fMRI Finds that Expectant Brains Predict Response to Anxiety Treatment

January 13, 2009
Chris Cole

Researchers report that high levels of activity in the amygdala "reflect patients' hypersensitivity to anticipation of adverse events," while high activity in the anterior cingulated cortex is associated with "a positive clinical response to a common antidepressant medication."

Researchers from the University of Wisconsin-Madison Waisman Laboratory for Brain Imaging and Behavior report that high levels of activity in the amygdala “reflect patients' hypersensitivity to anticipation of adverse events,” while high activity in the anterior cingulated cortex is associated with “a positive clinical response to a common antidepressant medication.”

Using functional magnetic resonance imaging (fMRI), the team examined patients who had generalized anxiety disorder (GAD) while they viewed negative and neutral images. Several seconds before each picture, participants were shown cues (circle for neutral, minus for negative), allowing them to know what to expect. Although no differences were seen between patients with GAD and healthy subjects in regards to brain activation in response to the pictures, those in the former group “displayed unusually high levels of amygdala activity in response to both anticipatory cues.” These responses suggest that patients with GAD are hypersensitive to anticipation of any stimuli even when they know that it won’t 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," said Jack Nitschke, assistant professor and clinical psychologist, School of Medicine and Public Health, and lead author of the study. "It suggests that there are differences in anticipatory brain processing in these individuals…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.”

Taking their research one step further, Nitschke and colleagues found an association between clinical improvement following eight weeks of treatment with venlafaxine and higher levels of pre-treatment brain activity in the anterior cingulated cortex in anticipation of both negative and neutral stimuli. "When you look within the GAD patient population, that area is what predicts whether they respond to this treatment," said Nitschke. "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 venlafaxine.

Noting that treatment selection is incredibly individualized in patients with anxiety disorders, as a range of diverse conditions that could also be accompanied by depression are at play, the researchers plan to examine patients with GAD who also have major depressive disorder. "This is a critical new direction that the field is already moving in — using fMRI to predict treatment response," explained Nitschke. "Hopefully, we'll be able to use that eventually to determine what kind of treatment to provide to people."