Volume 25 · Number 2 · Winter 2008
(Photo illustration: Jay Leek and Karin Higgins)
from the experts
• To remember important new information, link it to things you already know.
• Use memory tricks, such as bizarre images, to link a name to a person you recently met.
Where Are My Keys?
If we can understand how memory works we just might be able to fight its decline as we age — and find those keys — while also staving off Alzheimer’s, dementia and other serious disorders. At UC Davis more than 20 research teams are adding to our understanding of the mind and memory.
As brain functions go, memory is a mighty tool — or rather, it’s a whole kit full of marvelous gadgetry essential to human life.
Memory is a grand Erector Set, a souped-up scaffold of gray and white matter, electrical impulse and experience from which we build knowledge. Memory is a mental shortcut that saves us from having to endlessly relearn skills and information and allows us to move forward. It’s a been-there, done-that repository for our ABCs, how to tie our shoes, important phone numbers, the PIN for our debit cards.
Memory is a map, an internal GPS device that guides us on our daily paths, getting us from home to work or school or even around the house with little conscious thought. It’s a security camera, an alarm system — Something’s changed here. Obstacle or stranger ahead. That’s odd: I’m sure I shut the front door. Why is it open?
Memory is a living file drawer, a scrapbook, a shoebox of mental images and sticky notes — Yes, I know that face and I’ve been here before — that also cross-indexes people, objects, places and events with our emotions and all our senses. A scent or a snippet of song can transport us to another time and place and evoke waves of joy, anger or sorrow. Memory is a time machine. It’s the glue of our lives.
But memory, like any tool, can also fail us, leaving us chatting awkwardly with an acquaintance in the grocery store aisle while racking our brains — Oh, what is her name? — or standing perplexed in the garage, ruing our advancing age — What was I looking for? — or frantically searching the house, late for an appointment — Where are my CAR KEYS?
UC Davis scientists, while they can’t tell you where you put your keys, are making strides at better understanding the mechanisms of how memory works — where it lives in your brain, how it develops from childhood to old age and the many factors that can impair its performance.
These researchers bring an uncommon range of expertise to a discipline growing so fast that an American Psychological Association database counted 4,831 peer-reviewed journal articles on the topic in 2006, nearly double the number from a decade earlier.
UC Davis experts include neuroscientists who are pinpointing specific brain regions and pathways used for storing and retrieving memories, physicians who see firsthand the devastation of Alzheimer’s disease and other forms of dementia, psychiatrists trying to improve memory in people with schizophrenia and other mental disorders, and psychologists who study how children remember and forget and their reliability as eyewitnesses in court cases.
Memory research has grown dramatically at UC Davis in recent years, with more than 20 research teams looking at different aspects of memory.
Endel Tulving, a pioneering Canadian memory researcher, said that when he was a visiting scientist at the UC Davis Center for Neuroscience in 1993–96, he knew of just one UC Davis faculty member in the field, psychology professor Neal Kroll.
Tulving, who now chairs the Rotman Research Institute of Baycrest in Toronto, credited Kroll, who retired recently after 40 years in the psychology department, with helping to recruit the “young hotshots of the memory world” to the faculty.
“Now UC Davis is indeed firmly on the memory map of the world,” Tulving said.
A complex process
To understand how memory works, it helps to know something about the brain, particularly the largest part — the wrinkly, folded-up cerebral cortex with its left and right hemispheres, each with four lobes.
Sensory data — much of the stuff memories are made of — get processed by three of those lobes on each side of the brain. The occipital lobes at the back of the head handle vision. The temporal lobes on the side are involved in the senses of smell and hearing. And the parietal lobes, above the other two lobes, receive pain and touch signals and integrate those with the other sensory information.
The frontal lobes are often described as command central, involved in attention, judgment, planning, impulse control, personality and conscious thought. The frontal lobes also play a role in encoding and retrieving memories — and this is the function that is the focus of research by UC Davis investigators.
