Transcriber: Gabriel Meira
Reviewer: Hélène VERNET It is such a wonderful experience
to be here in beautiful Bermuda! Thanks for coming out today. Like most of you,
we don't get a lot of downtimes, but when I get some downtime,
I really love to read a mystery. It seems that our brains, our human brains with all
of our complex circuits, are uniquely designed to put
the pieces of the puzzle together and to solve mysteries. But one mystery that's really
been troubling me lately is the mystery of why, in the midst of a multibillion-dollar
antidepressant industry, depression rates continue to go up. About 300 million people across
the world today experience depression. And this isn't good, we need
to do better; it's unacceptable. It makes us think that maybe
there're some other suspects, some other clues where
we can get some information about how to come to the solution
and solve this mystery of depression. Well, one area where we spend
a lot of time looking for clues is neurochemistry. This makes perfect sense because our brains
are swimming in neurochemicals: dopamine, serotonin,
acetylcholine, glutamate. And they have a huge impact on
our behaviors, emotions, and thoughts. So it makes perfect sense to think
that we could take a pill that could change our neurochemistry
in ways that would make us feel better to be emotionally resilient. But there are challenges with this
because it's hard to mimic Nature, in that, if there is an imbalance that is
associated with something like depression, how do we make it take-a-pill and change the neurochemistry
in these natural ways? So it's not very precise, and, unfortunately, it doesn't reliably
help everyone who has depression. So it makes us think there're some
other clues and suspects out there. So being a neuroscientist,
when I go back to the drawing board - that drawing board is a brain - and I want it to be,
as I tell my students, "let's be brain whisperers of a sort
and see what is important to the brain," what really stands out to me is how our brains seem
to be designed and evolved to move our bodies around. We like to think that our brains
are about thinking, but movement is an incredibly
important behavior. If we think about the cerebellum
hanging off the back of our brains, it contains about 80%
of our brain's neurons. Eighty percent! Anf what does a cerebellum do? Well, a lot of things,
but it's most noted for its role in controlling
our motor coordination and the areas around the center
of the brain called the "striatum" also involved in coordinating
and facilitating our movement. In fact, individuals who have
Parkinson's or Huntington's disease have some impairment of this system. Then going from the middle
of our brain down to our ear is the motor cortex which is involved
in moving the specific muscles that are important for us
to initiate and carry out that behavior we want to carry out. And if you look at the proportion
of that motor cortex and the muscles that it's
coordinating and controlling, the area that controls
the hand is just proportionally large. It seems like Nature is telling us,
"Movement is incredibly important." And movement of our hands
is also very important. And if that's true,
what would happen if say, we decided that we weren't
going to move around as much? Maybe we're going to spend a lot
of time sitting down in front of screens. Would that have some impact
on our brains? Maybe so. And it's interesting to think
over the past century just how much our lifestyle has changed. It's about a hundred years ago - well, over these hundred years - but it is hard to believe
that in just 1939, the New York Times ran
an article about this invention that was revealed at the World's Fair. It was called "television".
It was really a "neat thing," they said. But they said it will never be more
popular than the radio because "what family has time
to sit in front of a TV in the evenings and not use
their hands to do work?" Wow! Things have really changed
over the last century and past generations. When I think about my own childhood, driving back to Talladega, Alabama,
to see my grandparents, I have vivid memories of how busy,
especially my grandmother was. After working in a factory,
her downtime was spent shelling peas or shucking corn or snapping
green beans on that front porch, only to be followed by freezing
and canning and preparing that food so that in the winter
when she would bring that food out and prepare these wonderful
Sunday dinners, I saw the pride on her face
because now, thinking back, she had to bring up these memories of the role she played
in providing that food for her family. And it really made me see this pride. And if someone was sick
in her community, I remember her saying -
I'm from Alabama - "Bless her heart! She couldn't
have her own garden, so I'm going to take her these vegetables, so at least she can prepare
them for the winter." Wow! how things have changed! I'm beginning to think
that maybe when we traded in our spears and our clubs
for selfie sticks, that maybe we've traded in
something really important for our brain. And what if our cultural
contemporary ideas of prosperity in which we work really hard to make enough money
to pay people to do the things our grandparents and ancestors
used to do very well for themselves, maybe that doesn't match
our brain's idea of prosperity, and maybe that mismatch
could lead to some contribution to psychiatric illness, these high rates
that we're seeing today. In fact, our ancestors' dependence
on their hands in interacting with the environment to provide the resources
just to live for that day, might have been the original Prozac,
the prehistoric Prozac, that perhaps we need to remember. But this idea isn't new. Charles Darwin,
who was the great naturalist, wrote that he had a lot of angst
when he was dealing and writing and musing about
this idea of natural selection and how controversial it was, and the impact it would have
