Monday, May 21, 2007
Constructive Memory and Memory Enhancement
BY WALTER GLANNON

In Jorge Luis Borges’ short story, “Funes the Memorious,” the character Ireneo Funes sustains a brain injury from an equestrian accident. Consistent with Borges’ penchant for irony, Funes does not develop amnesia but instead a condition in which he remembers every detail of everything he experiences. Speaking to the narrator, Funes says, “My memory, sir, is like a garbage disposal.” Funes becomes an invalid, a prisoner of a hyperactive system of memory consolidation and recall, unable to learn new things and anticipate the future because he cannot tolerate any additional experience. The narrator suspects that Funes “was not very capable of thought. To think is to forget a difference, to generalize, to abstract. In the overly replete world of Funes, there were nothing but details, almost contiguous details.” Because of his overloaded memory, Funes is unable to execute such cognitive tasks as problem-solving and decision-making. He is also unable to anticipate and plan for the future because be cannot forget the particular features of his experience.

The most famous actual case of this condition was neurologist A. R. Luria’s patient Shereshevkii, described in Luria’s book The Mind of a Mnemonist. His formidable ability to remember a vast amount of facts and events resulted in his inability to process new information. He was prevented from doing any work other than as a traveling mnemonist.

Research into the mechanisms of memory suggests that novel pharmacological agents could enhance the encoding and storage of long-term episodic and semantic memory of events and facts. “Smart” drugs targeting the transcription factor cyclic response element binding protein (CREB), which influences the encoding and storage of long-term memory, might increase memory capacity in our brains.¹ This effect might also be achieved through drugs that increased acetylcholine, the main neurotransmitter involved in the regulation of memory. Other pharmacological agents that might have a similar effect are ampakines, which can influence the neurotransmitter glutamate and promote better communication between synapses in the cortex. These agents might also enhance the retrieval of remembered facts and events from the hippocampus and other sites in the medial temporal lobes by the prefrontal cortex for short-term working memory in executive cognitive functions. Insofar as it would involve people with normal memory functions, enhancement would be different from the therapeutic use of drugs (such as the cholinesterase inhibitor donepezil and the glutamate antagonist memantine) to retard memory loss in Alzheimer disease. Memory enhancement could result in more effective cognitive capacities such as problem-solving and decision-making.

Yet there are other critical features of memory, consisting in more than mechanisms of encoding, storage, and retrieval. It is unclear what effects drugs designed to enhance these mechanisms might have on these other features of our ability to recall the past. It is possible that the drugs might do more to impair than improve the usefulness and value of memory.

A recent study by Demis Hassabis, published in the Proceedings of the National Academy of Sciences, sheds some light on the problem exemplified by Borges’ fictional character and Luria’s patient. The Hassabis study compared people with bilateral hippocampal amnesia with people whose episodic memory was intact. Whatever episodic memory the amnesiacs retained consisted in recalling trivial details of past events. They were unable to express the general meaning of these events and unable to imagine new experiences. This supports the hypothesis that remembering the past and imagining the future are interrelated mental capacities. Unlike the amnesiacs, Funes and Shereshevkii had a preternatural capacity for recall. Yet the fact that none of these individuals was able to capture the gist of the past suggests that what matters is not just how much one can recall, but how one recalls it. The ability to meaningfully recall the past and anticipate the future appears to depend as much on qualitative than on quantitative aspects of our episodic memory. Hassabis’s study suggests that increasing the quantity of memory might interfere with the qualitative capacity to make sense of past experience and simulate future experience. Among other things, this dual constructive capacity enables us to have an integrated and unified set of psychological properties necessary for our experience of ourselves as subjects that persist through time. While this requires a certain amount of memory storage and retrieval, it is more than a function of how many memories of specific details our brains can store, or how efficiently our brains can retrieve them for immediate cognitive tasks.

As Daniel Schacter and Donna Rose Addis point out in a recent essay in Nature, “Many researchers believe that remembering the gist of what happened is an economical way of storing the most important aspects of our experiences without cluttering memory with trivial details.” This is precisely what Funes, Shereshevkii, and Hassabis’s amnesiacs were unable to do. Schacter and Rose Addis also note that “information about the past is useful only to the extent that it allows us to anticipate what may happen in the future.” The extent to which we can learn new things depends on the meaning we can construct from our past. Memory is not just a reproduction of past events. The brain and mind do not function as a video recorder, or as a bank from which we withdraw particular memories of facts and events stored in specific sites. In addition to the hippocampus in the temporal lobe, regions in the frontal and parietal lobes play an important role in the dual capacity to give meaning to past experience and simulate future experience. The parietal lobe regulates our orientation to space and time. Together with the hippocampus, it provides a holistic representation of the environmental setting necessary for us to have and exercise the relevant dual capacity.

Even if drugs targeting CREB or similar factors could strengthen memory consolidation, increase memory storage, and expedite memory retrieval, it is unclear how these drugs could improve the spatial, temporal, and phenomenological framework in which past and future events are meaningful to and can be imagined by us. It is also unclear how they could influence the way the brain regions mediating memory respond to the external environment. If these drugs only affected quantitative and not also qualitative, constructive, aspects of memory, they could clutter the mind with trivial details and could impair at least some of our cognitive and other mental capacities.

