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)