New experiments by Christian Wood and colleagues suggest that the marmoset brain area 46 (A46) in the dorsolateral prefrontal cortex is key to a functional network that regulates positive and negative emotion-related processes. The findings relate directly to motivation and responsiveness to threat, which play important roles in depression and anxiety. The study also sheds some light on how non-invasive treatments such as transcranial magnetic stimulation and the drug ketamine may work within the dorsolateral prefrontal cortex to reduce depression and anxiety. Wood et al. show that inactivation of A46 blunts reward-seeking behavior (a hallmark of depression) and increases responsivity to threat (a hallmark of anxiety). They further identified a functional network, linking A46 with areas 32 and 25, that works to ameliorate the effects of A46 inactivation. These effects take place only within the left hemisphere of the marmoset brain, as some previous studies of neuromodulating therapies in patients have shown. A better understanding of this brain network could help to personalize treatments for depression and anxiety, as Michael Treadway discusses in a related Perspective.
Journal
Science
Article Title
Dysfunction in primate dorsolateral prefrontal area 46 affects motivation and anxiety
Article Publication Date
21-Aug-2025