Jack Nitschke, assistant professor and clinical psychologist at the University of Wisconsin-Madison School of Medicine and Public Health, says that high levels of brain activity in an emotional centre called the amygdala reflect patients' hypersensitivity to anticipation of adverse events.
At the same time, he adds, high activity in a regulatory region known as the anterior cingulate cortex is associated with a positive clinical response to a common antidepressant medication.
In a research article in the online edition of the American Journal of Psychiatry, the lead author writes that for individuals with anxiety disorders, the anticipation of a bad outcome can be worse than the outcome itself.
He points out that some people spend so much time worrying about getting into a negative situation or having a panic attack that the condition becomes debilitating.
"In an extreme situation, they might not even leave their home," he says.
With a view to finding out how the brain responds to anticipation, the researchers used functional magnetic resonance imaging (fMRI) to examine patients with generalized anxiety disorder (GAD) as they viewed a set of negative and neutral images.
The subjects were shown pre-image cues several seconds before each picture, so that they would know what to expect: a circle before a neutral image and a minus sign before an aversive image.
The researchers observed that GAD patients, though did not show any difference compared to healthy subjects in brain activation in response to the aversive or neutral pictures themselves, displayed unusually high levels of amygdala activity in response to both anticipatory cues.
Nitschke said that the response suggested that the patients were hypersensitive to the anticipation of any stimuli, even those they were told would not be negative.
"In response to both of those anticipatory signals, the GAD subjects - the anxious folks - are showing huge amounts of amygdala activation that is much more than what healthy control subjects showed," he said.
He further said that the high levels of amygdala activity seen in GAD patients reflected an indiscriminate and disproportionately large response to the idea that something negative might happen in the future, even in a lab setting where they knew nothing bad would actually occur.
"It suggests that there are differences in anticipatory brain processing in these individuals," he says, adding that the result has important implications for other related disorders as well.
"That's the crux of what's debilitating in people with anxiety disorders, whether it's panic disorder, obsessive compulsive disorder or post-traumatic stress disorder," the researcher said.
Nitschke said that the patterns of brain activity also seemed to hold predictive power for how patients would respond to treatment for their anxiety.
After brain scanning, the GAD patient participating in the study were administered an eight-week course of treatment with a common antidepressant called venlafaxine (Effexor).
The researchers said that clinical improvement on the medication was associated with higher levels of pre-treatment brain activity in the anterior cingulate cortex (ACC) in anticipation of both aversive and neutral stimuli.
They said that activity in the ACC, a regulatory brain region important for modulating emotional responses, has been shown to predict clinical outcome in patients with depression.
"When you look within the GAD patient population, that area is what predicts whether they respond to this treatment. What it suggests is that people who still have some residual functioning of that area are the people who are more likely to get better (with this drug)," says Nitschke.
Since anxiety disorders encompass a range of conditions with diverse symptoms and causes, Nitschke says, it becomes very important to select the most appropriate treatment approach for an individual patient.
Highlighting the fact that anxiety disorders are also frequently associated with depression, Nitschke's team revealed that they were planning to examine GAD patients with and without major depressive disorder.
"This is a critical new direction that the field is already moving in - using fMRI to predict treatment response. Hopefully we'll be able to use that eventually to determine what kind of treatment to provide to people," he said.