During electrical stimulation of electrode No. 24 … the patient stated that all faces in the room appeared indistinguishable.
—Trevor Mundel, et al., “Experience-Based Configural Face Encoding in the Human Right Fusiform Gyrus” preprint, The University of Chicago
My yellow cat has epilepsy. The first time I was to witness one of its seizures, a quasihuman scream, torn from some fabric of terror and despair, startled me awake at about 3 a.m. I found the cat convulsing behind the tall mirrored doors of a closet that stood partially open near the head of my bed. Gripped by sheer befuddlement, I bellowed and thrust the doors apart, shattering one of them, and saw the cat lying on its side, eerily gagging as if being throttled, while spasmodically, fiercely clawing against no visible threat beyond the shoes and slippers lined up in tidy rows in the closet. The spasms slowed, becoming more tortured, until it seemed certain that the cat was dying for lack of breath. Then the cat sat up on its front paws.
The convulsions had abruptly stopped. The scent of urine rose from the closet in the room’s sudden stillness. With huge black pupils, the cat stared straight ahead, as if absorbed in some terrible secret, and I had the 3-a.m. impression that shards of its meager self were returning from the jagged slopes of planets that the sane of this universe have never seen. My presence had no more effect on that stare than the bed or the floor lamp did. When, minutes later, the cat finally recognized me, it began to purr.
Standing there, conscious of the smell of pee and the first stirrings of regret over the smashed door, I recalled, through one of the connections that may or may not say something worth knowing about how the mind works, that the Grateful Dead had been in town several years before, playing at Soldier Field, next to the lake, in one of Jerry Garcia s last concerts. A bike path meanders past Soldier Field and its parking lots, where a whole shantytown of Deadheads in tie-dyed shirts had camped peacefully. They shuffled along the bike path in formations that suggested a flotilla of rafts with many agendas and few astrolabes. The day before the concert, approaching the rear straggler of one such group on my mountain bike, I slowed and slowed, hoping the gentle soul would notice me looming and puffing behind him. Instead I came too close and rode up his ankle with the knobby treads of the bike’s front tire. The action of the treads ripped a dirty Converse sneaker off the back of his foot, and when I braked, the tire pinned his shoe, and him, to the spot. He twisted awkwardly around to look at me. I do not remember his face. He said this: “Sorry, man.”
I do not remember his face. Memory aside, my notes on scientific topics are obsessive and, above all, dated, so that once a new closet door had been ordered (Rubenstein Lumber Company, 167 North Morgan Street, Chicago, tel: 312-666-4800), I combed both my notes and old newspapers in the library across the street from my apartment for any clue to a psychic link between grand mal and Garcia. This turned up: “We have a paucity of animal models that accurately represent human epilepsy,” a neurosurgeon had explained to me on that same afternoon, July 23, 1994, a Saturday.
The afternoon shone again when I read this line. I had rushed the end of the bike ride in order to be home for his call, which dealt with experiments involving slices of rat brain pierced by a pair of electrical probes in a dish. A potassium solution in the dish caused neurons in the brain slice to fire chaotically, as if it were beginning an epileptic seizure. Precisely timed jolts from one of the probes could make the seizing behavior stop. To achieve this end, the other probe monitored the brain’s own moment-to-moment pattern of firing and sent this information to a computer, which in turn calculated the time sequence of the jolts to be applied by the first probe. The neurosurgeon said that this general technique, called chaos control, for stopping seizures could someday jump straight from the in vitro experiments to human trials, since live animals—his “models”—are often useless in the testing of potential epilepsy treatments.
Not before trudging backward in time from the smashed mirror was it impressed upon me how astonishing this mathematical control of brain tissue was, this conductor waving a baton before an orchestra of potassium-drunk rat neurons. Much later an epileptologist explained to me why studying the disease in live animals was often not very effective. Among other reasons, mental disturbances have an intensely subjective quality; they must be described by those who suffer and receive treatment. Human epileptic seizures, for example, may be preceded by the aura—an unaccountable sense that someone has entered the room, a feeling of nausea, an apparent odor, or some other recognizable sign. “You can’t ask a cat if it’s having a déjà vu experience,” said the epileptologist.
This collision of subjectivity and the computable math of chaos generated a shower of sparks in my own mind. The metaphor itself, I knew, must be dancing like a St. Elmo’s fire among the associative sulci of my cortex, a realization that would have its own chaotic center of combustion. I wanted to know whether such techniques should be seen as just another mechanical procedure—no more a personal invasion than an X-ray of someone’s pelvis—or whether they would open the first, big-eyed gaze by science into an irreducibly human place, into once-hidden reflexes that could not be set apart from ourselves as easily as the bending of a joint or the contraction of a muscle or even the aimless flutter of an electroencephalogram. Could the dread of a 3-a.m. thought be skewered like an insect on a pin and displayed, in some virtual glass case of the future, with a crisp and technically accurate paragraph describing a prior belief that this well-studied specimen constituted the soul?
