Mind Alert
Can I touch your cerebral synapses this morning?
We’ll see.
I would like to begin with a general introduction before presenting
the specific brain research from my laboratory at UC Berkeley that
hold the promise of what I call “successful aging.”
In our democratic free society, the human brain has the privilege and
capacity to determine its own destiny. But no one said it was easy. It
has been said that aging is not for sissies, but in fact, life is not
for sissies. I frequently use the title “An Optimistic View of
Aging” when I present my research. Who wants to listen to a talk
called “A “Pessimistic View of Aging”? Yet recently
I was asked to speak at a retirement conference. I thought to myself,
the concept of “retirement” is contrary to my desires and
values in life. Should I really accept this challenge? And the answer
was “Yes.”
Have you ever looked up the word retirement in the dictionary? Retire
definitely has a negative connotation. It means to withdraw, resign,
regress, recede, abdicate, depart, and on and on. There is no synonym
indicating anything upbeat or forward-thinking or optimistic. We know
Robert Browning’s famous stanzas “Grow old along with me
/ The best is yet to be / The last of life for which the first was made…” What
an exhilarating perspective! His words certainly do not suggest the necessity
to resign, retreat, regress, recede or withdraw from life.
In light of the profound social changes and medical advances that have
taken place in American society, why has it taken so long to challenge
the very meaning of the word retire? Can’t we find a new word to
inspire us to move forward into a period that amounts to almost one-fourth
of our potential lifetime? I asked people all over the country to help
us find a substitute for retire: a single, acceptable, positive word
for this segment of our lives. I finally found one that I think currently
fills the need: redirect. In fact, the moment I heard the word I was
excited. Think about it –isn’t redirection what we wish to
do when we want to change our style of living after following a specific
pattern for so many years? I’m told that AARP wishes to drop the
R from its name, the American Association of Retired People. Why not
keep the R and change it to “Redirected”?
Redirect suggests moving in a different direction but continuing to
surround ourselves with stimuli to fulfill the remaining one-fourth of
our one hundred years.
My scientific research for the past many years has focused on the effects
of the environment on the brains – the external environment out
here and the internal environment inside each one of us. Our laboratory
experiments have focused on identifying factors that influence the well-being
of the brain, because the brain has the capacity to redirect its own
desires. What other cells can do that? That three-pound mass, which I
can hold in one hand, has the capacity to conceive a universe one billion
or more light-years across. Just think what those cells can do. The brain
is truly a phenomenal structure, and keeping it healthy for our entire
existence on earth is a goal we can and should aspire to. I am going
to touch upon five basic factors for maintaining brain health. You’re
going to say there’s nothing new about them, but I’m going
to be giving some scientific evidence of their benefit.
Number one, and in my mind the most important, is diet. What we feed
this brain significantly affects its well-being. Two, we must exercise
the body and the brain. Exercising not only the brain but the total body
is necessary to maintain a healthy brain. Three, we must challenge the
brain. It gets bored; we know that well. So we need newness, new things
in our life. And fifth–last but definitely not least—we must
share basic human love.
When studying the brain it is essential to keep in mind that development
and aging are a continuum. Your brain doesn’t just develop in the
first part of life and age in the last part. While your brain was forming
in the embryo, it was developing nerve cells at the rate of about 50,000
per second. Think of that explosive development—50,000 per second.
But before you were born you had already lost 50 percent of those cells.
Everybody worries about losing cells at the other end of the life cycle
when in reality you most more nerve cells before you were born.
Let’s start with a look
at the human brain, a phenomenal mass that weighs about three pounds—roughly
2 percent of our total body weight—yet gets a fourth of the cardiac
output. Have you ever watched your heart on an echocardiogram? I saw
mine the other day. I could see the valves opening and closing. What
a thrill to know exactly how it works. With every beat it pumps a fourth
of the cardiac output to the precious brain.
Equally wondrous is that no two human brains are alike. No two of you
will be listening to this lecture in the same way. No two of you will
wan away with exactly the same ideas and information. I hope you will
learn the message that I am trying to present about the dynamics of this
brain and about keeping the brain dynamic for a lifetime.
