Healthy Brain, Happy Life: A Personal Program to to Activate Your Brain and Do Everything Better (2016)

THE BIRTH OF AN IDEA:
How Does Exercise Really Affect the Brain?

As I neared the deadline for yet another science grant application to NIH (something I spent a great deal of time on as a science faculty member), I was becoming aware that my writing was going well—unusually well. My daily writing sessions were much more productive and even enjoyable compared to the stress-filled sessions of the past. Whereas it usually took me a week to write just one section of a grant application, I was now drafting more efficiently, fine-tuning more quickly, and enjoying the process a whole lot more. My attention was more focused and my thinking more clear. I made deeper, more substantive connections between my ideas and was doing so far sooner in the process than usual. This is when I began to suspect that there was a relationship between the regularity of my workouts and my supercharged grant-writing sessions. The writing just went more smoothly during a week when I exercised more than three or four times, compared to weeks when I slacked off and went to the gym only once or twice.

What was going on here? I realized that without knowing it, I had just conducted an experiment on myself! I varied my exercise regime (some weeks four or five exercise sessions and other weeks only one or two) and found that only with a higher frequency of exercise did I notice enhanced attention and the ability to make new and better thought “connections” in my writing. While focused attention is known to depend on the prefrontal cortex, the ability to make new connections or associations is thought to depend on the hippocampus.

This was fascinating! I knew there had been lots of progress in our understanding of how exercise could affect brain function, but I had not kept up with that literature—too busy getting tenure, I guess. So when I noticed these changes in myself, I dove into that neuroscience literature to see what was new.

What I found was an active and growing body of research that was deep into identifying all the different ways aerobic exercise affects brain function. These studies documented a range of anatomical, physiological, neurochemical, and behavioral changes associated with increased aerobic exercise. But the biggest surprise I got when exploring this literature was that one of the founders of this whole line of research was a scientist with whom I was very familiar: Marian Diamond.

It seemed like a sign.

It turns out that our understanding of the effects of exercise on brain function had its origins in the original studies that Diamond did on brain plasticity and the effects of raising rats in enriched environments on brain function. As I mentioned in Chapter 1, those early studies showed all sorts of brain changes when rats were raised in the enriched environments: The animals developed a thicker cortex because of the more extensive branching of the dendrites, more blood vessels, and higher levels of particular neurotransmitters like acetylcholine as well as increased levels of growth factors like brain-derived neurotrophic factor (BDNF). Acetylcholine was the very first neurotransmitter ever discovered, and the brain cells that use it send signals throughout the cortex as well as to the hippocampus and amygdala. Acetylcholine is an important modulator of learning and memory, and studies show that drugs that interfere with the action of acetylcholine result in memory impairments in both animals and humans.

BDNF is a growth factor in the brain that supports the survival and growth of neurons during brain development as well as synaptic plasticity and learning in adulthood. Not only that, but a truly exciting finding was reported in the 1990s, when researchers in California demonstrated that rats raised in an enriched environment had more new neurons in their brains than other rats. This process is called neurogenesis. While lots of new brain cells are born during our early development period (from infancy through adolescence), there are only two places in the brain where new brain cells are created in the adult brain. One is the olfactory bulb, the part of the brain important for sensing and processing smells (see Chapter 1), and the second is my old friend the hippocampus. But even more significant is that new brain cells are formed on a regular basis in the hippocampus of adult rats. The enriched environment also was linked to a higher number of hippocampal brain cells (but not in the olfactory bulb). Other studies showed that rats raised in enriched environments and that had more new hippocampal cells also performed better on a range of different learning and memory tasks, suggesting that all these new neurons were helping the rats learn and remember better.

But then neuroscientists began to wonder what it was about the enriched environment that was causing all these striking brain changes. Was it the toys? Was it the gaggle of other rats to play with? Maybe it was all that running around that the rats did in the Disney World–like environment. When scientists tested these factors systematically, they discovered that one contributed to the majority of the brain changes seen with an enriched environment: exercise. They found that all they had to do was give a rat access to a running wheel, and they would see most of the brain changes they observed in rats that were raised in the enriched environment. Indeed, this line of research in rodents has shown us how exercise affects the brain at the molecular, cellular, brain circuit, and behavioral levels.