There was also an entirely benign perspective on all of this neural probing, of course. Call it the view from the 3-p.m. cortex. As the neurosurgeon and mathematician Steven Schiff explained it to me once in an email, a central problem in neuroscience today goes like this: “Think a moment about the ‘binding problem’ … You are reading this text, decoding the images and thinking of the language it implies, formulating your response and scribbling notes on a pad. How are your perceptions ‘bound together’ at spatially disparate parts of your brain?” What’s needed is some generalized way of looking at the noisy, imperfect synchrony or coupling between the electric or magnetic or metabolic activity in those disparate parts. Making connections, realizing patterns—humans do those things well, but how? The same mathematical unraveling that applies to the chaotic patterns of epilepsy could indeed tease apart the fine weave that links ordinary neurons in the brain.
Still other facts could override the subtle soucis of the healthy. It is quite possible that insights like these could offer some peace not just to the ill but also to the incurably tormented—those whom drugs do not help and who cannot even benefit from the therapy of last resort: the removal of diseased or damaged foci of their brain from which seizures seem to emanate, like a subterranean explosion. During my immersion in these subjects, I have learned of children afflicted with 30 seizures a day. I have met other people with less-frequent seizures whose lives the disease has nevertheless smashed by preventing them from attending school or holding a job or escaping misery at its most personal levels. The most baffling and idiosyncratic disability of all turned up in a woman whose aura temporarily took from her the ability to distinguish between different faces. By stimulating her epileptic focus with an electrode prior to surgery, a team of physicians, led by another clinician-mathematician, John G. Milton of the University of Chicago, found that they could induce the state at will. The crucial position lay under an electrode, designated No. 24, in an array resting upon her brain.
this morning i whispered your name this morning the clouds dropped low over atlanta this morning the clouds this morning anna i whispered the clouds they covered all that we have forgotten this morning atlanta i whispered this morning
From one point of view, there is nothing particularly inscrutable about a neuron. Mathematically, ensembles of neurons merely show that simple entities interacting in simple ways can exhibit behavior patterns of incredible complexity. There are roughly as many neurons in the human brain as stars in our galaxy. Yet the Milky Way, with its 10 to 100 billion glowing orbs and their affiliated nebulae, dust, planets and cosmic small change, is in most respects a simpler object than the brain. It has become a cliché among cosmologists that the physiology and behavior of a single frog is more complicated than the large-scale evolution of the entire universe. Much of that complication can be traced to the frog’s crisscrossing network of neurons.
Focus on the essentials, however, and any one of those neurons, or nerve cells, is not such a messy thing. Each consists of a soma, or cell body, from which generally emerges a branching shrubbery of so-called dendrites and a single axon that ranges from less than a millimeter to more than two meters in length. The terminus of the axon often branches as well. Under the right conditions, a train of voltage spikes called action potentials ripple down the axon from the soma at speeds as great as 100 meters a second and more.
When those nerve impulses reach the axon tips, a chemical called a neurotransmitter can be released into a microscopic gap, or synapse. On the other side of that synapse is a dendrite, soma or axon of another neuron. The spritz of neurotransmitter is a form of communication from one neuron to another, in effect letting the second neuron know that the axon termini of the first are tingling with action potentials.
What induces a neuron to fire off a string of action potentials in the first place? It “integrates,” or adds up, all the information arriving from all the synapses it has with the axon termini of other neurons. A synapse may be excitatory—that is, tending to cause a recipient neuron to fire—or inhibitory, suppressing the firing. Envision a stock trader listening on three different phones, staring at prices on a computer screen and generally taking in the chatter and commotion of the other traders around her. At any moment the totality of that information might push the trader to take an action, such as buying or selling; or the tips from the bulls and bears might cancel each other so that the trader does nothing. Any particular neuron can receive inputs from as many as 100,000 synapses, leading to biological circuitry of unimaginable complexity—such as the trader.
Most of the knottiness follows from the connections themselves. But individual neurons do have tricks of their own, even when regarded as nothing more than circuit elements. In a noted experiment, John Rinzel of the Center for Neural Science at New York University, and the late Rita Guttman stimulated a squid giant axon with electrical current. At high values of the current, the axon fired repetitively, and at low values it was silent. At intermediate values, however, slight perturbations in the current could make it jump between the firing and quiet states, a phenomenon called hysteresis or bistability. Computer models have been made of bistable neurons linked into networks—perhaps a vast simplification of the brain. The models show the linked neurons behaving like dogs in the backyards of a big neighborhood: If one dog barks, all the rest may start up, but once they fall silent, most of them may sleep through the afternoon. “The network itself would be bistable,” Rinzel told me three years and six weeks after the Dead concert.
If epilepsy turned out to be a manifestation of bistability in the human brain, physicians would have been granted a clue on how to treat it. But I am getting ahead of myself.
Networks of just a few neurons display surprising and sophisticated behaviors in nature. If the tail fin of a crayfish is carefully removed, electronics can monitor the firing of its mechanoreceptor system. The small network of sensory neurons in this system soak up information from the surroundings directly. The system has a stimulus threshold: Swish the fin hard enough through water and hairs on the fins move, inducing the sensory neurons to send trains of spiky voltage impulses down their axons. But suppose you rig a machine to swish the fin back and forth gently enough that the stimulus is barely subthreshold, or too weak to generate a signal on the neurons. Now add noise to the oscillation. By noise I mean a random, herky-jerky motion. You might imagine that the noise would make it even more difficult for the mechanoreceptor to perceive the weak oscillation. It was the achievement of the biophysicist Frank Moss to show that as the noise amplitude is gradually cranked up, the receptor neurons actually begin to encode the oscillation in their patterns of firing with greater and greater fidelity.