How does your brain feel about studying itself? The brain itself has
no feeling: You can cut it and it does not feel the injury. Sensory receptors
in other tissues initiate the impulses that bring the pain sensations
to the brain for analysis. Let us look at this diagram of the (see Figure
Ia and Ib). For me to be talking to you now, one part of my brain is
firing: Broca’s area, which deals with motor speech. Some people
activate motor speech in a broader area, some a little further toward
the front. But it is generally in the inferior area.
For you to be looking at this diagram your visual cortex, in the back
of the brain, if firing. You see stars when you get hit on the back of
the head because your visual cortex has been jarred. For you to be listening
to me, a little area in your superior temporal lobe is being activated.
The area of the cerebral cortex responsible for hearing is very small
in comparison with the amount of cortex devoted to seeing. For me to
be moving my pointer, the motor cortex is firing. The highest cognitive
processing is going on in the prefrontal cortex, just behind your forehead.
The prefrontal cortex is responsible for such functions as initiative,
judgment, working memory, planning ahead, sequencing events, and so forth.
Each part of the cerebral cortex has a general function, but it is obviously
has its very specific functions as well.
Diet and Brain Growth
Let us now return to the five basic factors responsible
for keeping our brains healthy and active during our lives. The first
is diet. Yes, diet is vital to the brains just as it is to our body as
a whole. For the brain to grow healthily from infancy, it certainly needs
protein to maintain and develop its nerve cells and their branches. Here
is a nerve cell (Figure2). In the outer layers of your brain your have
several hundred billion nerve cells. The processes developing from the
cell body are called dendrites. Dendrites receive input from other never
cells. Integration of the input takes place in the cell body, resulting
in an electrical impulse that continues down the axon, a fiver from the
cell body leading to the target tissue. The tips of the axon are not
continuous with the receptive dendrites on the next nerve cell adjacent
to it – there is a gap between them. An electrical impulse travels
down the axon to the tips, and then a chemical is liberated to cross
the gap and stimulate the adjacent dendrites. This chemical is called
a neurotransmitter. The neurotransmitter is liberated, crosses the gap,
and then the electrical impulse continues through the new dendrites.
When we first started working in the field there were
perhaps five neurotransmitters known. The other day I called Floyd Bloom,
the former editor of Science magazine. I asked him, “How many neurotransmitters
are known today?” He said at least a hundred. SO you get a glimpse
of the magnitude of chemical reactions in our brains. It’s a wonder
that any two people ever think alike and understand each other with such
a dynamic nervous system that must keep all there transmitters in proper
balance.
I am spending time on dendrites and axons because, whenever
we talk about the growth of the brain during development, we are primarily
considering the growth of dendrites and axons and other connections they
are making with other cells and target tissues. One nerve cell can get
input from as many as 20,000 other nerve cells in one part of the brain.
But most cells don’t have that much input. Each cell can do a tremendous
amount of computation, and we have more than a hundred billion cells.
Now let’s take a minute to talk about how dendrites
develop. In the frontal lobe of a newborn human’s cerebral cortex,
just behind the forehead, we can see very few branches on the nerve cells
as they begin to develop. By the age of two an enormous amount of branching
is going on. However, not all those dendrites have made appropriate connections
yet, which is why two-year-olds are sometimes difficult to deal with.
When my husband and I were teaching in Africa in 1988,
we found that in Nairobi, Kenya, women would not eat protein while they
were pregnant because they learned that they delivered babies there were
too large. By reducing their protein intake while pregnant they delivered
smaller babies. My immediate question was “What effect foes this
reduced protein intake have on the infant brain?” When we came
back to Berkeley, we started an experiment involving pregnant rats. We
fed half the pregnant rats a normal, high-protein diet and gave the other
half a low-protein diet. The body weight of babies whose mothers were
fed the reduced-protein diet was 50 percent less than that of babies
whose mothers has a normal protein diet. And the brains?
Dendrites in those baby rats whose mothers had reduced
protein just did not develop fully. When we put those babies in enriched
environments with lots of objects to explore, their dendrites did not
increase significantly, as they did in babies whose mothers had a normal
diet and enriched living conditions. We learned that it is important
to have a protein-rich diet to grow healthy nerve cells that can respond
positively to enriched living conditions.
In a follow-up experiment, we gave the low-protein-diet
mothers high-protein diets after delivery and gave their babies high-protein
diets after they were weaned-and then we got those dendrites to grow.