The limits we have in our capacity to remember only so many fact and events may be necessary for an optimal balance between the storage and retrieval of memory. This balance in turn may be necessary for the neural framework that enables us to construct a holistic interpretation of our episodic memories and project ourselves into the future. One can question whether artificial manipulation of naturally designed memory systems that have served us so well stand much chance of improving and not impairing these systems. Although it is speculative, these agents might disrupt the balance between quantitative and qualitative aspects of different memory systems.

As memory researcher James McGaugh noted in testimony delivered to the President’s Council on Bioethics, we should be wary of inferring that if a certain amount of memory is good, then more memory is better. Our capacity to form and store more memories might leave us too focused on the past, which might alter our phenomenological experience of persisting from the past to the future. Our identities as persons and some of our cognitive capacities could be diminished by our ability to recall more facts and events that had no little or no meaning or purpose for us. Before we pharmacologically tinker with memory systems, we need to consider the different brain regions and the cognitive and imaginative mental capacities that mediate the content and meaning of memory. This is necessary to adequately assess the potential benefits and potential risks of memory-enhancing drugs. We should look to Funes, Shereshevkii, and the individuals with bilateral hippocampal amnesia as examples of the consequences we would want to avoid.

1. For some background see G. Lynch, “Memory Enhancement: The Search for Mechanism-Based Drugs,” Nature Neuroscience 5 (2002): 1035-1038, and T. Tully et al., “Targeting the CREB Pathway for Memory Enhancers,” Nature Reviews Drug Discovery 2 (2003): 267-277.

Comment on this essay.

Comments are sent to the forum moderator. Select responses may be posted.

A Phony 'War on Science'
Michael Gerson, Washington Post
“In their talk of a Republican war on science, liberals may be blinding themselves to a very different kind of modern war in which their own ideals are deeply implicated: a war on equality.”

It’s Not Immoral to Want to be Immortal
Arthur Caplan, MSNBC
“Despite a lot of hand-wringing and finger-pointing, it is not obvious that wanting to live a lot longer is evil or immoral.”

Science Is Leading Us to More Answers, but It's Also Misleading Us
David A. Shaywitz, Washington Post
“Consumers of scientific information must balance the hope we place in global biology with the skepticism this field has surely earned.”

Taking the Scary out of Breast Cancer Stats
Carol Tavris and Avrum Bluming, LA Times
“The media understand how deeply women fear breast cancer, and the result is that every study that seems to find a link between some new risk factor and the disease makes headlines everywhere.”

Dollars to Doughnuts Diagnosis
Albert Fuchs, LA Times
“Insurance doesn't make routine care affordable; it makes it more expensive by adding a middleman.”

Tainted Medicine
Jerome P. Kassirer, LA Times
“Disclosure of financial ties may give a scientist or researcher a clean conscience, but that doesn't erase the possibility of a conflict.”

Children's health can't be left to faith alone
Arthur Caplan, MSNBC
“Parents do not have the right to watch a child wither away while they pray.”

Transplant List Numbers Raise Doubts
Arthur Caplan, MSNBC
“The American people have a right to expect absolute honesty about the number of people waiting for a transplant at any time.”

An Epidemic No One Wants to Talk About
Robert E. Fullilove et al., Washington Post
“Simply put, we will never rid the United States of HIV and other STDs if our only weapon is medical treatment.”

Making Cells Like Computers
Erik Parens, Boston Globe
“Conceivably, we are on the verge of installing synthetic genomes in bacterial cells to create products we want. But we are still a long, long way from doing what most people mean by ‘synthesizing life.’”

Miracle Workers?
David Rieff, New York Times Magazine
“Even today, the oldest of all relations between patient and physician — that of supplicant to shaman — continues to exert its authority.”

Overselling Overmedication
Judith Warner, NYTimes.com
“Most of the critics decrying the over-medicalization of the American mind rest their arguments upon the bedrock assumption that people who have nothing wrong with them are being medicated for largely fictitious concerns.”

Ads Spur Urge for Drugs
David Lazarus, LA Times
“DTC advertising has turned prescription drugs into just another gotta-have-it consumer product.”

Food Politics, Half-Baked
James E. McWilliams, New York Times
“Lost in this rhetorical battle was a quiet middle ground where the benefits and drawbacks of genetically engineered crops were responsibly considered.”

Perpetrating the Autism Myth
Benjamin Kruskal and Carole Allen, Boston Globe
“The scientific evidence is clear: neither the MMR vaccine nor thimerosal (mercury) in vaccines has any relationship to autism.”

Closing the Barn Door After the Cows Have Gotten Out
Verlyn Klinkenborg, New York Times
“The real beneficiaries are the nation’s large meatpacking companies — the kind that would like it best if chickens grew in the shape of nuggets.”

Human Embryos Cloned: What Does It Mean?
Art Caplan, MSNBC
“Let's not be frightened by scare tactics into not funding research that may be the key to curing what is currently incurable.”

Don’t Ask, Don’t Tell Is Bad Policy for Cloned Food
Art Caplan, MSNBC
“All of this fear-mongering about clones has made Americans forget that cloning is nothing more than artificially creating twins.”