Memory as a process of encoding, storing and retrieving information involves many parts of the brain — with different areas called into action depending on the kind of information and how long we need to keep it in mind.
“Memory is not a unitary thing,” said Beth Ober, a professor of human development who studies memory and the aging brain.
Scientists often divide memory into short-term (or working) memory and long-term memory.
Short-term memory is what we use when we look up a telephone number and hold it in mind just long enough to make the call, and involves the prefrontal cortex within the frontal lobes. “This is like the RAM in the CPU part of the brain,” said Charles DeCarli, a neurology professor and director of the Alzheimer’s Disease Center.
When we want to remember an important person’s name, an event in our lives or directions to the grocery store, the information moves into long-term memory with the help of the hippocampus within the temporal lobe.
Long-term memory can itself be subdivided into declarative memory — including semantic or factual memory and episodic memory about past events and places — and procedural memory — how-to knowledge like the skills involved in riding a bike or playing the piano.
Aging seems to take its toll on the front part of the brain, DeCarli said. “Information, details, remembering the Gettysburg address and those kinds of things don’t decline. Factual information tends to increase with age, as does vocabulary. Information about our world increases with age. However, our ability to recollect information about immediate episodes in our life — what did I do yesterday? — declines somewhat with age. We think our capacity to process information decreases and less information goes to the hippocampus. That’s called the frontal aging hypothesis.”
Memory and children
How accurate are children’s memories and would you believe them in a court of law?
When Gail Goodman, distinguished professor of psychology, began asking those kinds of questions in the 1980s, she found few scientific studies on the reliability of child eyewitnesses. Her subsequent research findings on children’s truthfulness would put her in the center of debate over a number of sensational child-abuse cases and eventually would be cited in U.S. Supreme Court decisions.
The next time you’re greeted by someone who looks familiar but, for the life of you, you can’t remember why — take heart: You’re following in the footsteps, or missteps, of generations of intellectual giants.
Philosophers since the days of Plato have made the distinction between those two kinds of memory — that quick sense of familiarity and its often much slower cousin, recollection, which seems to require more and more prompting as we age.
Whether familiarity and recollection involve different processes in the brain or are flip sides of one mental coin has been disputed by modern neuroscientists.
Recent research by psychology professor Andrew Yonelinas provides evidence that the two processes are distinct, involving different parts of the brain.
Memory, since the 1950s, has been associated with the hippocampus. Shaped like a seahorse, the hippocampus is, evolution-wise, one of the oldest regions of the brain and sits within the temporal lobes — one on each side.
The hippocampus is involved in forming new memories about events, recalling past events and recognizing people and things we’ve seen before. It also handles spatial navigation.
But a neighboring region of the brain, the entorhinal cortex, has been linked by Yonelinas to familiarity. In a study of about 150 healthy people, Yonelinas found that the larger their entorhinal cortex, the better their abilities in recognizing faces or things they had seen before.
That area of the brain is of particular interest because it is one of the first areas damaged by Alzheimer’s disease, which gradually clogs the brain with abnormal proteins called amyloid plaques and neurofibrillary tangles.
In normal aging, Yonelinas said, it is the hippocampus that begins to shrink, affecting recollection but not familiarity, even in adults in their 20s and 30s. “Aging effects start pretty early,” he said. “My undergraduate classes hate this when I tell them, ‘Enjoy the next couple years because it’s all downhill from there.’”
Yet Yonelinas holds out hope that advances in understanding memory and the brain will lead to new treatments for Alzheimer’s and other memory disorders, as well as ways for healthy people to preserve their memories into old age.
“There’s been this explosion of cognitive science and memory, working on the links between the brain and behavior,” he said. “It seems like we are getting tantalizingly close to really having some broad practical applications.”
Is it senility?
A few “senior moments” of forgetfulness do not, in themselves, signal the early onset of dementia.