Furthermore, when we put the babies in enriched environments, their brains
benefited from the stimulation. These experiences and my ongoing studies
give me cause to worry about well-intentioned programs that focus on
children ages three through five. I believe that considerable money should
be directed toward good prenatal care. You can be certain that well-developed
embryonic and fetal brains are far more able to benefit later from Head
Start and other enrichment programs.
Returning to the dietary components that are key to
developing and maintaining a healthy brain, it has been validated that
choline is extremely important in the diet. Choline is necessary to form
an important neurotransmitters, acetylcholine, as well as enzymes that
help acetylcholine function appropriately. We have learned from Richard
Wurtman at the Massachusetts Institute of Technology that if you don’t
have enough Choline in the diet, the cell cannibalizes its own membrane
to make acetylcholine. So it’s extremely important to have choline
in the diet.
What are dietary sources of choline?
Soybeans and soy products. These days you will find
an increasing number of soy-based products on the shelves. We tofu advocates
have it with marmalade for breakfast.
Egg yolks. You say you are not going to eat egg yolks
because of their cholesterol, but if you have low cholesterol levels,
you can have egg yolks.
Peanuts. These are somewhat high in fat and sodium,
but use them moderately along with other source foods. My father always
had a big bowl of peanuts for us when we came home from school.
Liver. There are those who do enjoy liver! I do.
I mentioned only one neurotransmitter, acetylcholine,
but remember, you have about 100 different neurotransmitters serving
your body’s chemical needs. Other important ones are dopamine,
serotonin, and glutamate. You can look up the dietary sources for these
neurotransmitters in your spare time.
We have known for some time that vitamin B is essential
for the well-being of the nervous system. Let’s just take one B
vitamin, vitamin B6. B6 is important in the metabolism of amino acids,
which are related to the structure of protein. Vitamin B6 is vital to
the creation of neurotransmitters. What happens if we have a vitamin
B6 deficiency? Our memory is impaired, causing trouble with our ability
to register, retain and retrieve memory. A shortage of B6 also can lead
to nerve damage in the hands and feet. A few vitamin B6 sources: potatoes,
bananas, chicken breast, beef top round, turkey white meat, rice bran,
carrot juice, rainbow trout. Just a selection taken from the literature
to show you that there are many sources for B6.
Antioxidants are other important substances for the
care and feeding of the brain. Most everybody knows the major antioxidants,
vitamin C and vitamin E, and their food sources. The American Chemical
Society website lists rich sources of antioxidants—including blueberries
and strawberries. How many of us are aware that these are rich sources
in antioxidants?
We continue on just a little more on to interaction
of calcium and your parathyroid gland. Most people are familiar with
the thyroid gland in the neck, but did you know the parathyroid glands
act on cells in your bones to extract calcium for the bone in order to
raise your blood calcium. Everybody knows that calcium is important for
bone structure, but did you know that it is also important for nerve
impulse conduction? It is important for muscle contraction.
Exercise
Now let us turn to our second key factor in maintaining
a healthy brain: exercise. A recent article I read mentioned that lack
of exercise was responsible for increased incidence in sugar diabetes,
cardiovascular problems, obesity and depression. We know that exercise
improves skeletal muscle tone and function and that it helps our venous
return in our legs, indication the importance of keeping our legs active.
Exercise is essential to bring oxygen to all parts of the body—especially
the brain. What area of the brain has been shown to be subject to what
we call anoxia, or reduced amount of oxygen? The hippocampus (see Figure
Ib). The hippocampus deals with the processing of recent memory and visual
spatial processing. As we age and our blood vessels become less efficient,
it is very important to exercise to get oxygen through the vascular system
up to the hippocampus, as well as to the rest of the brain and body.
I like to always emphasize swimming as a good form of
exercise. When we get older we may walk a good deal using our lower extremities,
but do we use our upper extremities? Swimming exercises the entire body
including both upper and lower extremities. How many of you feel depressed
after you have sat indoors for several hours? I know I certainly do.
Exercise has been shown to benefit the balance of your neurotransmitters.