With increasing noise amplitude, that fidelity rises to a peak and then falls off as the oscillation is swamped completely. Perhaps it makes sense that this phenomenon, which has been named stochastic resonance, should have evolved to govern the perception of animals in the wild. Put yourself in the place of a crayfish or a cricket (whose perception of oscillatory wind currents, as generated by loudspeakers in a lab, has also been shown to exhibit stochastic resonance) that is about to be threatened by the swift and stealthy approach of a predator. Whether driven by the undulation of a fish’s body or the beating of a bird’s wings, oscillatory motions of the medium surrounding the prey in the presence of natural, random, wind gusts or water currents will serve as your warning of approaching death. Sensitivity amid the confusion of your environment will determine whether you, a lonely cricket, hop in time to escape that big, hungry, incoming beak.
You might take that tale as a mathematical parable: Stochastic resonance shows up in human neurons, too. If subjects rest a finger on a subtle, computer-controlled indentation that pulses up and down, the action may be imperceptible at first. But if either electrical or mechanical noise is added to the indentation and experimenters ask the subjects when they can feel the regular movements, the percentage of correct responses rises and then falls as the noise gets stronger. Other experiments have tested human proprioception, or the sense of where a limb is in space, when a sharpened tungsten wire is poked into the arm and vibrated against the radial nerve, about midway between the elbow and the shoulder. The noise created by nothing more than a 10-micrometer vibration could enhance a subject’s ability to sense whether his or her wrist had been flexed by a small angle—a degree or two.
Such research is unlikely to help “the disembodied lady” who was memorably described by Oliver Sacks in “The Man Who Mistook His Wife for a Hat”—a woman who had lost all sense of proprioception and had to relearn simple actions like walking and sitting up. But the results could provide relief in smaller ways. There is a project at Harvard Medical School to use stochastic resonance for improving the rehabilitation prospects of stroke patients and of diabetics and elderly people with peripheral neuropathy, a deadening of sensation in the extremities. The idea is to develop gloves and socks outfitted with hundreds or thousands of piezoelectric noise inducers. They might help patients maintain good posture while walking and keep them aware of numb limbs, reducing injuries (from falls) and infections (from sores that go unnoticed). “The sensory loop is so essential,” Casey Kerrigan, a rehab specialist at the medical school, told me once. “They use the feeling to relearn a motor task. This could really help.”
The relationship between stochasticity and sense could go deeper. Still other experiments have suggested that during precision motor tasks, the human brain and peripheral nervous system might actually generate their own internal noise in order to sharpen proprioception, like dentists who do their best work next to a television turned up loud.
houses across the mississippi those banks those bluffs a sunday a porch houses when the mississippi rose murky above the flats you stood on those bluffs those banks were mine the mississippi the flats a sunday houses above the flats houses a sunday when the mississippi rose a train bridge houses
In this mingling of physics, biology, mathematics and the habitat of the mind, there are hints that the attempt to understand neural complexity is not hopeless. The Darwinian tangled bank of interwoven neurons does seem to preserve some elements of simplicity. That includes stochastic resonance itself, whose existence mathematicians say depends only on the presence of noise and a weak signal in any system with some sort of threshold. Consider, as a general illustration of those elements, a coin resting in one of two indentations in the dashboard of a car that is winding along a country road. By themselves, centrifugal forces on the coin might not be enough to shove it from one receptacle to another. But if the road is bumpy or uneven enough, the lateral component of this “noise” could sometimes help centrifugal force nudge the coin across in one direction or the other. If the road is too rough, though, the coin can move whether the car is turning or not, and the “signal” of the curves gets drowned out.
The signature of stochastic resonance reveals itself there in the optimum noise level. The degree of force needed to push the coin from one side to the other is the automotive analog of a neuron’s stimulus threshold. There exist formulas filled with sines, cosines, epsilons and omegas to describe stochastic resonance in the most general terms, but those results are just one spanner in a mathematical toolbox that biology is beginning to open. Already far down the road in my obsession with these matters, I put it this way in a news article for Science in September of 1997:
Recordings of epileptic seizures, along with other studies of activity in human and animal brains, are linking neuroscience with a rarefied branch of mathematics called nonlinear dynamics. This discipline was born as theorists tried to make sense of the complicated rhythms of everything from wildly swinging pendulums connected by springs, to the patterns formed by chemical reactions on a metal surface, to wave trains steepening and crashing on a beach. Now a coterie of neuroscientists, biophysicists and mathematicians is finding that the same concepts can also help them understand the collective dynamics of billions of interconnected neurons in the brain.
The article went on to explain that, like water molecules in a Waikiki breaker, neurons and their interactions are certainly laden with reductionistic details—cation channels, myelin sheaths, postsynaptic potentials—that get fuzzed out in this picture. Nonlinear dynamics finds regular patterns by examining these systems in the large. This approach is nothing new, since you don’t learn to surf by studying the bipolar chemistry of liquid H2O, but by appreciating the collective dynamics of waves containing 1029 molecules and more.
