Healthy Brain, Happy Life (19 page)

RANDOMIZED CONTROLLED STUDY DESIGN

The gold standard for how to test the effect of an intervention like meditation or exercise on a group of people is to use what is called a randomized controlled study design. In these kinds of studies, people deemed appropriate for the study (the right age, background, and health status) are randomly assigned to either a test group or a control group. The test group is assigned to do the manipulation you are interested in studying, like exercise. The control group is assigned to do something that has all the elements of the thing you are doing in the test group but not the key element you think makes the most difference. So a good control group assignment for exercise would be slow walking, for example. Another important component is the idea that you are going to test. In this kind of study, you might test the idea that aerobic exercise improves memory function relative to the control manipulation of slow walking. To examine this idea, you will test both groups on their memory performance before and after either aerobic exercise or walking. Then you can ask if the aerobic exercise group improved their memory test scores significantly more than the walking group. If so, this would be a strong indication that aerobic exercise improves memory. The power of putting your subjects in groups randomly is that you can rule out that there were any major differences between the groups before the study started because you not only randomly assigned each person to a group but you have test scores before the intervention to show that there were no differences on the memory tests. This is the gold standard for experimental study design.

Fewer of these valuable randomized controlled studies have been done because they are much harder to carry out and generally more expensive than correlational studies. But what you get out of the randomized controlled studies that you can’t get from the correlational studies is the prescriptive aspects of exercise. With randomized controlled studies you can say, “We showed that
X
amount of
Y
kind of exercise improved
Z
brain function.” This is exactly the kind of information we need from research with humans. We don’t know what kind of exercise works best, what duration and activity level is best, or if men and women have different optimal exercise regimes for optimal brain health. And a big one we don’t know: What exactly is exercise doing to the elderly brain?

CAN EXERCISE MAKE ME SMARTER?

In contrast to all the work in the elderly, much less is known about the effects of exercise in healthy young adults. This is because it is generally thought that healthy young adults are at the height of their brainpower and therefore have little room to improve. In contrast, the cognitive decline in aging is a normal occurrence, so there is a larger window of possible improvement in this group relative to younger adults. But if there is little or no effect of exercise on brain functions in young, or at least youngish, adults, then why did I notice such a striking effect on my grant writing after my self-imposed exercise regime? The bottom line is that there were so few studies on the adult, nonelderly population that no strong conclusions could be made. I wanted to change that.

While neuroscientists had not made a lot of headway in examining the effects of exercise in healthy young adults, the possibility of creating a magic pill to make us smarter has fascinated us for ages. Books like the classic
Mrs. Frisby and the Rats of NIMH
(1971) and short stories like “Flowers for Algernon” (1959) have explored the possibility of making both men and rats smarter. In the movie
Limitless
(2011), Eddie Morra (played by Bradley Cooper) is a down-on-his-luck loser with bad hair and even worse clothes until he stumbles on an illegal but powerful pill that enhances cognitive power. After taking it, he immediately makes a ton of money on the stock market, gets a good haircut and a fancy new set of clothes, and is livin’ large. That is, until the side effects of his smart pills set in. In the end, he becomes so smart that he finds a way to engineer the magic pill so he suffers none of the side effects but retains all of the cognitive benefits: He runs for Senate and learns to speak fluent Chinese. Amazing! In
Rise of the Planet of the Apes
(2011), Will Rodman (played by James Franco) develops a new substance (this one came in the form of an inhalable gas) that improves cognitive function in Alzheimer’s disease patients by repairing the damage that the disease causes. The drug is too late to save his father, but his young pet ape Caesar gets a whiff and suddenly learns how to speak and take over an entire city! Now that’s one powerful drug. Clearly, a smart pill is an object of endless fascination.

But those are all works of pure fiction. Back in the real world, while exercise will probably not work as well as Eddie Morra’s pill or Will Rodman’s gas, I saw evidence in myself that intentional exercise could have a clear and noticeable effect on a range of brain functions that I used every day. And my review of the research showed that there was little known about the effects of exercise in young adults. Now I had the perfect opportunity to address this question with my “Can Exercise Change Your Brain?” class. My students would be exercising once a week for an hour, for the fourteen weeks of the semester. I was missing only two elements to turn this class into a real research study. The first was the ability to test the students’ learning memory and attention abilities both at the beginning and at the end of the semester. The second was a control neuroscience class that met for the same number of hours but that did not exercise, so I could also test those students at the beginning and at the end of the semester. While this study had many elements of a gold standard interventional study, it was not perfect. A true gold standard study would have randomly assigned students into either an exercise elective class or a nonexercising elective class with the same instructor for both. Instead, I gave exercise to the students who wanted to take the exercise class and compared them to students who did not sign up for the class and were being taught by a different teacher. While this was better than an observational study, we did not have the gold standard randomized controlled design because we couldn’t randomly assign students with no consideration for their own personal choice of class. However, this somewhat less than optimal design would do just fine. The other factor that I had to take into consideration was that the class met only once a week, so I would get only a once-a-week exercise boost in these students. Had I designed this study outside the classroom, I would have wanted the students to exercise something like three times a week. But, in the end, this was just a preliminary classroom experiment. I was doing it to engage the students in a new way in the experimental process, and we would discuss all the ways in which the experiment was not optimal; I’d make that part of the learning experience. In fact, with the relatively low number of students in the classes (relative to major clinical studies), I was stacking the decks against myself to see any effect. But then again it meant that if we
did
see any effect—any effect at all—that would be very exciting.

