Wednesday, October 01, 2003

Memory Research Finds a Talented Chronicler

Memory and Emotion: The Making of Lasting Memories

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Asking scientists what initially captured their interest in science is always interesting. For some, a particular teacher in high school or a certain course in college switched on the light. For others, exposure to a mentor early in their careers was fateful. At least in my generation, though, it was often something we read that moved us. For me, the book Microbe Hunters by Paul de Kruif—the mesmerizing tale of those who waged wars against diseases, particularly bacterial illnesses —was decisive. De Kruif was a microbiologist and pathologist who taught at the University of Michigan at Ann Arbor, but became widely known for popularizing medical science. First published in 1926, Microbe Hunters is still in print (available in paperback from Harvest Books), as well it should be. As a young man, I must have read that book 10 times. For a later generation, the inspiration may well have been James Watson’s The Double Helix: A Personal Account of the Discovery of the Structure of DNA, published in 1968 by Simon & Schuster, Inc. Watson’s book, besides being an account of the steps involved in elucidating the structure of DNA, introduced many young readers to the concept of the genetic code and the virtually unlimited opportunities it offered for the future of biological science.

Now, I suggest that James L. McGaugh’s Memory and Emotion: The Making of Lasting Memories may have something of the same impact on our current generation of budding neuroscientists. McGaugh, who is professor of neurobiology and behavior at the University of California, Irvine, and director of its Center for the Neurobiology of Learning and Memory, is a certified “old pro.” He has been investigating memory and related phenomena, and training some of the leading investigators in that field, for more than 50 years. Indeed, if, as he argues in Memory and Emotion, the genuinely scientific (that is, experimental) study of memory is only about a century old, then his own career spans half that history.

Admittedly, McGaugh’s prose style and tone could scarcely be less like the relentlessly dramatic narrative that de Kruif employed to draw in his readers. One need only compare a few chapter titles. From de Kruif: “Koch: The Death Fighter,” “Pasteur: And the Mad Dog,” and “Roux and Behring: Massacre the Guinea-Pigs.” From McGaugh: “The Mystery of Memory,” “Coaxing Consolidation: Making Memories Linger,” and “Memorable Moments.” In part, of course, this reflects a maturing of popular science writing over some 80 years; scientists today know that there is a wide popular audience for science writing, an audience accustomed to grappling with new concepts. This audience demands clarity and an engaging story, certainly, but not the breathless pace of a spy thriller. For the emergence of this scientifically engaged and literate populace—primed to read McGaugh’s new book—we owe much to Paul de Kruif and his like.

WHERE WERE YOU WHEN...

As a scientist, McGaugh has taken what I would call a systems approach. That is, he has asked: What are the memory circuits in the brain? Can they be altered? If so, how? And how can they be better understood? If I were teaching an undergraduate college course in neuroscience, with just a week or two devoted to memory and memory processing, I would assign this book to be read first.

One should not be put off by the title. Memory and Emotion is a broader presentation than the title implies. It is an overview of evolving concepts of memory, a history of those who have studied memory in both animals and humans, and a summary of where we now stand in understanding memory processes. What the title does reflect is McGaugh’s own area of expertise, which is the interaction of emotion and memory, particularly how emotions such as stress promote the consolidation of long-term memories. This concept is easy to illustrate, because we have recently marked the 40th anniversary of the assassination of President John F. Kennedy, an event endlessly cited as an example of how emotion can etch memories into our minds. Those of us over about 50 can tell you exactly where we were, what we were doing, and perhaps even what we were wearing when we heard the news of the assassination. For a younger generation—and all of us, of course—a similar memory enhancement will always be associated with the events of 9/11.

This phenomenon, a seemingly indelibly memorable moment, is often referred to as “flashbulb memory.” The term, attributed to cognitive scientists Roger Brown and James Kulik, denotes the retention of very vivid and long lasting details. Characteristically, McGaugh proceeds systematically in raising and addressing questions about flashbulb memory. Firstly, are the recalled flashbulb memories actually accurate? McGaugh demonstrates clearly that they are accurate, but often incomplete. It appears that the stronger a particular individual’s emotional response to an event, the more stable are memories of it over time. Secondly (and this is McGaugh’s own area of research) why do flashbulb memories occur? McGaugh’s investigations, and those of others, including many of his students, indicate that hormones released by stress are an important enhancing factor for memory and that these hormones appear to work through activation of a particular part of the brain, the amygdala.

McGaugh points to a key feature of useful memory—one we seldom ponder—namely, how selective our memory is. We remember things that are important to us and, just as usefully, forget other things or form weaker memories of them that gradually fade.