To continue with this brief exploration of psychohydrology, suppose you are lying awake at night, and for reasons you yourself do not fully understand, you are carefully timing the drips from a leaky faucet as they fall into a stainless-steel sink in the kitchen. Dripdrip drip … drip, drip, dripdripdrip dripdrip. Et cetera. Call the time interval between drip number n and the previous one Xn-x and the interval between n and the following one Xn. Each time there is a drip, imagine a point flashing on a two-dimensional screen in which the distance along one axis of a graph is Xn-1 and the distance along the other is Xn. The point will wander as if it were a ball rolling through a terrain of slopes, peaks, valleys and saddle-shaped regions. The precise topography of that terrain might depend on the details of all the plumbing between your nocturnal faucet and the metropolitan waterworks, not to mention the size of the leak, the fluid microturbulence inside the drops and the chemical hardness of the water. But for a particular set of conditions, the terrain is fixed, and in your insomniac moments you have managed to grasp the essential structure of a system that would otherwise be complicated beyond human ken.
The charm of the method is that you can apply it to any dynamical system with a fascinating rhythm. A sputtering laser, a surging electrical circuit, an orbiting planet, a fibrillating heart, the annual population of spiders in a meadow, the firing of globs of neurons in vitro or in vivo—they all reveal something of themselves in one of these plots, which are known as Poincaré sections. In this vision, the neural ensembles would be firing and monitored en masse, in some collective fashion, rather than as individuals. As soon as a complicated system like the neurons has been abstracted in this fashion, all sorts of games can be played with the point as it rolls about. In 1990 three physicists—Edward Ott, Celso Grebogi and James Yorke—developed the mathematics of a kind of generalized pacemaker, which they called chaos control, for pinning the system at specific places in the Poincaré landscape.
An ordinary, unimaginative pacemaker applies regular jolts to a system, such as an erratically beating heart, in order to force it back into what is called a period-one orbit (the term is used by analogy with whirling planets) in which Xn = Xn-x. That steady pattern corresponds to a regularly dripping faucet: drip drip drip drip. But the faucet, like any of the other systems, could display periodicity of a different kind: dripdrip dripdrip dripdrip or dripdripdrip dripdripdrip or drip dripdrip drip dripdrip drip dripdrip. The dripdrip sequence displays period-two behavior, since it takes two drips to repeat, and for similar reasons dripdripdrip and drip dripdrip are period-three sequences. More generally, the faucet can slip into and out of these and any number of more complicated unstable periodic orbits, or UPOs. The techniques of chaos control can trap the system near any one of these UPOs, not just at the period-one specialty of a pacemaker.
Certain chaotic raconteurs like to compare this feat to a walrus balancing a beach ball on its nose. It might be more like balancing a marble on a saddle: The Poincaré landscape around UPOs is saddle-shaped, so the point representing the system tends to fall away from them in what would be the direction of the stirrups, but does no more than roll back and forth in the perpendicular direction. Control consists of either nudging the saddle over as the system point is about to fall off, or nudging the point itself back up to the crown of the saddle. The nudges would be applied only now and then—whenever the system began falling away from the UPO, like the walrus occasionally twitching its nose to keep the beach ball from falling off—and not by imposing a pacemaker’s sledge-like regularity.
Practically speaking, controllers do the nudging by different means in the different systems. Moving the saddle corresponds to tweaking something physical about the system, like the resistances or inductances of a circuit or the defective washer in the faucet. Because manipulating the hardware is all but impossible in biological systems, experimenters turn to the second method for them, giving the system point a judicious push at just the right moment to put it back in the saddle. Just what this means was first demonstrated in 1992 with slices of rabbit heart in a dish. A nice hunk of ventricle beat regularly every 0.8 second if left to itself, a drip-drip pattern that might be represented symbolically as AAAAAAA …. Of course, experimenters did not leave the ventricle to itself, instead poisoning it with the drug ouabain, which speeded up the beating and induced arrhythmias. As the ouabain took effect, the heart began beating in a period-two pattern, with a long interval followed by a short interval (ABABAB …). Then the heart skipped in and out of period-four patterns (ABCD-ABCD …) and eventually started rambling all over the Poincaré map.
For cardiology buffs, the period-two pattern is called bigeminy and the period-four, quadrigeminy. (This might also be a good place to note that a senior researcher on the experiment was the aptly named Bill Ditto of the Georgia Institute of Technology.) Experimenters wanted to trap the rabbit heart at chosen UPOs, starting with period one, but not by hammering the preparation with electricity on every beat. They first watched the system point move around on the Poincaré map for a while. That told them the orientation and steepness of the saddles centered on the UPOs, just as looking at skiers from an airplane reveals a resort’s topography, even if the mountains look flatter than paper. The Poincaré landscape went into a computer. It could then anticipate how fast and in what direction the system point would leave any UPO it approached. The controlling nudge was cleverly applied by firing an electrode to shorten a beat interval as the point slipped off the saddle. In other words, the undisturbed beat pattern, as anticipated by the computer, would have taken the point away from the UPO; the truncated pattern, effected by jolting the rabbit heart, set the point right on top of the saddle again, popping away with a fixed periodicity.
