The Anxious Brain

“Since the 1960s, billions of dollars and probably millions of animals have gone into the search for new and better anti-anxiety medications,” said researcher Joseph LeDoux at an event this week on anxiety at the American Association for the Advancement of Science. But drug makers, who have spent years targeting points along a brain pathway described as the “fear circuit” in animals, haven’t had the success they sought; they have stopped funding many studies. Why?

LeDoux, a Dana Alliance member at New York University who has studied this circuit for the past three decades, argues that the term we use may have blinded us to what the circuit actually does. Instead of labeling it with a human feeling, it would better to call it an unconscious “defensive survival circuit.” Other inputs lead to the conscious feelings of fear and anxiety. For example, while hiking, we have already recoiled from the snake on the trail before our conscious minds have hit the danger signal. The two things happen so fast, though, it’s easy to think the feeling led to the action—but we’re committing the first sin of science: confusing correlation and causation, LeDoux said.


From left: moderator Mark Frankel, Joseph LeDoux, and Daniel Pine field questions from the audience.

So while some anti-anxiety drugs might not make us feel less anxious, they still may be working on this unconscious signaling, which we share with animals. For people, different treatments might be needed to dampen response and to relieve anxiety: They may have to be treated separately, perhaps the unconscious one first, he said.

LeDoux explained how he had come around to this idea during this talk and also at one we attended last year; he expounds upon it in his book Anxious, which came out last year. This time, he shared the stage with researcher and clinical doctor Daniel Pine; the two co-authored a recent paper in the American Journal of Psychiatry, “Using Neuroscience to Help Understand Fear and Anxiety: A Two-System Framework” (behind paywall; see also an NIMH summary of the paper).


Slide by Joseph LeDoux

“Joe is really interested in understanding how the brain lets us feel many emotions, including fear,” said Pine, chief of the section on development and affective neuroscience at NIMH. “But I’m also interested in using this knowledge” to improve treatments. Their collaboration, he said, was a good opportunity to show how science works best, and can lead to new ways to help people.

One area in which doctors wish to have better diagnostics and treatments is in helping children who show signs of persistent anxiety. Studies by Pine’s group and others show that anxiety is “incredibly common” in children, and usually it goes away as they mature. But “that minority of children who have persistent problems will mature into the majority of adults with mental illnesses,” especially depression, he said. “It’s important to treat anxieties because fixing it might prevent depression [later].”

In people with anxiety disorders, he now hypothesizes that something is wrong with the conscious and unconscious circuits, “but the reaction is so rapid they can’t tell you how, and you can’t solve it by talking about it,” he said. So he has tried a two-part therapy: Using a computer game that retrains attention, together with cognitive behavioral therapy. This approach is “one concrete way that basic science discoveries leads to treatments,” he said.

Pine thinks research into treatments will pay off first, before research that would help us better diagnose disorders. “We’re not going to get new tests really soon, but we are going to get new treatments.” fMRI, for example gives us clues to what might be going wrong in the brain and also a way to test if a drug is altering pathways, such as measuring amygdala activation when people are exposed to fearful faces.

Still, it’s important to remember that fear and anxiety are normal and useful feelings: A little bit of anxiety is needed to get you to study for the test, for example, but too much can make you too stressed-out (“flood the circuit” as LeDoux put it) and reduce your performance.

Here’s the full video from the event:

This event was part of the Neuroscience and Society series, supported by AAAS and the Dana Foundation. Previous sessions include Closing the Cognitive Skills Gap in Children (story, video) Growing Older and Cognition (storyvideo), The Science and Policy of Marijuana (storyvideo); Creativity, Genius, and the Brain (storyvideo); and Mental Illness Across the Ages (storyvideo). The next #neuroseries event will be in Spring 2017.

– Nicky Penttila


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