Where the brain harbors unconscious fears

December 15, 2004

Whether it's the jump-out-of-your skin fright from the attack of a horror movie villain or the pulse-pounding encounter with a snarling dog, people react to fearful situations according to their basic unconscious level of anxiety. Now, researchers have pinpointed a region of the brain that filters such threats through a person's basic anxiety level.

Amit Etkin, Joy Hirsch, Eric Kandel and colleagues at the Columbia University College of Physicians and Surgeons that a specific region of the amygdala shows greater activation in unconscious processing of threats for people with higher levels of basic anxiety.

The researchers said that their experimental technique not only pinpoints an important structure involved in the neural circuitry of processing fearful stimuli, but also offers a way to measure the success of therapies for anxiety disorders.

The researchers concentrated on the amygdala because the almond-shaped structure in the depths of the brain is known to encode the emotional content of memories. The amygdala's influence on such encoding determines, for example, how indelibly the memory of a trauma is imprinted on the brain.

In their studies, the researchers showed volunteer subjects images of fearful faces, while the volunteers' brains were being scanned using functional magnetic resonance imaging (fMRI). The sight of fearful faces has been shown in many studies to trigger a fearful response in people. In the commonly used brain imaging technique of fMRI, harmless magnetic fields and radio signals are used to measure blood flow in brain regions, which reflects brain activity.

In their experiments, the researchers first asked the volunteers to fill out a questionnaire that determined their basic level of anxiety. They then told the volunteers only that they were to identify the color of the faces they would see.

The researchers then presented the volunteers with either fearful faces or neutral faces as a control. To measure conscious processing of the fearful faces, the researchers simply showed the subjects the faces. To elicit unconscious processing, the researchers briefly presented a fearful face, followed quickly by a neutral face--a widely used technique called "backward masking."

The researchers found that conscious processing of the fearful stimuli triggered higher activity in the "dorsal" region of the amygdala. In contrast, unconscious processing elicited activity only in the basolateral region of the amygdala.

Importantly, Etkin and colleagues found that the activity in the basolateral region was higher in people with higher anxiety levels and that the people with higher anxiety tended to react more quickly in the color-identification task after seeing a "masked" fearful face versus a neutral face, a sign that they were more stimulated.

"These findings provide a biological basis for the unconscious emotional vigilance characteristic of normal and pathological anxiety, as well as a new means for investigating the mechanisms and efficacy of treatments for anxiety states," wrote the researchers.

They wrote that "This study provides an experimental probe for unconscious processes that is sensitive to an individual's information processing biases, which may be useful for understanding how anxiety disorders are maintained and how the anxious outlook of these patients can be modulated by different forms of therapy."
The other members of the research team include Kristen C. Klemenhagen, Joshua T. Dudman, and Michael T. Rogan, René Hen of Columbia University College of Physicians and Surgeons. The study was supported in part by the Howard Hughes Medical Institute, the Kavli Institute for Brain Sciences, the Neurobiology and Behavior Research Training Program (NICHD HD 07430), an NIMH MD/PhD NRSA fellowship to A.E., NSF graduate research fellowships to K.C.K. and J.T.D., and by Johnson & Johnson (J.H.). The authors of this paper have declared a conflict of interest: "Eric Kandel is one of four founders of Memory Pharmaceuticals and is chairman of its Scientific Advisory Board. Memory Pharmaceuticals is concerned with developing drugs for age-related memory loss. Some of these drugs are also useful in depression and schizophrenia."

Amit Etkin, Kristen C. Klemenhagen, Joshua T. Dudman, Michael T. Rogan, René Hen, Eric R. Kandel, and Joy Hirsch: "Individual Differences in Trait Anxiety Predict the Response of the Basolateral Amygdala to Unconsciously Processed Fearful Faces"

Publishing in Neuron, Volume 44, Number 6, December 16, 2004, pages 1043-1055. http://www.neuron.org/

Cell Press

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