Читать книгу The Forgetting: Understanding Alzheimer’s: A Biography of a Disease - David Shenk - Страница 11

There could be no happiness, cheerfulness, hope, pride, immediacy, without forgetfulness. The person in whom this apparatus of suppression is damaged, so that it stops working, can be compared … to a dyspeptic; he cannot “cope” with anything.

—FRIEDRICH NIETZSCHE

As found in the Pyramid Texts, from 2800 B.C., Ra was the Sun God, the creator of the universe and of all other gods. From his own saliva came air and moisture. From his tears came humankind and the river Nile. He was all-powerful and, of course, immortal—but still not immune to the ravages of time: Ra, the supreme God, became old and senile. He began to lose his wits, and became easy prey for usurpers.

Throughout recorded history, human beings have been celebrating the powers of memory and lamenting its frailties. “Worse than any loss in body,” wrote the Roman poet Juvenal in the first century A.D., “is the failing mind which forgets the names of slaves, and cannot recognize the face of the old friend who dined with him last night, nor those of the children whom he has begotten and brought up.”

It took several thousand years, though, for anyone to figure out how memory actually worked. Plato was among the first to suggest a mechanism. His notion was of a literal impression made upon the mind. “Let us suppose,” he wrote, “that every man has in his mind a block of wax of various qualities, the gift of Memory, the mother of the Muses; and on this he receives the seal or stamp of those sensations and perceptions which he wishes to remember. That which he succeeds in stamping is remembered and known by him as long as the impression lasts; but that, of which the impression is rubbed out or imperfectly made, is forgotten, and not known.”

Later came the ventricular theory of cognition, from Galen (129 – ca. 199 A.D.), Nemesius (fourth century), and St. Augustine (354–430). According to this notion, the three major functions of the brain—sensation, movement, and memory—were governed from three large, round fluid-filled sacs. Vital Spirit, a mysterious substance that also contained the human soul, was harbor to the swirl of memories.

From this model came cerebral localization, the theory that the various functions of the brain were each controlled by specialized “modules.” This model of specialization turned out to be generally correct (if radically different in the details from what Galen had imagined). In the early twentieth century, it emerged that the brain wasn’t really an organ so much as a collection of organs, dozens of structures interacting with one another in dazzling complexity. Deep in the center of the brain the amygdala regulates fear while the pituitary coordinates adrenaline and other hormones. Visual stimulus is processed in the occipital lobe, toward the rear of the skull. Perception of texture is mediated by Area One of the parietal lobe near the top of the head, while, just to the rear, the adjacent Area Two differentiates between the size and shape of objects and the position of joints. The prefrontal cortex, snuggled just behind the forehead, spurs self-determination. Broca’s area, near the eyes, enables speech. Wernicke’s area, above the ears, facilitates the understanding of speech.

The more researchers discovered about localization, though, the more they wondered about the specialized zone for memory. Where was it? If vision was in the back of the brain, texture on top, and so on, what region or regions controlled the formation of lasting impressions and the retrieval of those impressions?

Part of the answer came in 1953, when a Harvard-trained neurosurgeon named William Beecher Scoville performed experimental surgery on a twenty-seven-year-old patient known as H.M. He had been suffering from violent epileptic seizures since childhood, and in a last-ditch effort to give him a chance at a normal life, Scoville removed a small collection of structures, including the hippocampus, from the interior portion of his brain’s two temporal lobes. The surgery was a great success in that it significantly reduced the severity of H.M.’s epilepsy. But it was also a catastrophe in that it eliminated his ability to lay down new memories. The case revolutionized the study of memory, revealing that the hippocampus is essential in consolidating immediate thoughts and impressions into longer-lasting memories (which are in turn stored elsewhere).

Time stopped for H.M. in 1953. For the rest of his long life, he was never again able to learn a new name or face, or to remember a single new fact or thought. Many doctors, researchers, and caregivers got to know him quite well in the years that followed, but they were still forced to introduce themselves to him every time they entered his room. As far as H.M. was concerned, he was always a twenty-five-year-old man who was consulting a doctor about his epilepsy (he had also lost all memory of the two years immediately prior to the surgery). H.M. became perhaps the most important neurological subject in history and was subject to a vast number of studies, but he remembered none of the experiments once they were out of his immediate concentration. He was always in the Now.

