News Release

The machinery of forgetting fears

Peer-Reviewed Publication

Cell Press

While considerable research has been devoted to understanding the neural machinery involved in learning fears, less has been devoted to understanding how fears are diminished, according to Elizabeth Phelps and her colleagues.

Thus, they have performed experiments that reveal for the first time in humans details of the brain regions that become most active as fears are unlearned. The findings show that the walnut-sized brain region called the amygdala, which is a key structure in learning fears, is also involved in unlearning them. Also, they found that a connected area, called the ventral medial prefrontal cortex (vmPFC), appears to be critical for the retention of the extinction of fear.

Importantly, said the researchers, their findings mirror those of animal studies, providing one of the first demonstrations that the mechanisms of "extinction learning" may be preserved across species.

In their studies, the researchers asked volunteers to submit to experiments in which they would see either blue or yellow squares, with one color associated with a mild electric shock to the wrist, while the other was not. Before the experiments, the volunteers were allowed to set the level of the shock themselves so that it would be uncomfortable but not painful. The subjects' fear response was determined by measuring their skin conductance, which would increase with greater fear due to a rise in perspiration.

The subjects were first given a session in which the fear response was acquired. Then, on two subsequent days, they underwent sessions in which the fear response was extinguished. The extinction of the fear response was done by presenting the colored square previously associated with the shock, but without the following shock. Importantly, the researchers slowed extinction using a "partial reinforcement paradigm" in which the shock association with the square was gradually reduced, rather than immediately eliminated. Otherwise, said the researchers, the extinction learning would be too rapid in humans for analysis.

This analysis of the brain regions involved was done by conducting the experiments while the subjects' brains were being scanned by functional magnetic resonance imaging (fMRI). This widely used technique involves using harmless magnetic fields and radio signals to measure blood flow in targeted regions of the brain, which reflects the level of brain activity.

The fMRI studies revealed greater activity in the amygdala in response to the shock-associated square during fear acquisition--a finding that was expected from previous studies. However, an unexpected finding, said the researchers, was that during fear extinction the amygdala reversed its response, showing a greater response to the non-shock-associated square. This result, wrote the researchers, suggested that the amygdala was actively encoding information about the fear-related event and altered its response when new information was available during extinction as well as acquisition.

During the extinction phase, the pattern of activity in the vmPFC suggested that it was more involved in the retention of extinction learning, found the researchers.

"Understanding how fears are acquired is an important step in our ability to translate basic research to the treatment of fear-related disorders," wrote the researchers. "Understanding how learned fears are diminished may be even more valuable.

"The fMRI results support animal models suggesting that the amygdala may play an important role in extinction learning as well as acquisition, and vmPFC may be particularly important in the retention of extinction learning. The present results provide one of the first demonstrations that the mechanisms of extinction learning may be preserved across species," they wrote.

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Elizabeth A. Phelps,Mauricio R. Delgado, Katherine I. Nearing,and Joseph E. LeDoux: "Extinction Learning in Humans: Role of the Amygdala and vmPFC"

Publishing in Neuron, Volume 43, Number 6, September 16, 2004, pages 897–905.


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