I also learned the other day that exercise has been
shown to benefit children with hyperactivity problems. Are our children
getting enough exercise sitting in front of their computers and video
games all day long? Everyone should have planned exercise for possibly
one hour each day—just as you brush your teeth and eat your breakfast
daily.
Challenging the Brain
I have come to challenge, a third vital component of
brain health. What I am about to say has been validated by my years of
laboratory research. In terms of successful aging, it is not enough to
continue activities in the same groove, year after year, with the same
expenditure of mental and physical energy. Remember Alice in Wonderland,
who discovered that on the other side of the looking glass a person had
to move very fast to stay in the same place? The underlying laws of physics
Lewis Carroll was playing have their correlate in neurophysiology: the
brain needs new challenges if it is to remain a healthy, functioning
organ. Translated, if you like to do crossword puzzles and you have been
doing the same kind of crossword puzzles year after year, try more complicated
puzzles next time or introduce a new game that will challenge different
skills that are lying dormant.
In order to get ideas about human brain function we
look at rat brains, which have many of the same basic patterns of brain
structures as humans, only rat brains are the size of pecans whereas
our brains are the size of cantaloupes. I offer the results of one of
our rat experiments dealing with “enriched” and “impoverished” environments.
In the enriched environment, 12 rats live in a large cage and have objects
to play with. It is important to have something challenging in the cage
with these rats. In contrast, the impoverished environment houses a rat
who lives all by itself with no objects to challenge it. These two experimental
conditions were compared with a control group of rats living in three
to a cage in a small cage, which is the standard laboratory way of housing
rats.
Examining and comparing brain tissue from each of the
three groups yields a wealth of information. The outer layers, just like
those in our brains, are called the cerebral cortex. Cortex means “bark.” The
cortex is a dynamic structure—parts of the human cortex have sent
humans to the moon. The thickness of the cortex is one of the first measurements
we make because it is simple and lets us know if changes are occurring
in the constituents of the cortex, namely, neuron number and size, dendritic
growth, synaptic growth. In our little rats we an measure what happens
to the cortex when we put the animals in different environments. First,
we measured the difference in cortical thickness between 24 pairs of
enriches and nonenriched male rats. We found that the rats living in
enriched environments demonstrated some changes (increased thickness)
in the frontal area, no changes in the general sensory area and dramatic
changes—7 percent—in the visual cortex.
As in most of the work done with laboratory animals,
we wanted to determine whether female rats would respond in the same
way. When we measured the difference in cortical depth between 23 pairs
of enriched and impoverished nonpregnant female rats, we saw some changes
in the frontal area, some changes in the general sensory cortex, and
4 percent change in the visual cortex, not quite as much as in the males.
My students suggested that we challenge the enriched females to see if
we could bring that visual cortex up to the level of the males. Sure
enough, we did. How? We put obstacles in front of their food cups. Every
time they wanted to eat they had to climb over all those obstacles. Now,
did we try to bring the male general sensory cortex up to that of the
female? No, that’s an experiment we saved for future students to
complete.
Why is thicker better? Psychologists have tested the
rats living in enriched or impoverished conditions and found the enriched
rats ran maze tests faster than did the impoverished. Evidently more
dendrites—thicker cortices—indicate a greater ability to
solve problems. With humans, we purposely have to work harder as we age
to set up challenges for us. It’s hard to add additional challenges.
There are obviously different kinds of challenges. Here’s
another experiment we conducted on rats. We put a rat in one corner of
a maze and food in the opposite corner. The rat ran right to food. The
next day we put one barrier in the box. The rat had to run around the
barrier to find his food. The next day another barrier and so forth.
Pretty soon we had 19 barriers, so he really had to learn to get through
barriers to find food. Simple task. How much of the brain changes when
we challenge it with a simple task? We found 6 percent changes, but only
in his visual cortex. That’s a statistically significant difference,
but only in one area because the rat is only dealing with one kind of
challenge. In multi sensory enriched environments we change most of the
cerebral cortex, not just a single area.
A single-input challenge changes just a single area
of the brain. So children (or adults) sitting in front of computers all
day long are being fed a specific input. Multi sensory enriched environments
involve varied toys, sociability and changing stimuli. Now, you may ask,
what is most important in the enriched environment? Sociability—having
all the rats living together—or just being surround by challenging
objects? Other investigators conducted experiments in which 12 rats were
put in an enrichment case with no toys. An increase in the cerebral cortex
occurred but it was not as much as when 12 rats were in a cage with toys.