The Ditto device could trap rabbit hearts in the AAAAAAA, ABABAB, ABCABC or ABCDABCD patterns. “During chaos control, only every third or fourth beat was an electrically paced beat,” the team reported in one of a series of publications on the experiment. After speculating about basing “smart pacemakers” on chaos control, some of the team members went straight from rabbit hearts to rat brains, joining forces with Steven Schiff, a former co-director of the epilepsy program at the Children’s National Medical Center and now a professor of neurobiology and psychology at George Mason University. It was to discuss the latter experiments that I rushed home through Deadheads engaging in collective behavior along the lake. Like many chaos researchers, Schiff, a hypermath with a surgeon’s ostentatiously deliberate diction, first became interested in the subject by reading James Gleick’s “Chaos: Making a New Science” (Viking, 1987; this factoid sticks in my mind for a reason. Because of the similarity of our names, a few overlapping interests and the justified fame of Gleick’s work, I sometimes arrive at scientific conferences to find myself assigned a press cubbyhole bearing his name. Thus I have a message for the world: I am not James Gleick.)
The terse response from Schiff’s secretary to one of my earlier phone calls—“He’s in OR. Can I take a message?”—effectively informed me that I was not dealing with a laboratory dreamer. His long-term aim was to find new ways of treating focal epilepsy in its most refractory forms. Drugs are ineffective against those forms of the disease, and surgical removal of the focus carries the risk that patients will lose some degree of motor function, memory or language skills. Sometimes the focus sits so far within or behind eloquent cortex—the term of art for regions whose loss results in obvious deficits—so that surgery is unthinkable. Schiff explained epileptic foci as confused lumps of neurons that either never formed properly or were somehow scarred from an injury and reconfigured into a cranial Balkan region, ready at any time to erupt with dystopia and send shock waves ricocheting through the rest of the brain. Rewired was the word he used, with reference to neural connectivity.
The experiment itself was modest compared to those great goals, as Schiff continually stressed. It was performed on slices of rat hippocampus in a dish. Part of the limbic system, which in humans governs emotions such as fear or rage or joy and is often swept by waves of stimulation during a seizure, the hippocampus itself is critical for memory. A stiff potassium solution got the hippocampus jumpin’ and jivin’. More literally, its neurons began firing at irregular intervals in a way reminiscent of the so-called interictal spikes recorded before and after seizures in humans with epilepsy. As a first approximation at least, normal neural behavior is more like the unsynchronized noise of a crowd of people. The spikes appear when ensembles of neurons fire together, like an intoxicated orchestra being led by a mad conductor who changes the time signature, the key and the composer every few beats.
The Poincaré map for this hepped-up rat brain again revealed the system lingering around periodic points, then falling off the saddle. There were actually some advantages to working with brain instead of cardiac tissue. The brain was not in the process of dying, as the ouabain-poisoned heart was, and the times between successive interictal spikes could either be shortened—as in the earlier experiment—or lengthened. The difference was the neurons’ susceptibility to both inhibition and stimulation. A double pulse from the electrode, it turned out, forestalled an anticipated spike, while a single pulse quickened its arrival. The tempo became spiritoso but sane. “We achieved better control than in the heart,” an awed Bill Ditto told me by phone just after the Dead had left town. “This system in principle could have been much more irregular. It’s thinking. Or trying to. It’s really kind of scary. In the heart I never worried about, ‘I wonder if this things adapting to what we’re doing.’”
Because it is still unclear whether increasing or decreasing the periodicity might better avert seizures in the human brain, Ditto and Schiff also performed an exercise they dubbed anti-control, slapping the system away from periodicity whenever it got close. Where would the work go from there? As Schiff and I kicked that question around, it transpired that he had never read Michael Crichton’s “The Terminal Man,” the tale of Harry Benson, a man who has computer-controlled electrodes implanted in his brain to suppress a violent form of epilepsy. Of course the scheme eventually gets out of control and Harry Benson goes berserk. He is shot to death as he attacks one of the surgeons in a computer room. “Dr. Ross,” Benson says, advancing on her as she points a gun with a trembling hand, “you’re my doctor. You wouldn’t do anything to hurt me.” Far from showing the least discomfiture (I should have known better), Schiff complimented Crichton’s overall prescience and still makes a habit of citing the book in his review papers.
milan berlin prague toulouse venice milan the frankfurt steel station the american lady has no dollars to bribe milan berlin prague berlin prague the post communist conductor your face your voice the clochard in paris toulouse venice milan no dollars no francs i speak no french do you think i am stupid you are reading le figaro american lady has no dollars wagon-lit schlafwagen your face your voice toulouse venice milan le figaro stupid clochard gazetta dello sport it’s raining marseilles the american frankfurt your face your voice wagonlit schlafwagen keine couchette bitte milan Venice toulouse prague berlin milan venice milan
“We’re watching ‘The Nutty Professor!’”
George’s mother, wearing a bright floral blouse, tries to remain cheerful. Her son is sitting cross-legged on a hospital bed, facing the television, a mass of multicolored wires emerging from a dome of white bandages on his head and running to a tower of electronics and computer screens near the door of the small room. She and his physician, John G. Milton, director of the University of Chicago Epilepsy Center, are waiting for George to have a seizure so that traces from the scalp electrodes can be analyzed prior to surgery. This edgy watch is a standard phase of pre-op for the eventual removal of an epileptic focus. Despite treatment with phenobarbital and other drugs, George had 10 seizures in the past month, by his mother’s calendar, a rate ensuring that his behavior and the circumstances of his life still revolve around the disease. “They won’t let him back into a normal school, because they don’t have the people to take care of him,” she says.
