Dysfunction in primate dorsolateral prefrontal area 46 affects motivation and anxiety

Area of Science:

• Neuroscience
• Psychiatry
• Brain Stimulation

Background:

• The dorsolateral prefrontal cortex (dlPFC) is a key brain region for cognitive functions.
• Noninvasive brain stimulation of the dlPFC is a promising treatment for depression.
• The precise role of the dlPFC in emotion regulation remains unclear.

Purpose of the Study:

• To investigate the causal role of the dlPFC, specifically area 46, in emotion regulation.
• To explore the neural pathways involved in dlPFC function related to emotion.
• To understand the mechanisms of antidepressant action in relation to dlPFC circuitry.

Main Methods:

• Inactivation of dlPFC area 46 in marmoset models.
• Assessment of behavioral responses related to appetitive motivation and threat reactivity.
• Tracing neural projections from dlPFC to other brain regions.
• Pharmacological intervention with ketamine to examine its effects on dlPFC-mediated behaviors.

Main Results:

• dlPFC area 46 inactivation blunted appetitive motivation and heightened threat reactivity.
• These effects were lateralized to the left hemisphere and mediated via projections to the pregenual cingulate area 32.
• Ketamine treatment reversed motivational deficits via mechanisms in subcallosal cingulate area 25.

Conclusions:

• The dlPFC, through specific hemispheric pathways, plays a critical role in regulating both positive and negative emotions.
• These findings elucidate an integrated prefrontal network relevant to depression and anxiety.
• The study provides a neural basis for understanding treatment-resistant depression and optimizing therapeutic strategies.