Friday, December 05, 2008

Memoirs about Memory: Too Much vs. Too Little

By: Suzanne Corkin Ph.D.

Afraid of losing your memory? What if you remembered everything? Suzanne Corkin, a behavioral neuroscientist at the Massachusetts Institute of Technology, compares and critiques two recent memoirs by women who relate very differently with memory, adding insight from her own work.

Jill Price’s "The Woman Who Can’t Forget" and Sue Halpern’s "Can’t Remember What I Forgot: The Good News from the Front Lines of Memory Research" are two memoirs that describe opposite sides of the memory chip. Price has an extraordinarily good memory, but her recollections are so frequent and vivid that they disrupt her life. Halpern, though labeled “normal,” is anxious about the possibility, and maybe inevitability, of losing her memory. For Price, forgetting is a boon; for Halpern it portends cognitive decline with aging.

Price recounts her personal saga as a patient in search of answers about her uncanny ability to remember specific dates and events without even trying. Halpern, whose 1992 “Migrations to Solitude” was a New York Times notable book, gives a detailed account of her visits to clinics and laboratories to ask the experts: What is memory? How does it break down in disease? How can we fix it? Each author intends to leave the reader with an optimistic message, but only Price succeeds: in closing, she expresses hope for her future and for the possibility that her case study will benefit other patients. In contrast, by the time I finished Halpern’s book, I was convinced that the subtitle should have been The Bad News from the Front Lines of Memory Research. 

Too Much Memory

Price begins her story: “I know very well how tyrannical the memory can be. I have the first diagnosed case of a memory condition that the scientists who have studied me termed hyperthymestic syndrome—the continuous, automatic autobiographical recall of every day of my life from when I was age fourteen on.” The scientists to whom Price refers are James McGaugh, Larry Cahill, and Elizabeth Parker at the University of California, Irvine. They spent five years studying Price in their laboratory and summarized their findings in a fascinating article in Neurocase (2006).1 (In their paper, they gave her the initials A.J. to protect her identity; at the time, she had not gone public.) They began by describing Price’s history in some detail and then gave examples of her extraordinary autobiographical memory.

During Price’s visits to their laboratory, they quizzed her by giving her a date and asking her what had happened on that day. As rigorous scientists, they did not assume unquestioningly that all of her recollections were correct. Rather, they verified her responses against extensive diary entries, information from her mother, calendars, and the media. Price’s responses were highly reliable. For example, when asked about July 1, 1986, she replied, “I see it all, that day, that month, that summer. Tuesday. Went with (friend’s name) to (restaurant name).” The scientists later confirmed that the day of the week was indeed a Tuesday and that the event corresponded to a diary entry. Her memory for public events was equally amazing; when asked what happened on June 6, 1978, she correctly stated that Proposition 13 passed in California. And when given the date November 4, 1979, she knew that the U.S. Embassy in Iran was invaded on that day. Clearly, her ability goes far beyond that of most.

Price’s recollections are profoundly personal. An especially poignant example concerns her mother’s overriding concern with Price’s weight. She writes, “I put on weight, as so many people do when they go to college, and when I went home my mother harped about that. All the memories through the years of her nagging me about my weight were triggered, and they began to haunt me again relentlessly. Maybe that should have made me thrilled about being off on my own, but I felt nothing like that” (page 150). Although the book at times smacks of a TV serial, I did feel the emotional torment that Price experienced as a result of her out-of-control memory.

Since the 2006 publication of the scientific paper by the UC-Irvine scientists, other individuals with hyperthymestic syndrome have surfaced. One of them, Brad Williams, is a 51-year-old radio anchor who constantly amazes his family, colleagues, and the public with his memory prowess. He appeared on Jeopardy and just missed being champion. He also agreed to a contest with Google to see who could answer 20 questions about news events faster—and won. The public will soon have the opportunity to marvel at his lifetime of memory feats because his brother, Eric, a screenwriter, is producing a documentary titled Unforgettable (see the trailer on YouTube). Undoubtedly, more such individuals will emerge in the future, each with a fascinating story to share.

