Permanent Present Tense

by Suzanne Corkin

  How does the brain accomplish this amazingly complex feat? In 2001, neuroscientists Earl K. Miller and Jonathan Cohen posited that the prefrontal cortex orchestrates thought and action to achieve internal goals, such as deciding what to order for dinner. The neural circuitry in the prefrontal cortex, which supports working memory, allowed the woman in our example to maintain the words she just heard, to experience visual images and tastes of the food, to retrieve memories of her recent meals, and to examine her knowledge and opinions about food. In short, her choice was guided by top-down processing, using her experience to guide decision-making.23

  Top-down processes enable us to modulate the impact of diverse sensory information. These computations include planning a series of actions, managing goals, coordinating and monitoring automatic processes (such as reacting to a mouse in the kitchen), inhibiting powerful habitual responses, focusing attention selectively, and suppressing irrelevant sensory inputs so that we can generate internal representations of goals and how to attain them. The prefrontal cortex in the front of the brain guides the flow of information along pathways in the back of the brain and in areas under the cortex, which are crucial for problem solving and decision-making. One requirement of the prefrontal cortex is that it must be flexible—able to adapt to changes in the environment inside or outside of the body, and able to entertain new goals and procedures.24

  Henry’s working memory was sufficiently robust to allow him to play bingo, speak in sentences, and do simple arithmetic in his head. He was unable, however, to integrate his online thoughts with memories of the recent past. If he ordered a meal in a restaurant, he could make a choice based on what he liked and disliked before his operation, but he could not take into account what he had eaten the day before, whether he had to select low-calorie items to control his weight, or if he needed to limit his salt intake. Henry depended on his caregivers to fill in that information and much more. His daily life had many limitations because he lacked vital long-term memory capacities.

  What is it like to experience life with only short-term memory to rely on? No one would doubt that Henry’s experience was a tragedy, but he rarely seemed to suffer and was not continuously lost and frightened—quite the contrary. He always lived in the moment, fully accepting the events of daily life. From the time of his operation, every new person he met was forever a stranger, yet he approached each one with openness and trust. He remained as good-natured and pleasant as the polite, quiet person his high-school classmates knew. Henry answered our queries patiently, rarely getting angry or asking why he was being questioned. He understood his situation enough to know that he had to rely on others and willingly accepted help. In 1966, when Henry was forty, he visited the MIT Clinical Research Center for the first time. When asked who packed his bags for him, he answered simply, “It must have been my mother. She always does those things.”

  Henry was free from the moorings that keep us anchored in time, attachments that can sometimes be burdensome. Our long-term memory is critical to our survival, but it also hinders us; it prevents us from escaping embarrassing moments we have lived though, the pain we feel when thinking about lost loved ones, and our failures, traumas, and problems. The trail of memory can feel like a heavy chain, keeping us locked into the identities we have created for ourselves.

  We can be so wrapped up in memories that we fail to live in the here and now. Buddhism and other philosophies teach us that much of our suffering comes from our own thinking, particularly when we dwell in the past and in the future. We replay moments and events that happened before and spin narratives about what might transpire in the future, becoming mired in the emotions and anxiety of these stories. Often our thoughts and feelings have nothing to do with the concrete reality of the present. When people meditate, they may attend closely to their breathing or to a particular body part, or they may repeat a mantra—whatever helps them maintain contact with the present moment and avoid getting caught up in distracting thoughts and narratives. Meditation is a method for training the mind to have a new relationship with time, knowing only the present tense, unburdened by the power of memory. Dedicated meditators spend years practicing being attentive to the present—something Henry could not help but do.

  When we consider how much of the anxiety and pain of daily life stems from attending to our long-term memories and worrying about and planning for the future, we can appreciate why Henry lived much of his life with relatively little stress. He was unencumbered by recollections from the past and speculations about the future. As frightening as it seems to live without long-term memory, a part of us all can understand how liberating it might be to always experience life as it is right now, in the simplicity of a world bounded by thirty seconds.

