Dateline: 11/12/02

In a discovery that could bring rapid, non-drug relief to sufferers panic and anxiety disorders, researchers funded by the National Institute of Mental Health (NIMH) report having detected an "all clear" signal in the brain, that, when stimulated, turns off fear.

The research team, led by Dr. Gregory Quirk and Mohammed Milad, Ponce School of Medicine, Puerto Rico, have reported success in turning off panic responses in laboratory rats conditioned to freeze in fear when exposed to tones they associate with electric shock. 

Finding the Source of Fear
According to Quirk and Milad, our feelings of fear and anxiety come from an area in the front part of the brain called the prefrontal cortex. Electronically stimulating this area of the brain temporarily extinguishes fear and anxiety responses by mimicking the brain's own "safety signal," report the researchers.

"Repeated exposure to traumatic reminders without any adverse consequences causes fear responses to gradually disappear," explained Quirk. "Such reduction of fear appears to be an active rather than passive process. It doesn't erase the fear association from memory, but generates a new memory for safety."

Quirk and Mohammad first recorded the brain activity of rats as they were being fear-conditioned — taught to fear a certain tone by repeatedly pairing it with an electric shock. They then recorded brain activity as the conditioned fear was eliminated by repeatedly allowing the rats to hear the tone without the shock. Eventually, the rats no longer froze when they heard the tone.

Their findings, say Quirk and Milad, provide evidence supporting a hypothesis first put forward by Pavlov in 1927, that conditioned responses, like fear and anxiety, can be eliminated. The term "extinction" is used to describe the elimination of a conditioned response by repeatedly presenting the conditioned stimulus (the tone) without the related negative side-effect (the shock). 

Finding the Brain's 'Safety Signal'
By analyzing the brain activity data , Quirk and Milad were able to isolate specific neurons near the middle of the prefrontal cortex that became extremely active only when the tone was sounded without the shock. This activity, they surmised, proved to be the brain's way of signaling that the tone no longer meant a shock was coming -- i.e., the brain's "safety signal."

When these neurons were electrically stimulated, the researchers observed that rats conditioned to associate the tone with a shock immediately began to show little fear response. Eventually, the rats showed no fear of the tone even without the electronic stimulation. 

Possible Applications in Humans
The NIMH estimates that up to 8-percent of all Americans suffer from some form a variety of anxiety disorder, ranging from phobias to debilitating cases of obsessive-compulsive behavior and post-traumatic stress disorder. Current treatments of anxiety disorders typically involve either long-term programs of therapy called "intensive exposure therapy," or the use of powerful and potentially dangerous psychiatric drugs.

Quirk and Milad speculate that application of their research into stimulating parts of the prefrontal cortex using an experimental technique called transcranial magnetic stimulation will lead to faster, safer and drug-free relief for anxiety disorder patients.

• Quirk and Milad's study, titled "Neurons in medial prefrontal cortex signal memory for fear extinction," appears in the Nov. 7, 2002 edition of Nature magazine. (Paid subscription required for access to complete articles.)