on his family and friends and their ideas about religion
and the origin of our species. And he said that, when he would
walk around his property, and there was a path
called "the thinking path", that it would calm his nerves. He would put a rock at the gate,
and he would have his walking stick, and when he would walk around
that path he would knock that rock off to signify the effort that he had made. And if it was an especially
stressful day, he'd put two rocks. And in an even more, he might
have a three-rock walk, and he would have to walk three times
and knock that stone over. Well, he wasn't just realizing
that his behavior was important in regulating his emotions,
but he was even dosing himself whether or not he was going to have
one walk, two walks, or three walks a day. So this idea of behavior, he saw that it was important
for regulating his mental health. And in the days when cake mixes came out,
mostly women making the cakes those days, the first cake mix had everything
you needed to make the cake. You just needed to pour
the batter in the pan, but some very smart manufacturers noticed that women didn't take
as much pride in their cakes if they didn't have a little
skin in the game. So, they didn't have to,
but they took the egg and water, so you would have to add
the egg and the water. They get a bit more effort and
people were more proud of the cake. (Laughter) So, thinking that behavior
is important for our mental health, and that we can change our
neurochemistry through behavior as our ancestors have, caused me to think about a new word,
a word I just made up: "Behaviorceuticles." We can change our neurochemistry by taking a pill that will alter
our neurochemistry, or maybe we can change
our neurochemistry strategically by engaging in smart behaviors
that will change it in more healthy ways. Well, I was reading that,
about a hundred years ago, doctors used to prescribe knitting
to women in those days, that they described
as "overwrought" with anxiety. They didn't know why, but they saw
that it calmed their nerves, kind of like Darwin. Knowing now what we know about
neuroscience, this makes perfect sense. Serotonin is increased when
we're engaged in repetitive behavior. And knitting and making the stitches
is an example of repetitive behavior. As the knitter is thinking about
that beautiful scarf or hat, that she or he is making,
that increases dopamine. It's known as the pleasure
neurochemical of the brain, but it's mostly involved
with anticipation, looking forward to something. And as you think about the stitches
instead of the worries of the day, that probably calms
and reduces stress hormones. And if there was one neurochemical
that probably is a culprit, a suspect, in a lot of the mysteries related to
mental health, it's the stress hormones, cortisol for example. About 50% of everyone diagnosed
with depression has high cortisol levels. So anything we can do
to decrease the stress hormones is an important endeavor. And if we're knitting
in the company of friends, then that may increase oxytocin, and oxytocin is known
as the cuddle chemical, but it's important in fostering
positive relationships, and also probably reduces stress. So here you go, a behaviorceutical
with one activity of knitting. It may be cooking or
woodworking or gardening, but something that's reminding you that the result of your physical
effort is some reward. So, I'm a neuroscientist, so
we want to go back to the brain. Remember the drawing board here. And I was fascinated to see that the area of the brain
that is involved in reward, that is impacted in depression -
lack of feeling that reward - is the nucleus accumbens,
kind of lower in the brain. It has rich connections to that area
of the brain involved in movement called "the striatum". And those areas have indirect
and direct connections to the frontal cortex that is involved
in our decision making and planning. The more that we engage in behaviors where we can see
the result of our effort, those circuits are consolidating so that, as we go forward
for the next challenge in our lives, we have a little experiential
capital to bring with us, to remind us that what we do
can make a difference. We did produce that scarf,
we made that cake, we walked around the thinking path. I work with rats for a living. These are my colleagues
and they outsmart me all the time. As a scientist, we need evidence, so all of that theorizing
about our ancient humans and ideas about depression
started to make sense but, I wanted to take this to the lab. A lot of friends, people
who find out what I do, they ask, "But what can you
learn about our brains, our fancy-schmancy brains,
by looking at this very simplistic brain?" Well, it is true that it's small - it's 2 grams compared
to our about 1400-gram brain - but it has all the same parts,
all the same neurochemicals, and if I showed you a neuron, that individual cell in a human
brain versus a rat brain, you wouldn't be able
to tell the difference. So it's a wonderful model to start with. I realize that a rat is not a little
human, and we are not a big rat, but it's a good model -
well, some of us maybe. (Laughter) So, when I was thinking
about putting these rats to work - I'm thinking about this idea about work and producing products
that we're proud of - I needed something
the rats would work for, and our rats love Froot Loops. So, we had to get them
addicted to Froot Loops. Then I needed a task, and I thought
back of my grandmother's garden. And I wanted them to harvest something. So we came up with a task where
they would harvest Froot Loops, not fruit or vegetables,
but they would dig up Froot Loops. So they have this arena and we move
around these mounds of bedding and they were trained so that they
would see a mound and gently dig and voilà! there's a Froot Loop. And they had an opportunity
to get four of those every day. So it is not intensive training, it's about five or ten minutes