  Five

  Memories Are Made of This

  Our research with Henry focused on two kinds of investigation. One used brain-imaging tools to reveal the anatomy of his surgery and thereby show exactly what areas had been removed and what had been left behind. This level of detail is critical when neuroscientists are trying to relate the function in discrete brain areas to specific behaviors. The other kind of study harnessed cognitive tests to evaluate Henry’s memory and other intellectual functions. We knew from Milner’s testing in 1955 that his IQ was above average. Still, we wondered about other aspects of complex thought. In addition, it was important to assess his perceptual capacities to be sure that he was receiving accurate information about the world.

  The roots of memory formation are planted in our sensory organs as collections of separate threads. If we focus on our environment at this very moment, we realize that we are receiving different kinds of information simultaneously through our eyes, ears, nose, mouth, and skin. We are perceiving sights, sounds, smells, tastes, and touches. These diverse pieces of information are automatically channeled along separate pathways to our cortex where they are processed in areas specialized for each sensory modality. This material also reaches our hippocampus where the various sensations come together and memory formation begins. The process of laying down a memory requires back-and-forth communication between our hippocampus and the areas distributed throughout our cortex where the sensory information was first perceived. During this interaction, the hippocampus organizes the cortical components of a memory so they are available for retrieval as a whole memory and not a bunch of disconnected fragments. Together these traces contain a rich representation of our experiences.

  Because memory formation depends heavily on receiving valid information from the senses, it was necessary to establish the integrity of Henry’s sensory functions. If he could not perceive photos of faces normally, how could we expect him to remember them? The same was true for the other senses. For this reason, we considered it important to evaluate Henry’s sensory capacities and did so on and off from the 1960s through the 1980s. The evidence convinced us that his bad memory could not be dismissed as a side effect of impaired visual, auditory, or tactual perception.

  The demonstration that Henry’s memory could come to a standstill while his intelligence remained intact indicates that the capacity to form new memories is separate from overall intelligence. To establish conclusively that his acumen had survived, we conducted numerous experiments that examined Henry’s higher intellectual functions, such as problem solving, orientation in space, and reasoning. A tremendous boon to this effort was that Henry enjoyed test taking and was a very attentive and cooperative research participant. His pattern of cognitive strengths and weaknesses, demonstrated over years of research, helped define the scope of the amnesic syndrome, and of his preserved capacities. Henry harnessed many different abilities to compensate, as best he could, for his tragic memory impairment.

  When my colleagues and I first began studying Henry, we did not know exactly how much damage his brain had suffered as a result of Scoville’s surgery. The only information we had came from Scoville’s account of what he had taken out, which itself was only an educated guess. Over the next five decades, ne
w technologies gradually emerged that enabled us to examine Henry’s brain lesion in greater and greater detail.1

  We knew from Henry’s 1946 pneumoencephalogram that his brain appeared normal prior to his surgery. It took nearly half a century, however, to obtain an accurate picture of Henry’s postoperative brain. Brain imaging took a major leap forward in the 1970s with the invention of computed tomography (CT), which uses X-rays and a powerful computer to create cross-section images of the brain. CT enables doctors and researchers to examine brain structures slice by slice, focusing images to one plane at a time and eliminating interference from surrounding structures.

  In August 1977, I asked a colleague in the Department of Neurosurgery at Mass General to order a CT scan of Henry’s brain. The radiologist observed surgical clips in the region of the temporal lobe on both sides of Henry’s brain, deliberately left to control bleeding. Both temporal lobes were slightly atrophied (shrunken), and the Sylvian cisterns—the spaces between the temporal and frontal lobes that contain cerebrospinal fluid—were slightly enlarged on both sides, another indication of atrophy. Henry’s cerebellum showed similar evidence of shrinkage. The images showed no sign of a brain tumor or other abnormality. The CT scan confirmed only that he was missing tissue deep in each temporal lobe, but we were unable to judge exactly which structures had been removed and to what extent.