George snickers at that. Otherwise he does not have much to say. He is 12 or so, wearing shorts and a blue T-shirt with the word adidas printed over his heart. When a seizure is imminent, his face assumes a saturnine stare, his lips flare out and his left arm curls up tightly He falls, then tries to get up and run. The seizures last from two to seven minutes. But in the high-tech hospital room that would be costing $10,000 a day if the family were paying full price, George has not managed a seizure yet.
Milton, a very short, fit and gregarious mathematician (his Ph.D. is from McGill University in Montreal) turned clinician, jokes about the tense scene. “I told him, ‘If you get two good ones, you’ll be ready to go,’” he says, glancing for a reaction from George. Nothing. George’s attention is on “The Nutty Professor.” As I am leaving the room with Milton, he tries once more, reaching up to grab an angle of the steel box that partly shrouds the tower of electronics. “We’ve had them hanging off this corner!” Milton exclaims, grinning and lolling his head in caricature of a seizure. Nothing. He hurries down a corridor, still smiling, his lab coat flapping behind him as he rattles off details of George’s condition. The casual demeanor is probably more than a pose for Milton, who recently married into a family of professional golfers. In one of my first opportunities to speak with him, he reached me on a cell phone from the basement of his home, responding to my written request for a major interview on the nonlinear dynamics of the brain. Milton wanted to know if we could take care of the interview while he finished cleaning his clubs.
At the hospital, he describes the much more telling series of tests that await George if he is approved for surgery. His skull will be opened so that an array of small, disk-shaped electrodes can be placed under his dura mater, the tough covering of the brain. Those electrodes in their flexible packaging look like shrink-wrapped lozenges of some indeterminate flavor. Once George’s skull has been closed again, the electrodes will be used in two ways. First, they will receive signals passively during seizures, operating as a kind of radar to pinpoint the location of the epileptic focus. Second, the electrodes will be actively stimulated to map functional areas that must be avoided during surgery. When a particular electrode is stimulated, a patient s arm might twitch, or he might suddenly remember a long-forgotten scene or a piece of music. “I feel orange,” a patient told Milton once. He never figured that one out.
It is precisely during these routine procedures that Milton and Schiff and their colleagues could carry out the first, tentative tests of theories of nonlinear brain dynamics on consenting patients. Because repeated stimulation of the electrodes during functionality mapping has no lasting impact on patients, the chance of any side-effects in such tests is remote, “The Terminal Man” notwithstanding. The stimulation would simply be done in accordance with a chosen theory instead of randomly. There could be simultaneous monitoring of brain activity, with feedback, just as in the case of the rat hippocampus. Clinicians, of course, are rightly cautious, and while proposals have been made and protocols discussed—and early explorations begun—little is being reported publicly at this point.
The exact strategies and algorithms to be used will clearly depend on which dynamical theory a researcher favors for the epileptic brain. Milton, who claims that Canadian genealogical researchers have established his family’s probable descent from the man who wrote the words At which the universal host up sent/A shout that tore hell’s concave, and beyond/Frighted the reign of Chaos and old Night (mm-hm, the poet; a fact producing the inevitable scrub-room witticism that goes, “Have you read the John Milton trilogy? ‘Paradise Lost,’ ‘Paradise Regained’ and ‘Dynamics of Small Neural Populations’”), is not himself a booster of chaos and UPOs and all that. Milton is more of a bistability man. He says that physicians going all the way back to Hippocrates and Galen noticed that loud noises or other stimuli could cause someone to snap out of a seizure. One of his favorite stories involves a girl whose seizure broke off prematurely when her startled mother dropped a trash can, and there actually is an FDA-approved device on the market that does no more than electrically stimulate the vagus nerve, in the neck, every few minutes, bringing partial relief to some epilepsy sufferers who do not respond to other treatment.
No one really knows why the vagal nerve stimulator works, when it does. Milton sees bistability in the mist. Whatever the underlying and obscure complexities, the brain is being batted from state A to state B, Milton thinks. He is inclined to aim for a more sophisticated version of the vagal nerve stimulator that would sense the onset of a seizure and apply jolts directly to the region around the focus in the brain. There is not necessarily a disconnect between the Miltonian and Schiffian world views, since the diagnostics and the jolt philosophy and even the states A and B could turn out to be based on UPOs and chaos, although no one knows that yet, either. Chaos or no chaos, the central mystery is still the shockingly short journey between disease and health, convulsions and calm, paradise lost and regained. “Why should this happen at all?” asks Milton.
Lately he has had even more reason to raise his palms skyward, as though caught in some intellectual bunker in front of the 14th green, and pose that question to the gods. His encounter with prosopagnosia has brought home both the potential power and the almost whimsical specificity of direct monitoring and stimulation. The experience might also teach us something about our extraordinary ability to recognize and discriminate human faces. I caution that I have not yet had a chance to meet this patient, and am relying for my information mainly on a brief, published abstract describing the research and a longer preprint that has been submitted to a technical journal and kindly provided to me in advance by the authors.
