Researchers identify neurocircuit that controls the brain's response to fear

Columbia University Medical Center researchers have identified the neurocircuit that controls the brain's response to fear. Results suggest that it may be possible to understand psychiatric disorders, such as anxiety or depression, from the underlying neurophysiology - workings of the brain.

They accomplished this using an adapted version of an attention control test, and a neuroimaging machine that enables analysis of function in the brain.

Published in the Sept. 21, 2006 issue of Neuron, the research is a continuation of work led by senior author Joy Hirsch, Ph.D., professor of neuroradiology and psychology, and director of the fMRI Research Center at Columbia University Medical Center. In a previous Neuron paper (Dec. 16, 2004), Dr. Hirsch and team identified a structure in the brain important for emotional processing - the amygdala - that was shown to light up with activity when people unconsciously detect fearful faces.

"People are exposed to an ever increasing amount of stimuli in our everyday lives, and so we realized that the brain must employ a processing mechanism to prioritize and refine responses -we don't run away from every loud sound or unexpected sight," said Dr. Hirsch. "Following the discovery of the amygdala's role in fear response, we decided to explore the finer points of the neurocircuitry of fear - how it is regulated/controlled in the brain."

To accomplish the tricky task of studying fear in the brain, she turned to a method described in the Dec. 2005 Nature Neuroscience. In a paper featured on the cover of this journal, Dr. Hirsch and Tobias Egner, a post-doctoral researcher in her lab, described how the Stroop test, a psychological test of mental vitality and flexibility, can be adapted to enable the observation of control mechanisms in the brain, using a high-resolution version of functional magnetic resonance imaging (fMRI).

The standard Stroop test asks participants to name the ink color of a printed color word. Performance is typically worse if word and color are incongruent (e.g., YELLOW printed in red ink) than when the two attributes are congruent (RED printed in red ink).

For the 2006 Neuron paper, Dr. Hirsch and her team developed an emotional Stroop test with fearful and happy faces, with FEAR or HAPPY written across the images. Working with 19 healthy volunteers, the test was administered while participants underwent an fMRI scan.

Based on neural activity, they identified activity in the rostral cingulate (rACC) region of the brain - a region neuroscientists had not been previously able to define - which turned on/off the amygdala's fear response. For example, if FEAR was shown across a happy face, the amygdala would light up and then the rACC would quickly turn it off when the happy face registers. But if the face is fearful, the rACC would retain activity in the amygdala for a longer amount of time.

"This paper adds important regulatory circuit information about the fear response in the amygdala," said Dr. Hirsch. "For example, if someone is walking on an empty street at night and hears a loud banging sound in the near distance, the amygdala would immediately light up. But instead of always running in the opposite direction from the sound, once the source is determined, the rACC determines if action is needed or not. For example, if it was a car door slamming, the rACC would shut down the amygdala."

"Based on these findings, tailored treatments may someday be developed based on the biology of the person's disease," said Eric Kandel, M.D., Howard Hughes Medical Institute senior investigator, Fred Kavli Professor and Director of the Kavli Institute for Brain Sciences at the Columbia University College of Physicians and Surgeons (P&S), who was also involved in the research. "For example, if someone with anxiety has a disturbed functioning of part of the amygdala or a disturbed functioning of rACC control mechanism and treatment could be based on the individual's specific problem."

The research team that worked on the 2006 Neuron paper also included first author, Amit Etkin, an M.D./PhD student that worked in both Dr. Hirsch's and Dr. Kandel's research laboratories; Tobias Egner, a graduate student; and Daniel Peraza, a Columbia University Medical Center student.