In the clinical lexicon, this was a perfect case of anterograde amnesia, the inability to store any new memories. Persons with incipient Alzheimer’s disease exhibit a slightly less severe form of the same problem. The memory of leaving the car keys in the bathroom isn’t so much lost as it was never actually formed.

In a healthy brain, sensory input is converted into memory in three basic stages. Before the input even reaches consciousness, it is held for a fraction of a second in an immediate storage system called a sensory buffer.

Moments later, as the perception is given conscious attention, it passes into another very temporary system called short-term (working) memory. Information can survive there for seconds or minutes before dissolving away.

Some of the information stirring in working memory is captured by the mechanism that very slowly converts into a long-term memory lasting years and even a lifetime.

Long-term memories can be either episodic or semantic. Episodic memories are very personal memories of firsthand events remembered in order of occurrence. Before the baseball game the other day, I put on my new pair of sneakers, which I had gotten earlier that morning. Then we drove to the stadium. Then we parked. Then we gave the man our tickets. Then we bought some hot dogs. Then we went to our seats …

Now, days later, if I notice a mustard stain on my shoe, I can plumb my episodic memory to determine when and how it happened. If my feet start bothering me, my episodic memory will help me figure out whether it happened before or after I bought my new shoes.

Semantic memories are what we know, as opposed to what we remember doing. They are our facts about the world, stored in relation to each other and not when we learned them. The memory of Neville Chamberlain’s “peace in our time” is semantic.

They are separate systems—interrelated, but separate. An early-stage Alzheimer’s patient who cannot retain memories of where she put her keys has not forgotten what keys are for, or what kind of car she drives. That will come much, much later, when she starts to lose old semantic memories.

The experience with H.M. taught researchers that the hippocampus is key to long-term memory formation. Without that tiny organ, he was totally incapable of forming new, lasting memories. Alzheimer’s patients suffer the exact same systemic loss, but over several years rather than one surgical afternoon. For H.M., there were no new memories after 1953, period. In later years, he was unable to recognize his own face in the mirror. Real time had marched on, 1955 … 1962 … 1974, but as far as he was concerned, he was still twenty-five years old. If you are a young man, alert and intelligent, and you look into an ordinary mirror only to discover the face of a sixty-year-old perfectly mimicking your expressions, perhaps only then do you know the real meaning of the word horror. Fortunately, the extreme distress H.M. suffered during such world-shattering incidents was always immediately and completely forgotten as soon as his attention could be distracted by something happening in the new moment. Not remembering can sometimes be a great blessing.

The discovery of hippocampus-as-memory-consolidator was critical. What memory specialists have been trying to figure out ever since then is, once formed, where do these long-term memories actually reside? Are memories stored up in the front of the brain in the prefrontal cortex? On top, in the parietal lobe? In the brainstem at the base of the brain? Where?

One tantalizing theory emerged in the late 1950s: memories were everywhere, stored in discrete molecules scattered throughout the brain. A stampede to confirm this notion was set off by a 1962 Journal of Neuropsychiatry article, “Memory Transfer Through Cannibalism in Planaria,” in which the University of Michigan’s James McConnell eagerly reported that worms could capture specific memories of other worms simply by eating those worms. McConnell had trained a group of flatworms to respond to light in a noninstinctive way. He then killed these worms, chopped them up, and fed them to untrained flatworms. After eating their brethren, McConnell claimed, the untrained worms proceeded to behave as though they had been trained—they had somehow acquired the memory of the trained worms. It was the unexpected apotheosis of the old saying, “You are what you eat.”

Out of this report numerous research grants were born, some of which yielded tantalizing results. Three years after McConnell’s initial study, four California scientists reported in the journal Science that when cells extracted from the brains of trained rats were injected into the guts of untrained rats, the untrained rats picked up the learned behavior of the trained rats. These experiments apparently showed that specific, concrete individual memories were embedded as information in discrete molecules in the same way that genetic information is embedded in DNA, and that these memories were transferable from brain to brain. A later experiment by Baylor University’s Georges Ungar was the most vivid yet: Brain cells from rats that had been trained to fear the dark were transferred to untrained mice (ordinarily, neither mice nor rats fear the dark), who suddenly took on this new fear. Ungar even isolated a peptide comprising fifteen amino acids that he said contained the newly created memory. He called the transmissible fear-of-the-dark memory molecule scotophobin.

