1st memory-retrieval aid re amnesiacs & Alzheimer's patients

Picturing the Past: How Science is Mapping Memory (Part 3)
Posted by Amy Ellis Nutt, Star-Ledger Staff December 11, 2007 5:33PM
Categories: Health/ Science

CAMBRIDGE, England - He had looked through the photographs on the computer one by one and still remembered little. Not the walk through the winding streets of this medieval university town, or the restaurants where they'd eaten, or the wooden boats floating down the river Cam.

It had all taken place just a couple of weeks earlier, but the Alzheimer's patient had barely a shadow of a memory.

Gradually, though, some of the images stirred a feeling of remembrance, a few fragments here and there. And then one of the images stirred something else. It was a photograph taken inside King's College Chapel, showing its soaring, 80-foot-high ceiling, with the densely latticed fan vaults bathed in the warm butterscotch light of a winter afternoon.

The Alzheimer's patient remembered something, and what he remembered was a thought, as ephemeral as the sunshine momentarily caught in the ceiling's stony web.

"This should be one of the Seven Wonders of the World," he said to the doctor by his side.

A 500-year-old chapel, a photograph, a fleeting thought -- somewhere deep in the dying folds of the man's brain, bits of memory spilled out like presents from an attic closet: the walk, the restaurant, lunch with his doctor. The memory was still there.

Psychologist Emma Berry tells the story of her patient with a kind of wide-eyed wonder that belies her scientific demeanor. She is part of a small collaborative group of doctors and Microsoft engineers who live and work in Cambridge, some 60 miles north of London. Berry, a clinician at Addenbrooke's Hospital, is spearheading an unusual medical trial involving a handful of men and women with Alzheimer's disease or amnesia. The patients are testing one of the first tools ever designed to reinvigorate autobiographical memory, which is the recall of the facts and events of one's life.

The tool is a wallet-size device called a SenseCam, a digital camera worn around the neck, capable of taking thousands of photographs automatically. When the patient views them later, the images seem to stimulate the brain's sense of location, sparking an association that makes it easier for the person to hold on to personal, or autobiographical, memories.

When the patients did not wear the SenseCam, their recollections faded away within days. Unable to remember even recent events, their lives felt diminished.

"Without a past we aren't very interesting. All we can talk about is the weather," said Berry. "With the SenseCam, patients say sharing experiences again is sheer pleasure."

Unlike smell, sight, touch, taste and hearing, there is no sensory organ for location. That function is carried out by the brain, which provides a kind of virtual map of the world that allows a person to say "I am here" or "I was there." How the brain does this, however, has been a source of speculation for centuries.

Two years ago, Norwegian scientists identified this "map" in the entorhinal cortex, the gateway to the hippocampus, the brain's memory-making center. In humans, the inch-long entorhinal cortex is the primary processing center for the various sensations and elements of experience.

Like a factory-assembled car, these associated bits -- the smells, sights, sounds, even thoughts -- of an event are taken up by the nearby hippocampus and eventually consolidated into a memory.

"The sense of space and location are absolutely critical to understanding memory," said James Knierem, a professor of neurobiology and anatomy at the University of Texas Medical School at Houston. "Things occur in time and space and it's our spatial sense that allows us to reconstruct events. That's what memory is -- not a recording, but a reconstruction of what occurred."

And that reconstruction is powerfully stimulated by place.

"Memory is not abstract," said James McGaugh, director of the Center for the Neurobiology of Learning and Memory at the University of California-Irvine. "The cue conditions under which you learn information are on the average the best ones for recalling.

"If a college student takes a final exam in the same room where they learned the information, they get a higher score.

"And in another crazy experiment," he said, "students learning something under water remembered it better under water. . . . The cues around which we learn are very powerful in evoking recovery of memory. . . . If you learn something in the forest and go to the desert to retrieve it, it will not be as good."

In essence, the images stored on the SenseCam do the same thing. They take a person back to the place where the memory was first formed. The device is outfitted with a wide-angle lens and an infrared (body heat) detector, as well as light, color, sound, temperature and motion sensors. The presence of another person, a sudden noise, or any other environmental change triggers the camera to begin taking pictures.

In the absence of a sensory trigger, an internal timing device trips the camera shutter once every 30 seconds. Because it runs on a rechargeable battery, the SenseCam can be kept on for days at a time, and its pictures are easily downloaded onto a computer. Special software allows a person to review the images at varying speeds.

The device was invented several years ago by a former Microsoft engineer, Lyndsay Williams (who also developed the sensor technology used in such breakthrough products as Apple's iPhone).

