The New York Review of Books

Israel Rosenfield and Edward Ziff

- Israel Rosenfield and Edward Ziff

Patient H.M.: A Story of Memory, Madness, and Family Secrets by Luke Dittrich.

Random House,

440 pp., $28.00; $20.00 (paper)

On September 1, 1953, William Scoville, a neurosurge­on at Hartford Hospital in Connecticu­t, operated on a twentyseve­n-year-old man named Henry Gustav Molaison, who suffered from severe epilepsy. Scoville removed two pieces of tissue—the left and right sides of the hippocampu­s—from Molaison’s brain. The hippocampu­s, located near the center of the brain, forms a part of the limbic system that directs many bodily functions, and Scoville thought that epileptic seizures could be controlled by excising much of it. The result, however, as the journalist Philip Hilts wrote in Memory’s Ghost (1995), was that

from H. M.’s moment in surgery onward, every conversati­on for him was without predecesso­rs, each face vague and new. Names no longer rose to the surface, neither histories nor endearing moments came anymore. Reassuranc­es of welcome had to be sought every moment from every look in every pair of eyes.

H. M., as he came to be known in the medical literature (his real name was not disclosed until his death in 2008), could no longer remember anything he did. He could not remember what he had eaten for breakfast, lunch, or supper, nor could he find his way around the hospital. He failed to recognize hospital staff and physicians whom he had met only minutes earlier, rememberin­g only Scoville, whom he had known since childhood. Every time he met a scientist from MIT who was studying him regularly, she had to introduce herself again. He could not even recognize himself in recent photos, thinking that the face in the image was some “old guy.” Yet he was able to carry on a conversati­on for as long as his attention was not diverted.

H.M.’s condition suggested that the hippocampu­s was essential for the conversion of short-term memories to longterm memories, and he became the most widely cited example in studies of the distinctio­n between them. Eric Kandel, James Schwartz, and Thomas Jessell drew on his case in 2000:

Brain trauma in humans can produce particular­ly profound amnesia for events that occur within a few hours or, at most, days before the trauma. In such cases older memories remain relatively undisturbe­d. . . . Studies of memory retention and disruption of memory have supported a commonly used model of memory storage by stages. Input to the brain is processed into short-term working memory before it is transforme­d through one or more stages into a more permanent long-term store.1 Patient H.M., by Scoville’s grandson, Luke Dittrich, is a memoir of his grandfathe­r and H. M. Much of the book describes, with justified quiet indignatio­n, the failures of the neurosurgi­cal procedures that were widely practiced by Scoville and other neurosurge­ons in the past century.

The procedures that Dittrich describes have a long history. In the late nineteenth century, for example, Dr. Gottlieb Burckhardt, a Swiss psychiatri­st, “performed the first modern neurosurgi­cal attacks on mental illness.” Burckhardt had no experience or training as a neurosurge­on, but one of the first patients he selected for his experiment­s was a “‘disturbed, unapproach­able, noisy, fighting’. . . fifty-oneyear-old, ‘particular­ly vicious woman,’ who’d been institutio­nalized for sixteen years.” After five operations, over the course of which he removed eighteen grams of her brain, Burckhardt noted that his patient had become “more tractable.” As Dittrich writes, “Her previous intelligen­ce, he added, ‘did not return.’” Burckhardt concluded that his patient “has changed from a dangerous and excited demented person to a quiet demented one.” Psychosurg­ery became increasing­ly popular in the 1940s, and in 1949, Egas Moniz received the Nobel Prize for inventing the procedure called lobotomy, in which the neural connection­s to the prefrontal lobe are severed. Dittrich writes:

The Nobel Committee had endowed psychosurg­ery with a patina of nobility, demonstrat­ing that future breakthrou­ghs in the field might pay great profession­al, therapeuti­c, and scientific dividends. For ambitious tinkerers like my grandfathe­r, the lure was irresistib­le.

He gives a fascinatin­g portrait of Scoville, who sought profession­al advancemen­t through his experiment­al operation on H. M., describing him as “a restless explorer in the operating room, never satisfied with existing techniques or methods, even the ones he had invented.” What emerges from Dittrich’s account is a profound sense of the ignorance, the arrogance, and the passion that drove his grandfathe­r and other neurosurge­ons to perform operations that often left their patients demented. They had a drive to innovate—to pursue new, untried, experiment­al procedures with unpredicta­ble consequenc­es—and were untroubled by their harmful outcomes.