There is a big difference in memory loss in healthy and not-so-healthy aging, said Ober, who researches how people think and remember as they get older. “Forgetting a doctor’s appointment or mixing up who you said something to, that’s normal,” she said. “That’s not Alzheimer’s disease.”
When people forget entirely that they went to the doctor or had a conversation just a day earlier, Ober said, those are signs that something is wrong.
In Alzheimer’s patients, episodic memory gets progressively worse and moves backward in time — gradually erasing older and older events from their minds until, in the late stages, they can no longer remember their childhoods.
Working memory is also much more impaired by Alzheimer’s than in normal aging, making it harder not only to remember something someone just said but also to understand words that have different meanings in different contexts, Ober said.
But her research has shown that some kinds of memory persist longer than others in Alzheimer’s patients. “Maximizing the patients’ uses of these types of memory (while minimizing demands on episodic memory) in day-to-day activities can be very helpful in reducing stress and frustration on the part of care- givers as well as patients,” she said.
Alzheimer’s patients retain procedural memory — maintaining previously learned skills like knitting, playing a musical instrument or painting watercolors far longer than their ability to remember events, Ober said.
In early to moderate stages of Alzheimer’s, patients also can still categorize objects — putting, for example, fruits in one group and animals in another. They might remember what an avocado is — what it looks or tastes like — though forget the last time they had one.
“Semantic memory is much less affected in Alzheimer’s disease, at least early Alzheimer’s disease, than was previously believed,” she said.
That is because the shrinking hippocampus is not involved in semantic memory, Ober said. “Critical areas for semantic memory seem to include the anterior temporal lobe and portions of the frontal lobe, which are not significantly affected in mild-to-moderate Alzheimer’s disease or in normal aging.”
But even sharp-minded elderly people know that it can still take longer to recall a name or word that’s on the tip of their tongue. “That’s one of the things in normal aging that’s really frustrating to people — everything is slower,” Ober said. “You might need a few more reminders. It’s not like the information is gone. It’s still there. It just takes longer to retrieve it.”
Volunteers with varying degrees of forgetfulness come to Charan Ranganath’s lab at the Center for Neuroscience and try to memorize things — images flashing on a computer screen of people, landscapes and objects.
Some of these volunteers suffer from amnesia, Alzheimer’s disease, schizophrenia or other ailments or injuries that impair memory, but others are healthy adults — from undergraduate students to elderly people.
Each in turn puts on a stretchy red cap, with up to 64 wires running from head to machinery, and watches a mixture of old and new images, identifying which ones they recall seeing a few minutes before. That sofa, yes. This house, no. The two faces on the left are new, but the third on the right looks familiar.
The electrodes in the cap measure electrical activity in the brain. An infrared tracker at the same time follows the movements of their eyes, which can indicate recognition before the volunteer can click a button or say a word.
Some volunteers later visit the UC Davis Medical Center in Sacramento where imaging devices take pictures of their brains, tracking how blood flows to different regions as they learn and remember.
Ranganath, associate professor of psychology and member of the Center for Neuroscience, is an expert on the prefrontal cortex, which helps us keep information in line, set goals and pay attention — all critical precursors to remembering information. “It’s one of the most mysterious parts of the brain to figure out,” he said.
Working with Yonelinas’ team, the researchers use the data to develop mathematical models that predict from a person’s brain activity if he or she is remembering a face or an object. Such models, with accuracy of about 85 percent, help scientists to confirm links between brain function and memory — and to identify gaps in their understanding.
Ranganath said he hopes that such work, in the short term, will lead to better diagnostic tools. “Tests of memory that are used in the clinic by neuropsychologists and neurologists are very basic,” he said. “Our research tries to narrow down different memory processes so that we can develop more sensitive and specific tests. If we can do that, then we’ll be in a much better position to figure out whether a treatment for a memory problem is promising.”
