreds of = thousands=20 of other cells, some of which inhibit rather than encourage the = neuron=92s=20 firing. The neuron may in turn encourage or suppress firing by = some of=20 those same cells in complex positive or negative feedback=20 loops.

What excites Koch most about the thinking-cell = results is=20 the possibility that they may illuminate a fundamental component = of=20 cognition. Our comprehension of the world, he says, requires that = we=20 ignore much of the data flooding in through our senses. When we = turn on a=20 TV or reminisce about a movie, our brains somehow instantly = compress raw=20 sensory data into meaningful concepts and categories. This feat = may be=20 accomplished at least in part, Koch says, by cells that represent = not just=20 this or that particular image of Rocky but "the platonic ideal of = Rocky."=20

Quiroga notes that a short story by a fellow Argentinian, = Jorge=20 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=20 who, after falling from a horse and striking his head, becomes = gifted, or=20 cursed, with photographic recall of every minute experience. He is = so=20 overwhelmed by the infinitude of his perceptions that he retreats = into a=20 darkened room. "To think is to forget a difference, to generalize, = to=20 abstract," Borges writes. "In the overly replete world of Funes = there were=20 nothing but details." Unlike Danny, Funes had lost the capacity to = perceive the platonic ideal of Rocky.

In Danny=92s hospital = room,=20 weighty philosophical issues yield to more practical concerns, = like=20 getting a tray on rollers properly positioned over his lap. "I=92m = not an=20 engineer, just a scientist," Quiroga says apologetically as he = struggles=20 with the balky tray. He eventually succeeds with the help of Emily = Ho, who=20 is an engineer, and the team=92s chief troubleshooter.

As = other=20 researchers come and go, Ho remains in Danny=92s room, manning the = amplifiers, computers, and other equipment. When the readouts from = Danny=92s=20 microwires go haywire, Ho starts checking lights and other = appliances that=20 might be causing electrical interference. Within minutes she = traces the=20 problem to the remote-controller that Danny uses to make his bed = go up and=20 down. After she unplugs it, the readouts return to = normal.

The=20 atmosphere in the room is surprisingly cheery. One reason is the = frequent=20 presence of Danny=92s father, Bill, owner of a carpeting business. = Although=20 silence reigns during experiments, so that Danny doesn=92t get = distracted,=20 between sessions Bill teases both the researchers and his son. At = one=20 point, Ho, watching signals from Danny=92s neurons scroll across a = computer=20 screen, tells him that he=92s got "great brain cells."

"Are = you=20 kidding?" Bill exclaims. "He=92s got lousy brain = cells!"

Danny grins,=20 even more so later after his father fumbles a styrofoam container = of=20 Chinese food, sending chicken chunks skidding across the floor. = "Who=92s got=20 the lousy cells?" Danny chortles.

Bill turns serious when = asked why=20 he and his wife agreed to let their son participate in these = studies.=20 "It=92s a duty," Bill says. Danny, Bill points out, has benefited = because=20 many other patients before him have volunteered to be subjects for = research. In the future, people suffering from epilepsy or other = brain=20 disorders may benefit from what the UCLA team learns from Danny.=20

For his part, Danny says he enjoys hanging out with the = scientists=20 and doing the experiments--"as long as there=92s no=20 math."

Selected Works

Books

Rational = Mysticism:=20 Dispatches from the Border Between Science and=20 Spirituality
Houghton Mifflin, January 2003.

The End of = Science:=20 Facing the Limits of Science in the Twilight of the = Scientific=20 Age
Broadway Books, 1996

The = Undiscovered Mind:=20 How the Brain Defies Replication, Medication, and=20 Explanation
Free Press, 1999

Where Was God = on=20 September 11? A Scientist Asks a Ground-Zero = Pastor.
With=20 Reverend Frank Geer. Edited and with an Introduction by = Robert=20 Hutchinson. Brown Trout, 2002. Royalties go to Help the = Afghan=20 Children Inc.

Misc. Writings

Can a Single = Brain Cell=20 Think?
Researchers have found evidence for the = controversial=20 "grandmother-cell" theory. Discover, June 2005.

Brain Chips and = Other=20 Dreams of the Cyber-Evangelists
An essay in the = Chronicle of=20 Higher Education, June 3, 2005

Do Our Genes = Influence=20 Behavior?
An essay published in the Chronicle of = Higher=20 Education, November 26, 2004.

Keeping the = Faith in My=20 Doubt
An essay published in the New York Times, = December 12,=20 2004

The Myth of = Mind=20 Control: Will Anyone Ever Decode the Human = Brain?
Cover story=20 for Discover Magazine, October 2004.

Why I Can't = Embrace=20 Buddhism
A critique of Buddhism, published online by = Slate=20 (slate.msn.com) February 12, 2003.

Peyote on the=20 Brain
Published in Discover Magazine, February 2003. = A=20 profile of the Harvard psychiatrist John Halpern and his = five-year=20 study of peyote use by members of the Native American = Church.

More Than Good = Intentions: Holding Fast to Faith in Free Will
An = essay=20 published in the New York Times, December 31, 2002.

A Holiday Made = for=20 Believing
An essay published on the oped page of the = New York=20 Times Christmas Day, 2002.

Selected = Articles,=20 1986-Present
A list of articles written for = Scientific=20 American and other publications.

Outtakes from Rational = Mysticism=20 (published here only)

Why I Gave Up = On=20 Zen
An account of Horgan's efforts to achieve satori = in a Zen=20 class.

The Professor = of Pure=20 Consciousness
A profile of the mystical philosopher = Robert=20 Forman, founder of The Forge.

The Psychedelic = Sorcerer
A profile of the German anthropologist and = authority=20 on shamanism Christian Ratsch.

The = Anti-Gurus
A=20 profile of Diana Alstad and Joel Kramer, authors of The Guru = Papers.

A Modern = Catholic=20 Mystic
A profile of the Benedictine monk Brother = David=20 Steindl-Rast.

Beyond = Belief
A=20 profile of the British Buddhist Stephen Batchelor.

The Myth of = the Totally=20 Enlightened Guru
A profile of the guru Andrew Cohen, = founder=20 of What Is Enlightenment?, with digressions on Yogi Bhajan = and Amrit=20 Desai.

Quick Links

Horgan writes in Science & Spirit = magazine about=20 whether war is inevitable.

Horgan updates his views of science's limits = in "The=20 End of Science Revisited," Computer Magazine, January=20 2004.

Horgan defends his end-of-science argument = on The=20 Edge.

Horgan responds to Kevin Kelly, Paul Davies, = Lee=20 Smolin, and other Edge critics.

Horgan bets=20 Michio Kaku $1000 that superstrings won't pan out.

Authors=20 Guild

E-mail John=20 Horgan

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