a day for about six weeks, but they're building those connections
between the reward areas of the brain and the motor movement areas of the brain
to produce effort-based rewards. Well, for proper science
you need a control group to compare to this experimental group. So, our control group was a group
that we put in the same arena, and we gave them Froot Loops
regardless of what they did. So my students like to call,
the experimental group, where their reward was contingent
upon their behavior, "The worker rats," and the rats that got
the reward no matter what - there wasn't a contingency there -
"The trust-fund rats." So we have the worker rats
and the trust-fund rats. (Laughter) So we've done several studies - I see you can relate
to that a little bit - where we wanted to put
our worker rats to the test, to see if this effort-based reward
training generalized to other things. So we like to expose them
to new challenges, like swimming - they've been in a lab,
they've never been in water. Well, the effort-based reward worker rats
are more likely to dive down, like little rats scuba divers,
to explore the environment. They showed more evidence
of effective coping. And when we look at their brains,
I think brains are gorgeous here, they show more evidence
of neuroplasticity, that fertilizer, brain-derived
neurotrophic factor, more complex connections with the neurons. So, we see this neuroplasticity. For the interventions
and therapeutic approaches that we have currently for depression, most of those directly or
indirectly increase neuroplasticity, but here we're doing it naturally. But that was with training. We wanted another way
to stimulate effort-based rewards that was more spontaneous. So, we've known for a while that if you put a rat
an exciting and engaging world, something called "enriched environment,"
kind of a Disneyland of sorts, they're busier and they
have more neuroplasticity and it seems to be great for their brains. So we did this. We also look at artificial
kind of manufactured stimuli, and more natural stimuli. So, we have our country rats
and our city rats. They seem to be equally smart,
but our country rats seem to have an edge
on emotional resilience. So, they are more like
those effort-based reward rats that will go out, the bold ones. And also, with our effort-based reward
rats, we see lower stress hormones and higher hormones of resilience, and remember we said
that was important for mental health. Interestingly, we also found that when we have a group
of rats in an enriched environment and a group of rats
in just a standard environment, they do things more together, not only
engaging with their environment, but through cooperation. So, we've actually shown that their
oxytocin that we talked about increases when they're engaged
in these natural enriched environments doing things together. And that's important
for our "behaviorceutical" cocktail. This doesn't surprise me,
because recently in Denmark, they showed that humans -
they followed about a million - who grew up in a household
with more green around it, shrubs, trees, were up to 55% less likely
to experience depression in their lives. If we could bottle that,
that would be amazing. So, where does that leave us? We're not going to go back to the cave
or to being hunters and gatherers. We're here in this advanced
technologically rich world, and we benefit in many ways from that, but looking back at what we know
about our ancestors and the brain, and my wise rats, I think it reminds us that we need to remember
our evolutionary roots as we go forward
in this world of technology and have a little bit
of those effort-based rewards, especially if it's related
to Nature in some way, to help us with our mental health. I had an experience
where I got to put this to the test to see if an engaged enriched environment would allow the rats
to show healthier brains, and I had a colleague who asked me, "Kelly, can you teach
a rat to drive a car?" I thought "why would I want
to do that? That's not natural." This goes against everything I thought,
but we drive cars and before I knew it, we were talking about
how you'd get a rat to drive a car, and how you'd shape it to go in. We decided that we'd grab
the little copper bars, and of course, they would be
driving to a Froot Loops tree. That's their drive-in. If you've ever wondered if you
can teach a rat to drive a car, yes, you can. Not only can they drive,
but they can steer, they're autocorrecting, right? This blew my mind, but
more relevant for this story is when we looked at rats that were
in an enriched environment versus the standard environment. The rats in the enriched environment, when
we took them through the ropes of driving to see how long it would take
them to learn to drive, the criterion for robust driving,
they learned in 22 trials. The standard rats, we don't
know how long it would take, they never really learned to drive. This blew our minds
that the enriched environment made our rats better
learners of technology. So, we think that our enriched rats
would get their driver's license, but not so much for the rodents,
they would be denied. (Laughter) So, as we think about our brains
and what they evolved to do, the idea of taking a single pill
and being able to replicate what goes on in our brains naturally
seems just about as unreasonable as thinking that we could take
a pill to be a better parent. You just can't do that,
you have to go through the ropes. You have to have
those experiences to go forward. You have to have the behavior
that leads to "behaviorceuticals" to change the neurochemistry
in healthy ways. So, I started with a mystery,
what's going on with our brains? why are these rates increasing? And looking back and thinking
about how our behavior can change not only our neurochemistry
but our neuroanatomy, I think that the solution and clues
may have been in our hands all along. Thank you. (Applause)