We now know that exercise alone can actually double the rate of neurogenesis in the hippocampus in rodents by increasing the total number of new neurons that are born, enhancing their survival (many of the new cells die) as well as speeding their maturation into fully functioning adult brain cells. These new neurons are not born just anywhere in the hippocampus but in only one specific subregion, called the dentate gyrus. When I read this, I felt like going to the gym and working out even harder! Exercise in rodents also increases the number of dendritic spines on the neurons in the dentate gyrus; these spines are budlike appendages on the neurons’ dendrites, the branchlike structures where neurons receive information. Exercise also increases the total length, complexity, and spine density of the dendrites. Thus it is not surprising that the total volume of the dentate gyrus also increases with exercise. Spine density in other regions of the hippocampus and the adjacent entorhinal cortex (which I studied as a graduate student) is also increased significantly by exercise. Spines are where the axon of one neuron contacts the dendrites of the next neurons; the more spines on a neuron, the more communication is happening. Another robust change researchers confirmed with exercise alone was the growth of new blood vessels throughout the brain (including in the hippocampus), which is called angiogenesis.

The physiological properties of the rodent hippocampus also change after exercise. This physiological phenomenon is called long-term potentiation (LTP), which is a long-lasting change in the electrical response between two groups of neurons. We study this change by stimulating the connections between the two groups of cells in the hippocampus with an electrical current. If you stimulate one of the pathways within the hippocampus with multiple fast bursts of electric current this will increase the response you get from a weak electrical stimulus to that pathway compared to the same weak stimulus given to the pathway before the burst of current. LTP is widely considered to be a major cellular mechanism for learning and memory. LTP is enhanced in the brains of rats that have been exposed to exercise. One key factor that might be contributing to these effects is the increase in BDNF because we know that BDNF can also enhance LTP. But BDNF is not the only factor that increases with exercise. As I mentioned in Chapter 4, in addition to all these anatomical and physiological changes, exercise also increases the brain levels of serotonin, norepinephrine, dopamine, and endorphins.

Given that exercise increases the number of new brain cells, beefs up the size of the cells in the hippocampus, enhances BDNF and LTP, and increases the level of transmitters and growth factors floating around the brain, the next logical question is, Does exercise enhance the function of the hippocampus? Do rats that exercise more remember better? Indeed, many studies have shown that rats that have either undergone environmental enrichment or exercise alone perform better on a wide range of memory tasks that we know depend on the hippocampus. These include spatial maze tasks, memory-delay tasks, recognition-memory tasks, and a range of memory-encoding tasks. In these latter tasks, rats are asked to differentiate between similar items during a memory task. Memory encoding is a function that neuroscientists believe specifically depends on the dentate gyrus, the subdivision in the hippocampus where all those new neurons are born. More generally, as we first learned from H.M., the hippocampus is known to be important for both learning (acquiring new information) and retaining that information. You can’t learn information and store it as a long-term memory without a hippocampus, but information learned before an injury to the hippocampus remains intact. While we know the hippocampus is critical for the formation of our long-term declarative memories for facts and events, we still don’t know exactly how it does this amazing feat. That’s the topic of an enormous amount of current neuroscience research. I believe that things like LTP are involved and levels of BDNF also help the process, and we also know a lot of the molecular pathways involved. However, we are still filling in all the pieces of our understanding of exactly how the hippocampus in general and the dentate gyrus in particular (the part of the hippocampus where those new neurons are born) work to form all the new memories that we make every day.

On the other hand, I don’t need to know exactly how it works to appreciate the fact that memory performance is better with exercise. Now this was exciting news! If rats that run have better memories, then people who exercise should also have better memories, right? I certainly noticed an improvement in my own ability to make connections or associations in memory I know depends on the hippocampus, and studies in rodents suggested that I was on the right track.

CRAFTING MY OWN BRAIN HACK

Then I had an idea.

You know when you come up with an idea that you are so excited about you simply can’t wait to make it happen? That’s how I felt. The idea started with my desire to get up to speed on this exciting new neuroscience literature on the effects of exercise on brain function. As any teacher worth her salt knows, the very best way to become familiar with and understand a specific area of research is to teach a new course on it. So I decided to teach a new neural science elective course on the effects of exercise on brain function. I was feeling especially energetic and creative from all the exercise I was doing and was inspired to develop the new class because of my own exercise experience. What if I brought exercise into the class and not only told the students about the neuroscience underlying the effects of exercise on brain function but actually let them experience the effects of exercise themselves? Of course the form of exercise I wanted to use was intenSati—my exercise of choice at the time. I just knew that adding exercise to the classroom would bring the course to a whole new level and send motivation for learning the material through the roof.