I also made the explicit decision to use intenSati as the exercise in my experiment because of its integration of conscious intention. I chose it instead of using a more “pure” form of aerobic exercise, like treadmill running or pure aerobics or kickboxing, because my goal in this study was to examine the effect that I saw in myself. I wanted to determine if this particular approach held up in a study; if it did, then in future studies I could separate out the individual effects of the affirmations and exercise. I also thought that intenSati would engage and motivate students and be a better fit for my classroom-based study than having the students do a hard-core treadmill run every morning before class.

It turns out that a control neuroscience class that didn’t exercise was easy to find in my department. The expertise in human testing was little trickier. Because I did not have much experience testing humans, I sought out help in this arena. But just as the ideas were swirling around in my mind, I happened to run into a colleague who became my collaborator on this project. Scott Small, a neuroscientist and neurologist from Columbia University, happened to walk by as I was sitting on the steps at the main entrance of a convention center in Washington, D.C., resting my feet after a morning of walking around a big neuroscience gathering. We started chatting, and I told him of my new interest in exercise and the brain and my plans to teach the new class. Turns out he and his colleague Adam Brickman, another neuroscientist and neurologist at Columbia, were also studying the effects of exercise on cognition in humans! They were interested in collaborating and getting more data from healthy young adults to support their first findings. I was thrilled at the prospect, and when we got back to New York we starting planning our new exercise research study based on my class. Sometimes you make the best science connections just sitting on some steps, resting your feet.

EXERCISE AND NEUROGENESIS

What did we think exercise would actually do to the brains of my healthy, young, high-functioning neural science majors at NYU? The answer to this question comes from the studies on the effects of wheel running on hippocampal neurogenesis in rats, which I described earlier.

This whole line of research had a really exciting and controversial history dating back to the 1960s. It took a lot of work to convince people that neurogenesis could actually take place in the adult brain. For a very long time, it was believed that once you reached adulthood, no new neurons could be born in your brain. This idea was established and widely held in the neuroscience community well into the 1990s, despite the fact that two decades earlier a couple of researchers from Boston University published the first evidence that new brain cells could be generated in the adult brains of rats.

Unfortunately, by that point, the idea that the adult brain was fixed was so strongly entrenched in the minds of scientists that this early study did not make much of an impact. After about twenty years, those early researchers were finally vindicated in a series of studies using more modern (and more convincing) approaches to show definitively that shiny new neurons were born in adulthood in both the hippocampus and the olfactory bulb. Not only that, but in 1998 an international team from Sweden and the United States provided the first direct evidence that neurogenesis was occurring in the adult human hippocampus. They did this in a very clever way. In rodents, you can confirm the presence of newly born neurons only by first injecting the brain with bromodeoxyuridine (BrdU), then sacrificing the animals and examining their brains. Brain cells that incorporate this chemical have recently divided (that is, they were recently “born”), and many such cells were seen in the adult rat hippocampi. The researchers knew that BrdU is commonly used to test for cell growth/division in tumors in cancer patients, so the research teams went out and obtained permission from cancer patients who had been injected with BrdU to examine their brains after they died. From the brains they were able to examine, the researchers found that, just as in rats, these adult patients had BrdU-stained cells in their hippocampi (remember that we all have two hippocampi, one on each side of the brain). This confirmed that in adult humans, just like in adult rats, new hippocampal cells are born.

This is the question we would focus on in my “Can Exercise Change Your Brain?” class. That is, would the increased aerobic exercise from the intenSati class I would teach enhance neurogenesis in the hippocampi of my students and, as a consequence, improve memory function? We were seeing indications of improved cognitive functions in the elderly after exercise, even though neurogenesis decreases as we age. My class would test the idea that young NYU students would have heightened levels of neurogenesis and, therefore, have a good possibility of benefiting from increased aerobic exercise. We would not be looking directly at neurogenesis, but would measure it indirectly based on the students’ performance on cognitive tasks that depended on the brain areas where the new brain cells were being born. This is the idea we were going to test.