Part 3 of the TED Radio Hour episode Headspace.
About David Anderson's TED Talk
Neurobiologist David Anderson explains why psychiatric drugs don't always work, and how researchers are working to find targeted forms of treatment — including his own experiments with fruit flies.
About David Anderson
David Anderson is the Seymour Benzer Professor of Biology at the California Institute of Technology. He is also an investigator at the Howard Hughes Medical Institute.
By studying the brains of lab mice and fruit flies, he searches for answers to some big questions: How is emotional behavior encoded in the brain? Where do depression, anxiety and other emotions originate in the brain?
By looking at how neural circuits give rise to emotions, Anderson hopes to advance a more nuanced view of psychiatric disorders.
GUY RAZ, HOST:
It's the TED Radio Hour from NPR. I'm Guy Raz. Our show today, Headspace, ideas about our approaches to emotional well-being.
DAVID ANDERSON: You know, all of us have family members that have dealt with some aspects of anxiety or, you know, depression, other things, and friends as well.
RAZ: Or us - or we have.
ANDERSON: That's right.
RAZ: And that's actually what led David Anderson, who's a neurobiologist, to study the connection between the brain's circuitry and our emotions.
ANDERSON: Emotion is absolutely central to understanding everything that happens in our brain.
RAZ: But that's actually a kind of unusual thing for a neurobiologist to focus on. Because most people like David, who study the circuitry of the brain, are concerned with how we think, and not many scientists look at that same circuitry to understand how we feel.
ANDERSON: Our perceptions, our decision-making, our actions, our planning - everything is affected by emotion. And yet, emotion has been relegated sort of to the area of psychology. And it's really frustrating to see how primitive the state of medicine is. And it's because of our deep lack of understanding of the underlying biology.
RAZ: For example, think about how medicine works when it comes to our bodies.
ANDERSON: If you're suspected of having a cancer diagnosis, you go to your doctor and you get bone scans, biopsies, blood tests, liver function screens.
RAZ: But when it comes to our minds...
ANDERSON: If you worry that you might be depressed, you go to your doctor and you get a questionnaire.
RAZ: So David's idea is that as much as we're able to open up about our emotions, there are still so much more our brains can tell us about how they work. So why don't we have a more scientific approach to mental health? Here's David Anderson's theory, as told on the TED stage.
(SOUNDBITE OF TED TALK)
ANDERSON: Part of the reason for this is that we have an oversimplified and increasingly outmoded view of the biological basis of psychiatric disorders. We tend to view them - and the popular press aids and abets this view - as chemical imbalances in the brain, as if the brain were some kind of bag of chemical soup full of dopamine, serotonin, and norepinephrine. This view is conditioned by the fact that many of the drugs that are prescribed to treat these disorders, like Prozac, act by globally changing brain chemistry as if the brain were indeed a bag of chemical soup. But that can't be the answer because these drugs actually don't work all that well. A lot of people won't take them or stop taking them because of their unpleasant side effects. These drugs have so many side effects because using them to treat a complex psychiatric disorder is a bit like trying to change your engine oil by opening a can and pouring it all over the engine block. Some of it will dribble into the right place, but a lot of it will do more harm than good.
Now, an emerging view is that psychiatric disorders are actually disturbances of neural circuits that mediate emotion, mood, and affect. When we think about cognition, we analogize the brain to a computer. That's no problem. Well, it turns out that the computer analogy is just as valid for emotion. It's just that we don't tend to think about it that way. But we know much less about the circuit basis of psychiatric disorders because of the overwhelming dominance of this chemical imbalance hypothesis.
Now, it's not that chemicals are not important in psychiatric disorders, it's just that they don't bathe the brain like soup. Rather, they're released in very specific locations and they act on specific synapses to change the flow of information in the brain.
RAZ: So the way we behave, the things we do, the way we feel - they're electrical currents.
ANDERSON: Yup. And there are very telling, although anecdotal, examples from the work of a famous neurosurgeon in Canada, named Wilder Penfield, who was stimulating different regions of the brain with electrical current. And in some patients, that brief electrical stimulation could evoke a whole emotional response like a feeling of panic, or sudden crying and sadness, by stimulation of particular neurons in particular circuits.