That’s right: I was going to bring aerobic exercise into the university classroom for the first time ever, so students could literally experience the positive effects of exercise as they were learning about what exercise was doing to their brains. With this idea, my “Can Exercise Change Your Brain?” class was born. It would be uniting two of my greatest joys—teaching and exercising—in a unique way. I was already imagining the format of the course: We would start out each class with an hour of intenSati and finish with a ninety-minute lecture/discussion starting with the history of the study of the effects of exercise on brain function. I would end the semester with the studies in humans, describing what we currently know about how exercise affects cognition.

I was beyond excited!

But I knew I was getting a little bit ahead of myself, and I needed to figure out how I was going to get an intenSati instructor into my classroom every week to teach in my class. The problem was that there was no money available to hire an instructor to teach the exercise part of the class. As a professor of neural science at NYU, I am expected to teach all aspects of the courses I design. Well, the obvious solution in my exercise-soaked mind was to learn how to teach intenSati myself.

To tell the truth, a secret part of me was just looking for a good excuse to learn how to teach intenSati. I remember the day I became aware of my desire to teach this class for the first time. I was standing in the studio waiting for an intenSati class to begin, and I started chatting with Pattie, a very sweet woman whom I had become friendly with in class. She mentioned casually that she had taken the teacher-training class and how much she loved it. My ears perked up immediately! I thought you had to be some kind of fitness goddess or triathlete to take a teacher-training class. But Pattie was just like me—a regular person who happened to be a devoted student in the class. I was intrigued, and I was more than a little envious that she had learned the secrets to teaching the class that had kept us both coming back time and time again. So, when the possibility that I needed to be the one to teach the intenSati part of the class surfaced, I jumped at the chance.

I think the other reason I was so excited to learn how to teach the class was that the idea woke the inner Broadway diva in me, who had been snoozing for a very long time. Granted, I would not be belting out “Defying Gravity” from Wicked, or “Let It Go” from Frozen, but I would be shouting affirmations with the beat of the music and leading the whole class in the mini–dance routines that made up intenSati. Maybe this was my chance to bring a little bit of Broadway onto my own private stage: the academic classroom.

Yes, there were lots of reasons motivating me to jump right into teacher training. But there were other reasons that held me back. For one, the fear of becoming a big fat Broadway-style flop. I was a great student in class, where I could follow all the instructions with ease, but could I actually be the one to give the instructions and not mess up? Second was the possibility of ridicule by my faculty colleagues, most of whom generally had a much more conservative style of teaching than I did. There were no other courses taught either in my department or at the whole university that I knew of that resembled this course at all. It was brand-new territory.

I would have to put myself out there in a way I never had before—not just before those who would take my class—and in spandex—but for all my faculty colleagues. They would think I was crazy. I knew it. And because I was going to be teaching in our main neural science classroom, the whole class and I would be front and center for anyone walking past to see us jumping, punching, and kicking (not to mention the heart-pounding music in the background that was bound to attract attention). Just thinking about the various ways that my plan could unfold filled me with a mixture of fear and excitement. And that’s when I knew this wasn’t just a silly fantasy; I had to do it. So before I could change my mind, I signed up for the intenSati teacher-training class at the gym and wrote up and submitted my class syllabus. There was no turning back now.

Despite the fact that I had never taught an exercise class before, I jumped right in. The five days of intenSati teacher training in New York translated into eight hours a day at the gym, studying the physical movements associated with the class but also learning about the ideas behind the practice, including aspects of positive psychology, personal coaching, and how to motivate people more broadly.

THE EXERCISE PLOT THICKENS

Soon after I first came up for the idea for the class, I realized that it had the makings of something more than just a unique new undergraduate experience. It had the makings of a full-on research study with human subjects who happened to be my students.