Price and Williams, and the neuroscientists who have studied them, are baffled about how they perform memory feats that most other people cannot. We do know that learning and memory take place over time, and in the laboratory we can examine the stages of memory formation. A current framework for studying memory in humans tries to isolate encoding, storage, and retrieval processes, but memory is really not that simple. In addition, one would like to know whether imaging their brains would reveal any structural, connectional, or functional differences from the brains of people with ordinary memory. Such work is in progress at Irvine, and Price notes in her book, "My brain scans show that my brain has some structural features that are a great deal different from the norm” (page 95). To complete the picture, a thorough personality evaluation would be useful to see whether particular traits may have nourished Price’s hyperthymesia. We can count on McGaugh, Cahill and their colleagues to ask the right questions and tell us what these extraordinary minds teach us about the organization of human memory, and also how the brain’s process of rewiring based on experience can go awry.

Too Little Memory

Sue Halpern’s father had vascular dementia and died at age seventy-seven. His profound memory impairment and its devastating effect on his last years seized her attention. She wondered about the underpinnings of his sickness, prompting a series of questions about how memory decline is diagnosed and treated. Glimpses of the clinical science and basic science that she caught from the popular literature fascinated her, and she decided that she wanted to know more. To this end, she embarked on a quest for knowledge about memory. She enrolled as a healthy volunteer in several clinical studies and became one of the “worried well.” Appropriately, the first chapter of the book is titled, “Anxious.”

Halpern’s book is tirelessly researched. She interviewed more than 50 clinicians and scientists over a period of several years. She chose to undergo a structural magnetic resonance imaging (MRI) scan, a functional MRI scan, a positron emission tomography (PET) scan, a single photon emission computed tomography (SPECT) scan, and neuropsychological testing. In addition, she learned about various basic science investigations in animals and humans that aim to uncover the biology of aging and age-related disease. Halpern describes diseases, neuroimaging methods, and cognitive tests in language that the layperson can understand. She writes lucidly and tries to show a healthy skepticism about promised breakthroughs that never materialized. Still, I fault the book on two counts: the subtitle, "The Good News from the Front Lines of Memory Research," which gives readers expectations that are not realized, and the inaccurate reporting of many scientific facts (examples to follow).

The Bad News

Reading this book, I wondered when I would get to the “good news.” Finally, in chapter 8, I got a morsel. Halpern writes, “Exercise alone appeared to improve cognition” (page 186) and “memory improved in humans who exercised. That was now known” (page 205). This tidbit of encouragement was juxtaposed with an abundance of negative messages, such as “Almost every drug in development fails” (page 138) and, quoting Steven Ferris, “There’s nothing that has been proven so far in an FDA-regulated quality sense to improve memory in normal brain aging. In the end, the proof will be made in the human pudding, and it hasn’t been made yet” (page 180). And last but not least: “[If the neurologist] made a diagnosis of Alzheimer’s, the best he could offer was a prescription for drugs that did not work very well, and a referral to social services, and good wishes” (pages 227–228). And so the book ends, with the final bit of bad news from the front lines of memory research.

Inaccurate Reporting

Our society needs books written by non-scientists that don’t turn off the general reader by sounding overly “scientific” but nevertheless transmit up-to-date research findings. Halpern’s book is an attempt at that kind of communication. Like many other trade books, however, Halpern’s falls short of this goal. The reason is that she (I suspect) and many other pop authors don’t immerse themselves in the scientific literature. Instead, they rely on interviews with clinicians and scientists as a substitute for going to the library. Then they write a book. The result can be a compendium of significant errors and a slippery use of facts.

Halpern writes at length about “breakthrough” treatments that amount to what strikes me as snake oil. She highlights neuroscientists with panaceas and panacea-based research programs. These individuals take meager scientific findings and make claims for them that are not supported by the evidence. In some cases the beneficiaries are the scientists themselves, or even commercial entities such as TV channels.