Then one rat was placed in the enrichment cage by itself with toys. Its
cortex changed much less than that of rats who lived with toys and other
rats. So both sociability and challenge are important. I can tell you
how researchers got the rat living alone with the toys to experience
greater changes: They gave it methamphetamine, and it ran around and
interacted with the toys. We certainly do no recommend this approach!
Thus, we’ve been able to show that these experimental conditions,
the stimulus objects plus the friends, were both necessary to create
the most significant changes to the brain.
Another condition we wanted to investigate besides the
thickness of cortical tissue in these experimental groups was the impact
of enriched and impoverished environments on a substance called lipofuscin.
Lipofuscin is an “aging pigment” that accumulates in your
brain as you age. It is thought to interfere with the normal functioning
in nerve cells. You do not want nerve cell bodies filled with an aging
pigment because they normally are busy producing proteins to supply their
many functions. We found that rats put in enriched environments produced
less of the aging pigment in their brains. Just another plus for having
challenge and activity in the brain throughout one’s lifetime.
Brain Challenges and the Immune System
Our most recent research has focused on human beings.
A secret passion of mine was to find a relationship between the cerebral
cortex and the immune system. The immune system is, of course, extremely
important to our health at all ages, and certainly it is critical to
successful aging. The results of our research, which are just being published
now, made it into the press around the world. We learned a great deal
about people who challenged their cerebral cortex to affect their immune
systems, even thought they didn’t know that’s what they were
doing.
From our animal studies we’ve learned that the
dorsolateral frontal cortex was related to the functioning of the immune
system: The dorsolateral frontal cortex was deficient in immune-deficient
animals. How did we learn that? In 1980, the French stripped off most
of the cerebral cortex in their mice and they found that this process
affected the number of circulating T cells in the blood. We had to find
out which part of the large cortex specifically affected the immune system.
Eventually we found an area on both the right and left
cortices that was thinner in immune-deficient female mice. (These immune-deficiency
studies were all done with female mice because the French started with
females.) The immune-deficient mice had no thymus gland, which is responsible
for producing T cells. The thinner cortical area is called the dorsal
lateral frontal cortex. The rest of the cortex was fine as far as we
could measure. When the thymus was transplanted back into the immune-deficient
animal, the deficiency in the cortical area was reversed. So we know
we have an area of the cerebral cortex related to the immune system.
It was my dream to find this area of the cerebral cortex,
because it is under voluntary control. I say I want to pick up this pointer,
I do it. That’s voluntary control. Can we voluntarily, then, stimulate
this area? We learned that experimenters had given schizophrenic patients
what is called a Wisconsin Card-Sorting Test, which is good for clinically
testing psychological factors. While the patients were undergoing the
card-sorting test, they had a PET scan, which showed that the test activated
the dorsolateral frontal cortex.
Most people haven’t heard of the Wisconsin Card-Sorting
Test because it’s primarily used clinically. We wanted a card game
that everybody had heard of—say, bridge. The game of bride uses
working memory. It uses planning ahead. It uses sequencing and initiative
and judgment. All of these are functions of this part of the cortex.
We had 12 women come to the lab to play bridge with
one another. We took blood from them before they started playing to measure
the initial level of their T cells. Then we took blood from them after
playing bridge for an hour and a half, and found that they had significantly
increased a specific type of T cell. The before-and-after data were exciting
to us because we found a significant increase in their CD4-positive T
lymphocytes. We did not find such a T cell increase in the blood samples
of the control women who did not play bridge, but sat listening to quiet
music during the time the others were playing bridge.
We were terribly thrilled with these new results. Clearly,
the cerebral cortex plays a role in controlling the immune system. Now
we have to learn to “educate” that dorsolateral cortex and
help keep our immune system healthy. This is just a preliminary study.
It has to be replicated and followed through. But to me it was a very
exciting moment.
Now, what happens if the brain is damaged? Our students
conducted another series of experiments in the late 1980s to find out.