Given the exciting research on the effects of exercise in rodents (and the enthusiastic articles in the popular press coming out all the time), one would expect a rich literature on the effects of exercise in humans. But it is relatively modest and biased either toward studies of the effects of exercise in the elderly population (typically defined as sixty-five years old and older) or the effects of exercise on school-age children. There is very little information on the effects of exercise on healthy adults, like me. In other words, there is an enormous number of important questions left to answer in the human population. The studies focused on the elderly consistently show that the amount of average physical exercise reported over the lifetime is strongly correlated to your brain health as you age, with the highest levels of overall exercise correlated with the best brain health. For example, one representative study surveyed 1,740 participants over the age of sixty-five who did not have cognitive impairments and asked about their exercise frequency, cognitive function, physical function, and depression levels. Scientists then followed up with these same people six years later asking how many of the subjects developed dementia and/or Alzheimer’s disease. They then went back and looked at how much the people who did or did not develop dementia or Alzheimer’s disease exercised over their lifetime. The big take home was that people who reported exercising three times a week or more had a 32 percent reduced risk of developing dementia. Anyone with family or friends with dementia can appreciate that a 32 percent risk reduction is big . . . really big. It’s these findings and others like it that have encouraged researchers to try to more fully understand the cognitive effects of exercise, and whether those effects might be maximized. Similarly, studies in school-age children have shown that aerobic fitness has a small but positive relation to academic achievement, and body mass index (BMI) has a negative relation to academic achievement (that is, high BMI is associated with lower levels of academic achievement).

But these studies alone are not the final word on this topic. Not by a long shot. These kinds of studies are called correlational because they come to a conclusion by comparing/correlating self-reported levels of exercise (researchers have no control over the amount or quality of exercise and cannot judge the accuracy of the self-reports) with the subject’s current state of brain health. While such studies suggest the possibility that the level of physical activity over a lifetime has an effect on brain health and dementia as one ages, there are also other possible explanations that cannot be ruled out. For example, maybe all the people who exercised more came from a higher socioeconomic status. Or maybe all the people who exercised more were just overall healthier, with better and stronger hearts. This would suggest that socioeconomic status or overall health defines how healthy and free of dementia your brain is when you get older and not amount of exercise. For these reasons, the conclusions from correlational studies, while informative, are far from definitive. For example, in addition to the studies I mentioned that link higher levels of exercise to lower incidences of dementia, other more direct studies have also linked increased levels of exercise to better learning and memory performance. Again, it’s a promising direction, but still not conclusive.

So what’s more powerful than an observational study? The gold standard is what’s called an interventional study. Another term for this same style of study is randomized controlled study. For this kind of study, you take a group of subjects and randomly assign them to either an exercise group or a control group that does not exercise. In this way the experimenter has direct control over the manipulation being done. Then you are able to compare the performance of the exercise group to that of the control group to determine if exercise has any significant benefit relative to the controls based on the factors that you’ve determined. Few of these gold standard types of exercise studies have been done in the elderly, but such studies have shown that an exercise intervention for several months to a year results in sharper attention, faster response times, and improved visuospatial functions (cognitive functions that require manipulating visual and spatial information in memory). Indeed, the largest and most consistent effect in the elderly seems to be on attention or the ability to focus or concentrate on discrete aspects of information while ignoring other perceivable information. Improved attention is an effect that I noticed clearly in myself with increased exercise. Similarly, one randomized controlled study showed an increase in the size of the hippocampus in elderly subjects who exercised for a year, which is consistent with findings in rodents. Another study reported significant increases in vasculature in the hippocampus after a three-month exercise regime, associated with subtle improvement on a memory task.

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.

fMRI

fMRI stands for “functional magnetic resonance imaging.” Like standard MRI (see “MRI” on page 54), fMRI is also done with a big magnet but it detects the change in blood flow related to the energy used by the brain. We know that when a brain area is active, blood flow to that region increases and, in addition, there is a change from oxygenated to deoxygenated blood in highly active areas (the brain is the single highest user of oxygen in the body). fMRI provides an indirect measure of activity in specific brain areas by detecting changes in blood flow and oxygenation levels and is the most common tool used to measure brain activity in people.

A memory-encoding task.

(Reproduced with permission from Brickman, A. M., Khan, U. A., Provenzano, F. A., Yeung, L. K., Suzuki, W., Schroeter, H., Wall, M., Sloan, R. P., and Small, S. A. “Enhancing Dentate Gyrus Function with Dietary Flavanols Improves Cognition in Older Adults.” Nature Neuroscience 17 (2014): 1798–803.)

This is where my Columbia University colleagues Scott Small and Adam Brickman came in. They had used a human brain imaging technique similar to functional magnetic resonance imaging (fMRI) to study active brain areas as subjects performed various tasks.