Those advances would be just a beginning, he said. Neuroscientists envision a time when prosthetic implants could take over memory functions for patients with hippocampus or other brain damage.
“People 20 years from now will look back on what’s going on right now, and it will seem like kindergarten.”
The heart of healthy memory
If you’re concerned about preserving your memory, take good care of your heart.
It turns out that all that advice for protecting your cardiovascular system is also good preventive medicine for your memory and your brain.
“Too many people are walking around with diabetes, hypertension and high cholesterol, which could be treated,” DeCarli said. “Our research here at the Alzheimer’s Disease Center strongly suggests vascular disease damages the brain in a way that makes us more susceptible to the effects of Alzheimer’s disease. We believe that if you could treat these people more aggressively then, in fact, we are likely to reduce the incidence of Alzheimer’s disease.”
In healthy aging, as the hippocampus begins to shrink, some kinds of memory — like recalling names or what you did yesterday — do tend to get worse, but memory for vocabulary and factual information stays stable or can even improve with the years.
But Alzheimer’s disease, strokes, heart attacks, head trauma and other brain damage can wreak havoc with memory in a variety of ways, often irreversibly and, in the case of Alzheimer’s, progressively so.
“There’s a difference between aging well and aging badly,” Ranganath said.
In a recent study of healthy elderly people, DeCarli, Ranganath and Yonelinas found that, while some had small hippocampuses, others showed evidence of tiny strokes. The strokes had gone previously unnoticed, but MRI images revealed bright white patches where the white matter, or the channels of communication in the brain, had been damaged.
In a battery of memory tests, both groups had trouble remembering things learned several minutes before. But the people with mini-stroke damage also had trouble concentrating. Scans showed they were less able to activate their prefrontal cortex — and the greater the stroke damage, the worse the effect was.
Aging is the biggest risk factor for both stroke and Alzheimer’s, said DeCarli. A 65-year-old person has a one in four chance of developing one of the two illnesses by the time he or she turns 85. And the 85 and older population is the fastest growing age group in the country.
The memories of many seniors are at risk. About half of people 65 years and older have hypertension, DeCarli said. Added on top of that are escalating rates of obesity and diabetes, which put people at higher risk for hypertension, heart disease and stroke.
DeCarli said a rise in dementia and other memory disorders may be, in part, because people live longer. “We are actually suffering the effects of our goodness. What used to happen was people smoked and didn’t control their blood pressure, and they died at age 50 of vascular disease. We’ve made it halfway. What we need to do now is take the next step into truly healthy living.”
Research at UC Davis could help more people take those steps toward better health and memory.
With a global epidemic in type 2 diabetes, DeCarli, Ranganath, Yonelinas and John Olichney, an associate professor of neurology, are launching a large-scale study of how diabetes affects memory. In a separate study, assistant psychology professor Simona Ghetti is working with UC Davis Medical Center colleagues to examine what low blood sugar does to the memories and developing brains of children with type 1 diabetes.
At the same time, Ranganath and psychiatry associate professor Daniel Ragland are using brain-imaging research to understand why and how schizophrenia disrupts memory. “Schizophrenia has a devastating effect on memory and, in fact, patients’ degree of memory problems can reliably predict whether the patient will ever be able to return to work or live independently,” Ranganath said.
Other UC Davis studies involve people who developed amnesia after suffering heart attacks that cut off oxygen to their brains.
Such studies, researchers say, bring together an unusual combination of medical and scientific experts using sophisticated imaging methods and pen-and-paper tests to study memory in both healthy and memory-impaired volunteers.
“We are, therefore, in the unique position to be able to put together all of this information in order to understand memory in a number of different ways,” Ranganath said.
“UC Davis is probably one of the leading institutions in the world in terms of cognitive neuroscience and memory,” DeCarli said. “There is just an incredible amount of exciting work going on, on a whole bunch of different levels.”
Kathleen Holder is associate editor of UC Davis Magazine.