We found that if you lesion the left motor cortex in a young, sexually
mature rat, it will lose the function of its right forepaw. They did
this to a number of rats, and then put half in nonenriched (control)
environments and half in enriched environments. When they looked at the
brains of rats placed in nonenriched conditions, they found that dendrites
did not grow very much around the lesion, on the opposite side or back
in the sensory area of the cortex. But in the enriched environment those
dendrites grew significantly. The dendrites grew around the lesion. They
grew in the opposite side and they even grew back in the somato-sensory
cortex. From these findings we can only conclude that, even when brain
damage is present, animals living in a stimulating environment are able
to compensate for the damage. Look at the promise that holds for our
species who receive some degree of brain injury. Newness
Versus Overstimulation.
What happens if you overstimulate
or over enrich the brain? My
conversation with a pediatrician concerned that children are being
constantly bombarded with new experiences inspired the following
experiments. In our previous experiments with rats we just
changed the toys in the cage two or three times a week. “Newness” is
an important part of challenge, so we had to change the toys. Otherwise,
the brain at first increases and then decreases with boredom. It
needs stimulus to keep those dendrites extended. In our new
experiment, instead of changing toys two or three times a week,
we changed the toys at seven o’clock at night, eight o’clock
at night, nine o’clock at night, four nights a week for four
weeks.
We bombarded those little rats with stimulation. We
didn’t know if we were going to see huge brains, or not—that’s
the fun of research. It
seems that the significantly different results we had recorded between
the enriched and nonenriched rats in our original experiments did not
continue to increase when we stepped up the frequency of changing the
toys for the enriched group.
So, with too much coming in we did not increase the
enrichment effect; it was less. Stress reduces the cortex at the same
time that enrichment tries to increase it. What
stress factor is involved? Corticosterioids
coming from the adrenals. Corticosterioids reduce the cortical
thickening. We take out
the adrenals and the cortex grows significantly. It
shows how much the cortex is normally being held back by Corticosterioids.
The lesson for humans? Too
much stress decreases the dimensions of the cortex and is detrimental
to our well-being at any age. So when we teach for the schools we mention
that children must learn in environments with more enrichment than
stress. Too much stress decreases the dimensions
of the cortex.
Love and Nurturing
Our last subject,
oddly enough, is love. A
little background: We had started our experiments using young rats,
which are readily available and easy to work with. We
found they were growing dendrites with enrichment. We then decided to raise our rats to
see if we could change the brain in middle-aged rats. So
we raised rats up to 600 days of age, equivalent to 60-year-old humans. We
put half in enriched conditions and half in nonenriched conditions,
and we could still find increases in the cerebral cortex with enrichment
to the brain. But we were beginning to lose the animals
at 600 days, so we could not come up with conclusive results on middle-aged
rats.
Following the publication
of our findings, I was invited to the German Academy of Sciences to
report on my work. While
I was there, I was struck when a scientist there who said that the
German rats lived to be 800 days. I
came back to Berkeley wondering how were we going to get our rats to
live longer?
We tried to figure
our what was missing in the design of our experiment. When I would talk with groups of older
folks around the country, I felt that many of them just weren’t
getting enough attention, enough TLC, enough daily kindness. Sure,
they had their televisions, they had good food, but where was the love? We
didn’t see it. So we decided to give our rats love.
Instead of just putting
them in little cages when the rat cages were being cleaned, we held
the rats against our lab coats and we petted them. We
got those rats up to 766 days, put half of them in non-enriched environments,
and at 904 days—equivalent to 90-year-old-people—we were
still finding thicker cortical tissue among those rats maintained in
enriched conditions. Number
one, we got them to live longer. Number
two, we got those brains to change. How
can we not conclude that stimulating the brain works its magic right
up until the end, and may even prolong life? Why
do you think Arne and I haven’t retired?
We used to believe
as scientists that the loss of dendrites was an inevitable correlate
of the aging process. It
was simply our fate. Yes,
it takes concerted attention to stave off the “inevitabilities” we
have accepted for so long, but is the price really that high? Is
it too much work to follow a healthy diet, enjoy plenty of exercise,
seek out new challenges and get lots of love? My
own life and work have been enriched immeasurably by two statements
I absorbed many years ago. How
fortunate that my English family crest states, “Love conquers
all.” My Swiss grandmother
added, “In spite of all difficulties, upward and onward.”
A good combination.
|