The basics of the story are quickly told. A 23-year-old, right-handed nurse with a decade-long history of medically refractory seizures was unable to distinguish the faces of people in her presence at the time of her aura. Lesions of the posterior right hemisphere, where the patient’s epileptic focus was located, are known to cause the condition, prosopagnosia, on a permanent basis, and the study of such cases has greatly augmented what is understood about the processing of faces by the human brain. But because the syndrome often comes about in the context of a stroke, physical trauma or a brain tumor, disentangling prosopagnosia from other, more generalized deficits can be difficult. The patient agreed to allow a study by Milton and several colleagues of her transient condition with imaging and electrodiagnostic equipment (the first time this had been done) during routine tests with a subdural electrode array as she was being prepared for epilepsy surgery.
First, Milton presented her repeatedly with faces and monitored the evoked potentials, or electrical response, on the electrodes. The response was maximal at electrode No. 24, located in a specific cortical region called the right fusiform gyrus, which had been identified as important for human face processing in previous studies. The seizure focus itself was about 2.5 centimeters anterior to this electrode. Milton also checked the response to other types of visual stimuli: The evoked potential for strings of numbers and letters was maximal at an electrode a centimeter away from No. 24, and the small array picked up no response at all to checkerboard patterns of various colors and check sizes. Natural scenes did produce maximal responses at No. 24; but compared to those for faces, they were delayed and of lower amplitude.
The next step was to stimulate No. 24 electrically. At baseline— that is, when the patient was in a normal state and the electrode was not being stimulated—she had no obvious problem with face processing. That changed when a 10-second train of square-wave pulses carrying 0.002 amps of current was applied to electrode No. 24. At that point, according to the report, “the patient stated that all faces in the room appeared indistinguishable. She was fully aware of the locations of faces and even the presence of specific facial features and denied any other alterations of perceptual experience. She was able to correctly describe alterations made to observers’ faces, e.g., removal of spectacles or placing red rectangular tape on the cheek of one observer.”
In these results, the study team saw support for a sort of holistic theory of face recognition: “This is unequivocal evidence that prosopagnosia can be attributed to a discrete cortical region and is not directly related to other disturbances in visual function. In addition … the cortical localization of featural processing [i.e., the recognition of individual facial features] appears to be distinct from the stimulated region which is critical for face discrimination.” It seems that we do not perceive a turned-up nose, a full, impish smile, a sweeping jawline, darkly arching brows, and gradually put it all together before recognizing my cousin Shelley. We recognize or do not recognize in a flash, taking the entire face in and treating it as an irreducible percept.
How does such complex processing take place all at once? Further measurements indicated that the brain may be comparing any particular face to a stored template or standard face that has been built up from experience. The processing, which might be thought of as a subtraction of each face from the template, is quick but not instantaneous, apparently taking from 0.15 to 0.20 seconds. Milton and colleagues came to those conclusions not by stimulating electrode No. 24, but by taking a closer look at the evoked potentials on the electrode as the patient was suddenly presented with images of different faces. Unfamiliar faces produced the quickest and strongest deflections of the potential. Progressively slower and weaker responses were generated by the faces of the patient’s physician, her mother and electronically “averaged” constructions that smeared together the features of many people. Still less vigorous responses followed images that were harder to recognize as such—grainy pictures or fragments showing half a face or just a pair of eyes.
For an image that is manifestly a face, the greater the deviation from a norm based on experience and familiarity, the stronger the response based on the evoked potential of electrode No. 24. After the tests, the patient had major brain surgery in hopes of suppressing both the seizures and the auras. “She’s doing pretty well,” one of the team members told me by phone the other day. For the first time in her life, she is able to hold a steady job in her chosen field, nursing. Occasionally, early in the morning, she experiences slight, unexplained distortions of familiar objects like the knobs on a television set. By and large, she is, thankfully, leading a normal life, her former existence having bequeathed to the world one answer to the question of how much of us is switchboard and how much is spirit and whether there is any essential difference at all.
green foothills two weeks the spring two weeks we climbed we clambered dry months came two weeks green foothills brown months dry months the chinook brought fires over the ridge at night like floating red hair we climbed two weeks the spring we climbed we clambered the chinook the trees went up like roman candles green foothills dry months brown months the chinook brought fires red hair we climbed the spring two weeks green foothills
One passage from “The Terminal Man” has remained stuck in my memory since I read it in high school, a remembered image that still sparks an electric wiggle of response at the least provocation. Leafing now through a copy of the book that is due at the city library on APR 23 1999 (as sloppily stamped on the circulation card below 18 other dates beginning with SEP 29 1997), I see that in the pages leading up to that passage, a surgical team is stimulating electrodes in Harry Benson’s brain—the routine task of mapping out areas of functionality. A technological whiz named Gerhard pushes a button to stimulate electrode No. 1 and Benson tastes a ham sandwich. Gerhard stimulates electrode No. 2 and Benson feels that he has to go to the bathroom. As the procedure wears on, Gerhard’s mind wanders. He recalls when, early in his career, he requested a brain to dissect. With a stack of neuroanatomy texts to guide him, Gerhard remembers, he scraped and scraped and scraped until the brain had been frittered away to nothing.
