The Science of the Brain: A Beckman Perspective

The HALT project at Illinois studies the effects of exercise on cognition.
The HALT project at Illinois studies the effects of exercise on cognition.

Whether it involves “mental fitness” or “brain training” or developing a healthy mind, the general topic of cognitive health is a trendy one these days. It’s an area where science and popular culture overlap, and Beckman Institute researchers have been thrust into the middle of this timely discussion.

Advances in technology, such as improved imaging techniques, are providing exciting new insights into brain function and physiology. The topics of how we can improve cognitive functions such as memory and learning, maintain cognitive processes as we age, or even reverse cognitive loss due to disease have become as widely discussed in the popular culture and media recently as they have been in the scientific community for the last decade or so.

Sometimes the news stories, headlines, and product ads don’t always carry the caveats and cautionary notes sounded by researchers. Beckman faculty members have been leading researchers in the areas of cognitive health and neuroscience for many years, and are often called upon by the national media for their expertise.

Some of the media spotlights have shone on so-called brain training programs, while others have taken an overall look at what the current scientific literature is telling us about our brains, cognition, and health. We asked several Beckman faculty members whose research is highly engaged in these areas for input on what the research tells us about what is known, what is suggested, and what is not yet proven regarding cognition and neuroscience. We looked at four (sometimes overlapping) topics: the growth of new brain cells (neurogenesis), the cognitive benefits of exercise, brain training, and transfer of skills (whether improvement from training on one task transfers to improvement on other tasks), and issues surrounding the loss of cognitive function due to aging and diseases like Alzheimer’s.

NEUROGENESIS

For many years, science told us that the growth of new brain cells was a finite process – once we reached our 30s, neurogenesis stopped. In the past decade or so, the evidence (much of it coming from Beckman researchers) has tilted toward a theory that new neurons can be formed in certain regions of the brain.

Along with the change in thinking about neurogenesis, Beckman neuroscientists have produced research on brain plasticity suggesting that brain morphology and, consequently, cognition can actually be shaped by activities like exercise or environmental factors such as culture. Research involving exercise or fitness has become paramount to both discussions.

“There are very few studies that examine fitness training effects on human brain structure and function. Most of them have been done by us,” said Beckman’s Art Kramer, a leading researcher with colleague Ed McAuley in the area. “They do suggest positive effects, both in terms of how well the brain functions and in brain structure – how much of it you have using measures of change in brain volume.”

Kramer, a Professor of Psychology and Director of the Biomedical Imaging Center at Beckman, said there is also a large and increasing literature on research done with animals that shows both learning and memory improvements and neurochemical changes in the brain with improved fitness.

“Both the animal and human research is pretty solid with respect to fitness effects on brain structure, brain function, neurochemistry, learning and memory, and cognition,” Kramer said.

Exercise has become an important tool for researchers studying its effects on neurogenesis and cognition. In March, Newsweek magazine reported on a paper published in the Proceedings of the National Academy of Sciences that it said took exercise-induced neurogenesis found in animals and “extended that principle to humans for the first time.”

Kramer said the study’s results are narrower than that description.

“What this study showed was that a measure of cerebral brain volume which has been related to neurogenesis in the dentate gyrus in mice as a function of improvements in aerobic fitness is also associated with fitness improvements in a small, middle-aged group of humans – that is the measure of cerebral blood volume, not neurogenesis,” Kramer said. “So, we still do not have a direct measure of exercise-induced neurogenesis in humans.”

William Greenough, Co-chair of Beckman’s Biological Intelligence research initiative, has been publishing peer-reviewed papers showing experience effects on brain plasticity since 1972 and was the first to show in a 1985 paper that more new glia (non-neuronal brain cells that provide protection and support for neurons) were formed in animals in enriched environments. He said the results reported in the PNAS paper confirmed what has been shown in animals for many years by a co-author of that paper (Fred Gage) and others.

Greenough said rather than thinking that exercise creates new neurons, exercise should be thought of as a mediating factor in neurogenesis.

“Exercise can tweak the rate at which some brain areas make neurons,” Greenough said. “What is still up in the air is whether, with the right exercise, you can turn on a region that’s not normally making neurons.”

Even though neurogenesis has been correlated with improved cognitive function, a causal relationship has not yet been shown. NeuroTech group member Justin Rhodes is creating multi-generational mice models for future research efforts that will, among other projects, test whether exercise can produce learning improvement without the production of new neurons.

“We know that there are areas of the brain that continuously generate new neurons throughout adulthood and one of those areas is the (hippocampal dentate gyrus),” Rhodes said. “It turns out that exercise produces a tremendous increase in the number of new neurons that are found in that area.”

Rhodes’ research will try to isolate the neuronal factor by blocking the formation of new neurons, and then exercising the mice to see whether they still show learning improvement.