THE VALUE OF FORGETTING

With a foundation of scientific explanation in place, McGaugh goes on to raise questions about memory-enhancing compounds. A huge public interest has developed in the possibility of memory enhancement, as evidenced by multi-million dollar sales of herbal and other remedies of questionable efficacy. But would a genuinely effective memory pill really be a good thing? McGaugh points to a key feature of useful memory—one we seldom ponder—namely, how selective our memory is. We remember things that are important to us and, just as usefully, forget other things or form weaker memories of them that gradually fade. In making this point, McGaugh refers to the remarkable mnemonist described by Russian neurophysiologist Alexander Luria and to the phenomena of the hugely powerful but selective memory talents of autistic savants. For these persons, the ability to remember remarkable amounts of information can be disabling. In the end, McGaugh (rightly, by my standards) downplays the potential benefits of non-specific memory enhancing foods and medications.

Still more burdened by memory are those who, as a result of the overwhelming emotional storms of experiences in battle, devastating accidents, or horrific abuse, create memories that are relived again and again in all their searing emotional reality. “It is estimated that perhaps ten to fifteen per cent of those who have traumatic experiences have post-traumatic stress disorder (PTSD),” writes McGaugh. For some, PTSD is a lifetime affliction, but an unusual feature of the disorder may hold out hope. Although the memory of the traumatic experience itself is created immediately, the other symptoms of PTSD may not be. Stress hormones may “incubate” PTSD over time, McGaugh suggests, so that the “result may be a positive feedback loop, in which subclinical PTSD may escalate into clinical PTSD.” Hope lies in the lively possibility of preventing the development of PTSD by blocking the actions of the stress hormones —in effect, by preventing the consolidation of long-term memory. Evidence now suggests that beta blockers may do exactly this.

AWAITING A NEW PIED PIPER

Readers just beginning their investigation of memory should realize that an entire, major aspect of modern memory research is simply not represented in this book: the investigation by Nobel laureate Eric Kandel of Columbia University and others of the cellular mechanisms involved in memory. The systems approach to memory, typified by McGaugh, and the cellular approach, typified by Kandel, have been difficult to bring together. As good as McGaugh’s book is, I hope that some pair of scientists like McGaugh and Kandel will collaborate to produce a similarly readable and enticing volume covering the whole field. If that were to occur, we might have to say “Move over, de Kruif, move over, Watson, a new Pied Piper has appeared on the scene.”

For all of that, though, I warmly recommend Memory and Emotion. Its final chapter, an overview entitled “Memorabilia: Summing Up,” is only two-and-a-half pages and ought to be read first. If that chapter does not entice the aspiring young scientist to dive into the book, he may be well advised to think twice about choosing a career in neuroscience. McGaugh has issued an invitation to adventure for any reader who has wondered about how our brains achieve one of their most extraordinary—and still mysterious—feats.  

EXCERPT

From Memory and Emotion: The Making of Lasting Memories, by James L. McGaugh. © 2003 by James L. McGaugh. Reprinted with permission  of Columbia University Press.

Thus, these two major adrenal stress hormones, epinephrine and cortisol, that have quite different ways (and pathways) of affecting the brain, have a common action in influencing norepinephrine functioning within the amygdala that is critical for modulating memory consolidation. These two stress hormones are very busy in helping us manage our lives. They have many important and complex duties to perform in helping us deal with the immediate physiological consequences of stressful events. They are part of our emergency “first-aid” kit; but they both also do double duty. In addition to providing emergency physiological aid, they both also serve the highly important function of strengthening our memories of the stressful events that caused their release from the adrenal glands. Yes, there is nothing like a little stress to help create strong, long-lasting memories of events we have experienced.

There is, however, an important and interesting caveat. The effects of stress on recalling previously learned information are yet another matter. Did you ever have the experience of “blocking” in an exam, an interview, a court testimony, a public speech or even the reciting of a marriage vow? Well, most of us have had such experiences. They are usually real memory failures, not fabricated excuses for poor memory performance (of course, fabrication is also possible). In two experiments, Dominique de Quervain and Benno Roozendaal and their colleagues have shown that, in human subjects as well as rats, a brief stressful experience impairs retrieval of well-established memories. The impaired retrieval lasts for about an hour. Additionally, they found that the retrieval impairment was due to the release of corticosterone (rats) or cortisol (humans) as it was blocked by a drug that prevents the synthesis and release of adrenal glucocorticoids. Thus, a little stress is not always good for memory—it can temporarily impair our ability to recall or retrieve even well-learned information. Although it is too late to correct your grade on an exam taken long ago, you may well wish you could inform the teacher who graded your exam that your poor performance was caused by your glucocorticoid receptors (maybe).  



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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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