Chapter I
1. Dr. Fred Gage of The Salk Institute and researchers at Sahlgrenska University Hospital in Sweden discovered new cell growth in the hippocampus, an area of the brain closely tied to learning and memory, in five patients ages fifty-five to seventy. See the November 1998 issue of Nature Medicine for a full report. Using similar techniques, Elizabeth Gould of Princeton University and Bruce S. McEwen at Rockefeller University reported that new cells are constantly being generated in the hippocampus of adult monkeys. (See Proceedings of the National Academy of Science, Vol. 95.)
2. Over the past ten years, the issue of whether brain cells die with normal aging has been reexamined by a number of scientists, using much more accurate methods than previously available. The conclusions are clear. Studies such as those by Stephen Buell, Dorothy Flood, and Paul Coleman at the University of Rochester have found that in normal people, even very late in life, the actual number of nerve cells really doesn’t change much. So it’s likely that most of the nerve cells you had when you were twenty are still very much alive when you’re seventy. Even the magnitude of mental decline in normal aging has been overstated: At least 90 percent of the population will age without having to deal with the severe impairments brought about by diseases or strokes.
3. In an influential study published in Science (Vol. 206) and expanded in Brain Research (Vol. 214), Stephen Buell and Paul Coleman found that neurons in the aging human hippocampus (a brain structure critical in learning and memory) actually grew longer dendrites. Interestingly, in the brains of individuals afflicted with Alzheimer’s Disease, this growth did not occur. It appears, therefore, that many neurons retain the capacity to grow even late in life.
4. A long series of investigations by Dr. Michael Merzenich at the University of California, San Francisco, has shown the adaptability of connections in the adult brain. For example, in the brains of adult monkeys trained to use certain fingers to get food, the areas of the brain responsible for processing the sense of touch from those fingers gradually took over much larger regions. This means that the brain was able to “rewire” to accomplish something important like getting food, and devoted more “brain horsepower” to the skills required, in this case the sense of touch in certain fingers. Recent findings by Dr. Jon Kaas at Vanderbilt University and Dr. Charles Gilbert at Rockefeller University have shown directly that neurons in the adult brain can actually grow new “wires” to connect to one another.
5. The beneficial effects of neurotrophins have been documented in hundreds of experiments at leading universities throughout the world. In our own experiments at Duke University Medical Center, we (Lawrence C. Katz, A. Kimberley McAllister, and Donald C. Lo) found that adding extra neurotrophins to a neuron almost doubled the size and complexity of the dendrites that branch off the neuron. And since the computing power of a brain cell is determined by the complexity of its pattern of dendritic branches, this doubling of growth suggests that neurotrophins can literally add more mental horsepower. We were also quite surprised to find that simply adding neurotrophins was not enough. The nerve cells had to be sending or receiving impulses in order to respond to them. The message was clear—adding neurotrophins to active neurons made dendrites grow. Conversely, we found that removing neurotrophins made dendrites atrophy (which suggests one reason that brain inactivity leads to mental decline).
6. The first neurotrophin was discovered almost fifty years ago, when two scientists, Rita Levi-Montalcini and Victor Hamburger, working at Washington University in St. Louis, discovered a substance that not only kept certain types of nerve cells alive but also caused them to sprout many new branches. Levi-Montalcini and another scientist, Stanley Cohen, purified this substance, which they named Nerve Growth Factor, or NGF. It turned out that NGF occurred naturally throughout the body but was scarce in the cerebral cortex. NGF was the first member of what became a family of neurotrophins (from the Greek word trophe, which, loosely translated, means “to nourish”).
In the early 1980s Yves Barde at the Max Planck Institute in Munich, Germany, finally succeeded in purifying a molecule from the brain that behaved just like NGF. Called Brain-Derived Neurotrophic Factor, or BDNF, it was found almost everywhere in the brain, including the cerebral cortex. Neurotrophins have powerful effects on the machinery of the brain. Research by Bai Lu at the National Institutes of Health, Erin Schumann at Caltech, and Tobias Bonhoeffer at the Max Planck Institute in Munich has shown that neurotrophins help increase the strength of connections in the hippocampus, a part of the brain that is critical for learning and memory. Experiments by O. Lindvall and P. Ernfors of University Hospital in Sweden, using animals, suggest that the neurotrophins may protect neurons from damage when parts of the brain undergo a stroke or are damaged by other trauma.