RAZ: Now, an experiment like that, it's kind of hard to do with human subjects today. Wilder Penfield did his in the early 20th century. So David's figured out a different way to find where specific brain circuits influence specific emotions. And instead of humans, he uses...
RAZ: What's a Drosophila? Sorry.
ANDERSON: It's commonly referred to as a fruit fly.
RAZ: A fruit fly.
ANDERSON: Yeah. It's just amazing to me that something so small packs so many complex and interesting behaviors into its tiny little brain.
RAZ: OK so you might be wondering, how can fruit flies tell us anything about human emotions? Well, it turns out you can trigger something that is, neurochemically speaking, pretty similar to human emotion in the brain of a fruit fly. So David and his colleagues design an experiment to see...
(SOUNDBITE OF TED TALK)
ANDERSON: If flies could be provoked into showing the kind of behavior that you see by the proverbial wasp at the picnic table, you know, the one that keeps coming back to your hamburger the more vigorously you try to swat it away, and seems to keep getting irritated? So we built a device, which we call a puff-o-mat, in which we could deliver little brief air puffs to fruit flies in these plastic tubes on our laboratory bench and blow them away. And what we found is that if we gave these flies in the puff-o-mat several puffs in a row, they became somewhat hyperactive and took a while to calm down. More puffs, or more intense puffs, make the state last for a longer period of time.
RAZ: Now, that hyperactivity, even though we're talking about the brain of a fruit fly, actually relies on the same chemicals you and I have in our brains.
(SOUNDBITE OF TED TALK)
ANDERSON: That's right - flies, like people, have dopamine, and it acts on their brains and on their synapses through the same dopamine receptor molecules that you and I have. Dopamine plays a number of important functions in the brain including in attention, arousal, reward. And disorders of the dopamine system have been linked to a number of mental disorders including drug abuse, Parkinson's disease and ADHD.
RAZ: OK so dopamine functions differently in the brain depending on where in the brain you're talking about. So in some areas, it can make you hyperactive, and in others, it can calm you down.
ANDERSON: And in order to understand what's going on in a particular disorder, like ADHD or depression, we need to understand the where in the brain as well as the what.
RAZ: We can't do that in humans - at least, not yet - but in the brains of the fruit flies...
ANDERSON: We were able to see where in the brain this dopamine receptor was expressed and to find out where that dopamine receptor actually had to function in order to control this calming down.
RAZ: And once David found the dopamine receptor, he could put the fly under a powerful microscope.
ANDERSON: You're literally peering down a lens into the brain of a living fruit fly...
ANDERSON: ...And watching neurons blink on and off while that fly is behaving or smelling or responding to some other stimulus.
RAZ: OK this is not brain surgery. It's fly brain surgery. And at this level of detail, David can actually take that tiny fruit fly dopamine receptor and turn it off and on.
(SOUNDBITE OF TED TALK)
ANDERSON: So when we take away the dopamine receptor and the flies take longer to calm down, from that we infer that the normal function of this receptor - and dopamine - is to cause the flies to calm down faster after the puff. And that's a bit reminiscent of ADHD, which has been linked to disorders of the dopamine system in humans. So slowly, I began to realize that what started out as a rather playful attempt to try to annoy fruit flies might actually have some relevance to a human psychiatric disorder.
RAZ: Is there a connection you can make between what you're finding and what might actually be an effective way to treat some of these illnesses?
ANDERSON: I would say it's a little too early for that. I wish there were, but we are able to identify the genes that are turned on in individual types of neurons, and that might lead to the discovery of new potential drug targets.
RAZ: So if today, right, when you are treated with Ritalin for ADHD or Prozac for depression, could you imagine in, like, 50 years, not actually taking a pill but getting something like an electrical pulse, you know, to specific a part of your brain?
ANDERSON: You could imagine getting an electrical pulse, but you could also imagine delivering an electrical pulse to your brain by taking a pill. So technologies are developing now that allow us to activate neurons with chemicals that act on a receptor for the drug, which is genetically targeted to a particular type of neuron. And the pill would only go to the part of the brain where you need it to correct the symptom. To go back to this engine oil analogy, you'd be pouring the oil into the place where the engine oil goes and not just slopping it all over the engine block. That's the dream.
RAZ: David Anderson is a neurobiologist and a professor at Caltech. You can see his full talk at ted.com. Transcript provided by NPR, Copyright NPR.