The theory that emerged out of these experiments was of memory as a distinct informational molecule that could be created organically in one brain, isolated, and then transferred to another brain—even to the brain of another species. Its implications were immense. Had this cold fusion of an idea been validated rather than widely discredited not long after Ungar’s paper was published in Nature in 1972, it is clear that ours would be a very different world today: Memory swaps. Consciousness transfers. Neurochemical behavioral enhancements that would make Prozac seem like baby aspirin. The rapid decoding of a hidden science of memory molecules might well have spawned a new type of biochemical computer that could register, react to, and even create memory molecules of its own. Laptops (or cars or stuffed animals) could be afraid of the dark or partial to jazz or concerned about child abuse. Memories and feelings could be bottled and sold as easily as perfume.

But that world did not, and cannot, emerge. The memory transfer experiments, while entertaining and even seductive—DNA pioneer Francis Crick was among the many prestigious scientists on board for a while—were ultimately dismissed as seriously misguided). The idea of transferable memories strained credulity to begin with; to suggest that one animal’s specific fear could travel through another animal’s digestive tract, enter its bloodstream, find its way to the brain, and turn itself on again in the new host mind was an even further stretch.

And then there was the problem of physical mass. Skeptics calculated that if specific memories were contained in molecules the way Ungar suggested, the total number of memories accumulated over a lifetime would weigh somewhere in the vicinity of 220 pounds. The brain would literally be weighed down by thought and ideas.

After a decade or so, the notion and burgeoning industry of memory molecules crumbled into dust. It is now one particularly humiliating memory that many neuroscientists would just as soon not retain. What has grown up out of that rubble over the last thirty years is a very different understanding of memory—not as a substance but as a system. Memories are scattered about; that part the memory molecularists had right. Memory is everywhere. But it is everywhere in such a way that it is impossible to point to any one spot and identify it with an explicit memory. We now know that memory, like consciousness itself, isn’t a thing that can be isolated or extracted, but a living process, a vast and dynamic interaction of neuronal synapses involved in what Harvard’s Daniel Schacter elegantly terms “a temporary constellation of activity.” Each specific memory is a unique network of neurons from different regions of the brain coordinating with one another. Schacter explains:

A typical incident in our everyday lives consists of numerous sights, sounds, actions, and words. Different areas of the brain analyze these various aspects of an event. As a result, neurons in the different regions become more strongly connected to one another. The new pattern of connections constitutes the brain’s record of the event.

The power of the constellation idea is reinforced by the understanding of just how connected the 100 billion neurons in the brain actually are. A. G. Cairns-Smith, of the University of Glasgow, observes that no single brain cell is separated from any other brain cell by more than six or seven intermediaries.

The molecular basis for these synaptic constellations that can be reignited again and again (though never in precisely the same configuration), is a biochemical process called long-term potentiation (LTP) that intensifies the affinity between specific neurons after a significant connection is made. Think of an ant farm, with worker ants constantly building new tunnels among one another; once a tunnel is built, transport becomes many times easier; an easy, natural connection has been created between those two points. With memory formation and retrieval, pathways are at first built and later simply used. Each notable experience causes a unique set of neurons to fire in conjunction with one another. As a result, those connections become chemically more sensitive to one another so that they can more easily trigger each other again. With that unique constellation of synapses, one has created a permanent physical trace of the original sensation. Neurologists call these memory traces “engrams.”

The ant farm analogy also applies in another important way: Neurobiologists have found that memory formation is slow. Long-term memories can take many months or even years to fully form.

Long-term memories are durable, but not unassailable. They can last a lifetime, but from the first moments are subject to influences from other memories and experience. Inevitably, as they age and are evoked again and again, all memories change in character.

This is part of the brain’s famous plasticity, its ability to adapt to life’s events. Plasticity makes us as much creatures of our own experience as we are products of evolution. Not everything in the brain is adaptable, of course; much of it comes “hard-wired,” genetically preprogrammed to specialize and perform specific tasks such as processing light and sound, regulating heart rate and breathing, and so on. But the regions reserved for fine motor skills, intelligence, and memory are more like soft clay, able to take on a definite shape and yet remain constantly responsive to new stimuli.