My major objection is to Halpern’s erroneous description of the amnesic patient H.M., whom I studied from 1962 through his death Dec. 2. According to Halpern,

The reason why so much was known about how a small ridge at the bottom of the brain, one on the left, the other on the right—the hippocampus—controls short-term memory was that in 1946 a nine-year-old boy fell off his bicycle. After the accident the boy began to experience unremitting seizures, seizures so severe that when he was sixteen, with no prospect for a decent life, his doctor removed a part of his temporal lobe, including his hippocampus, hoping to eliminate the tissue that he believed was causing the young man’s body to convulse uncontrollably. It was a radical move, but the doctor was right—the operation cured the young man of his seizure disorder. But it turned out that without a hippocampus, the young man was no longer able to make new memories. He could find his way to his childhood home, but not to the house where he lived after the operation. He greeted his doctors each day as if they had never before met. Over the years, when he looked in the mirror, he saw a stranger too old to be himself; his self-image had been fixed in his brain in the days and weeks leading up to the operation. (page 53)

Let me set the record straight. The hippocampus is not located at the bottom of the brain. It is situated above the ears, toward the middle of the brain. Considerable scientific evidence indicates that the hippocampus and the surrounding cortex are critical for the establishment of long-term declarative memory (not short-term memory). In 1935 (not 1946), H.M. was knocked down by a bicycle. His minor seizures began a year later, at age 10; his major seizures began at age 16. His operation occurred at age 27 (not age 16). The removal was restricted to the medial part of the left and right temporal lobes, including the hippocampus. The operation did not cure H.M.’s seizure disorder. His seizures were reduced in frequency, but for the rest of his life he took anticonvulsant medication and had seizures.

The statement concerning H.M.’s sense of self is also inaccurate. When he looked in the mirror he was not shocked. He showed no change in facial expression, his conversation was matter-of-fact, he did not seem to be at all upset, and on one occasion, when asked, “What do you think about how you look?" he replied, "I'm not a boy," illustrating his sense of humor. H.M.’s sense of self included knowledge of his ancestors, preoperative personal semantic knowledge (i.e., general information about the world), memories of his childhood that included vacations with his parents, and information about a number of relatives (although he could provide only the gist of these events without any specific details about time and place). In addition, amnesia is not an all-or-nothing condition, and even H.M. from time to time had meager conscious recollections of information encountered postoperatively. For example, he knew he had a memory impairment, he could draw the floor plan of his postoperative home, and he had some slight knowledge about a handful of celebrities. The interested reader can learn more about H.M. in a paper I authored in "Nature Reviews Neuroscience" in 2002.2 Halpern and other popular science writers would be well advised to pay closer attention to the scientific literature.

Common Themes

What do Price and Halpern have in common? Both authors acknowledge that memory is a critical component of one’s sense of self. When Price reached adolescence, her autobiographical memories became more numerous and vivid. Here’s how she interprets this enhancement: “The most interesting explanation to me is that most people have more memories from this time period because it is in these years that we are generally formulating and fixing in our minds our sense of self, and memory and self are closely intertwined” (page 101). For her, the flood of memories gave rise to a negative self-image and an unhappy life. In the epilogue, she considers whether she would have been better off without her exceptional memory. Her answer is, “Despite all the pain it has caused me, if I could choose, I would keep my memory, because it’s made me who I am” (page 246). Price has learned to live with, and perhaps even appreciate, her unusual persona, and she accepts the challenge of keeping it under control. Brava!

Halpern also believes that we are what we remember: “It is not just that the brain codes in terms of spatial-temporal patterns, it’s that our memory is what places us, as individuals, in space and time. It’s through our memory that we know where we are, and where we are going, and who we are, and who we believe others know us to be” (page 221). That said, the challenge of understanding memory persists.

References

1. E. S. Parker, L. Cahill, and J. L. McGaugh, "A Case of Unusual Autobiographical Remembering," Neurocase12 (2006): 35–49.

2. S. Corkin, "What’s New with the Amnesic Patient H.M.?" Nature Reviews Neuroscience 3 (2002): 153–160.



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Bill Glovin, editor
Carolyn Asbury, Ph.D., consultant

Scientific Advisory Board
Joseph T. Coyle, M.D., Harvard Medical School
Kay Redfield Jamison, Ph.D., The Johns Hopkins University School of Medicine
Pierre J. Magistretti, M.D., Ph.D., University of Lausanne Medical School and Hospital
Robert Malenka, M.D., Ph.D., Stanford University School of Medicine
Bruce S. McEwen, Ph.D., The Rockefeller University
Donald Price, M.D., The Johns Hopkins University School of Medicine

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