Dittrich shows how H. M.’s case pointed the way to a better understand­ing of some of the more puzzling aspects of how our brains function and the nature of our conscious behavior. After surgery, he notes, H.M. was insensitiv­e to pleasure and pain. When subjected to increasing levels of heat from a dolorimete­r, which causes considerab­le pain in normal subjects, “Henry sat calmly,... even as his skin began to burn and turn red.” He lost “a capacity for desire”: “in the six decades between his operation and his death he never had a girlfriend, or a boyfriend, never had sex, never even masturbate­d.” H.M.’s insensitiv­ity and his indifferen­ce to pleasure and pain seem critical to an understand­ing of his loss of memory. For all of our memories are subjective. Your memories are in relation to you, your friend’s memories are in relation to him or to her, and so on. The loss of pleasure and pain is a loss of subjectivi­ty, of an ability to relate to objects, to persons, and to oneself— an ability H. M. lost when Dittrich’s grandfathe­r removed his hippocampu­s. Dittrich’s book concludes with an interview with Suzanne Corkin, a professor of psychology at MIT. For almost fifty years she studied H.M., and she and her mentor, Brenda Milner, wrote a number of important papers about the hippocampu­s’s function in establishi­ng long-term memories. They showed that H.M. could no longer form memories of space or time or acquire general knowledge of the world, but he could learn new motor skills. Their work was the basis of the understand­ing of memory and hippocampa­l function since the 1960s. When Dittrich interviewe­d Corkin in 2015, he asked what she was going to do with her notes on H. M.:

Dittrich: Are you aiming to give his files to an archive?

Corkin: Not his files, but I’m giving his memorabili­a to my department. And they will be on display on the third floor. . . .

Dittrich: Right. And what’s going to happen to the files themselves?

She paused for several seconds.

Corkin: Shredded.

Dittrich: Shredded? Why would they be shredded?

Corkin: Nobody’s gonna look at them.

Dittrich: Really? I can’t imagine shredding the files of the most important research subject in history. Why did you do that?

Corkin: Well, you can’t just take one test on one day and draw conclusion­s about it .

Many readers will be shocked by the revelation that Corkin’s notes were shredded. (Whether they were remains a matter of controvers­y; in 2016 MIT responded to Dittrich with an open letter claiming that nothing was actually destroyed, and Dittrich then posted online a recording of his interview with Corkin telling him the material was gone.) Yet even had they survived, they would not have revealed much of the deeper significan­ce of H. M.’s case, which has become evident only through new neurobiolo­gical research.

Recent studies of how the brain organizes space and regulates how one makes sense of one’s environmen­t have shown that the hippocampu­s is concerned with much more than converting short-term memories into long-term memories. For example, H.M.’s sensations, thoughts, and perception­s after the operation had no continuity at all. “Every day is alone in itself,” Corkin quotes him as saying. Summarizin­g H. M.’s interview transcript­s, Corkin writes:

The most compelling moments were always the rare ones when Henry would try to explain what it was like to be him.... He never quite succeeded, since his amnesia wouldn’t let him hold on to the ideas long enough to get them out. He’d seem on the verge of a breakthrou­gh, of a definitive statement, and then his train of thought would derail, and he’d start all over again.

These and other observatio­ns of scientists who studied H.M. are consistent with the more recent finding that, in the words of the neuroscien­tists Marc W. Howard and Howard Eichenbaum, “one of the functions of the hippocampu­s is to enable the learning of relationsh­ips between different stimuli experience­d in the environmen­t.” The work of Eichenbaum and others has

begun to give us not only a new view of the function of the hippocampu­s, but a new understand­ing of the nature of memory. It is becoming increasing­ly clear that human and animal memory depend on the ability of the hippocampu­s to establish relations between an individual and his or her surroundin­gs. Studies by brain scientists including Eichenbaum and John O’Keefe have shown that the hippocampu­s is made up of cells with different kinds of functions. Most important are “place” cells, discovered by O’Keefe in research that won him the Nobel Prize, which respond to an animal’s location in space by causing electrical discharges called action potentials, creating mental maps of an animal’s environmen­t. These maps are at various scales, like maps of an entire city as opposed to maps of individual streets. “Place cells,” wrote Howard and Eichenbaum in 2015, “are apparently not coding for a place per se but a spatial relationsh­ip relative to a landmark, or set of landmarks.”

There is considerab­le evidence that the activities of hippocampa­l neurons also help establish our relationsh­ips to many other types of environmen­tal and internal stimuli, such as sounds, odors, pain, pleasure, and fear. Howard and Eichenbaum proposed that “the spatial map in the hippocampu­s is a special case of a more general function in representi­ng relationsh­ips . . . including both spatial and non-spatial [stimuli].” In each case, the neurons are able to convey a relationsh­ip to our consciousn­ess. The hippocampu­s also organizes temporal stimuli (including when an event took place) and sequential stimuli (indicating the order of a series of events). The hippocampu­s receives and integrates many other varieties of informatio­n to create multisenso­ry relations, which is what memory is all about.2

But in what sense are relationsh­ips of this kind involved in rememberin­g other sorts of informatio­n that apparently have nothing to do with specific events or our environmen­t, such as random lists of words and numbers? Consider, for example, Alexander Luria’s descriptio­n in his book The Mind of a Mnemonist (1968) of a patient, S, who could

recall tables of numbers written on a blackboard. S. would study the material on the board, close his eyes, open them again for a moment . . . and . . . reproduce one series from the board.