7. Hans Thoenen of the Max Planck Institute in Munich and Christine Gall of the University of California, Irvine, revealed the direct correlation between the production of growth factors and nerve cell activity. Experiments by Anirvan Ghosh and Michael Greenberg at Harvard and Ben Barres at Stanford further showed that this activity-dependent neurotrophin production formed more neural branches and connections, acting, in effect, like a self-fertilizing garden.
8. One example of this kind of stimulation is the patterns of brain activity required to produce a phenomenon called long-term potentiation, or LTP. LTP is a long-lasting change in the strength of synapses between neurons and it has been clearly linked to learning and memory. The same kinds of stimulation that produce LTP also cause increases in the levels of neurotrophins like BDNF.
1. About fifty years ago, a scientist named Karl Lashley trained rats to run a maze for a food reward, and then removed ever larger parts of their cortex to determine when they could no longer “remember” the maze. To his surprise, he found that he could remove about 90 percent of the cortex, and the animals could still find their way! By concluding (wrongly) that only 10 percent of the brain was required for memory to function he missed the more important fact that there are many different forms (representations) of the same memory stored in many different places. When the rats were learning to run the maze, they formed associations among all their senses—they felt, heard, saw, smelled their way through the maze. They had built a net of associations. When one set of associations was destroyed—like those based on vision, for example—they could still rely on their auditory or tactile memories to find their way to the food.
2. And TV viewing is passive. Your sensory systems are involved in only a very limited way, and you are watching someone else perform interesting or exciting activities. But in the brain, watching another person doing something is no substitute for doing it yourself. Indeed, there is direct evidence from animal experiments done by Marion Diamond at University of California, Berkeley, that rats who simply watched other rats playing in an enriched environment derived no brain benefits, while the animals who were actually playing grew larger nerve cells.
3. Michael I. Posner, Marcus E. Raichle, and Steve E. Peterson at Washington University in St. Louis used functional brain imaging to follow the amount of brain activity in different areas when subjects were asked to come up with a verb to go with a list of new nouns. When first presented with a novel list, large areas of the cortex lit up, showing increased levels of brain activity in several distinct areas of the cortex. After fifteen minutes of practice, when the task had become routine and automatic, activity in those same areas returned to baseline levels. If the subjects were then given a new list, robust activity returned. These researchers also concluded that the brain uses different areas to generate novel responses and automatic (rote) tasks.
4. For a more detailed discussion see: Dr. John Allman, “Tracing the Brain’s Pathways for Linking Emotion and Reason,” New York Times, December 6, 1994.
5. Research by Anthony Damasio and Ralph Adolphs at the University of Iowa has shown how dramatically emotions can enhance memories. The researchers showed a group of people a series of photographs with a simple story about a father taking his daughter to the zoo. Weeks later, when the same people were asked to recount the story, they could recall it only in the vaguest terms. They couldn’t remember if it was a son or a daughter…whether she was a blonde or brunette—or even precisely where they were headed. When the scientists changed the emotional quality of the story and pictures to one in which a father takes his daughter to the zoo and she is hit by a car while crossing the road, the memory of the narrative was vastly improved.
6. Long-term studies by groups such as the MacArthur Foundation and the International Longevity Center at Mount Sinai Hospital in New York City reveal that individuals who are most successful at coping with aging and have maintained the best-preserved mental capacities are those who have active social and intellectual networks. Similarly, a three-year study conducted at the University of Southern California showed that people in their seventies who stayed physically and socially active retained their mental faculties much better than individuals who didn’t. See Successful Aging by Drs. John W. Rowe and Robert L. Kahn for summaries of these and other similar positive findings.