Memory constellations, then, are not fixed, immutable collections of memories, but ever-variable collections of memory fragments that come together in the context of a specific conscious moment. Any common free-association experiment is a vivid illustration of this point. For me, at this moment, the word “cat” prompts → a thought of Brownfoot, my boyhood feline friend → the garage roof she used to leap from → the 1971 T-top Corvette my father used to drive → the tragicomic month in which Mom wrecked this car twice → a feeling of malaise associated with my parents’ divorce years later. This instant montage of memories is neither chronological nor predictable, even by me. If someone were to prompt me with “cat” tomorrow, depending on my mood or recent experience, I might think of the cat that my daughter called to yesterday outside our house. Or it could be that Brownfoot will come to mind, but that from there I will shift to an image of my playing her dentist, and then I might think of my own current dentist and how I’m way overdue for a cleaning. That guilty feeling might then trigger another distant idea, related only by a parallel feeling of guilt. And so on.

Taken together, this interconnected universe of constellations in each of us forms the core of who we are. Our life’s ocean full of memory waves wash against one another to create a complex and ever-adapting character.

The director Martin Scorsese is an interesting memory-character study, mostly because he seems to forget very little compared to others. He remembers not just every shot and crew credit from each of the thousands of movies he’s seen, observes the New Yorker’s Mark Singer, but also every detail of every book, song, and personal experience he’s had in fifty-plus years—“all of it,” Singer writes, “seemingly instantly retrievable.”

Singer depicts the Scorsese memory constellation in action. After a colleague criticizes a piece of film dialogue as “too piercing,” Scorsese is instantly thrown into an interconnected memory odyssey:

He was reminded of the old Harry Belafonte calypso tune “The Banana Boat Song”—or, rather, a parody of same by Stan Freberg, which included a reference to “piercing,” and that reminded him of another Freberg routine, a parody of the television series Dragnet, which in turn reminded him of Pete Kelly’s Blues, a feature film directed by Jack Webb, the star of Dragnet. The production designer of Pete Kelly’s Blues, in which Webb played a bandleader during the twenties, was a Disney veteran who brought to it a remarkably vivid palette, a reality-heightening Technicolor glow reminiscent of the live-action Disney children’s films of the forties.… And, Scorsese further recalled, Pete Kelly’s Blues had a screenplay by Richard L. Breen, whose name, curiously, Webb had heralded before the title. When the picture was released, in 1955, the year Scorsese turned thirteen, he followed it from theatre to theatre, as was his habit.… [He then recalled all the specific theaters he used to frequent.] One particular Saturday afternoon double-feature at the Orpheum came to mind: Bomba the Jungle Boy and Great White Hunter.…

The pathways linking engrams can be built on temporal, intellectual, or aesthetic associations, and when the mind really wanders, during daydreams or at night before sleep sets in, it’s amazing what sort of involuntary memory leaps one makes, from impressions that often have no logical or logistical relationship but which share a texture or smell or emotional fragment. What’s more—and this may be the single most important point to understand about memory—every time a memory is recalled, new trails are made.

The act of remembering itself generates new memories. Which means that Emerson was exactly right when he noted in his journal: “Most remembering is only the memory of memories, & not a new & primary remembrance … HDT [Henry David Thoreau] noticed this to me some time ago.” Overlap, in other words, is not only built into the biology of memory. It is the very basis of memory—and identity. New memory traces are laid down on top of a foundation of old memories, and old memories can only be recalled in a context of recent experiences. Imagine a single painting being created over the course of a lifetime on one giant canvas. Every brush stroke coming into contact with many others can be seen only in the context of those prior strokes—and also instantly alters those older strokes. Because of this, no recorded experience can ever be fully distinct from anything else. Whether one likes it or not, the past is always informed by the present, and vice versa.

Scores of experiments confirm the malleability of old memories, and horror stories of False Memory Syndrome are by now widespread. The psychologist Elizabeth Loftus has spent the better part of her career documenting the ease with which false memories can be planted—accidentally or on purpose. Often, these false memories lead to wrongful convictions. In 1979, twenty-two-year-old marine corporal Kevin Green was convicted of second-degree murder for the brutal beating of his wife and the death of their full-term fetus. His wife had testified after coming out of a coma that Green, her own husband, was the attacker. Sixteen years later, the real attacker, a total stranger, confessed to police about that and six other murders. It turned out that Green’s guilt had been suggested to his wife early on in her rehabilitation. By the time it came to trial, she had created a memory so clear that she was able to confidently testify against her husband.

“Eyewitness misidentification … is known as the single greatest cause of the conviction of the innocent,” says attorney Barry Scheck. He describes a typical scenario: “You can have as many as five witnesses who begin in kind of a soft way, saying, ‘That might be the guy,’ and then, like wet concrete hardening, the [memories] get fixed to the point that by the time they get to the courtroom, they’re saying ‘That’s the man.’”