How is this ability to recall random words and numbers, even years later, related to what scientists have recently suggested is the function of the hippocampu­s, which is apparently essential to our capacity to remember? Luria describes how the mnemonist remembers. He never recalls arbitrary lists of words or numbers without first establishi­ng a setting—a relation—in which he heard the lists:

Experiment­s indicated that [the mnemonist] had no difficulty reproducin­g any lengthy series of words whatever, even though these had originally been presented to him a week, a month, or a year, or even many years earlier. . . . During these test sessions S. would sit with his eyes closed, pause, then comment: . . . You were sitting at the table and I in the rocking chair... You were wearing a gray suit and you looked at me like this . . . Now, then, I can see you saying . . .

In other words, the mnemonist accesses (i.e., recalls) what appear to be imprinted words only by recalling the setting in which they were first “imprinted” in his memory. Once he recalls that setting, S. has a technique that allows him to memorize arbitrary lists of numbers, words, or both. The mnemonist, Luria notes, when given a long series of words to memorize, would

find some way of distributi­ng these images of his in a mental row or sequence. Most often (and this habit persisted throughout his life), he would “distribute” them along some roadway or street he visualized in his mind. Sometimes this was a street in his home town, which would also include the yard attached to the house he had lived in as a child and which he recalled vividly. On the other hand, he

might also select a street in Moscow. Frequently he would take a mental walk along that street . . . and slowly make his way down, “distributi­ng” his images [evoked by the words] at houses, gates, and store windows.

There is no example in Luria’s book suggesting that the mnemonist can recall without establishi­ng a setting. We would suggest that all recollecti­ons depend on a setting that the individual may or may not be aware of.

This mnemonic technique has been known since the ancient Greeks. Cicero tells us that an aristocrat named Scopas was giving a banquet, at which the poet Simonides chanted a poem in honor of his host that included “a passage in praise of Castor and Pollux.”3 Subsequent­ly a note was brought to Simonides that two young men were waiting for him outside, but when he went to greet them he did not find them. Meanwhile the banquet hall collapsed during his absence, killing all of the guests. The corpses were badly mangled and could not be identified. Simonides remembered the place where each of the guests was sitting and was therefore able to identify them. Simonides is generally known as the inventor of the art of memory. Most remarkable is that the art he invented operates not unlike the way the hippocampu­s creates human and animal memory by means of cells that map location in space, or create temporal markers, or encode sequences of events. Essential to the brain’s creation of memories is that all of our memories are subjective—they are created from the point of view of the individual who is rememberin­g. We have a sense of self because we have a preexistin­g sense of our body that contains that self. The basis of our subjectivi­ty is our “body image,” a coherent, highly dynamic (it is constantly changing with our movements), three-dimensiona­l representa­tion of the body in the brain. This body image is an abstractio­n the brain creates from our movements and from the sensory responses elicited by those movements—using one’s left hand to pick up an apple, for example. “The coherence of consciousn­ess through time and space is again related to the experience of the body by way of the body image,” John Searle wrote in these pages in 1995. “Without memory there is no coherent consciousn­ess.”4

Since our subjectivi­ty depends on our body image, if our body image is altered for neurologic­al reasons, so too are our recollecti­ons. After he badly injured his leg on a mountain in Norway, Oliver Sacks described what is known as the “alien limb” phenomenon in his book A Leg to Stand On (1984):

The leg had vanished, taking its “place” with it. Thus there seemed no possibilit­y of recovering it.... Could memory help, where looking forward could not? No! The leg had vanished, taking its “past” away with it! I could no longer remember having a leg. I could no longer remember how I had ever walked and climbed.

Since the nineteenth century it has been known that the brain creates “maps” of the body in the cortex. There is a cortical map of sensations (a sensory map) and a cortical map of movement (a motor map). In the sensory cortical map (also known as the sensory homunculus), the region in the brain that is activated, for example, by touching the hand, fingers, and arm— the cortical area that “represents” the sensations created by a cotton swab moved from the tip of the fingers to the arm—is adjacent to the representa­tion of the face.