Crichton’s intent is to illustrate the density, the complexity, the mystery of the brain. Myself, I have always been tempted to see in that empty dissection table the fruitless end of any purely scientific search for human quiddity. Il suo cervello svapora—the Italian way of saying that one is worn out mentally, one needs a vacation. Literally, “one’s brain evaporates.” Of course, we have more than the glories of science to lead us to the dewy essence of ourselves, and we should follow those other meadow paths with equal passion, equal tenacity. This morning I purchased a Grateful Dead CD. It was a new experience for me. Once, long ago—long before I collided with the Deadhead along the lake—a car with the Colorado license plate SUGRE ran me down as I rode my bicycle to work. The impact was a glancing one, and although the bicycle slid under the wheels of the car and was mangled, I suffered no more than a fall. What stunned me more than the impact was sitting on the asphalt and watching the word SUGRE recede as the car sped away. I heard a car door open and slam shut behind me. A very concerned woman appeared in my field of view. She asked if I was all right, then assured me that the hit-and-run driver would certainly be caught, because his vanity plates were based on the famous Grateful Dead song called “Sugaree.”
The plates turned out to be stolen. The driver was never caught. Hoping somehow to complete the synaptic circle of association, I bought a CD with that song on it, but the late Garcia, who is apparently the vocalist, mumbles a lot, and the lyrics are far from revelatory. As a hedge, however, I also bought a CD by the band called Grand Mal, whose offerings were of course right next to those of the Grateful Dead in the store. All the girls and boys/Are like wind-up toys/Like broken machines, shout the Anglophone members of Grand Mal, and I can work with that. What we have here, aside from inept trochaic trimeter, is an exaggeration of Cartesian dualism in which the observers in their intense threnody consider that only they have escaped the mathematical limit of complete soullessness. This stance recalls the stories, whether accurate or not, of Cartesian vivisectionists laughing at the agony of cats under examination, since their screams were regarded as nothing more than the sounds of damaged machines grinding to a halt. Well, I don’t agree.
Like a good experimentalist, I have been keeping a close eye on my own yellow cat. Today it was rolling around on its back in a bar of sunlight, licking its paws and batting at the fat, charcoal cat, apparently as content as could be. The yellow cat has four or five seizures a year. For days or weeks after each one, it avoids the room in which the seizure occurred, except to slink about in search of something it seems to believe is hiding in there. Unlike the charcoal cat, which scratches at its own reflection in the closet mirrors and seems to make a game of staring at people in them, the yellow cat showed no interest in that other world until, one day, after a particularly violent seizure, it froze in front of the expanse of glass, terrified of its own wide-eyed reflection. I had to pick the cat up and move it. Soon it again lost interest in reflections.
Steven Schiff and I have continued the correspondence that began sometime after the day we spent talking about controlling chaos in a dish. He remains stonily unimpressed by my cat observations, but is always available to discuss the latest academic and clinical research on the rhythms of the brain. When it comes to the crazy firing of epilepsy, Schiff is lately intrigued by the ideas of a mathematician named Predrag Cvitanovic, who has shown that the shortest (meaning the briefest) unstable periodic orbits of any system reveal the most about its underlying structure. It is as if, in some sort of “Tommy” scenario, you wanted to reconstruct a three-bumper pin-ball machine just by listening to a few games. The fleeting periodicity of the ball rattling between two or more of the bumpers would tell you more than a distant rebound off one of the walls. In the epileptic brain, the configuration of the bumpers might correspond to a damaged and otherwise unknowable pattern of connections among the neurons themselves.
Those ideas, like stochastic resonance, chaos and bistability, should also have a story to tell about the intricate rhythms of the healthy brain, which on a very quiet day might sound more like a 100-story arcade of interrelated video games, dart boards, pinball machines, bowling alleys and basketball courts all being used at once and heard from half a mile away. The question of how some or all of those rhythms are linked, correlated, mutually dependent at any moment is in fact a central one. What binds together our disparate perceptions and thoughts and motor responses into a coherent whole? How would either invasive probes (electrodes) or noninvasive ones (magnetic fields generated by electrical currents in the cortex and measured extracranially; positron emission tomography; functional magnetic-resonance imaging) uncover that coherence if they were monitoring various regions of the brain?
Grasping those correlations will likely require a far deeper understanding of the brain than called upon in studies of solitary rhythms, no matter how complicated. A new and more encompassing notion of synchrony itself might be needed. Rather than audible rhythms, Schiff asks me to imagine barefoot children playing together on a beach. The diagnostics, whatever they are, record only the footprints. If some of the children are walking together in a tidy row, then ordinary mathematics ought to be capable of picking out those footprints and determining that they are correlated, coordinated. But what if some of the children are building a city of sandcastles, having a game of tag or playing hide-and-go-seek in the dunes along the beach? How could anyone read the pattern of their footprints if the children drift between all three activities among thousands of other beach-goers who are creating their own footprints while walking dogs, flying kites, chasing Frisbees, playing volleyball, searching for a sunny opening in the crowd and folding out lounge chairs?
Yet the children are on the beach. They are building sandcastles and hiding in the dunes. There is mystery walking barefoot upon the sands of human consciousness.