In one particular study, they asked subjects to commit a complex figure to memory (called memory encoding) and then identify that same complex image relative to similar complex images. Here is the protocol: As subjects performed this challenging memory-encoding task, Brickman and Small saw that the same specific subarea of the hippocampus where all the new neurons are born lit up like fireworks. The fact that this region was very active during the task, suggests the possibility that if we were able to use exercise to rev up this same brain area and create more new brain cells, we might see even better performance on this task. So the idea, or hypothesis, that we tested in this study was, Would an increase in aerobic exercise improve performance on this memory-encoding task?

And what does it mean that exercise can improve memory encoding? My lab and others are testing the idea that increased aerobic exercise enhances neurogenesis in the hippocampus, and those new hippocampal cells (because we know they are more excitable than the cells that have been there for a long time) improve our ability to encode, or lay down, new long-term memories. In particular, there is evidence that these newly born hippocampal cells help differentiate between incoming stimuli that have similar characteristics. For example, when I try to remember whether Julia or Pam came up after class to ask a question, it’s the new hippocampal cells that help differentiate between the two, who both happen to have medium-length brown hair. What are the implications? That long-term exercise can increase the number of new cells in the hippocampus and might significantly improve our ability to lay down new memories for as long as that level of neurogenesis (and exercise!) lasts. I don’t know about you, but my memory-encoding abilities could always use some help, and understanding how this works and how to maximize this effect is one of the major goals of my lab.

Combining exercise and academics was an innovative element of my class, but turning the class into a real research study was even more exciting. This way, not only would the students become the research subjects but I could also include them in the act of analyzing the data. As part of the class, the students would have a chance to study the data from their own class (names removed, of course) and the control class to determine if exercise had really improved their memory function. While these students had all done lab courses, this kind of data analysis is generally done in a working research lab. We had brought the research lab to the classroom! What better way to apply the knowledge that they would be obtaining during the semester through my lectures and our discussions than to analyze the findings from a real experiment?

TRANSFORMATIONS CONTINUE

The intentional exercise I had been practicing not only inspired me in my teaching and research but was starting to shift the way I approached other parts of my life as well. After a little break following Cabin Boy and Car Boy, I was ready for the next step. I had two main questions for myself. How do I build a richer social life and how could I make myself feel ready and open for a lasting relationship?

After striking out with my first matchmaker, I decided to try it one more time with a different matchmaker—after all, Car Boy and Cabin Boy were both reasonable on paper, maybe I just needed someone with a new and different male dating roster. I met this next matchmaker in the lobby of a very cool hotel, and she seemed to be connected to all the right people and said all the right things. I signed up, and she connected me with a businessman and a doctor, both fairly nice and both decidedly not for me.

Then I seemed to hit it big. Through the matchmaker, I met a very sweet and intelligent lawyer. He lived in the city, and his name was Art. This one stuck. Neither of us had dated very much in the past few years, and we were both eager to find a steady relationship. We made a great couple—for a while—enjoying dinner together, weekends at his place in New Jersey, and occasional outings to the theater. Then Art and I got to the stage of our relationship where our various differences became more and more pronounced. And I thought I had a possible solution.

I would hire a personal coach. When I wanted some help in the dating department, a professional matchmaker seemed to do the trick. Now that I needed help improving my relationship, maybe a life coach would help. My gym sometimes offered free life-coaching sessions, so I signed up for a thirty-minute trial with coach Marnie.

Marnie was amazingly perceptive and immediately started helping me understand how I was in my relationship with Art and how I was in my relationships in the rest of my life. It turns out, I had a lot of things to clean up in my relationships overall. I had been focusing so much of my attention on my work, I hadn’t paid enough attention to the maintenance of my personal relationships. I learned quickly that it was not so much that I didn’t know how to have strong personal relationships, I just needed to focus more of my attention on them and they would start to thrive in the same way my career was thriving. I also needed more than a little guidance to get this process started, which is what I got in spades from my coach.

What did this relationship cleanup process look like? My favorite example involves a surprising target of my mission: a doorman in the co-op building where I live in New York. One of my negative personality traits that I identified with my coach is that I am very easily insulted. Even worse, once insulted, I don’t try to repair the hurt; I just stew. On top of that, I can hold a grudge for a very long time. You can imagine that a long-time grudge against my doorman, someone I rely on and see several times a week, not in my house but essentially outside my front door, is a prime candidate for cleanup!