  By the mid 1970s, mounting evidence from animal and human tests had convinced scientists that the hippocampus was vital for converting short-term memory into long-term memory, but we still needed direct proof that the hippocampus was responsible for Henry’s amnesia. Another CT scan, conducted in 1984, simply verified the results of the 1977 study. Because these scans showed just the spaces in his brain and not the anatomy of what remained, we sorely needed a better tool.

  In the early 1990s, we were finally able to thoroughly assess the damage that had been done to Henry’s brain, thanks to the development of magnetic resonance imaging (MRI), which had been invented in 1970. Commercial scanners became available in the early 1980s, and MRI evolved into a mainstream tool by the end of the decade. MRI is superior to CT in distinguishing one brain area from its neighbors. Like CT, MRI takes cross-section images, but instead of relying on radiation, uses radio waves and a powerful magnet to obtain precise images of tissues. The magnetic field forces hydrogen atoms to align in a particular way, while the radio waves bounce off the hydrogen protons in the body and produce a signal. Different types of tissues give off different signals, which a computer can re-create as black-and-white images.2

  Using MRI scans, we could look through Henry’s scalp and skull to see his brain. With this new method we could identify small brain structures and get a clearer picture of the damage than with CT scans. Before MRI, the only way to see the brain’s anatomy in detail was to look at it directly, during either a surgical procedure or an autopsy. Henry’s first MRI scan in 1992, at Brigham and Women’s Hospital in Boston, was an exciting moment for all of us who had spent decades studying him. For the first time, we had a clear view inside what was perhaps the most studied brain in the world.3

  Henry’s brain generally looked normal for a man of sixty-six, with the exception of his cerebellum—the grooved bulb near the brain stem that supports motor control. In the 1960s, we could only infer this damage from abnormalities in his neurological examinations, but the MRI images showed a shriveled cerebellum, surrounded by extra space filled with cerebrospinal fluid. Although we knew that Henry’s cerebellum was abnormal, we were struck by the extent of the atrophy. This damage was due to the drug-related death of neurons. For many years, Henry had taken Dilantin to prevent seizures, until the drug caused ringing in his ears. In 1984, his doctors replaced the Dilantin with a different seizure medication, but the tinnitus did not subside. Dilantin left him with other permanent disabilities—loss of feeling in his hands and feet, and challenges with balance and movement. Henry strolled from place to place in a slow, unsteady gait, his feet far apart for stability—symptoms of the cerebellar atrophy that was so striking in his MRI scans.

  As the scans moved into the interior of the temporal lobe, we could see that the operation forty years before had left an irretrievable absence—two nearly symmetrical gaps in the middle of Henry’s brain. Missing was the front half of each hippocampus and the areas that interface with the hippocampus—the entorhinal, perirhinal, and parahippocampal cortices. Also removed was most of the amygdala, an almond-shaped group of structures that supports emotion. The entire lesion in Henry’s brain extended just over five centimeters from front to back, far less than the eight centimeters Scoville had estimated. Approximately two centimeters of hippocampus still remained in each half of the brain, but this residual tissue was useless: the pathways carrying information to it had been destroyed (see Fig. 3).

  During the MRI scanning sessions, Henry was, as usual, an agreeable subject. He was not claustrophobic inside the scanner, and afterward we would serve him lunch—a sandwich, tea, and his favorite pudding or pie. Henry was a gourmand, and as he aged, his belly grew so rotund we worried about fitting him into the MRI’s tubular scanner. After Henry came out of the scanner, my colleagues at the imaging center were always eager to have a conversation with him, so he often attracted a small group of fans. But he never questioned why he was such an attraction, taking it all in stride.

