More than one hundred years ago, Sigmund Freud proposed his pioneering theory that hidden desires in our subconscious drive much of human behavior. While those theories have fallen out of favor in recent decades, scientists are now revisiting some of them – with new brain imaging tools. The hope is that having a direct window into the brain’s hidden processes will shed new light on anxiety disorders, and perhaps help to assess how well behavioral therapies, such as psychoanalysis, target the intricacies of the unconscious mind.

“One of the reasons people departed from Freudian concepts was because they weren’t very testable,” says Ronald Cohen, professor of psychiatry at Brown University in Providence, RI. “These types of [imaging] experiments would potentially be a more direct way of testing ideas that rose out of traditional psychoanalytic theory.”

One of Freud’s theories held that after a traumatic event, people might unconsciously associate a normally benign stimulus, say, a friendly golden retriever, with a previously fearful event, such as getting bitten by a Rottweiler. This theory seems to be true in the case of post-traumatic stress disorder (PTSD). Harmless sights and sounds, for instance, such as a bus traveling on down a street, can trigger a panic attack in someone with PTSD who was once involved in a bus crash. Furthermore, the sufferer may not be immediately able to pinpoint the cause of his or her anxiety attack.

Now scientists are using brain imaging techniques to explore how the unconscious fear signal may be turned up in people with PTSD and other anxiety disorders. To study the brain processes underlying anxiety, researchers use functional magnetic resonance imaging (fMRI) to measure a person’s brain activity while he or she looks at threatening signals, such as a picture of a fearful face. These frightening pictures will spark activity in the part of the brain known as the amygdala, which is part of the evolutionarily ancient brain involved in processing emotion and fear. To study the unconscious aspects of fear and anxiety, the researchers flash the ominous picture so quickly that subjects don’t consciously notice it – the brain reacts to the image, even though the person cannot determine whether or not they actually saw it.

Last year, Amit Etkin and collaborators at Columbia University showed that people who score high on anxiety tests have a stronger amygdala response to fearful faces when those images are presented below the level of conscious perception than people who score lower on the tests. Their findings suggest that the way people respond unconsciously to the world around them could also affect their daily anxiety levels.

Now the Columbia researchers want to determine if this lab observation can be used therapeutically. To do so, they plan to study 25 people with generalized anxiety disorder, first to determine whether this exaggerated amygdala response is present in people with the disorder, then to see if cognitive behavioral therapy – one of the best-established forms of talk therapy – can reduce the exaggerated unconscious response.

“We can use imaging as a way of evaluating the outcome of therapy,” says Eric Kandel, a Nobel-prize winning neuroscientist at Columbia University who’s collaborating on the project. “Maybe we can take people who have a large [anxiety] signal and turn it down as the result of a therapeutic experience,” he says.

People with PTSD show a similar exaggerated amygdala response to fearful faces. Jorge Armony, the Canada Research Chair in Affective Neuroscience at McGill University in Montreal, is studying both PTSD patients and people who have recently experienced a traumatic event and may develop PTSD. Armony and his team want to see if they can use the amygdala signal and other factors to predict who is vulnerable to the disorder and who will be resistant to therapy. “After 6 to 12 months, some people recover – what’s the difference between people who recover and people who don’t?” Armony asks.

While fMRI measures of unconscious processes are useful for studying populations of people with an illness, they’re not yet precise enough to diagnose an individual with a particular disorder, says Armony. “We can say that [statistically] a person with PTSD will have an exaggerated amygdala response, but that doesn’t mean that everyone will have it.”

Hans Breiter, a neuroscientist at Harvard Medical School, one of the first researchers to study amygdala activity with fMRI in the mid-1990s, agrees that a more extensive evaluation of the neurological changes in psychiatric disorders is necessary before the technique can have clinical applications. “This approach is promising and is the right first step, but scientists will need to study larger numbers of people with fMRI to get a better sense of the variability in brain functions that underlie anxiety and depression,” he says. “They may have very different [brain activity patterns] and may have very different therapeutic needs.” He predicts those larger-scale studies will happen within the next five years.

Breiter and other scientists are optimistic that fMRI can one day be used to evaluate the benefits of therapy, but they say it’s unclear what brain signals, conscious or unconscious ones, will be the most effective measure.

“The question still remains, how important are these subconscious phenomena?” says Cohen at Brown. “From a cognitive behavioral perspective, the conscious aspects of depression and anxiety are more important.”

Both Etkin at Columbia and Armony at McGill are also using fMRI to study conscious processes, such as attention, in people with anxiety disorders; and they plan to examine how these different factors may be important in different anxiety-related diseases, such as depression and eating disorders.

“There’s information processing going on in the brain that’s completely outside of awareness, which previously we could only investigate with psychoanalysis,” says Tom Insel, director of the National Institutes of Mental Health in Bethesda, MD. “Now you can track [those processes] with neuro-imaging – a tool that may be much more compelling.”

This is the second part in an occasional series exploring how new approaches to brain imaging could improve treatment for neurological and psychiatric disorders. The first installment, published on December 20, examined how patients can use real-time fMRI images of their own brains to control chronic pain.