The perceived insult happened very soon after I moved into my building. I tried to schedule a furniture delivery with the doorman on duty. But unlike my other friendly and helpful doormen, this one seemed quite curt in his interaction with me. He told me that he was not sure if he could schedule the delivery and that I had to check with the super to be sure. He seemed a little annoyed at my question and was not particularly helpful.

I then started to notice that he never seemed very friendly when I walked through the door. Even more annoying was that I saw him interact with other residents in what seemed like a much friendlier way than he ever acted with me. He never engaged me or went out of his way to help me. In the end, I started to dread seeing him at the door and interacted as little as possible with him because it was so clear that he didn’t like me.

That next Christmas, I prepared my annual tips for all of the building staff. I just could not bring myself to give this doorman a tip when I dreaded seeing him at the front desk, so I decided he would not be getting a tip that year. I knew that was a drastic (some might say foolish, childish, immature—fill in the blank) move, but I did it anyway, and then immediately regretted it for the rest of the year.

When I mentioned this to my coach, Marnie, as one of the relationships I had to repair, she asked me if I had ever spoken to him about why he was rude that first day. I said no. Then she asked if perhaps I had been a little cold to him, which might have influenced the way he interacted (or did not interact) with me. I admitted that my behavior could indeed be viewed as cold. My coach made me realize that this whole time, I had been making up a story in my own head that this doorman did not like me, even though I had been the one giving him the cold shoulder. She reminded me that this was a key relationship to clean up for me because this guy was a critical part of my extended home. He, like the other doormen in my building, knew all about me: what take-out I ate, which dry-cleaning shop I went to, and which friends visited me and when. Doormen often know about your romantic relationships before your BFF because they are the first ones to see who arrives early and stays late and who doesn’t go home at all. She said that the only way to turn this relationship around was to confess my theory about him to him, and see what he said. And she helped me work out what I was going to say. Yikes!

I remember sitting in my bedroom on the morning I knew he was working, going over my speech in my mind and really not wanting to go downstairs. I was experiencing that sick feeling that comes before you take your most important final or right before you go on stage for the first time. I somehow managed to stand up and make my way downstairs. When the elevator doors opened, I marched right up to him and said in a slightly trembling voice, “Hi. I wanted to ask you something. I first wanted tell you that I think the entire staff at this building is great and I appreciate all the great service. But, as you know, Christmas is coming up again, and I wanted to tell you that I felt so bad that I did not give you a tip last year at Christmas. I didn’t give you a tip because I have this idea that you don’t really like me, and I wanted to talk to you about this.”

Yikes—I had actually said it.

He looked totally stunned.

It took him just a second to recover before he assured me he harbored no ill-will toward me. Instead he said that his style was to stay professional and stay out of people’s business and suggested that that behavior might have been mistaken for him not liking me. He pointed out that he was very different from some of the other doormen who liked to talk to all the residents and ask questions about their lives.

My key realization was that he seemed genuinely surprised that I thought he did not like me.

I thanked him for his honesty and told him I must have just completely misinterpreted him. I reiterated that I thought he and the entire door staff did such a great job and I looked forward to rewarding everyone at Christmas.

This was maybe not the most elegant conversation I ever had, but I did what I had gone there to do. I thanked him again and awkwardly ran out the door. I nearly cried with relief as I went flying down the street to the subway, trying to get as far away from that stressful, yet successful conversation as I could.

But was it worth it?

Yes.

This embarrassing, awkward, difficult, and stress-inducing conversation completely shifted our relationship. Both of us now had permission and motivation to focus on positive interactions, and we were both about 300 percent more friendly every single time we saw each other after that, including that very night when I came back home. It was like my own little Christmas miracle.

This was just one example of how I was shifting the relationships in my life. More important, I was becoming more and more sensitive to the health of all the personal relationships in my life, and I was on a mission with the help of my life coach to fix them.

How did this relationship fixing work out with Art? I realized I had to ask myself why I wanted to fix this relationship. Was it because I loved him and wanted to spend the rest of my life with this man, or was it that I liked the idea of being with someone even if he was not particularly compatible with me. Art was very kind-hearted and very smart, both of which I appreciated. But in the end, we didn’t share a great deal of lifestyle traits. Probably the most telling difference was that he had very few friends in New York, and he was not social at all. He enjoyed hanging out with me but was not interested in meeting or knowing my growing group of friends. In the end I wasn’t sure he would like or get along with them very well anyway. I realized that while just a short time before, I had been just as isolated socially as he was, I had clearly and deliberately changed that in my life, and staying with him would be like moving back to those days of social isolation that I had worked so hard to change. He also had no interest in good food, which was challenging for me in the very beginning and another clear sign that we were just not meant to be.