Initially, the SenseCam was developed as a possible tool to augment memory.

"She kept losing her keys," Ken Wood, deputy managing director of Microsoft's Cambridge research lab, said of Williams, "and she wanted a mechanism to find her keys, or to remember the brand of wine she had at dinner three weeks ago. In practice, that's not a particularly good application of SenseCam."

A neuropsychologist at Addenbrooke's, Narinder Kapur, saw a TV interview with Williams, who is now developing imaging devices to reduce global warming. He told his colleague, Berry, he thought the SenseCam might be useful for their patients in the Memory Aids clinic. Berry became the go-between, working part time at Addenbrooke's and part time at the Microsoft Cambridge research facility, the oldest of Microsoft's four international labs.

"Most memory aids are prospective: Post-it notes, alarms, pagers," Berry said. They remind people that something is about to happen. By contrast, the SenseCam is retrospective.

"SenseCam is about helping people remember their past," said Berry. "This is the first tool that's ever been successful for helping with autobiographical memories."

MEMORY CUES

Martin Conway, one of the world's leading memory experts, has been working closely with the SenseCam project. A cognitive psychologist at England's University of Leeds, Conway believes the SenseCam succeeds because it stimulates the brain's memory-retrieval system. While autobiographical memories are processed in the entorhinal cortex and consolidated in the hippocampus, they are stored in various locations throughout the brain.

"Memory is all about the power of cues," said Conway. "As long as you can find a cue to activate some of the knowledge, you can start to remember. But you can't predict what you're going to remember, and that's one of the fantastic features of SenseCam. It has the same psychological property our brains have. With SenseCam you have no control over what gets photographed, just as you typically have no control over what you're going to remember."

But if you can stimulate a key association in the sensory chain that makes up a memory, then the greater your chance for retrieval, according to Conway. For SenseCam users, that key association appears to be the sense of location. Like plump raindrops that suddenly release a summer's worth of smells from the sunbaked earth, a series of photographic images triggers a cascade of associations, unlocking the memory.

The where of an experience reveals the what.

"The SenseCam could be fantastic -- a terrific tool," said Howard Eichenbaum, director of the Center for Memory and Brain at Boston University. "Most folks haven't thought about memories as being contextual in terms of space, but the SenseCam could be helping by stimulating whatever remaining cells are in the entorhinal cortex."

For a little more than a year, psychologists at Addenbrooke's have been testing the device on a handful of people with memory disorders, such as mild Alzheimer's disease and anterograde amnesia (the inability to remember new and recent experiences). For these few patients, the SenseCam acts as a kind of electronic diary, a backup system for their broken brains.

One of the first to test the device was a 63-year-old woman from England's Isle of Wight. After suffering severe encephalitis in 2002 that damaged central areas of her hippocampus, she was unable to remember for more than a day or two the details of new experiences or the names and faces of people she met. Slight in stature, the dark-haired woman (her husband asked that their names not be used) wears the SenseCam whenever she takes a trip or goes on a special outing.

As part of the 11-month trial, she viewed images from the SenseCam the day after an event or trip, and then again every other day for two weeks. Before she viewed the images, her husband would ask her what she remembered of the event, and he would record the recollected details in a notebook.

The couple repeated this procedure, but without the use of the SenseCam, so that the researchers had a baseline condition against which they could measure their results.

Without the SenseCam, the woman remembered, on average, 2 percent of an event one week later. With the SenseCam, but without viewing the images for one month, she remembered 80 percent of the event. Without viewing the images for three months, she still remembered more than 75 percent of the event, even when the experience had taken place nearly a year earlier.

"It was truly astonishing," said Berry. "When she first used it, her husband called us and said, `She has a memory, she has a memory!' He felt he had his wife back."

MAKING SENSE

Karen Downes calls it a "brilliant invention." The 57-year-old woman, who lives with her husband, Jim, in Wisbech, about 40 miles north of Cambridge, has early-onset Alzheimer's. Last year Jim, who is 60, noticed he had to repeat simple questions to his wife; Karen noticed she was losing things and forgetting where she had been.

"I would meet people, and the next day I wouldn't know them," she said.

After tests revealed the beginnings of Alzheimer's, Georgina Browne, another clinical psychologist at Addenbrooke's, offered Downes the opportunity to participate in the SenseCam trial.

"When I first put it on, I thought, oh boy, I don't know if I can walk around with this. People will stare. Now, if people do stare, I tell them what it is. I don't want to give it back."