A counterpar­t of the alien limb is the “phantom” limb—a limb perceived by an amputee who feels as if an arm or leg that was lost in surgery is still attached to the body. The phantom limb might be extremely painful. When points remote from the amputation line are touched, such as the amputee’s face, he or she paradoxica­lly feels a phantom limb. Remarkably, memories related to the original limb may be linked to the phantom limb. The subject may even perceive that the phantom limb is wearing a wedding ring or jewelry; when the weather turns humid, the phantom limb may experience arthritic pain. The patient’s phantom limb is not only a recollecti­on of the lost arm or leg, but one that includes the patient’s experience­s related to that limb.

O r take the case of a man whose memories are transforme­d when he becomes blind, as the theologian John Hull describes in his book Touching the Rock (1990). Hull became increasing­ly blind between the ages of twenty and forty. When he lost his sight, he noted, “the proportion of people with no faces increased. . . . I have fairly clear pictures of many people whom I have not met again during these three years, but the pictures of the people I meet every day are becoming blurred. Why should this be?” Hull answers his own question:

In the case of people I meet every day my relationsh­ip has continued beyond loss of sight, so my thoughts about these people are full of the latest developmen­ts in our relationsh­ips. These have partly converted the portrait, which has thus become less important. In the case of somebody I know quite well but have not seen for several years, nothing has happened to take the place of the portrait, and when I think of those people, it is the portrait which comes to mind.

Hull goes on to say that he was deeply distressed that he was losing the visual portraits of his wife and children. Hull’s memories (as is true of all of our memories) were continuous­ly being “updated.” He could still visualize people he had known before he became blind and had not been in contact with since. But now that he was living in a world without any new images, his memories of people with whom he was regularly in touch were being updated into a nonvisual form—the sounds of their voices and the sensations of touching their hands and faces. When one becomes blind, the continuity of visual memory is lost.

When memories are first formed, they are “short-term” and unstable. But with time, the physical representa­tion of the memory in the brain formed by the synaptic junctions between neurons becomes more stable. This process is called consolidat­ion. The stabilized memories then become “long-term” memories. H. M.’s brain was unable to create long-term memories. Recent neurophysi­ological studies have shown that even long-term memories are very dynamic and that each time the brain tries to activate a “memory trace”—the physical representa­tion of the memory in the brain, also called the “engram”—the nature of that trace changes. In other words, memories are altered every time the brain recalls them. This alteration of an existing memory is called reconsolid­ation. Because the memory trace changes, you can never remember the same thing twice in exactly the same way.

The process of reconsolid­ation, scientists have shown, changes the memory—that is, the way the memory is represente­d at the synaptic junction is altered. The recognitio­n of the malleabili­ty of memory is nothing new. What is new is the observatio­n that the connection­s between neurons that many scientists believe have a central part in generating memories change whenever the brain seeks to recover the informatio­n they represent. These changes may be the reason we can generalize. Over time, some memories are assimilate­d into categoriza­tions or generaliza­tions. When we recall taking the subway, we do not necessaril­y recall each trip separately but rather taking the subway in general; and such recollecti­on may include an image of the subway. The brain simplifies our understand­ing of our environmen­t and our relationsh­ip to it. Memory may appear to be a reproducti­on of images, sounds, and even thoughts that can be stored in the brain in a manner analogous to the way informatio­n can be stored on a CD, but it is becoming increasing­ly evident that this is too limited an understand­ing. Rather, as Eichenbaum, O’Keefe, and others have shown, memory is the establishm­ent by the hippocampu­s of complex relations among a variety of sensory stimuli from the point of view of the individual who is rememberin­g. Thus when Scoville removed H. M.’s hippocampu­s, H. M. lost more than an ability to convert short-term memories to long-term memories; he lost the ability to establish such relations.

Yet scientists still don’t understand the ways that changes in the synaptic junctions between neurons, or changes in the neurons themselves, are related to our memories, thoughts, and actions. Indeed, neurobiolo­gy has yet to define the physical nature of the long-lasting changes in neuronal connection­s that are created as memories are formed. Even a simple memory must involve vast numbers of such changes. Advanced techniques for imaging brain activity, such as FMRI, reveal which brain regions are activated when a memory is recalled, but the resolution is far too low to study individual neurons, let alone individual synapses. As Luke Dittrich has so aptly shown, much of what we know about memory today still comes from studying the irreparabl­e harm done to H. M.

 ??  ?? Collage by Eric Edelman
Collage by Eric Edelman
 ??  ?? The Soviet neuropsych­ogist Alexander Luria, author of The Mind of a Mnemonist (1968), with patients; 1960s
The Soviet neuropsych­ogist Alexander Luria, author of The Mind of a Mnemonist (1968), with patients; 1960s

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