It sounds like an easy decision to make, but it wasn’t. I feared that if I ended it with Art, I would never find anyone else for the rest of my life. But the decision was basically made for me. We were just not getting along, and there was no choice but to break it off with him.

While the development of my new exercise class was an exhilarating part of the transformation I was going through, my breakup with Art was an equally important, and very painful, part of the same process. At the heart of this was me becoming more self-aware. That may sound obvious. But keep in mind how focused on science and my work I had been for the previous twenty years. Did I love my career? Did I love the work I did in my lab? The research? The reading? Yes. But I was realizing that if I wanted a more full, balanced life, I had to literally rebalance my own brain–body connection, with more focus on the body part of the equation. Then I began to seek this same kind of balance in my relationships; I wanted more from them. This became a process of becoming more aware of what I really wanted in life. I had spent years focused on the goal of getting tenure and working hard, loving the science that I did but putting anything that got in the way of my job on the back burner. I focused so much on my work goal that I didn’t pay nearly enough attention to the present moment. I still had a way to go, but this whole process was one of starting to pay more attention to my emotions and desires, my likes and dislikes, and being more open to what was going on at that moment instead of focusing so much on trying to control the future.

And that’s part of what my regular exercise provided: a constant focus on the present moment. You really can’t be thinking about the future when you’re in the middle of a serious workout session, especially an intentional workout like I was giving myself. For those sixty minutes of intenSati class, I felt completely connected to myself: my thoughts, emotions, and physical movement. I was all one—body and brain. I was supremely aware of how I felt, how my feelings changed during class, and all my emotions that came during and after the workout, from annoyance to joy to peace to relief to exuberance. I experienced a moving meditation in which I was able to be in the present moment, allowing myself to experience what my brain and body were telling me.

This sensory, intensely emotional, physically charged experience became the catalyst to figure out what I really wanted to do with my life, with no expectations and no preconceived notions. What can bring me joy? What do I no longer need if it doesn’t bring me satisfaction or joy?

TAKE-AWAYS: EXERCISE AND NEUROGENESIS

• Exercise is responsible for the majority of the positive brain changes seen with environmental enrichment, including increases in the size of the cortex, enhanced levels of growth factors like BDNF and neurotransmitters like acetylcholine, and enhanced growth of blood vessels in the brain (angiogenesis).

• Both exercise and enriched environments enhance neurogenesis, or the birth of new brain cells, in the hippocampus.

• The increased levels of BDNF stimulated by exercise help the growth and development of these new brain cells.

• Exercise also enhances the volume and size of the hippocampus, increases the number of dendritic spines on hippocampal neurons, and enhances the physiological properties of hippocampal neurons as measured by LTP.

• In humans, most studies of the effects of exercise have been done in the elderly.

• In studies in the elderly, higher levels of exercise are correlated with lower incidence of dementia later in life. This is an example of an observational study.

• In elderly people, randomized controlled studies (interventional studies) have shown that increased exercise can improve attention and increase the size of the hippocampus.

BRAIN HACKS: HOW DO I INCREASE MY EXERCISE? PART I

If you don’t have hours in the day to exercise, here are some ideas that I use in my own life to get that regular exercise practice going in just four minutes:

• Walk up the stairs to your favorite upbeat song (like “Happy” by Pharrell Williams) until the song is over, then take the elevator the rest of the way up.

• Challenge a friend or coworker to do a combination of desk push-ups and squats at work for four minutes a day (or multiple times a day for a whole week). Then challenge someone else.

• While you are brushing your teeth for four minutes, do a rotation of deep knee squats and side bends (face toward the mirror and slowly lean your body to the right and then to the left, stretching out the ribs on the side opposite to the direction that you are leaning). To make the side bends more difficult, wrap a big towel on your head as if you were drying your hair; it makes your side abs work even harder.

• Keep it fun by playing a four-minute game of tag with your kids, or borrow someone else’s kids to play it with.

• Set a timer for four minutes and clean up as much of your home or office as you can as fast as you can. Try cleaning the bathtub or doing some speed vacuuming or mopping; that can really work up a sweat and it will last only four minutes!

• Be a kid again by using a Hula-Hoop for four minutes. It’s an amazing aerobic workout for your abs and core.