Wisbech is located in the middle of the Fens, the low-lying former marshland of eastern England where fruits and vegetables are still grown in the rich alluvial soil. The Downeses live on a cul-de-sac that sits right up against a potato field in a neighborhood of small modest homes. On a brisk autumn afternoon, baskets of colorful pansies hung from the windows of the Downes house.

"I'm a happy person," Karen said. "I've got loads of favorite memories. My children have brought me nothing but pride. . . .

"It's not a bad thing to have Alzheimer's, I don't think that way at all. You know, it knocks you off at first, but you have to be positive."

Her husband, who took early retirement a few years ago from his job as a hospital technician, is acutely aware of how much easier it is to be optimistic about life with the SenseCam.

"It's helped Karen recall a lot of things she would not ever have remembered without it," he said. "If she hadn't had the SenseCam, I don't think she'd be as healthy as she is now, or remember as much as she does."

MURRAY'S CONTRIBUTION

Sitting side by side in the den, the couple review SenseCam images on Jim's laptop. The photographs are from 10 months earlier, when a dog trainer visited the couple's home.

As Jim flips through the pictures on the computer, Karen does not recognize the woman.

"Who is she?" she asks. "I don't remember her coming here. . . . That was here?"

The images float by, one by one: Jim talking to the visitor, Karen showing the woman photographs. Then suddenly a new image: They are in the living room and the couple's German shepherd, Murray, has just jumped up on the visitor.

"Oh, I remember this!" shouts Karen, smiling and laughing. She names the woman and says: "The dog psychologist. She didn't know a thing about dogs, did she? And we had to pay 185 pounds an hour! She told us to take him for a walk, then give him some dog food. A lot that did!"

An image of a room and a dog, and the memory comes tumbling back into consciousness.

Three hundred SenseCams have been built by Microsoft's principal hardware engineer, Steve Hodges. With about 130 components, each device costs less than $1,000.

"We can put together 30 in a week," said Hodges, who also is head of the sensors and devices group. "A machine could do it in a minute, and a lot cheaper."

Microsoft does not usually participate in clinical trials, he said, nor does it engage in much hardware research, but "Microsoft sees the value in us working on things that might be of interest to them and might prove medically useful."

According to Wood, the company's deputy managing director, Microsoft is not close to having a product for market. At the same time, the SenseCam trial is being expanded. A recent $600,000 grant has allowed Berry and the others to set up collaborative studies in a half-dozen countries, including the United States.

For Hodges, whose expertise is in computer vision and robotics, the opportunity to work on a project with a direct medical application is exhilarating, but he is cautious and refuses to say how long it might be until the SenseCam is commercially available.

SMELL THE ROSES

More and more, experiments in the laboratory, the clinic and with people who have exceptional abilities are elucidating the primacy of place in memory.

Because experiences cannot happen outside of space, it is logical that a sense of location should play such a prominent role in remembering. But memories, like experience, can be chaotic and random, and which ones remain through the storms of aging and disease are as unpredictable as which houses are spared by a hurricane.

Even in healthy older adults, memory begins a slow decline after the age of 27, according to Nobel Prize-winning neuroscientist Eric Kandel, with 60 percent of 70-year-olds experiencing at least a moderate loss of memory. Half of that 60 percent eventually will develop Alzheimer's.

"People with Alzheimer's don't care about heart attacks, they don't care about their kidneys, they care about their memory," said Irvine's McGaugh. "Memory is what enables it all."

But if science is still years away from a cure for Alzheimer's, recent research has vindicated the resiliency of the brain's memory system. The success of Berry's SenseCam, the identification of at least two people with superior autobiographical memory, and the development of a transgenic "Alzheimer's mouse" in which memory loss was reversed, point even beyond resiliency. The brain's ability to find a way back to memories, despite a memory system damaged by disease or injury, suggests that more of our experiences remain with us than previously thought.

"My view is not every bit of information from every experience gets in," said Conway. "But what does get encoded, I think, probably stays there forever or until the physical substance is gone. . . . If you consider that most memories are stored in the connections between neurons, and most neurons in the neocortex have 10,000-plus connections with other neurons, that's rather a lot of storage space. So I think it's all there. It's not accessible -- a lot of it gets overridden; some of it is just fragments. But it's all there."

For scientists exploring the boundaries of memory, the stakes couldn't be any higher. Without the capacity to remember, they say, human beings are bereft of the past and incapable of envisioning the future. All that is left is an interminable gray present.

"God gave us memories," wrote the author J.M. Barrie in 1922, "that we might have roses in December."