“If you exercise the animals and they’re not able to produce neurons and they still show the improvement in learning, then that shows that new neurons are not necessary for new learning improvement,” Rhodes said. “But if it blocks the learning then you know that they are necessary. That’s a way that we can really test a causal mechanism.”

Research has shown where neurogenesis takes place in the brain: in the dentate gyrus of the hippocampus and in the olfactory bulb.

“Every (other area) is highly debatable. But those two areas, not debatable,” Kramer said. “And those new neurons are born as a function of exercise.”

EXERCISE AND COGNITION

The effects that exercise can have on cognition has blossomed into such an important area of study that Newsweek magazine featured “Exercise and the Brain” as the cover story for its March 26, 2007, issue. A series of “Health for Life” articles led off with a story on how exercise can boost brainpower. Kramer, Greenough, and Beckman colleague Charles Hillman were quoted, with Hillman’s study of grade schoolers adding another answer in the affirmative to the question of whether exercise benefits mental performance.

“People have been slow to grasp that exercise can really affect cognition, just as it affects muscles,” Hillman said.

Of all the research results on cognitive interventions, the effects of exercise on cognition have proven most compelling. That’s according to Kramer, who has been researching and reporting on this and related issues for many years, and is often called on by media such as Newsweek and CBS for his expertise.

Kramer has led several investigations that have strongly suggested beneficial cognitive effects from exercise. Kramer and colleague Stanley Colcombe did a meta-analysis of 18 intervention studies involving the cognitive effects of aerobic fitness on older adults that was published in in 2003. Kramer said that paper and other analyses of various types of studies, including epidemiological ones, point to the positive cognitive effects of aerobic exercise.

A report by Kramer, lead author Colcombe, and others in 2006 titled Aerobic Exercise Training Increases Brain Volume, found that “cardiovascular fitness is associated with increases in the volume of brain tissue in aging humans. Furthermore, the results suggest a biological basis for the role of aerobic fitness in maintaining and enhancing central nervous system health and cognitive functioning in older adults.”

Those benefits, Greenough said, are good only if exercise is maintained.

“Many of the effects of exercise that appear to be beneficial require that exercise be continued,” Greenough said, adding that animal research shows that while exercise plays a role in forming new neurons, the brain’s ability to keep them also has a lot to do with environment.

“It’s been shown that if the animals are where they can be in either an enriched environment or not, or where they can have access to exercise or not, exercise seems to control more of the production of neurons,” he said. “The retention of neurons seems to be better explained by the enriched environment. It’s as if they are produced on speculation. If things work out right they get used and they get incorporated into the wiring diagram and stay.”

Kramer said much of the research in this area began with work done by Waneen Spirduso at the University of Texas at Austin, who was reporting as long ago as 1975 on the topic of fitness and cognitive function.

Rhodes said the research line is still a young one. But, thanks to the continuing development of imaging techniques, increased knowledge of genetics, and more funding, the literature is growing rapidly as to the impact of exercise on cognition.

“There are many things that change with exercise,” Rhodes said. “That’s why it’s so difficult to find out which one of those changes is actually casually related to the enhancement of cognitive performance. Of course, that’s what everyone wants to know, because if we can figure that out we might be able to figure out therapies that can enhance learning in a more direct way.”

Thanks to research led in large part by University of Illinois faculty, researchers are learning more about the effects of exercise and fitness with each new study.

Kramer said this much is already known: “The fitness literature is pretty clear that you get fairly broad effects on different aspects of cognition from fitness training with fairly modest amounts of improvement in fitness.”

SKILL TRANSFER OR DOES “BRAIN TRAINING” REALLYWORK?

Computer programs and other materials promising improved brainpower through “brain training” techniques are increasingly popular. But do they, in fact, increase general cognitive functions such as decision making and memory processing through “brain exercise” programs that can costs hundreds of dollars?

For Kramer, the research so far isn’t convincing.

“The question is, can people really transfer cognitive skills learned in the laboratory or from commercial computer-based training program to skills and tasks in everyday life such as remembering a shopping list, driving an automobile in traffic, and rapidly learning a set of new skills in a job setting. And the answer, for the most part, is such transfer of training has not been convincingly demonstrated,” Kramer said.

It turns out that researchers can see improvements in the specific tasks people are tested on. But that is different than taking specific improvement on task performance and generalizing to overall improvement in cognitive skills.

One study cited as answering the question in the affirmative and published in the Aug. 2006 issue of the Proceedings of the National Academy of Sciences tested the program from the Posit Science Corporation.

The PNAS paper contains a conflict of interest statement that said all of the paper’s authors had a financial connection to the company. The company’s founder, chief scientific officer, and paper co-author, Michael Mezenrich, is a professor at the University of California at San Francisco, a member of the National Academies of Science, and a well-respected researcher into the neural origins of higher brain function.