  In 1993 and from 2002–2004, we performed several more MRI studies on Henry. By then, MRI analysis techniques had improved, and we could measure more precisely the amount of brain tissue that had been removed or spared. Once we had clearly defined the anatomy of Henry’s brain lesions, we had the exciting opportunity to link his impairments to the damaged areas, and his good performance to the spared areas. MRI evidence strongly supported the conclusion that the medial temporal-lobe structures removed from Henry’s brain are crucial for long-term declarative memory, the conscious retrieval of facts and events. Henry’s memory was severely impaired, regardless of the kind of test (free recall, cued recall, yes/no recognition, multiple-choice recognition, learning to a criterion), stimulus material (words, digits, paragraphs, pseudo-words, faces, shapes, clicks, tones, tunes, sounds, mazes, public events, personal events), and the sensory modality through which information was presented to him (vision, audition, somatosensory system, olfaction). His impairment was not just severe; it was pervasive. This anterograde amnesia, which characterized his postoperative life, boiled down to deficient acquisition of episodic knowledge—memory for events that happened at a specific time and place—and of semantic knowledge—general knowledge about the world, including new word meanings.

  An important finding in the MRI scans was that, beyond the hippocampus, a bit of medial temporal-lobe tissue was left behind on both sides, the back part of his parahippocampal gyrus (perirhinal and parahippocampal cortices). We entertained the possibility that this spared cortex, known from studies in monkeys to be important for memory, was engaged when, from time to time, Henry would surprise us by consciously remembering something he had no business remembering. He could draw the floor plan of a house that he moved into after his operation; he could recognize complex color pictures up to six months after he had studied them; and he could describe a few details about celebrities who had become famous after his operation. The perirhinal and parahippocampal cortices receive information from other cortical areas, and this stored information was likely used in building these memories. Evidence from experiments in animals and humans suggests that the different medial temporal-lobe structures act independently and can mediate behavior flexibly, via conversations with specific cortical-processing streams. These cortical mechanisms enabled Henry, in everyday life, to occasionally retrieve bits of stored information about the world.

  The MRI images also revealed that the vast expanse of cortex on both sides of Henry’s brain was normal. Thus, his cortical functions—short-term memory, language capacities, perceptual abilities, and reasoning—were undisturbed. In addition, circuits within Henry’s hea
lthy cortex and areas underneath supported several kinds of nondeclarative memory, skills and habits learned without conscious awareness. Henry’s case showed us that these capacities are independent of the hippocampus.

  I arrived at MIT in 1964 after completing my PhD at McGill University. I was a research scientist in what was then the Psychology Department. It was a growing department energized by scientists who represented disciplines ranging from neuroanatomy to psycholinguistics. The atmosphere was stimulating and collegial. Our chair, Hans-Lukas Teuber, was a German immigrant and an influential figure in the study of the brain. My own mission upon arriving at MIT was to establish a lab that focused on patients with neurological disorders. Over the years, the patient groups included veterans from World War II and the Korean War who had sustained head injuries, and patients who had undergone psychosurgery at Mass General. In investigating these groups of patients, I conducted a broad examination of their cognitive and motor functions, and my expertise grew beyond my PhD research, which had focused on the sense of touch. I was always particularly interested in memory, and in the late 1970s began studying patients with Alzheimer disease and other neurodegenerative disorders. In the 1980s, my colleagues and I expanded our study of aging to include alterations in the brain and related behaviors in healthy women and men. All along, my lab continued to study Henry intensively, interspersing studies on him with those on other types of patients.

  The MIT Clinical Research Center (CRC), the base of all this testing, was established in 1964 as part of a larger movement to create federally funded centers for academic research on human diseases. During the administrations of John F. Kennedy and Lyndon B. Johnson, the federal government’s role in healthcare expanded, and biomedical research was one of the beneficiaries. The resulting clinical research centers, funded by the National Institutes of Health, were instrumental in applying scientific techniques to studying disorders in a clinical setting. Our CRC was a small, ten-bed unit, situated on a single floor of an unobtrusive brick and concrete building on the MIT campus. It was designed with overnight accommodations for patients, allowing easy access to our testing rooms on the same floor.