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Worried sick

New insight on the neurobiology of anxiety


Date: April 18, 2016
Sitio web del Weizmann

It is known that anxious people have a tendency to respond to ordinary experiences in an overly emotional way, yet the mechanisms are not well understood. A recent study by neurobiologist Prof. Rony Paz of the Weizmann Institute shows evidence that anxiety is biologically based.

The new study, published in Current Biology in March, shows that people diagnosed with anxiety are less able to distinguish between a neutral, “safe” stimulus - in this case, the sound of a tone - and one that is objectively stress-inducing, because it was previously associated with losing money. In other words, anxious people show a behavioral phenomenon known as “over-generalization” of outside stimuli. Moreover, Prof. Paz and his colleagues showed that these differences were reflected in the activity of certain brain regions through functional magnetic resonance imaging (fMRI).

The scientists trained patients diagnosed with generalized anxiety disorder to associate three distinct tones with one of three outcomes: money loss, money gain, or no consequence. The participants were then presented with one of several new tones and were asked whether the tone was one they had heard before while in training. If they were right, they were rewarded with money.

The best strategy would be to take care not to mistake (or generalize) a new tone for one they had heard in the training phase. But people with anxiety were more likely than healthy controls to think that a new tone was one they had heard earlier. That is, they were more likely to mistakenly associate a new tone with the earlier experience of money loss or gain. Those differences were not explained by differences in participants’ hearing or learning abilities. The research shows that they simply perceived sounds that were earlier linked to an emotional experience differently.

“We show that in patients with anxiety, emotional experience induces plasticity in brain circuits that lasts after the experience is over,” says Prof. Paz. “Such plastic changes occur in primary circuits, and these later mediate the response to new stimuli. The result is an inability to discriminate between the experience of the original stimulus and that of a new, similar stimulus. Therefore anxiety patients respond emotionally to the new stimuli as well and exhibit anxiety symptoms even in apparently irrelevant situations. They cannot control this response: It is a perceptual inability to discriminate.”

The study was a collaboration between psychiatrist Dr. David Israeli, Head of Psychiatry at Kaplan Hospital in Rehovot, and Prof. Paz, and it was led by Dr. Offir Laufer, then a PhD student in Paz’s group.

Imaging derived from fMRI scans of the brains of people with anxiety and those of healthy controls revealed differences in the activity of several brain regions. These differences were mainly found in the amygdala, a region related to fear and anxiety, as well as in the primary sensory regions of the brain. These results strengthen the idea that emotional experiences induce long-term changes in sensory representations in anxiety patients’ brains.

The findings might help explain why some people are more prone to anxiety than others. The underlying brain plasticity that leads to anxiety isn’t in itself bad, Paz says. “Anxiety traits can be completely normal; there is evidence that they benefitted us in our evolutionary past. Yet an emotional event, sometimes even a minor one, can induce brain changes that can potentially lead to full-blown anxiety,” he says. Understanding how the process of perception operates in anxiety patients may help lead to better treatments for the disorder.


This work was supported by I-CORE; ISF; the EP7 Human Brain Project; and Minerva-Foundation grants.

Prof. Rony Paz’s research is supported by the Adelis Foundation; the Sylvia Schaefer Alzheimer's Research Fund; the Irving and Dorothy Rom Family Discovery Endowment Fund; Pascal and Ilana Mantoux, Israel \ France; the Minna-James-Heineman Stiftung; and Gary and Kary Leff, Calabasas, CA.


Prof. Rony Paz

Prof. Rony Paz