The company’s Web site states that its program is “proven to improve memory and processing speed” but Kramer says claims about transfer of improvement in cognitive function from a commercial program or laboratory training experiment to everyday cognition have yet to be convincingly shown.

A large clinical trial called Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE) was designed to train groups of participants between the ages of 65 and 96 in cognitive skills like memory, speeded processing, and reasoning while a control group received no training. The overall goal of the trial was to “link specific cognitive and perceptual interventions to broader behavioral outcomes.”

The research, reported in the Dec. 20, 2006, issue of JAMA found that some of the subjects, trained on specific skills such as identifying and locating visual information quickly, showed long-term cognitive improvements on those specific tasks as much as five years later.

Beckman researcher Elizabeth Stine-Morrow said the results on the long-term effects were surprising, but the evidence for transfer of those skills outside the lab was limited.

“What’s interesting about that finding is that it’s very provocative to show that you have this little modest training–that is very, very narrow–and then five years later you’re still showing effects,” Stine-Morrow said. “From our point of view it must have changed something about the way those individuals have engaged experiences or have done things in their daily lives to retain these skills.

“The investigators did show some transfer, but the transfer was to self-reported ratings of difficulty in performing everyday activities. What they showed the five-year gains on were the very task specific performances.”

Stine-Morrow said the ACTIVE study is valuable for showing plasticity and for adding to the literature on skill or task improvement.

“You can change mental abilities and can change how older adults perform in these different tasks,” she said. “All the effects are very narrow and we see that in the literature on expertise. If you look at what experts can do, expert chess players, expert bridge players, expert pilots, they can do exactly what they’ve been trained to do and what they practice every day.”

Denise Park studies how different interventions could improve cognitive health as Co-director of the Center for Healthy Minds at Beckman. While transfer of skills is not yet borne out by the research, Park says that interventions such as learning new skills have shown the potential to improve cognitive performance.

“Acquisition of new skills is important,” Park said. “The brain is based on connections. Novelty forges new pathways.”

COGNITIVE LOSS DUE TO AGING, DISEASE

One of the most exciting potential benefits of exercise-induced neurogenesis is the possibility of slowing or even reversing cognitive loss due to aging or diseases like Parkinson’s and Alzheimer’s.

Greenough said more neuroscience research is going toward alleviating diseases like Alzheimer’s.

“More and more work is going to be directed to clinical problem areas like Alzheimer’s and Parkinson’s,” he said. “We’ve done a pretty job of doping out, and by we I mean not my group but the collective wisdom in the field, situations under which neurogenesis either occurs or can be made to occur. The real question now is can we take advantage of it.”

Taking advantage would mean targeting neurogenesis toward certain areas of the brain so that new neuron growth would slow or perhaps even reverse cognitive loss due to disease or aging. Since new neuron growth has been shown to take place almost exclusively in the dentate gyrus of the hippocampal formation and the olfactory bulb, new methods for targeting the “right” regions for neurogenesis would be crucial for more widespread effects on behavioral ability.

The hippocampus is central to memory processing, so increasing neurogenesis in that region could lead to improved memory. Greenough said there are many other brain regions and functions that could potentially be important in fighting disease and cognitive loss.

“There is some data, and this is really very important, saying that the corpus striatum can make new neurons under some conditions but not under resting conditions,” he said. “That has enormous implications for Parkinson’s disease because that’s the principal structure where you have secondary cell loss underlying Parkinson’s disease.”

Greenough said researchers should also look at the potential found in glial cells, which serve to protect and support neurons.

“My attitude is we shouldn’t ignore the other cytogenesis that’s going on,” he said. “Number one, there is the possibility that certain kinds of glial cells, under some conditions, seem to be able to change themselves into neurons. In addition, the glial cells and other cells actually put out trophic factors that can help the survival of neurons.”

Greenough said enough research exists to show that intervention strategies targeting disease could work.

“There are two ways you can look at a therapeutic intervention for disease,” Greenough said. “One is that it provides resilience so that the disease has less impact once it comes. So you’re sort of getting the nervous system ready in advance. The other is more of a repair mode, that is, take the diseases as they are, and do something that will fix it. There is enough evidence in the literature to suggest that both modes exist and have a reality with regards to exercise as an intervention in the Parkinson’s arena.”

Again, the fitness factor appears to play a key role in lessening the effects of cognitive loss.

“What the research suggests, not uniformly but very consistently, is that if you’re fit at time 1 with everything else being equal – equal education, socioeconomic status, many, many other factors – that you will have better cognition, better memory, better decision making at time 2, and the probability of you being diagnosed with Alzheimer’s or vascular dementia will be diminished,” Kramer said.

This article is part of the Spring 2007 Synergy Issue, a publication of the Communications Office of the Beckman Institute.