Summary: A new study identifies brain area 46 in the marmoset dorsolateral prefrontal cortex as a key regulator of mood-related behavior. When this region was inactivated, the animals showed less interest in rewards and heightened sensitivity to threats, mimicking depression and anxiety symptoms.
Researchers also discovered a functional network connecting areas 46, 32, and 25 that helps counterbalance these effects, but only in the left hemisphere. These findings highlight how brain circuits underpin motivation and emotion, with implications for targeted treatments using ketamine or non-invasive brain stimulation.
Key Facts:
- Depression Link: Inactivation of area 46 reduced reward-seeking, resembling depressive symptoms.
- Anxiety Link: The same inactivation heightened responses to threat, resembling anxiety symptoms.
- Treatment Insight: The network may explain why ketamine and brain stimulation therapies alleviate mood disorders.
Source: AAAS
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.
About this depression and anxiety research news
Author: Christian M. Wood
Source: AAAS
Contact: Christian M. Wood – AAAS
Image: The image is credited to Neuroscience News
Original Research: Closed access.
“Dysfunction in primate dorsolateral prefrontal area 46 affects motivation and anxiety” by Christian M. Wood et al. Science
Abstract
Dysfunction in primate dorsolateral prefrontal area 46 affects motivation and anxiety
The dorsolateral prefrontal cortex (dlPFC) is a higher-order brain structure targeted for noninvasive stimulation for treatment-resistant depression. Nonetheless, its causal role in emotion regulation is unknown.
We discovered that inactivating dlPFC area 46 in marmosets blunts appetitive motivation and heightens threat reactivity.
The effects were asymmetric—dependent on the left hemisphere only—and were mediated through projections to pregenual cingulate area 32.
The antidepressant ketamine blocked the appetitive motivational deficits through mechanisms within subcallosal cingulate area 25, an area linked with treatment success in dlPFC noninvasive stimulation.
Our data uncover an integrated prefrontal network for area 46 that contributes to positive and negative emotion regulation that may be core to our understanding of symptoms and therapeutic strategies for treatment-resistant depression and anxiety.