Part of the deep attraction to the idea of distinct memory molecules was that it connoted the ability to replay old memories like videotapes on a VCR—just as they were originally recorded. But the biology of memory constellations dictates that there is no such thing as pure memory. Recall is never replay.

But why? Why would millions of years of evolution produce a machine so otherwise sophisticated but with an apparent built-in fuzziness, a tendency to regularly forget, repress, and distort information and experience?

The answer, it turns out, is that fuzziness is not a severe limitation but a highly advanced feature. As a matter of engineering, the brain does not have any physical limitations in the amount of information it can hold. It is designed specifically to forget most of the details it comes across, so that it may allow us to form general impressions, and from there useful judgments. Forgetting is not a failure at all, but an active metabolic process, a flushing out of data in the pursuit of knowledge and meaning.

We know this not just from brain chemistry and inference, but also because psychologists have stumbled upon a few individuals over the years who actually could not forget enough—and were debilitated by it.

In his New Yorker profile, Mark Singer wonders if Martin Scorsese is such a person—burdened by too good a memory.

Was it, I wondered, painful to remember so much? Scorsese’s powers of recall weren’t limited to summoning plot turns or notable scenes or acting performances; his gray matter bulged with camera angles, lighting strategies, scores, sound effects, ambient noises, editing rhythms, production credits, data about lenses and film stocks and exposure speeds and aspect ratios.… What about all the sludge? An inability to forget the forgettable—wasn’t that a burden, or was it just part of the price one paid to make great art?

For some perspective on the inability to forget, consider the case study that psychologists call S. In the 1920s, S. was a twenty-something newspaper reporter in Moscow who one day got into trouble with his editor for not taking notes at a staff meeting. In the midst of the reprimand, S. shocked his boss by matter-of-factly repeating everything that had been said in the meeting—word for word.

This was apparently no stretch at all for S., who, it emerged upon closer examination, remembered virtually every detail of sight and sound that he had come into contact with in his entire life. What’s more, he took this perfect memory entirely for granted. To him, it seemed perfectly normal that he forgot nothing.

The editor, amazed, sent S. to the distinguished Russian psychologist A. R. Luria for testing. Luria did test him that day, and for many other days over a period of many decades. In all the testing, he could not find any real limit to his capacity to recall details. For example, not only could he perfectly recall tables like this one full of random data after looking at them for just a few minutes:

And not only could he efficiently recite these tables backwards, upside down, diagonally, etc., but after years of memorizing thousands of such tables he could easily reproduce any particular one of them, without warning, whether it was an hour after he had first seen it, or twenty years. The man, it seemed, quite literally remembered everything.

And yet he understood almost nothing. S. was plagued by an inability to make meaning out of what he saw. Unless one pointed the obvious pattern out to him, for example, the following table appeared just as bereft of order and meaning as any other:

“If I had been given the letters of the alphabet arranged in a similar order,” he remarked after being questioned about the 1–2–3–4 table, “I wouldn’t have noticed their arrangement.” He was also unable to make sense out of poetry or prose, to understand much about the law, or even to remember people’s faces. “They’re so changeable,” he complained to Luria. “A person’s expression depends on his mood and on the circumstances under which you happen to meet him. People’s faces are constantly changing; it’s the different shades of expression that confuse me and make it so hard to remember faces.”

Luria also noted that S. came across as generally disorganized, dull-witted, and without much of a sense of purpose or direction in life. This astounding man, then, was not so much gifted with the ability to remember everything as he was cursed with the inability to forget detail and form more general impressions. He recorded only information, and was bereft of the essential ability to draw meaning out of events. “Many of us are anxious to find ways to improve our memories,” wrote Luria in a lengthy report on his unusual subject. “In S.’s case, however, precisely the reverse was true. The big question for him, and the most troublesome, was how he could learn to forget.”

What makes details hazy also enables us to prioritize information, recognize and retain patterns. The brain eliminates trees in order to make sense of, and remember, the forests. Forgetting is a hidden virtue. Forgetting is what makes us so smart.

One of the worst things that I have to do is put on my pants in the morning. This morning I kept thinking there is something wrong because my pants just didn’t feel right. I had put them on wrong. I sometimes will have to put them on and take them off half a dozen times or more.… Setting the washing machine is getting to be a problem, too. Sometimes I’ll spend an hour trying to figure out how to set it.

—B.

San Diego, California