What is it about?

Brain mechanisms underlying how we react in rewarding and threatening situations The paper describes how changes in activity in area 14, a region of the frontal lobes of the brain, can affect responses to reward and threat. We tested the responses of marmosets, a small monkey, to the presence of an unfamiliar human, which can induce mild anxiety. These anxiety-like responses were considerably heightened as a result of enhanced activity in area 14. However, this increased responsivity to a threat is only seen when the threat is uncertain. It would appear that this area is not engaged when the threat is more imminent and certain. An example of this was an experiment where the animals learned that a sound predicted the presentation of a rubber snake behind a glass panel (a short, 20-minute test carried out once every two weeks on a maximum of 6 occasions). Marmosets are afraid of snakes; they therefore develop responses to the sound that predicts the presence of the snake, such as increases in blood pressure and vigilant behaviour. In this case, these expressions of fear-like behaviour are not affected by changes in area 14 activity. Meanwhile, we found that increased activity in area 14 reduces the anticipatory arousal responses that marmosets make in the presence of a sound which predicts access to a box of marshmallows, the marmosets' favourite treat, producing an "anhedonia-like" effect.

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Why is it important?

Anhedonia, or the loss of pleasure, is a core symptom of depression, a disorder affecting millions of people worldwide. Anxiety states also affect millions of people and often accompany depression. Here we observe effects resembling both these symptoms as a direct result of the induced increase in activity in area 14 in marmosets. This also mirrors changes in activity reported in a similar region during brain imaging of people with depression. You may ask, why do we have to make these changes in an animal if we can already see these changes in humans? The answer is simple: we do not know specifically which symptoms are linked to these changes. We also do not know whether these changes are causing these symptoms, or if they are a result of the symptoms, themselves. These are important questions because over 30% of people with depression and anxiety are not effectively treated by current therapies, and even if they are, we don’t know how and why one therapy works in one person but not another. One of the most likely explanations is that the underlying causes of depression and anxiety in the brain differ between individuals thereby necessitating the need for individualised treatment strategies. The studies described here, together with other work from our lab, help us to understand how disruptions in activity in different regions of the frontal lobe can lead to a similar phenotype or symptom, such as anxiety-like or anhedonia-like behaviour. This shows us how these symptoms can have different underlying causes and provides us with insight into the varied neurobiological substrates of depression and anxiety.


Anxiety and depression are having an immense impact on our society today. I hope that this article provides some insight into the work carried out to help us to understand them. Research into anxiety and depression is made challenging by the fact that they are diagnosed on the basis of symptom profiles, some of which can be very distinct between two people diagnosed with the same disorder, and some which are common to multiple diagnoses. I therefore hope that you will find this informative, in that it offers a perspective into how we are addressing these issues by studying activity changes in brain areas which can be linked to specific symptoms.

Zuzanna Stawicka
University of Cambridge

Read the Original

This page is a summary of: Ventromedial prefrontal area 14 provides opposing regulation of threat and reward-elicited responses in the common marmoset, Proceedings of the National Academy of Sciences, September 2020, Proceedings of the National Academy of Sciences, DOI: 10.1073/pnas.2009657117.
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